MODULE 4

PHARMACOLOGY &
PHARMACOKINETICS
TOXICOLOGY
INCOMPATIBILITIES & ADVERSE DRUG
REACTION

PHARMACOLOG
Y

Pharmacology ➢Study of selective biologic activity of drugs

➢Study of substances that interact w/ living systems through chemical processes, especially by binding to regulatory
molecules &
activating or inhibiting normal
processes
✸Medical Pharmacology is the area of pharmacology concerned with the use of
chemicals
in the prevention, diagnosis, and treatment of disease, especially in humans. Drugs ➢
Articles recognized in the official USP, official Homeopathic Pharmacopeia of the US or the official NF, or any supplements to any of them

➢Articles for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals. ➢Articles, other
 than food intended to affect the structure or any function of the body of man or other animals ➢Articles intended for use as
component of any articles specified in clause 1, 2, or 3: but does not include devices or their components parts

or accessories. ➢Substances that act on biologic systems at the chemical (molecular) level and alter their
functions(Katzung)

✸Drug receptors The molecular components of the body with which drugs interact to bring about their effects
✸ Nature of drugs Drugs are chemicals that modify body functions. They may be ions, carbohydrates, lipids, or
proteins.
They vary in size from lithium (MW 7) to proteins (MW 50,000) Branches of Pharmacology
Pharmacodynamics is a branch of pharmacology that focuses on the study of biochemical & physiological effects of
drugs & the
mechanisms by which they produce such effects. ” what the drug does to
the body” deals with interaction of drugs w/ receptor molecular consequences Biological effect study of the biochemical
& physiologic effects of drugs in biological systems Pharmacokinetics is the quantitative measurement of drug absorption,
distribution, and elimination (i.e., excretion and metabolism) and
includes the rate processes for drug movement into the body, within the body, and out of the body. ”What the body does to
the drug” examines the moment of drug over time through the body Pharmacotherapeutics Rational use of Dugs in the
management of diseases Toxicology branch that deals w/ the undesirable effects of chemicals on living systems, from
individual cells to complex ecosystems Classification of Drugs:
♦ Functional
modifiers
Alters certain physiologic functions & activities of body
cells Examples:
• Sensation of pain (analgesics,
anesthetics)
• Tachycardia (beta-
blockers)
• Morphine narcotic analgesic; pain
perception
• Bevacizumab for cancer; inhibit VRGF (vascular endothelial growth factor) -
vascularization ♦ Replenishers
Replaces/ replenish endogenous substance that are lacking/ deficient/
absent Example:
• DM type 1
(Insulin)
• Pernicous Anemia (Vit
B12)
an autoimmune disease when immune system produces antibodies that target the parietal cells of the
stomach that
leads in inhibiting/ decrease HCL & Intrinsic Factor (which are important in VitB12 absorption *having pernicious
anemia can lead to Megaloblastic Anemia (cause neurologic effect) *Vit B12
absorbed in terminal ileum; sources: meat products *Causes of VitB12 deficiency:
a. Chronic use of Proton pump Inhibitor b. H2 Blockers c.
Diphylobotrium latum (fish tapeworm) competes in Vit B12
absorption
• Diarrhea (ORS)
♦ Diagnostic Agents
Diagnosis or confirmation of diagnosis of certain
diseases Example:
• Edrophonium (Tensilon®) Myasthenia
gravis
• Pulmonary challenge test; diagnosis of bronchial asthma
(Histamine)
• Radiopaque; to visualize the outline of the GIT (Barium
sulfate)
 • Dobutamine
Schemia
• Dobutamine/ Dipyridamole used in pharmacologic stress
testing
• Tc99m stratum
Thallium 201
Dx: Myocardial Ischemia O2 cells are still
viable
Myocardial Infarction no O2 supply cells are dead (necrosis)
♦ Chemotherapeutics Agents
Agents used to kill/ inhibit growth of cells considered as foreign to the
body
• Anti-infectives
• Anti-microbials
• Anti-
neoplastics
• Anti-cancer
Principles of Pharmacodynamics: Mechanisms of
Drug Action

Classification of mechanisms based on the concepts of

target proteins

i. Non target protein-

mediated
a. Direct chemical
interaction
• Chelating
agents
o Dimercaprol for Pb, Ag, Hg, Ar o EDTA (emergency treatment for hypercalcemia,
control of Ven arrhythmia due to digitalis o Calcium EDTA (Treatment of acute &
chronic lead poisoning) o Defuroxamine (Desferal®) for Fe toxicity
• Neutralization
reactions
o Antacids Mg++ & Ca++ for HCl o
Ammonium chloride o Sodium bicarbonate
b. Colligative mechanism/mass effect
• Lactulose
• Mannitol (osmotic diuretic – renal tubule-early loop of
henle)
Creates a n osmotic gradient across renal tubule c.
Counterfeit incorporation
• Affects gene
transcription
• (purine & pyrimidine analogues; ex. Flucystosine, 5FU, &
antimetabolites)

ii. Target protein-

mediated
a. Structural
proteins:
• Tubulin, proteins present in microtubules (colchicines, vinca
alkaloids)
• Keratin (Griseofulvin increase absorption w/ fatty food through pinocytosis) b.
Regulatory
1) Transport
 Proteins
(a) Voltage-gated Na channels detect changes in
environment
• Inhibited by: Local Anesthetics, Class I Antiarrhythmic, Phenytoin, Carbamazepine (b) Voltage-
gated Ca channels
• Blocked by CCBs (-
dipine)
• Non-DHP (Verapamil, Diltiazem) (c) Voltage-gated
K channels
• Blocked by class III antiarrhythmic
(Aminodarone)
• Sulfonylureas – Type 2 DM ; insulin secretagogues 2)
Enzymes
• MAO (Moclobemide, Phenelzine, , Isocarboxazide, Tranylcypromine Selegeline) -
MPITS
M – Selective MAOA

inhibitors PIT - Non

selective S - Selective
MAOB inhibitors
• COMT (-capones) management in
PD
• ACE (-prils) –aka
Kininase
• COX
(NSAIDs)
• AChe (Organophosphates) 3) Carrier Molecules (Na-
K ATPase, K-H pump, Re-uptake 1)
• Na-K ATPase pump
(Digoxin)
• K-H ATPase pump (proton pump inhibitors; -prazoles 4)
Receptors
Receptors A molecule to which a drug binds to bring about a change in function of the biologic system
Functional macromolecular component of a cell w/ a specific stereochemical configuration w/ which a ligand interacts in a lock
& key fashion initiating a chain of biochemical events that leads to a therapeutic effect * Receptor site Specific region of the
receptor molecule to which the drug binds * Receptor affinity of the drug a factor that will determine the number of drug-
receptor complexes formed. * Inert binding molecule or site A molecule to which a drug may bind without changing any function
*Spare receptor Receptor that does not bind drug when the drug concentration is sufficient
to produce maximal effect; present when Kd > EC50 * Effector Component of a system that accomplishes the biologic effect after
the receptor
is activated by an agonist; often a channel or enzyme molecule Type I (Ionotropic) receptors; 9ligand-gated ion channels)
• Channel linked receptors
• Controls movement of ions in & out the cell
• Effect seen in milliseconds
Examples:
o Nicotinic receptors (ligand-gated Na channel)
Benzodiazipine Frequency Phenobarbital Duration o Inhibited by NMBs & ganglionic blockers o GABAA receptors (CI channel)
o Inhibitory NT o Facilitates iflux of CI inons resulting to hyperpolarization o Stimulated by benzodiazepines, barbiturates) Type II
(Metabotropics) receptors (Signal transduction pathway or effector system)
• 7-transmembrane spanning receptors (serpentine receptors)
• G protein linked
Gs activate adenylyl cyclase: increase cAMP or the release of secondary messenger
- Beta receptors
B1 increase contraction rate (heart) B2 bronchodilation (lungs) Gi inhibit adenylyl cyclase; decreases cAMP
-Alpha-2, 5-HT1A , muscarinic, histamine receptors Go unknown Gq Increase phospholipase C activity (splits Phospatidylinositol
4,5-bisphosphate);
increase IP3, DAG, & cytoplasmic Ca2+
-Ex, alpha-1 receptors, muscarinic Gt increase cGMP phosphodiesterase: decrease in cGMP
 - Effects seen in seconds Type III (Enzyme-linked) receptors translocation of glucose trensportation
• Tyrosine kinase (insulin)
• Guanylyl cyclase (cGMP as 2nd messenger)
• Conversion of GTP to GMP
• Involved in the action of NO
• Effects seen in minutes
• Example:
o Insulin receptors o ANP receptor (Atrial natiuretic peptide) Type IV (Gene-transcription-linked) receptors
• Nuclear or Cytoplasmic receptors
• Effects seen in several hours
• Examples
o Steroid receptors (glucocorticoids, minercorticoids) o Thyroid hormone receptors o Sex hormones Type I, II, III (located in the
cell membrane) Type IV (cytoplasm/ nucleus)
Ganglionic blockers, Nn
Trimethapan Mecamylamine Hexamethoprim Neuromuscular blockers, Nm succinylcholine “Kiss & α1- Gq α2- Gi β1-Gs β2-Gs
Kick” M1-Gq M2-Gi M3-Gq
DNA DNA RNA CHON MAOi
DNA synthesis Transcription Translation
Properties of
Receptors:
(a) Saturability a finite number of receptors per cell, or per weight of tissue or protein is present as
revealed
by a saturable binding curve (b)
Specificity Lock & key fashion of drug-receptor interaction
Dugs should be structurally complementary to the receptor (c) Reversibility The
drug should bind to receptors then dissociate in its non-metabolized form
This distinguishes receptor-drug interaction from enzyme-substrate interactions
Drug-Receptor Interaction/ Drug protein target
❖ Affinity ability to bind to a receptor ❖ Intrinsic activity ability to generate a series of
biochemical events leading to an effect/ biological changes

Mechanism of Drug Action: Agonist binds and causes a response (A drug

that activates its receptor upon binding)
whose responses resembles the effect of the endogenous ligands. interact w/ specific cellular
constituents, known as receptors, and elicit an observable biological response have both affinity for
the receptor & intrinsic activity Example: Bethanecol directly stimulates cholinergic receptors & is thus
an agonist Full Agonist produces all the expected effect of the binding to a receptor to the target
protein
Example: Morphine – opioid receptor Partial Agonist
have no intrinsic activity but have affinity
cause opposite effect produces some of the expected effect Interact w/ the same receptors as full
agonist; however their affinity for the elicit the same maximum response Have lower intrinsic activity
than full agonist; however their affinity for the receptor can be greater than , or less than, or equal to that of
full agonist. Example: Nalbuphine (Nubaine®) -analgesic
-has no bradicardiac effect Inverse Agonist
a drug that inhibits baseline level of activity, in the absence of agonist)
a ligand which produces an effect opposite to that of an agonist occupying the same
receptor

Antagonist Inhibit the actions of

agonist
Pharmacological Antagonist -lack intrinsic activity & produce effects by competitively & noncompetitively inhibiting the
action of the
endogenous molecules of the receptors -A drug that binds without activating its receptor and thereby
prevents activation by an agonist a. Phamacologic – Pharmacodynamic Antagonists
Produces an effect opposite that an agonist by binding to same
receptor
 Epinephrine – Propanolol (B1 receptor)
Organophosphate – atropine (M receptor) may
be two types:
Competitive Antagonist act by interfering w/ binding of the endogenous ligand to the receptor as
the agonist
-A pharmacologic antagonist that can be overcome by
increasing the
concentration of agonist in a reversible manner -There is shift of the agonist log-concentration-effect curve to the right w/out a
change in the slope or aplitude Example: Propanolol competes w/ catecholamines for binding w/
adrenergic B-receptor Tamoxifen competes w/ estrogen receptors fro binding w/ estradiol
Noncompetitive Antagonsit (Irreversible) acts by interacting w/ the non-ligand binding site of the
receptor
(e.g, through covalent modification), such that normal binding
of the endogenous ligand to the receptor is irreversible
inhibited
(A pharmacologic antagonist that cannot be overcome by increasing agonist
concentration) Example: Monoamine Oxidase (MOA) inhibitors such as tranyl
cypranine
(Parnate) initially interact w/ MOA in a reversible manner but then form covalent adducts that irreversible
inhibit MOA b. Pharmacologic – Pharmacokinetic Antagonist
produce an effect opposite that of an agonist or reduce the effect of the agonist by modifying the
agonist’s ADME
Cholestyramine (bile acid binding
resin)
Can also bind digitalis, warfarin & Vitamin ADEK (reduce absorption) Phenobarbital & Warfarin
interaction
Enzyme inducer (phenol) reduces effects of warfarin c. Chemical Antagonist
react w/ one another, resulting in the activation of both compounds.
antagonize other drugs by direct chemical
interaction
[A drug that counters the effects of another by binding the agonist drug (not the receptor)] Example: The anticoagulant
heparin, an acidic polysaccharide, is chemically
antagonized by protamine, a basic protein, via an acid-base interaction. Chelating agents can be used as
antidotes for metal poisoning
Ethylenediaminetetraacetic acid (EDTA) chelates calcium
& lead Penicillamine chelates copper Dimecaprol
chelates mercury, gold, antimony, & arsenic
Deferoxamine - Fe oversoe
d. Physiologic (Functional)
Antagonist
act independently at different receptor sites often yielding opposing
action.
(A drug that counters the effects of another by binding to a different receptor and causing opposing effects) produce
antagonistic physiological action through binding at separate/different receptors.
*The adrenergic & cholinergic nervous system frequently produce this type of
antagonism
Example: Epinephrine & acetylcholine action the sympathetic & parasympathetic autonomic
nervous
system, respectively & their effects are antagonistic to each other. Epinephrine = Bronchodilation (B2)
+ Vasodilation (A1) Histamine = Bronchospasm + Vasodialtion Inc HR due to Atropine (M blocker)
Dec HR due to B-blocker e. Partial Antagonist inhibit the endogenous ligand from binding the
receptor but possess some intrinsic activity
Example: Nalorphine is partial antagonist for opiate receptor f. Neutralizing Antagonist
occurs when two drugs bind w/ each other to form a inactive compound Example: Digoxin-
binding antibody used in digoxin overdose
acts by sequestering the drug resulting in the formation of an inactive
complex
Types of Chemical Bonds; (Molecular aspects of
Binding)
a) Covalent strongest bond (irreversible effects) b) Electrostatic very common type due to the attraction
between oppositely charged groups c) Hydrogen a strong interaction which arises from the sharing of
hydrogen atom between an acidic & basic groups d) Van der Waals weak interaction between polar or
nonpolar molecules e) Hydrophobic major driving force for nonpolar drug or receptor binding site

Regulation of
Receptors:
I. Downregulation/ desensitization/ refractoriness - may explain the development of tolerance to
drugs
- maybe homologous (receptor itself) or
heterologous
(include downstream proteins that participate in the
signaling)
• Downregulation vs. Desensitization (reversible after laps of time) II.
Upregulation/ supersensitivity

Dose- response relationship (dose-response

curves)
o Classical Receptor Occupancy Theory Ariëns and
Stephenson:
KA A = R ⬄AR stimulus response Receptor Occupancy is given by the response to the drug
Langmuir Adsorption Isotherm: [A]/([A]+ Kd) A+
where Kd= dissociation constant of drug-receptor A
complex × Efficacy × R receptor
Kd
Total Receptor-mediated
number
stimulus:
Response = f (ENtotal . Xa/ (Xa Relationship between
+ Ka) is an equation showing occupancy of receptor &
Relationship between response to the drug
occupancy of receptor &

1. Graded dose-response curve shows the relationship between the degree of response w/ dose,
ie lowering of BP (a) Efficacy is the capacity to produce an effect
represents the ability of a drug to accomplish a specified effect o Ceiling effect maximum achievable response o Ceiling Dose minimum
produces the maximum effect (maximum allowable dose) (b) Potency is a measure of drug activity expressed in terms of the amount requ
an effect of given intensity.
reflects the amount of drug (the dose) required to cause an effect. (EC50) dose that produces 50% of the maximum
response. (c) Slope degree of change in response w/ dose (d) Variability, in effectiveness of a drug given to the same Px at
different times can be due to:
o Physiological factors (circadian rhythm) o Pathological factors (disease states/ health status) o Drug-induced variation (receptor down-regu
population of Px (Genetic/ environmental) 2. Quantal dose-response curve (shows how a population respond (quantal event) to a given
c
or death) plots the cumulative # of respondents may it be beneficial effect w/ increasing dose. ♦ Selectivity of
Drug Action
*The ratio (relationship) between the dose of a drug required to produce undesired effects (toxic or lethal) & the dose required to produce t
(therapeutics) 1. Therapeutic Index is a relative measure of the safety & effectiveness in laboratory studies.
used to indicate the ability of adrug to produce the desired therapeutic effect relative to a toxic effect.
• TD50 (Median Toxic Dose) the minimum dose that is toxic of the population

• ED50 (Median Effective Dose) the minimum dose that is effective for 50% of the population 2. Margin of Safety is more practical
term to describe the relative safety & effectiveness
is the ratio of the:

• TD0.1 (Minimal Toxic Dose) the minimum toxic dose for 0.1% of the population
• ED99.9 (Minimal Effective Dose) the minimum effective dose for 99.9% of the population
 Variation in Drug Responsiveness:
• Idiosyncracy (genetic differences which affects the drug metabolism)
• Hyporeactive vs. Hyperreactive
• Tolerance & Tachyphylaxis
• Mechanism of variation in Drug Responsiveness
Alteration in the concentration of drug that reaches the receptor
o Some may be predicted on the basis of age, weight, sex, disease state, or kidney & liver function of the px. Variation in concentration of
endogenous receptor ligand
o Propanolol will markedly slow the HR of Px whose catecholamines are elevated (pheochromocytoma) but will affect the
resting HR of a marathon runner Alteration in number or function of receptor
o Downregulation/ upregulation of receptors o May be used to explain withdrawals from long term use of drugs
Changes in components of response distal to receptor
o Clinically, changes in these post receptor processes represent the largest & most important class mechanisms that causes
variation in responsiveness.
Principles of Pharmacokinetics
Pharmacokinetics The actions of the body on the drug,
including absorption, distribution, metabolism, and elimination. Elimination of a drug may be achieved by metabolism or by excretion.
Processes: L Liberation
A Absorption D Distribution M Metabolism E Excretion R Response Transport Processes: Transport mechanism of the drug which it moves across
1
⇨ Movement of molecules from region high to low (along concentration gradient;) ⇨ Non-energy requiring (no external energy) ⇨ Major absorption process of most drugs (Predominant tra
Slowest process (inversely proportional to the membrane thickness) ⇨ Important process for small lipophilic molecules ⇨ Ex: Aspirin Factors affecting process:
(a) Fick’s law of diffusion Q = A × d (C1 –C2)/h
Where: Q= flux (movement of molecules) A= surface area of membrane d= diffusion coefficient
Most Drugs are absorbed or transported by passive diffusion, which depends on:
-pKa value of the solution -pH of the Solution -Lipid solubility of the unionized form
C1= higher concentration (soure) C2= lower concentration (destination) h= thickness of the semi-permeable membrane (b) Concentration gradient
Permeability Coefficient
the ratio of the number of molecules crossing per unit time to the concentration gradient (c) Particle size (d) Liposolubility degree of ionization (relation
form of the drug)
partition coefficient 2. Carrier-mediated transport
Features:
(a) Saturability
• Follows saturable kinetics (Michaelis-Menten, Enzyme kinetics)
• Ex. ASA <600 mg/day (1st day)
• ASA >600mg/day (0th order) (b) Selectivity
• Carriers have a specific stereochemical configuration, & will only allow transport of molecules that have configuration that fit into the carries binding site
competition/ inhibition
• Ex. Isoniazid & Vit B6
• Must be taken hours apart (About 2-3 hrs)
• Otherwise will compete for the carries & will inhibit each other (d) “poisoning” Example of carrier-mediated transports: (1) Active Transport movemen
concentration gradient (low to high)
requires energy (energy-consuming)
The Ileum sac of Guinea Pig is used fast transport process
for testing of Active Transport. important for polar molecules Ex: Na-K ATPase pump (sodium pump) (2) Facilitated Transport movement along c
gradient
no energy required Ex: Vit B12 (Cyanocobalamin), glucose uptake 3. Carrier Mediated In
1.) Vesicular Transport process of engulfing particles
doesn’t require aqueous solution to be absorbed Ex: Sabin Polio Vaccine Forms: Phagocytosis engulfment of large particles
Pinocytosis engulfment of small particles
cell drinking energy requiring important for large lipophilic molecules Ex: Griseofulvin, Vit ADEK (these drugs must undergo micelle formation) P
Endocytosis Absorption of material across a cell membrane by enclosing it in cell membrane material and
pulling it into the cell, where it can be released. Ex: Taking up of Glucose by the Insulin Receptor. Exocytosis Expulsion of material from vesicle

accomplished the primary mechanism of neurotransmitter release *Permeation Movement of a molecule (eg, drug) through the biologic medium
Drug permeation Most drugs are administered at a site distant from their target tissue. To reach the target, they must
permeate through both lipid and aqueous pathways. Movement of drugs occurs by means of aqueous diffusion, lipid diffusion, transport by special carriers, or by exocytosis and endocytosis
2.) Convective (Pore) transport transport thru water filled pores
 Factors affecting transport:
(a) Pore size (diameter is 7-10 A) allows passage of substances w/ MW around 150-400 (small substances only) (b) Charge of the pore lining
of ions w/ opposite charge) (c) Electrochemical gradient (same as concentration gradient) (d) Solvent drag- solvent may drag in ions or molec
channels 3. Ion-Pair Transport mechanism by which you transport drug w/ large ions

Note: Passive, Carrier-mediated, Convective transport (Drug must be in aqueous solution)

Pinocytosis (drugs must be in micellar forms)

Liberation
Dosage form to solution Release of Drug from the Dosage form should be in aqueous solution dissolution (rate-limiting step)
highly modifiable\able process For drugs to be absorbed they must be liberated from the dosage form & from an aqueous solution
Factors affecting liberation
o Formulation dependent factors (Tablet hardness, dissolution, & disintegration) Exceptions: Parenterals, Solutions

Effects: 1. Formulation of salt *alkali metal (soluble group)

2. Formulation of prodrug
in-vitro in-vivo Advantages: 1.) enhances drug absorption
Example: enalapril (ester) -esterase enalaprilat (carboxylic group) 2.) Facilitates the drug reaching its target site 3.) alter drug solubility
*chloramphenicol (water-solubility)
chloramphenicol palmitate ( slightly water-solubility) 4.) Facilitate formulation of dosage form
*methylprednisolone methylprednisolone acetate methylprednisolone Na succilate

(slightly H2O-soluble) (H2O-insoluble) (H2O-soluble)

Depot phase liberates the drug to slower rate

Absorption
from site of administration to systemic circulation is a physical phenomenon
Kinetic rate & extent of drug entry into the systemic circulation Physiologic rate & extent of disappearance of drug from site of administration *A drug
physiologically but not pharmacokinetically (ex: Metoprolol) Factors affecting absorption:
• Pharmaceutical factors (particle size, physical state of the drugs)
*chemical structure
Ex: Aminoglycosides the only bactericidal among protein synthesis inhibitor
polar drugs side effect: nephrotoxicity *variation in particle size *Natur
-Polymorphism exist two or more crystalline forms
Amorphous more soluble than crystalline Crystalline Example: Insulin short acting = 30-90 minutes after administration
= 100% amorphous Intermediate = NPH (Neutral Protamine of Hagedorn)
= 5-6 hours = 30% amorphous + 70% crystalline Long = 12-24 hours
= 100& crystalline Anhydrous -more soluble
vs. Hydrous
-less soluble -hydrolysis resis
Ex: Enteric Coated prevent GI irritation
protects drug from stomach aid enhances absorption Fick’s law of diffusion
• Gastric Emptying Time (Factors that increase/ decrease GET)
*when gastric emptying time increase, the gastric emptying rate decreases, the absorption rate decreases. Factors GET ( GER)
• High CHON/ fat
• Cold food
• Gastric ulcers
• Stress
• Vigorous exercise
• Lying on the left side
• Drugs (Antidiarrhea- antimotility agents)
• Hunger
Factors Influencing Gastric Emptying: 1. Volume of Liquid intake 2. Type of Meal Fac
• Spicy foods
• Extreme temp. of meal
• Gastrectomy
• Depression
• Mild Exercise
• Lying on right side
• motility enhancing agents:
metoclopramide domperidone cisapride]
3. Osmotic Pressure 4. Physical state of Gastric content 5. pH of the Stomach 6. Drugs to be taken 7. Body position 8. Viscosity of stomach content 9. Em
Disease State 11. Presence of bile salts 12. Exercise 13. Age of a person
• Diabetes Mellitus
Mechanism of Absorption of Drugs (in order of their importance):
*Gastric-Emptying rate limiting step for absorption of oral solution
1. Passive Diffusion 2. Convective/Pore Transport
• Dose size administered
• pH of the absorbing environment (affects ionization of the drug)
• area of the absorbing surface (lungs biggest SA, small intestines
• degree of perfusion
3. Active Transport 4. Facilitated Transport 5. Ion pair Transport 6. Vesicular Transport
• Physical factors that affect absorption
- Blood flow - Surface area for absorption - Contact time
Distribution
transport or net tansfer of drugs from the systemic circulation to the site of action describes the movement of drug
molecules across different body compartment
Physiologic Factors affecting distribution:
Cardiac output: volume of blood pumped by the heart per minute
- Px with CHF may have delayed drug effect due to poor distribution Regional blood flow (% of CO that reaches specific
tissue)
- Fraction of the CO going to particular organs/ tissues - Organs w/ high RBF (liver (25%), kidney(25%), lungs(100%), brain) - Organs with
low RBF (bone, adipose) - Capillary Permeability - *Capillary delivery oxygenated blood to tissues; smallest vein two important
parameters of drug distribution: o PB (Protein binding) o Vd (volume of distribution)
● Protein Binding limits the access of drugs to certain body compartment
binding of the serum proteins decreases distribution
• Free form (unbound) can reach the site of action, metabolized, excreted
• Bound form (serves as reservoir)
• Examples of proteins & substrates
o Albumin weak acidic (dominant) o Alpha 1 glycoprotein weak basic
drugs o Globulin binding formones
• Significant protein binding= 80%; Penicillins have >97%PB
• Significant of PB
o Provide slow release form of a drug (repository, resulting to extended affect) o Limits access to certain body
compartment o Can make the drug prone to drug-drug interaction
• Examples of drugs with high protein binding:
o Diazepam, Diditoxin, Indomethacin, Tolbutamine, Warfarin, Midazolam o These drugs cam compete w/ each other
o Results to increase effect (toxicity) of the object drug o The known importance of protein binding: Transport
function reflected w/ drugs of low solubility in water Buffer function to maintain a relatively constant
concentration

Drugs that are more than 90% bound to plasma proteins:

- Amitryptilline - Chlorpromazine - Cloxacillin -
Flurazepam - Lidocaine - Lorazepam - Naproxen -
Phenylbutazone - Penicillin - Phenytoin - Propanolol -
Warfarin

Decrease Albumin Level:

- Pregnancy - Nephrotic Syndrome - Trauma - Chronic Liver
Disease - Burns

Factors affect the protein binding drugs:

- Pregnancy - - Hypoalbuminemia - - Uremia
• Examples of drugs with high Vd:
• Atropine, CHloroquine, Digoxin, Fluoxetine, Imipramine & TCAs, beta blockers
• Examples of Drugs with low Vd:
• Chlorpropamide, Furosemide, Tolbutamine, Valproic Acid, Warfarin
• Significance: Management of Toxicities/ drug overdose
• Drugs w/ low Vd= hemodialysis (alternative treatment)
• Drugs w/ high Vd = hemodialysis (useless) (Katzung) Apparent Volume of Distribution and Physical Volumes Apparent Volume of Distribution (Vd) is

pharmacokinetic parameter that reflects the above determinants of the distribution of a drug in the body. Vd relates the amount of drug in the body to th
the plasma.
Average values for some physical volumes within the adult human body.
Compartment Plasma Blood Extracellular T
Volume (L/kg BW) 0.04 0.08 0.2 0.6 0.2-0.35
Distribution phase The phase of drug movement from the site of administration into the tissues The Larger the Volume of Distribution, the more e
distribution
● Volume of distribution is the hypothetical volume of fluid where drug is disposed
the ratio of the amount of drug in the body to the drug concentration in the plasma or blood Extent of Distribution of drugs is effected by:
- Plasma protein binding - pH Rate of Distribution of drugs is effected by:
- Blood perfusion - Membrane permeaility
• Hypothetical volume of body fluids necessary to dissolve a given amount of drug to a concentration equal to that in the plasma
• Theoritical Volune
• Application Vd 1. Loading Dose
Vd = dose
Cp 2. Predict the location of drug
• Significance:
o May be used to compute loading dose o Identification of most likely compartment of dictribution of a given drug
• Correlation with body fluids:
o Total body fluids = 60% of BW (Males)
= 50-55% of BW (Females) o Intracellular fluids = 40% o Extracellular fluids = 20%
Interstitial = 15% Intravascular = 5% o Approximate Volume of Distribution of
Ex: For a 70 Kg Px
o Total/Whole body fluids =40/42 L o Intracellular fluids = 25-30 L o Extracellular fluids = 10-20 L
o Interstitial = 10.5 L o Intravascular = 3.5 L o Circu
*Water compartment
where drugs can be found 1. Plasma compartment
high-molecular weight &
highly protein bound 2. ECF low molecular weight &
hydrophilic 3. Total body water
low molecular/ hydrophobic
Metabolism aka biotransformation
lipophilic into more water-soluble or polar, pharmacologically inactive, & readily excretable form Objectives: conversion of xenobiotics to a form less tox
excretable. Exceptions:
o Inactive (prodrug) to active form
o Phenacetin to Acetaminophen o Prontosil to Sulfadiazine o Enalapril to Enalaprilat o Allopurinol to alloxanthine o Active t
o Diazepam to Nordiazepam to Oxazepam o Atracurium to laudanosine o Eserine to Rubreserine o Codeine to Morphine o Non-toxic to toxic form
o Malathion to Malaoxon o Acetaminophen(Paracetamol) to NAPQI Location:
o Primarily in the liver o Kidney (Imepenem metab by dihydropeptides in the kidney) o Intestines o Blood First-pass metabolism
Extraction ratio : ER = CLliver
; where Q is hepatic blood flow (about 90L/hr in a 70kg patient)
Q Systemic bioavailability : F = extent of absorption f × (1 − ER) Drugs with extensi
propanolol, catecholamine, meperidine, morphine, pentazocine First-pass Effect (presynaptic elimination) describes the phenomenon whereby drugs m
(not chemically degraded) following absorption but before reaching systemic circulation Hepatic first-pass effect may occur following P.O. & deep rec
may be avoided by using sublingual & buccal routes of administration Pulmonary first-pass effect cannot be avoided by intravenous, buccal
Phases (Ma
1. Phase I Reactions that convert the parent drug to a more polar (water-soluble) or more reactive
product by unmasking or inserting a polar functional group such as –OH, –SH, or –NH2 usually involves conversion of drugs to active from by addition
functional group. Oxidation, Reduction, Hydrolysis
dominant among phase I reaction Phase I Drug-Metabolizing Reactions (Functionalization Reaction A. Oxidation – dominant
Reaction Type Typical Drug Substrates Oxidations, CYP450 dependent
- Hydroxylation
Aromatic Hydroxylation Phenobarbital, Propanolol, Phenytoin, Warfarin, Ethinyl Estradiol Aliphatic Hydoxylation Pentobarbital, Chlorpromazine, Ibuprofen
Caffeine, Morphine, Theophylline - O-dealkylation Codeine, Dextromethorphan, Indomethacin - N-oxidation Meperidine, Acetaminophen, Nicotine - S-oxid
Chlorpromazine, Cimetidine, Thioridazine, Omeprazole - Deamination Amphetamine, Diazepam
A partial list of drugs that significantly INDUCE P450-mediated drug metabolism in humans: CYP Family Induced
Kinetic of Metabolism: 1st order concentration dependent kinetic
imporatant in maintenance of your steady state
constant fraction of a drug Example: 100mg 80mg 64 ...... *20% 0th order concentration independent
increase in the rate of metabolism saturable kinetic/Michaelis-Menten constant amount Example: 100mg 80mg 60 ...... *20mg
Drugs that are Extensively Metabolized by First Pass Effect:
-Lidocaine -Isoproterenol -Nitroglycerin -Morphine -Meperidine -Prpoxyphene -Propanolol -Salicylamide -Entazocined
Important Inducers Drugs Whose Metabolism Is Induced
1A2 Benzo[a]pyrene (from
tobacco smoke), Carbamazepine, Charcoal-broiled foods, Cruciferous vegetables, Omeprazole
Acetaminophen, Clozapine, Haloperidol, Theophylline, Phenobarbital, Rifampin, Omeprazole Tricyclic Antidepressants, (R)-Warfarin, Tamoxifen
2C9 Barbiturates, Especially
Phenobarbital, Phenytoin,
Barbiturates, Celecoxib, Chloramphenicol, Doxorubicin, Primidone, Rifampin Ibuprofen, Phenytoin, Chlorpromazine, Steroids, Tolbutamide, (S)-Warfar
Phenobarbital, Phenytoin, Rifampin
Diazepam, Phenytoin, Topiramate, Tricyclic Antidepressants, (R)-Warfarin
2E1 Ethanol, Isoniazid Acetaminophen, Enflurane, Ethanol (Minor), Halothane 3A4 Barbiturates,
Carbamazepine, Corticosteroids, Efavirenz,
Antiarrhythmics, Antidepressants, Azole Antifungals, Phenytoin, Rifampin, Pioglitazone, St. John's Wort Benzodiazepines, Calcium Channel Blockers, Cyclosporine, Delavirdine, Doxorubici
Erythromycin, Estrogens, HIV Protease Inhibitors, Nefazodone, Paclitaxel, Proton Pump Inhibitors, HMG-Coa Reductase Inhibitors, Rifabutin, Rifampin, Sildenafil, Ssris, Tamoxifen, Trazodo
A partial list of drugs that significantly INHIBIT P450-mediated drug metabolism in humans. CYP Family Inhibited
Inhibitors Drugs Whose Metabolism Is Inhibited
1A2 Cimetidine, Fluoroquinolones,
Grapefruit Juice, Macrolides, Isoniazid, Zileuton
Acetaminophen, Clozapine, Haloperidol, Theophylline, Tricyclic Antidepressants, (R)-Warfarin
2C9 Amiodarone, Chloramphenicol,
Cimetidine, Isoniazid, Metronidazole, Ssris, Zafirlukast
Barbiturates, Celecoxib, Chloramphenicol, Doxorubicin, Ibuprofen, Phenytoin, Chlorpromazine, Steroids, Tolbutamide, (S)-Warfarin 2C19 Fluconazole
Diazepam, Phenytoin, Topiramate, (R)-Warfarin 2D6 Amiodarone, Ci
Ssris
Antiarrhythmics, Antidepressants, Beta-Blockers, Clozapine, Flecainide, Lidocaine, Mexiletine, Opioids 3A4 Amiodarone
Cimetidine, Clarithromycin, Cyclosporine, Diltiazem, Erythromycin, Fluoroquinolones, Grapefruit Juice, HIV Protease Inhibitors, Metronidazole, Quinine, S
Antiarrhythmics, Antidepressants, Azole Antifungals, Benzodiazepines, Calcium Channel Blockers, Cyclosporine, Delavirdine, Doxorubicin, Efavirenz, Ery
Estrogens, HIV Protease Inhibitors, Nefazodone, Paclitaxel, Proton Pump Inhibitors, HMG-Coa Reductase Inhibitors, Rifabutin, Rifampin, Sildenafil, Ssris
Trazodone, Vinca Alkaloids
Suicide inhibitors are drugs that are metabolized to products that irreversibly inhibit the metabolizing enzyme.
▪ Ethinyl Estradiol
▪ Norethindrone
▪ Spironolactone
▪ Secobarbital
▪ Allopurinol
▪ Fluroxene
▪ Propylthiouracil Oxidations, CYP450 Independent
- Amine Oxidation - Dehydrogenation
CYP3A4 -responsible for the highest
fraction of clinically important drug interactions resulting from metabolism
(MAO) Epinephrine Aldehyde, Chloral Hydrate, Ethanol, Olefins, Aro
Reductions
- Nitro-Reduction - Carbonyl-Reduction
Chloramphenicol Nalo
Hydrolyses - Esters - Amides
Aspirin, Clofibrate, Procaine, Succinylcholine Indomethacin, Lidocaine, Procainamide 2. Phase II (Con
increase water solubility by conjugation of the drug molecule w/ a polar moiety such as glucuronate, acetate, or sulfate almost always involved in the
& formation of its polar form. allows attachment to small, polar & ionizable endogenous compounds allow the termination or attenuation of a biologic
protect the body against chemically reactive compounds or metabolites
Reaction Type Typical Drug Substrates (a) Glucuronidation Acetaminophen, Diazepam, Digoxin, Morphine, Sulfamethiazole, Chloramphenicol (kernicte
glucoronosyl transferase is inducible (Phenobarbital) - Available source of D-glucuronic acid - Responsible for functional groups that can combine en
glucuronic acid - Require an active center as the site of conjugation (b) Acetylation Clonazepam, Dapsone, Isoniazid, Mescaline, Sulfonamides, Hydrala
-Expression of glucoronosyl transferase is subject to genetic polymorphism
Fast Acetylators
-Eskimos -Orientals (Filipinos/Asians)
Slow Acetylators -Egyptians -Mediterranean Jews (c) Glutat
Ethacrynic Acid, Reactive Phase I Metabolite of Acetaminophen -Neutralizes chemically reactive substances - Back-up mechanism for paracetamo
 Conjugation Deoxycholic Acid, Nicotinic Acid (Niacin), Salicylic Acid (e) Sulfation Acetaminophen, E
- Only phase II reaction present in neonates (only well-developed metabolic pathway in neonates) (f) Methylation Dopamine, Epinephrine, Histamine, Norepinephr
- Important in biosynthesis of many endogenous substances like epinephrine & melatonin - Constitutes only a minor pathway for conjugating d
*Paracetamol (Acetaminophen) -sulfation NAPQI -glutathione conj.
N-acetylparaquinoneimine (hepatotoxic form)
Enzyme inhibiton- Enzyme Inducers
induction “GPP PARK Sa
Enzyme-inducers stimulate the release of Mall”
CYP450 ▪
Consequences: Low therapeutic levels of active Griseofulvin
drug ▪
( decrease efficacy) Prodrug (increase in efficacy) Toxic Griseofulvin
metabolite (increase toxicity) Cross-induction stimulated by ▪ Phenobarbital
auto & foreign induction Foreign-induction stimulates another (Barbiturates)
drugs Auto-induction stimulate its own metabolism ▪ Phenobarbital
(Carbamazepine) Enzyme-inhibitors competitive inhibition (Barbiturates)
Consequences: Active object drug (increase efficacy; ▪
intoxicity) Phenytoin
Prodrug (decrease in efficacy) ▪
Toxic metabolite (decrease Phenytoin
toxicity) ▪
Enzyme Phenylbutazon
Inhibitors e
“sickfaces.com” ▪
▪ Sodium Phenylbutazon
valproate e
▪ ▪ Alcohol
Isoniazid (chronic)
▪ Alcohol
▪
(chronic)
CImetidine
▪
▪
Rifampicin
Ketoconazole
▪
▪
Rifampicin
Fluconazol
▪
e
Carbamazepin
▪ Alcohol
e
(Acute)
▪
▪ Carbamazepin
Ciprofloxacine e
▪ ▪
Erythromycin Sulfonlurea
Enzyme Inducers ▪
“GPP PARK Sa Sulfonlurea
Mall”

Genetic Polymorphism variation in the DNA sequence that is present at an allele frequency of 1% or greater in apopulation
variation in the expression of enzymes (rapid/slow acetylators, CYP polymorphism) 1. CYP 2D6 polymorphism (increased risk of cardiot
Thioridazine & antidepressants (Poor Debrisoquin Metabolizer)
CYP 2D6 most studied 2. Acetylation - HIPS: Hydralazine, Isoniazid, Procainamide, Sulfonamide(causes Steven Johnson Syndrome
(very notorious in causing SLE) Isoniazid peripheral neuropathy; Isoniazid toxicity (treated with Vitamin B6) *Genetic Polymorphism variation in
the expression of enzymes
 EM – Extensive Metabolizers PM – Poor Metabolizers UM – Ultra Rapid
Metabolizers NAT2 N-acetyltransferase
HIP: hydealazine, INH, Procainamide
cause Drug-induced SLE Fast acetylators: Asia – Extensive Metablozers Slow Acetylators:
Caucasian – Poor Metabolizers CYP2D6
Tamoxifen
M-
ect *UM -
effect
▪
Sulfanamide
▪
Chloramphenico
l
▪
Omeprazole
▪
Metronidazole

▪
Herbs:
▪ Grape
fruit
▪ Valencia
oranges
▪
Meprobamate

Herbs: St. John’s

CYP2D6 Endoxifen Codeine
wort
CYP2D6
Morphine
*PM -
effect *UM -
effect

Sites of Biotransformation/ Metabolism

• Liver
• Stomach
• Intestine
• Lungs
• Skin
• Kidney Factors affecting drug Metabolism
Age Differences Species & Strain Differences Hereditary or Genetic
Factors Sex Differences Enxyme Induction Enzyme Inhibition

Regioselectivity - denotes the selective metabolism of two or more similar functional groups, or two or more similar atoms that are
positioned in different regions of a molecules
Elimination final loss of the drug from the body; constitutes metabolism & excretion
General Requirements: water-soluble (polar) Routes of excretion: Renal, Biliary, Lungs, Skin, Mammary, Intestinal
Total body clearance drug elimination rate divided by plasma drug concentration Renal drug excretion major route for polar, water-soluble, drug
(<500g/mol)
a. Glomerular Filtration passive process by which small molecules & drugs are filtered through glomerulus b.(Proximal) Tubular Reabsorption foll
Diffusion.
*Lipid-soluble/ non-ionized are reabsorbed from the lumen back to systemic circulation c. (Distal) Active Tubular Secretion is a carrier-mediated ac
Probenezid – Penicllin (competes for tubular excretion) *Renal Clearance volume of drug in the plasma, that is removed by kidney
Renal primary site of excretion of polar drugs with MW NMT 400-600
Dependent on GFR (glumerolus filtration rate)
GFR -passive
afferent ⇨efferent
Tubular secretion = active transport
Malpighian Body/ Nephron
- the actual unit in the kidney where
lemimination & reabsorption takes place Tubular reabsorption = passive Determination of GFR Inulin clearance (substance is freely excreted but is n
secreted Creatinine Clearance (CLCr) primary marker of renal function; ratio of creatinine excretes
measurement of GFR Creatinine end-product *24 hr urine collection ClCr= Creatinine Clearance(mL/min) CCr= Serum Creatinine (mg/dL)
Determine urine creatinine, plasma creatinine, & 24hr urine volume
CLCr= [UrineCr] x Vol or urine (mL)
[PlasmaCr] 1,440 mins *Cockroff & Gault Equation (for adults)
CLCr(Male)= ( 140-Age ) BW in Kg Note: if unit given is
72 x Plasma Cr in mg/dL μmol/L (convert to mg%)
Renal Impairment Based on Creatinine Clearance (estimated creatinine clearance) Normal Renal Function Mild Renal Function
CLCr(Female)= 0.85 (CLCr of male) *Schwartz & Associates (for children) M
CLCr= 0.55 body length (cm)
CCr
Moderate Renal Function Severe Renal Function ESRD( end-stage
renal disease)
Ex: 75 yo female weighing 60Kg w/ a CCr mg/dL. If the regular dose of Gentamicin is 240 mg OD, at what dose should this
be adjusted for this patient?
Adjusted dose= CLCr(Px) x regular dose where: N CLCr= 100mL/min
CLCr (Normal) CLCr (female)= 23.02mL/min; Adjusted dose= 55mg IV OD
Biliary: polar with MW exceeding 400-600; becomes important pathway when there is no significant enterohepatic recycling
Biliary excretion – enterohepatic recirculation
is the phenomenon that drugs emptied via bile into the small intestines can be reabsorbed from the intestinal lumen into systemic circulation. Ex: Tetra
rifampicin, digitoxin Ex. of drugs w/ enterohepatic recirculation: Morphine, Ethynylestradiol Hepatic Clearance volume of plasma-containing drug that
liver per unit time
Extraction ratio is the fraction of drug that is irreversibly removed by an organ or tissue as
the plasma-containing drug perfuses that tissue Blood flow 1.5L/min; altered by exercise, food, disease, drugs Intrinsic Clearance CLint, the ability of

remove the drug independently

of blood flow Lung: for volatile drugs Skin/ sweat Intestines Mammary glands
Volume of Distribution (Vd)= CL/Kel Rate of Elimination = CL x Cp
= Kel x Vd x CP Clearance (CL)= rate of elimination/C
= Kel x Vd where: Kel=0.693/t1/2 =(0.693/t1/2) x Vd t1/2 =(0.693 x Vd) CL Elimination phase *half-life(t1/2) The phase time of drug required inact

or removal the concentration from the body by by 1/2; metabolism t1/2= 0.693
k or excretion
>80mL/min 50-80 mL/min 30-50 mL/min <30 mL/min Requires dialysis
Urine date: too, [dDu/dt]maxo, Duoo Plasma Data: tmax, Cmax, AUCo oo
Oral Drug Administration
Drug is
Gastrointestinal tract Mesenteric swallowed
circulation
Bioavailability & Bioequivalence
Bioavailability (F) measures of both rate & extent of drug entry into the systemic circulation
The fraction (or percentage) of the administered dose of drug that reaches the systemic circulation Relative Bioavailability comparison of the AUC
against the AUC of standard
is the availability of the drug from a drug product as compared to a recognized standard Relative bioavailability = [AUC] A [AUC] B Absolute Bioavailab
of the AUC of a test drug to an IV
is the systemic availability of a drug after extravascualr administration (eg, oral, rectal, subcutaneous, transdermal) compared to IV dosing. Absolute bio
[AUC] PO/ dose PO
[AUC] IV/ dose IV Two methods in determining bioavailability:
o Drug plasma concentration vs. time graph o Cumulative urinary extraction data The important Bioavailability (F) parameter:
Cmax = max drug plasma concentration (measure the extent and rate of absorption) Tmax = time needed to reacx AUC = Area under the curve
measure the extent of drug absorption (most important) is the integral of drug blood level over time from zero to affinity. The graphic area under a p
concentration versus time after a single dose or during a single dosing interval Plasma level time curve:
a.) Onset of Action time to reach MEC b.) Duration time remain above MEC c.) Intensity proportional to the number of receptors d.) MTC min
concentration e.) MEC (minimum effective concentration) The plasma drug concentration below which a patient's
response is too small for clinical benefit f.) therapeutic window between MEC & MTC *Peak & trough The maximum and minimum drug concentrat
during repeated dosing cycles *Area Under First Statistical Moment I,e., it is the area under Curve the curve mathematically observed for the defined
AUMC time & = concentration 0 oo
,
t − C − dt
versus time Bioequivalence when pharmaceutical equivalents or alternatives displays comparable bioavailabilities
is achieved if its extent & rate of absorption are not statistically significantly different from those of the standard when
administered at the same molar dose the absence of a significant difference in the rate & extent to which the active ingredient or active moiety in pharmaceutical
equivalent or alternatives becomes available at the site of drug action when administered at same molar dose under similar conditions in an appropriately designed study (FDA,2003) Bioeq
requirement The FDA considers two product BE if the 90% Cl of the relative mean Cmax, AUC(0-t), and AUC(0-χ) of
the test to reference should be within 80% -125% in the fasting state. Pharmaceutical alternatives Same therapeutic moiety/API
Different salts, esters, or complexes Different dosage forms Different strength Ex: tetracycline phosphate 250mg tetracycline HCl 250mg Pharmaceutical Equivalence
Same dosage form Same salts or esters Same route of administration Same strength/concentration Ex: Chlordiazepine HCl 5mg cap (branded) (generic) Pharmaceutical Sub
of dispensing pharmaceutical alternatives
Example: Ampicillin suspension & ampicillin capsules

Nifedipine 5mg cap & nifedipine 20mg GITS tab Therapeutic Alternatives Different active ing.
Same therapeutic effect or pharmacologic class Example: Ibuprofen -aspirin Therapeutic Equivalence Are pharmaceutical equivalents contain identical amounts of th
ing. In the same dosage form & route of administration. Therapeutic Substitution Process of dispensing a therapeutic alternative

Compartment Models: AUC, t1/2, Cmax, Tmax

Hepatic portal vein

Systemic Circulation

Liver D B
F
CE A
Loading dose -Maintenance dose ♦ Maintenance dose
Dose given to maintain a steady stae of drug concentration in the body Dosing rateSS= rate of elimination
= CL x TC If drug is given by a route that has a BA less than 100% Dosing rate oral= Dosing rate/
Foral If intermittent dose are given: Maintenance dose= (Dosing rate/ F) x Dose Interval ♦
Loading dose
LD = Vd x TC Maintenance Models in PK
Order of reaction (Kinetics) First order

Zero order

Compartment Models
One compartment rate constant Kcl= elimination rate
model
constant Cp= plasma
concentration
Two compartment
model

Where: Ka= absorption or admin

 Where: K12system
&K21=transfer
rate constant

Models &
Compartment
Models mathematic description of a biologic
used to express quantitative relationshipsCompartment a group of tissue w/ similar blood flow &
drug affinity
is nor a real physiologic or anatomic region Open-one compartment model instantly distributed
for an extravascular administration Open-two compartment model does not instantly distributed
for an intravascular administration Central Compartment sum of all body regions in which the drug
concentration
is in instantaneous equilibrium Disposition loss of drug from the central compartment
distribution ⇨ metabolism ⇨ excretion Peripheral Compartment sum of all body regions in which the drug eventually
distributes
but is not in instantaneous equilibrium Subdivided into: Shallow & Deep Comparment Noncompartment methods
requires comparison of the area under the curve
Mean Residence Time (MRT) aka “Mean Transit Time” or “Men Sojourn Time”
average time for the drug molecules to residue in the body Mean Absorption Time (MAT) the difference betwee
MRT & MRTIV
after extravascular route is used Steady-state Vd ration of the amount of drug in the body at
steady state
& average steady state drug concentration

Units:
O-order: conc. /time Suspension exhibit a zero order reaction. Solution &
1st order: 1/time 2nd Radioactive substances exhibit a first order reaction.
order: 1/conc. time
Nonlinear Pharmacokinetics aka. “capacity-limited”, “dose-dependent”, saturation pharmacokinetics
at high concentration = may show zero-order at low concentration = may show first-order
Graph (IV)
Graph (EV,oral)
How to determine if behavior is 1 or 2 compartment: 1. Graphic Method

Determine Cmax Draw a line connecting the last 3-4 teminal points If the Cmax is below the line (1
compartment) 2. Natumen Method

Divide all the terminal points into 2 sets Draw straight line for each of the sets of points Determine the slope of the lines Determine If the slope slope di

is less = (V1 than - V0)/V1x 10% (1

100 compartment) 3. AUC method
Determine the total AUC Determine AUC above the back-extrapolated line connecting the downward points Determine %AUC above the line = (AUC abo
x 100
If %AUC is less than 5% (1compartment)
Noncompartment Methods: (requires comparison of the areas under the curve
▪ Mean Residence Time (MRT) aka “mean transit time” or “mean sojourn time”
average time for the drug molecules to reside in the body.
▪ Mean Absorption (MAT) the difference between MRT & MRTIV after extra route is used.
▪Steady-state VD ration of the amount of drug in the body at steady state & average steady-state drug concentration
Dose Calculation (a) Half-life

t1/2=0.693/Kel Determination of elapsed half-life: # of elapsed t1/2=total time/ t1/2 Ex: Compute for the amount of drug remaining in the body 6

of a 500 mg single IV dose, if the t1/2 of the drug is 2hrs? 3 of elapsed t1/2 = 6hrs/2hrs = half-life elapsed= 12.5% remaining drug
Amount remaining = 0.125(500mg)=62.5mg A given drug is administered as 1000mg single IV dose. 10 hrs after administration, the total amount in the
 is the t1/2 of the drug?
Determine % remaining = (250mg/1000mg)x 100= 25% Determine the corresponding elapsed t1/2 of
25%=2 t1/2 # of elapsed t1/2=total time/ t1/2 2= 10hrs/ t1/2 t1/2= 5hrs (b) Continuous IV infusion
Steady state=concentration of drug in the plasma is maintained w/in a specific range
-Time to reach SS is dependent only on the t1/2 -In SS the rate of admin= rate of elimination -
So: same as the rate of infusion (RO)= rate of elimination

RO = CL x CP RO = (Kel x Vd) x CP -Since SS is achieved, the CP=CSS -So: RO= CL x CSS

RO= (Kel x Vd)x CSS (c) Multiple IV bolus

-The rate of administration = dose size per given dosing interval
Ex: 80mg IV q8 Rate of admin = 80mg /8 Rate of admin = DM / T where: DM (maintenance dose); T (interval) Since, rate of
admin = rate of elimination

DM / T = CL x CSS

= (Kel x Vd) x CSS DM = CL x CSS x T

= (Kel x Vd) x CSS X T (d) Multiple extravascular/ oral doses

-Ex: 500mg tab q12 -Rate of admin = F. DM/ T where: F (bioavailability)

F. DM/ T = CL x CSS

= (Kelx Vd) x CSS DM = (CL x CSS x T) /F

Ex: If the desired therapeutic concentration of theophylline is !)mg/L, at what dose should theophylline be given, a. IV & b.oral, for a Px weig
Theophylline has a t1/2=8hrs & a Vd = 0.5L/Kg. The desired dosing interval is 12hrs. The BA of oral tabs is 0.9.

(IV intermittent bolus) DM = (Kel x Vd) x CSS x T

= (0.693/8hrs) (0.5L/Kg)(70Kg)(10mg/L)(12hrs) =363.8 mg

(oral dose) DM = (CL x CSS x T) /F = 363.8/ 0.9 = 404.2 mg

Biopharmaceutics deals with the physical & chemical properties of the drug substance, the dosage form, and the body & the biological effectiveness o
a drug upon administration. Biopharmaceutics Classification System (BCS)
CLASS Solubility Permeability Comments
Class 1 High High Dissolves rapidly & well-absorbed Class 2 Low High Dissolution limited & well-absorbed Class 3 High Low Permeability limited C

Difficult in formulating a drug product

Clinical Pharmacokinetics is the application of pharmacokinetics principles
for the rational design of an individualized dosage regimen. Objectives: a. Maintain of an optimum drug concentration at the receptor site
b. Minimization of any adverse or toxic effect Toxicokinetics application of pharmacokinetic principles to the design, conduct
& interpretation of drug safety evaluation studies Population Pharmacokinetics Study of sources & correlates of variability in drug concentrations am
are the target patient population
Important Terms
*Modern Biopharmaceutics is the study of the relationship of the physic chemical properties & in vitro behavior of the drug & drug product *Bioequiva
are pharmaceutical equivalents that have similar bioavailability * Drug Product finished dosage form that contains active ing *Drug product selectio
choosing or selecting the drug product in a specified dosage form *Equivalence Relation in terms of Bioavailability, therapeutic response, or a set of es
standards of one drug product to another. *Chemical equivalents are pharmaceutical equivalents *Generic Name established, nonproprietary, or co
active drug in a product * Chemical Name name used by organic chemist to indicate chemical structure of the drug *Brand Name trade name; priva
manufacturer *ANDA (Abbreviated New Drugs Application) filed by manufacturer for approval to market generic *NDA (New Drug Application) s
marketing *Reference listed Drug RLD; is generally branded name drug that has a full NDA
Identified by FDA as the drug product on which an applicant relies when seeking approval of an ANDA
*Rate-limiting step slowest step in a series of kinetic processes *Parenteral Routes
Intra-arterial -Joint space Intrasynovial -Joint fluid are
Intrathecal -Spinal column Intra-arterial -Arteries
Intracardiac -Heart Intravenous, IV -Into the vein Intramuscular, IM -Into the muscles Intradermal, IB/ Intracutaneous -Into the skin
Subcutaneous, SC/ Sub-Q, SQ/ hypodermic
IM exhibits depot effect
-Under the Skin
Receptor Site Theory Lock & Key Hypothesis States that the drug molecules must “fit into a receptor” like a key fits into a lock” (intrinsic activity Induc
postulates a complementary relationship between the drug molecule & its active site
provides for mo\uttual conformational changes between the drug & its receptor Hypothesis of Clark Percentage of receptors occupied
advances the idea that maximum pharmacologic effect can be obtained if all the receptor occupied Hypothesis of Ariens & Stephenson
Occupation Theory State that effectiveness lasts as long as the receptor is occupied Hypothesis of Paton Rate Theory
States the effectiveness does not depend on the actual occupation of receptor of the drug, but upon obtaining the
proper stimulus
Fick’s Law Diffusion/ passive diffusion Cockroft & Gault Creatinine clearance differences base on patient’s weight, age & sex Noyes-Whitney Equa
rate Henderson-Hasselbalch Equation Buffer equation
describes the relationship between the ionized & non-ionized form of a drug as a function of PH & pKa Vanslyke Buffer Capacity Fluid Mosaic Theor
membrane is made up of bi-lipid layers & fluid protein molecules Jellife Equation creatinine clearance may be computed for adults w/ unstable renal fu
Drug Evaluation & Regulation
Mutagenic An effect on the inheritable characteristics of a cell or organism—a mutation in the DNA; usually tested in microorganisms
with the Ames test Carcinogenic An effect of inducing malignant characteristics Teratogenic An effect on the in utero development of an organism resul
structure or function; not generally heritable Placebo An inactive "dummy" medication made up to resemble the active investigational formulation as much
lacking
therapeutic effect Single-blind study A clinical trial in which the investigators—but not the subjects—know which subjects are receiving active drug and w
receiving placebos Double-blind study A clinical trial in which neither the subjects nor the investigators know which subjects are receiving placebos; the
by a third party IND Investigational New Drug Exemption; an application for FDA approval to carry out new drug trials in humans; requires animal
data NDA New Drug Application; seeks FDA approval to market a new drug for ordinary clinical use. Requires data from clinical trials as
well as preclinical (animal) data Phases 1, 2, and 3 of clinical trials
Three parts of a clinical trial that are usually carried out before submitting an NDA to the FDA
Positive control A known standard therapy, to be used along with placebo, to evaluate the superiority or inferiority of a new drug in relation
to the others available Orphan drugs Drugs developed for diseases in which the expected number of patients is small. Some countries bestow certain co
advantages on companies that develop drugs for uncommon diseases
FDA ratings of drug safety in pregnancy. Category Description A Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester
evidence of a risk in later
trimesters), and the possibility of fetal harm appears remote B Either animal reproduction studies have not demonstrated a fetal risk but there are no cont
pregnant women, or animal
reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trim
no evidence of a risk in later trimesters) C Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and t
controlled
studies in women, or studies in women and animals are not available. Drugs should be given only when the potential benefit justifies the potential risk to t
positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (eg, if
the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective) X Studies in animals or
demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience
or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or m
pregnant
Major Concept Description Drug safety and efficacy
Standards of safety and efficacy for drugs developed slowly during the 20th century and are still incomplete. Because of heavy lobbying by manufacturers
are still not applied to nutritional supplements and many so-called alternative medications. Preclinical drug testing
All new drugs undergo extensive preclinical testing in broken tissue preparations and cell cultures, isolated animal organ preparations, and intact animal
to determine the full range of toxic and therapeutic effects. Clinical drug trials All new drugs proposed for use in humans must undergo a series of tests
tests are regulated by the FDA
and may be accelerated or retarded depending on the perceived clinical need and possible toxicities. The trials are often divided into 3 phases before ma
PHARMACOTHERAPEUTICS
Pharmacotherapeutics is the study of rational drug use in the management of disease. AUTONOMIC
PHARMACOLOGY
 some of the metabolism also happen
*Neurotransmitter stores in vesicles
-because amine containing, protect against MOA,

COMT *Enzyme ⇨ Acetylcholine

⇨ acetylcholinesterase
Central
Nervou
s
Syste
m
Peripher
al
Nervous
Sytem
*ganglia any neurons outside the
ANS

Central Nervous system composed of brain &

spinal cord Peripheral Nervous System includes
neurons located
Cranial Central Nervous system composed of brain &
Nerves: spinal cord Peripheral Nervous System includes
I. Olfactory II. Optic neurons located
III. Oculomotor outside brain & spinal
IV. Trochlear cord Afferent bring information from periphery
V. Trigeminal VI. to the CNS Efferent carry signals from brain &
spinal cord
Abducens VII.
Facial VIII. Nervou
Auditory s
IX. Facial Syste
X. Auditory/ Vestibuulocochlear XI. m
Glossopharyngeal XII. Vagus XIII.
Spinal accessory XIV.
Hypoglossal
close to the spinal cord Parasympathetic
leave the CNS from the brain &
Affere
lower portion of the spinal cord
Enteric increase gastric secretion
nt
Effere
Three nt
parts: Anatomy & Physiology of
1. Presynapse synthesis, release & ANS
storage of -2 neuron system -presence
Neurotransmitter; NT release Presynaptic of ganglia outside ANS
receptor a receptor located on the nerve ending
from which the transmitter is released into the synapse; modulates the release
of transmitter 2. Synaptic Cleft where neurotransmitters
release
outside brain & spinal
 cord Afferent bring information from periphery first nerve cell;
to the CNS Efferent carry signals from brain & located within the
spinal cord CNS Postganglionic neuron emerge from the
outside brain & spinal brain & spinal
cord Afferent bring information from periphery located within the
to the CNS Efferent carry signals from brain & CNS Postganglionic neuron emerge from the
spinal cord brain & spinal
to the
periphery Preganglionic Neuron
first nerve cell;
Somati Somatic Efferent Neurons involve in the voluntary
control
c
Sytem
Sympathe
ti c
Enteri
Sympathet c
cord & make a synaptic
ic
connection ganglia

of functions such as contraction of the skeletal muscles essential

to the for locomotion Autonomic regulates the everyday
periphery Preganglionic Neuron requirements;
first nerve cell; resp
to the (orga
periphery Preganglionic Neuron

⇩ Acetyl CoA Choline 3

Postsynaptic receptor a receptor located on the distal side
of a synapse, for example, on a postganglionic n
effector cell

Dilation enlargement of expansion

of a hollow organ or cavity Constriction compression of an organ
 or causes a hollow organ
Autonomic Nervous System (Characteristics)
Criteria Sympathetic (Adrenergic) Parasympathetic (Cholinergic) 1. Anatomy
a. Origin Thoracic & lumbar region of the
spinal cord (Thoracolumbar)
Brain & Sacral area of Spinal cord (Craniosacral: III, VII, IX, X) b. Location of ganglia Close/ near to spinal cord Within or nea

Preganglionic Short Long Postganglionic Long Short d. Preganglionic fiber branching Extensive Minimal e. Distribution Wide L
response Diffuse Discrete 2.
a. Preganglionic Acetylcholine Acetylcholine b. Postganglionic NE, Epi, Dopamine Acetylcho
a. Ganglionic Nicotinic Nicotinic b. Target organ/ Neuroeffector α1, α2, β1, β2 Muscarinic, Nicotinic 4. Responses (Actions on Effe
organ)
a. Heart Tachycardia (increase contractility) Bradycardia (decrease contractility) b. Eyes Mydriasis (dilated) Meiosis (constricted) c.
Bronchodilation Bronchoconstriction d. Gut sphincter Contraction (closure) Opening
Gut walls Relaxation Contraction e. Urinary bladder
Detrussor Relaxation Contraction Trigone & Sphincter Contraction (closure) Relaxation (opening) f. Sweating From Apocrine Gl
G
Male Stimulation of Ejaculation Stimulation ofErection Female Relaxation of Uterus h. Blood Vessel
Skeletal Muscles Dilation Skin, Mucous membrane, Splanchnic
Constriction
i. Lachrymal gland Stimulation of Tears j. Salivary Gland Thick, viscous secretion Copious, watery secretion k. Adrenal Medulla S
NE l. Kidney Secretion of Renin:
β1 increase α2 decrease
Sympathetic (Adrenergic) Parasympathetic (Cholinergic) “alice in the wonderland syndrome” D -diarrhea Dry as a bone -anhydrosis
U -urination
-dry mouth Hot as hell -hyperthermia
M -meiosis
-decrease sweating Red as a beet -vasodilation
B -bradycardia
/flushing, tachycardia Blind as a bat -cycloplegia (blurring of vision)
-mydriasis, Glaucoma
B -bronchial spasm/ contraction
E -Emesis
Mad as a hooter -CNS: agitation
confusion psychosis
L -Lacrimation S -Salivation
S -Sweating
Receptor Characteristics The major receptor systems in the ANS include: Cholinoceptors, Adrenoceptors, & Dopamine Receptors
SYMPATHETIC RECEPTORS:
Adrenergic A nerve ending that releases norepinephrine as the primary transmitter;
also, a synapse in which norepinephrine is the primary transmitter
Adrenoceptors A receptor that binds, and is activated by, one of the catecholamine transmitters or hormones
(norepinephrine, epinephrine, dopamine) and related drugs Also referred to as adrenergic receptors, adrenoceptors are divided into several subtypes:
are located on vascular smooth muscle, presynaptic nerve terminals, bloo
(lipocytes), and neurons in the brain. are further divided into 2 major types, α1 and α2. Beta Receptors are located on most types of smooth mus
some presyna
and lipocytes as well as in the brain. are divided into 3 major subtypes, β1, β2, and β3. Dopamine Receptors (D, DA) are a subclass of adrenoce
different distr
are especially important in the renal and splanchnic vessels and in the brain. Although at least 5 subtypes
exist, the D1 subtype appears to be the most important dopamine receptor on peripheral effector-cells. D2 receptors are found on presynaptic nerve termin

other types of dopamine receptors also occur in the CNS. Dopaminergic A nerve ending that releases dopamine as the primary transmitter;
also a synapse in which dopamine is the primary transmitter Characteristics of some important ADRENOCEPTORS in the ANS.
Receptor G
 Location Major Functions Second
Protein

Messenger Alpha1 (α1) Gq Effector tissues: smooth muscle, glands Ca2+( BP) , causes contraction, secretion IP 3, DAG
Smooth Muscles: Contraction
vascular SM: cutaneous splanchnic Vasocontriction prostatic & bladder Urinary Retention ( closure of internal
sphincter of the bladder) radial muscles of iris (eyes) Mydriasis (dilation of pupil) ciliary muscles Cycloplegia Pilomotor Goosebum
Increased peripheral resistance Alpha2 (α2) Gi Presynapse: Central NS Vasodilatio
Acetylcholine; Insulin) -sedation; depression
cAMP
Post synapse: Peripheral NS Vasoconstriction Beta1 (β1) Gs Cardiac muscle (heart) Tachycardia
+Inotropism (increase cardiac contractility) +Dromotism (increase heart rate) +Chromotism (increase electrical conjunction across the heart) - veloc
cAMP
JG/ Juxtaglomerular (Kidney) Increase renin release Beta2 (β2) Gs Smooth Muscle, Relaxation cAMP
Vascular Smooth Muscles Vasodilation Skeletal Muscles Contraction (intracellular movement of K) Liver Glycogenolysis (Increase Release Of Glucago

Tachycardia ( heart rate, force) Lungs Bronchodilation Uterus Uterine Relaxation Peripheral NS Slightly Decreased Peripheral Resistance Beta3 (β3) G

Lipolysis cAMP Dopamine Gs Smooth muscle Relax renal vascular smooth muscle cAMP *Peripheral
D1 Renal vasculature
Splanchnic blood vessels
Vasodilation ( GFR - dieresis)
D2 GIT GIT motility (loss of peristalsis)
-constipation *Central: D2-D4 CNS -behavioral changes
-Perception regulation -modulation of motor activities
PARASYMPATHETIC RECEPTORS:
Cholinergic A nerve ending that releases acetylcholine; also, a synapse in which the primary transmitter is acetylcholine
Cholinoceptors Also referred to as cholinergic receptors, these molecules respond to acetylcholine and its analogs.
are subdivided as follows: Muscarinic Receptors receptors respond to muscarine (an alkaloid) as well as to acetylcholine.
The effects of activation of these receptors resemble those of postganglionic parasympathetic nerve stimulation. Location: autonomic effector cells (includ
endothelium, smooth muscle, presynaptic nerve terminals, and exocrine glands). Evidence (including their genes) has been found for 5 subtypes, of wh
important in
peripheral autonomic transmission. All 5 are G-protein-coupled receptors. Nicotinic Receptors are located on ion channels and respond to acetylcho
another acetylcholine mimic (but not to muscarine) by opening the channel. The 2 major nicotinic subtypes are located in ganglia and in skeletal muscle
nicotinic receptors
are the primary receptors for transmission at these sites. Characteristics of the most important CHOLINOCEPTORS in the Peripheral Nerv

Receptor Mechanism Location Major Functions/response M1 Gq-coupled Nerve endings

(nerve that supplies GIT)
IP 3, DAG cascade GIT Acid secretion M2 Gi-coupled Heart, some nerve endings (nerve th

cAMP, activates K+ channels bradycardia, -dromotism M3 Gq-coupled Effector cells: smooth muscle, glands, endothelium IP
Smooth muscles:
Circular muscles (eyes) Ciliary muscles (eyes) Contraction -miosis
-accommodation (cyclospasm) Lungs Bronchospasm/ Contraction (bronchoconstriction)
Lachrymal Glands Lacrimation Salivary Glands Salivation Sweat Glands (Ecrine)
GIT walls Relaxation GIT sphincter Increase gastric peristalsis Gut walls Gut sphincter Contraction Opening Urination Urinary Bladd
Contraction Trigone Relaxation; voiding Glands (Exocrine) Increased secretion (thermoregulatory sweating,
lacrimation, salivation, bronchial secretion, gastrointestinal glands) N (neural) N Ion channel (stimulate by opening of inwardNa channel)
ANS ganglia, CNS Complex stimulatory effects, for example, nicotine
(elevation of mood, alerting, addiction), physostigmine (convulsions); excessive concentrations may cause coma
 Parasympathetic
Stimulation Sympathetic neurons
neurons

N(muscular) M Ion channel Neuromuscular end plate (skeletal muscles) Depolarizes, evokes action potential

Contraction *NM (muscular) belongs to somatic NS (excluding in ANS) cAMP, cyclic adenosine monophosphate; DAG, diacylglycerol; I
trisphosphate
Autonomic effector cells or tissues Cells or tissues that have adrenoceptors or cholinoceptors which,
when activated, alter the function of those cells or tissues, for example, smooth muscle, cardiac muscle, glands Baroreceptor reflex The neuronal hom
mechanism that maintains a constant arterial blood pressure;
the sensory limb originates in the baroreceptors of the carotid sinus and aortic arch; efferent pathways run in parasympathetic and sympathetic nerves H
A compensatory mechanism for maintaining a body function at a predetermined level,
for example, the baroreceptor reflex for blood pressure
I. AUTONOMIC DRUGS ♥ Sympathetic Drugs - “Fight or Flight" stimulus
Adrenergic Agonists (Sympathomimetics) A. Direct-Acting Adrenergic Agonists directly act on receptors Nonselective Agonist stimulate α, β, D (one or m
Natural Catecholamines: β < α Low doses: β-receptors; High doses: β + α
Epinephrine Adrenin®, 1st line cardiac stimulant (in advance life support)
For anaphylactic shock (too much vasodilation) Decrease systemic absorption of anesthetic. Management of Glaucoma Hormone released from adrenal medulla, neurotransmitter in
vasoconstrictor
Phenylethylamine N-methyl transferase =
Norepinephrine Epinephrine Metabolite of NorEpi/Epi:
3-Methoxy-4hydroxy mandelic acid / Vanillylmandelic Acid (VMA)
Epicaine®
Epinephrine+ Lidocaine
Dopamine & NorEpi - most useful for
hypodynamic septic shock w/ Hypotension
Norepinephrine Inotrop®, Levolin®, Levophed®, Norepin®, Norphed® 1st line inotropic agent in the management of Septic Shock Dopamine Cardiofast®, Dokard®
Myocard® 1st line bronchodilator in acute asthma attacks Selective Agonist stimulate one type of receptor
β- nonselective agonist
Isoproterenol alternative inotropic IV infusion for shock states or acute Heart Failure β1- selective agonist
Dobutamine Cardomin®, Dobuject®, Dobulex®, Dobutrim® DOC in Management of Cardiogenic shock & acute HF β2- selective agonist
Isozsuprine Duvadilan®, Duvaprine®, Isoxilan®
Ritodrine Terbutaline Bricanyl®, Bricalin®, Pulmonyl®

Tocolytics used to control premature labor (for relaxation of uterus) Asthma- COPD (Chronic Obstructive Pulmonary Disease) Short-acting β2- selective agonist Sa
Salbutamol + Ipratopium Activent®, Ventolin® Combivent®, Duavent®
1st line bronchodilators

in acute asthma attack Anti-asthma: Salbutamol + Guaifenesin Pulmovent® Metaproterenol Alupent®

Reliever for acute attacks Controller for maintenance

Pirbuterol Long-acting β2- selective agonist Salmeterol β2 entry of K into the cell
cause hypokalemia then Arrhythmia for symptomatic of bradycardia
Salmeterol + Fluticasone in diskus Formoterol SE: Tachycardia, Palpitations, Hypokalemia, Tremors,
Tolerance Formoterol + budesonide Salmeflo® Seretide®
Atock®, Foradil® Symbicort®
Alternative controllers in
Bronchial Asthma management of Hyperkalemia
α1- selective agonist
Phenylephrine + Chlorphenamine + Paracetamol Bioflu®, Neozep®, Decolgen Forte® Phenylephrine + Paracetamol No drowse Decolgen® Phenylephrin
Brompheniramine Dimetapp® Phenylephrine + Dextromethorphan + Paracetamol Tuseran Forte®
α1 nasal Management decongestant
of hypotension local vasoconstrictor w/ local anesthetic Management of Arrhythmia (Methoxamine)
-Exacerbate HTN due to vasoconstricting effect, Methoxamine Oxymetazoline Tetrahydrozoline
-rebound congestion Drixine®
-precipitate urinary retention tolerance *must be given less than 5days
Xylometazoline Otrivin® Tetryzoline Eye-mo red eyes®, Visine Refresh® α2- selective agonist
Clonidine Catapres® α2 effects: Presynaptic
Uses: Mx of HTN Nasal Spray Alternative Mx for ADHD *HTN: Urgensive =180/100
Emergency = organ/tissue
complications
Methyldopa upon entering the body, it will be converted Apraclonidine Brimonidine Alphagan® Brimonidine + Timolol Combigan®
to alpha-methylnorepinephrine effect on hemolytic anemia, especially on toxic
doses (Comb’s Test – test for hemolytic anemia) AntiHTN for pregnant Me
Gestational Hypertension (like:hydralazine, Labelol, Nifedipine) Guanfacine Guanabenz
SE: sedation, depression, hepatotoxicity (CI: Elderly)

D1- selective agonist

adjunct or alternative in Mx of HTNsive crisis
Fenoldopam
SE: diuresis
vasodilator B. Indirect-Acting Adrenergic Agonists only affect the levels of catecholamines
Ephedrin
MOA: Stimulate release of NE into the cleft SE: USES: Nasal Decongestant
Exacerbate hypertention Risk for Tachycardia Mx of acute Hypotension (Hypotension in surgery) C. Centrally-Acting Ad
alternative for ADHD Amphetamine /Methamphetamine
Sympathomimetic drug that facilitates the release of catecholamines from adrenergic nerve endings
USES: Mx of ADHD (Attention deficit Hyperactive Disorder)
Anorexiant Methylphenidate/ Mephenidate Concerta®, Ritalin® Phentermine Duromine® Phenmetrazine Preludin®NA
DOC for ADHD
Narcolepsy *Phenylpropanolamine
SE: Increase Risk of Addiction
Risk for Pulmonary Hypertension
Phenylpropanolamine/ PPA PPA + Chlorphenamine + paracetamol Disudrin®, Sinutab Strength ®
causes
hemorrhagic stroke
* Catecholamines - are phenylethylamine w/ orthodihydroxy substitutions in the phenyl ring. * Two Carbons - can separate the amino from the phenyl ring that will produce maximal sympath
Beta-1 receptor agonist selectivity - is conferred in beta phenylethylamine structure.
Adrenergic Antagonists (Sympatholytics) A. Alpha Blockers Nonselective α-Blockers α-Blockers Vasodilation
a. Irreversible: Phenoxybenzamine DOC for Carcinoid Syndrome b. Reversible:Phentolamine Regitine®
CLINICAL USES:
Selective α1-Blockers (-zosin)
Mx of HTN, especially w/ Pheochromocytoma as initial Therapy
Prazosin Doxazosin Alfadil XL®
Clinical applications of βblockers.
Application Drugs Effect Hypertension Atenolol, propranolol,
metoprolol, timolol, others
Mx of urinary retention in BPH (Benign Prostatic Hyperplasia)
- α-blockers are most appropriate, especially in male elderly Mx of erectile dysfunction Mx of Raynauds syndrome (finger are unduly reactive) Alfuzosin Xantral®, Fozal®, Profuzosi
Hyzin®, Hykor® Tamsulosin Harnal®, Prozelax®, Pimax®
IMPORTANT SE: Orthostatic/ Postural Hypotension & Syncope
(First-dose Phenonemenon)
Selective α2-Blockers
Yohimbine/ Rauwolscine/ α-yohimbine B. Beta Blockers
I. Based on Selectivity
Non-Selective: the rest of the -olos & -alols β1 Selective : [BBEAAM] Bisoprolol Concore® Bisoprolol + Hydrochlorothiazide Ziac® Betaxolol Betoptic®, Ke
β-Blockers DOC 1st line for drug CSAP for (Chronic HTN esp. Stable if with Angina prior history Pectoris)
of MI *its overdose, can be managed w/ Calcium Supplementation
Esmolol
MOA: Block β, in heart Acebutolol
Ability to decrease rennin release (JG cells) Atenolol Atenolo + Chlorthalidone Metoprolol Tenormin®, Tenoretic® Neobloc®, Angimel®, Cardiotab®
CLINICAL USES: Mx of Angina Pectoris
Mx of arrhythmia Mx of sympathetic symptoms of hyperthyroidism II. Based on Intrinsic Sympatomimetic (ag
Carteolol Mikelan® Labetolol
Mx of Glaucoma Mx of stable CHF(Congestive Heart Failure) Mx hypertension Prophylaxis f
SE: Mask symptoms of Hypoglycemia (use with caution for DM patients) Pindolol III. Based on Membrane Stabilizing Activity [PPALM]
Pindolol
Bradycardia Heart Block Dyslipidemia Hyperuricemia Propanolol Inderal® A
Rebound Hypertension CI: CHF (Congestive Heart Failure)
If taking Calcium Channel Blocker(has same effect w/ Beta Blockers
Metoprolol
*Bisoprolol, Esmolol, Atenolol, Metoprolol cardioselective I.
Based on the Presence of Alpha-Blocking Activity
*Acebutolo least likelihood of casing rebound tachycardia & hypertension Mixed
α-β Blockers
Labetalol Carvedilol Betacard®, Cardipres®, Carvid®, Xicard®, Psicardiol®
among β-blockers *Esmolol has the shortest duration of action (t 1⁄2 = 10 minutes)
can be used as treatment for the mx of cardiac manifestations of
Teophylline or Caffeine overdose *Carvedilol, Bisoprolo, Metoprolol in low dose, have been proven in clinical
trials to be useful in the mx of stable CHF *Chinese patients are most likely to be more sensitive to the effects of β-
blockers
Reduced cardiac output, reduced renin secretion, other
Reduced cardiac rate and force
Angina pectoris Propranolol, others Arrhythmia prophylaxis after myocardial infarction
Propranolol, metoprolol, timolol
Reduced automaticity of all cardiac pacemakers
Supraventricular tachycardia Propranolol, esmolol,
acebutolol
Slowed or blocked atrioventricular conduction velocity; blocked reentry
Decreased mortality, mechanism poorly understood Slowed rate of ca
Heart failure Carvedilol, labetalol, metoprolol Hypertrophic cardiomyopathy Propranolol
Mechanism not understood
Migraine prophylaxis Propranolol Familial tremor, other types of tremor, "stage fright"
Propranolol Reduced β2 alteration of neuromuscular transmission; possible CNS effects
Reduced cardiac rate and arrhythmogenesis; reduced conversion of T4 to T
Thyroid storm, thyrotoxicosis Propranolol, esmolol 3 Glaucoma a Timolol, others (to
secretion of aqueous humor

♥ Parasympathetic Drugs - “Rest & Digest" stimulus

SE: DUMBBELSS Cholinergic Agonists (Parasympathomimetics) A. Direct-Acting Cholinergic Agonists stimulate directly cholinergic receptors
Choline Esters Acetylcholine hydolyzed by Achase
Acetylcholine prototype
no clinical use because of widespreasd effects & rapidly hydrolyzed by Acetylcholinesterase Primary transmitter at cholinergic nerve endings (preganglionic ANS, postganglionic parasym
sympathetic to
(Urecholine®)
thermoregulatory sweat glands, and somatic neuromuscular end plates) Bethanechol
USES: Bladder and bowel atony, for example, after surgery or spinal cord injury *Betanecho & Carbachol Resistant to Acetylcolinesterase Butanechol Methacoline diagnosis of a
(Ophthalmic topical: Isopto carbachol®)

(Ophthalmic intraocular: Miostat®, Carbastat®) for glaucoma Cholinergic alkaloids

Pilocarpine (Isopto Carpine®)
(SR inserts: Ocusert Pilo-20®, Ocusert Pilo-40®) causes contraction of ciliary muscle fibers attached to the trabecular meshwork & sclera spur. opens the trabecular meshwork
humor outflow alkaloids from Pilocarpus sp. USES: Sjögren's syndrome (increases salivation)
Tertiary Amines:

Well Absorbed -Pilocarpine -Arecoline Quaternary Amines: Less Absorbed Arecoline from betel nut (Areca catechu) -Muscarine Muscarine Alkaloid found in mushro
Major overdose: convulsions, paralysis, coma
Nicotine Lobeline Cevimeline (Evoxac®) Varenicline (Chantix®) B. Indirect-Acting Cholinergic Agonists

Short-acting anti-cholinesterase Edrophonium Tensilon®

MOA: Inhibitor of cholinesterase;
amplifier of endogenously released Ach USES: Diagnostic agent for Myasthenia Gravis Intermediate-to-long-acting (Carbamates) carbam
bearing quaternary or tertiary ammonium groups Neostigmine Prostig®, Prostigmin®
CLINICAL USES:

Dx & Mx of Myasthenia Gravis(mostly) Mx of Atropine poisoning Mx of neuromuscular blocker toxicity Mx of Glaucona Mx of ileus Mx of urinary retention & BPH Mx of Alzheimer’s Diseas
quaternary amine; poorly absorbed USES: Antidote for Tubocurarine Poisoning
Tx Myasthenia gravis Physostigmine aka, Eserine
Tertiary amine; more lipid soluble; well absorbed USES: Reversal of severe atropine poisoning (IV);
occasionally used in acute glaucoma (topical) Pyridostigmine Pyrinon®, Mestinon®, Regonol®
USES: Treatment of myasthenia gravis Galantamine Reminyl® Ambenonium Mytelase® Demecarium Himorsol® Very long-acting (Organophospates) organic d
USES: Tx of open-angle glaucoma Insecticide and scabicide (topical) Insecticide only
acid Ecothiophate Phospholine® Malathion A-lices® Parathion Isofluorop
for Alzheimer's disease
Rivastigmine Exelon® Tacrine Cognex® 1st line treatment for Alzheimer’s Disease Donepezil Aricept®, Donezepil®
Biosynthesis of Catecholamines
Synthesis & Release of Acetylcholine 1. Tyrosine uptake
1. Synthesis of Acetylcholine 2. Tyr DOPA (Tyrosine hydroxylase)
-transport of choline inhibited by 3. DOPA Dopamine (DOPA decarboxylase)
hemicholinium 4. Vesicular uptake of Dopamine
2. Uptake into Storage vesicles 5. Dopamine NE (Dopamine β-hydroxyl)
-protected from degradation NE Epi (PENMT) -Phenylethanolamine-N-methyltransferase)
3.Release of Neurotransmitter 6. Release
-botulinum toxin- blocks release -spider venom- promotes release
Reactions involved: Methylation
Hydroxylation Decarboxylation
4. Binding to Receptor 5. Degradation by Acetylcholinesterase
Ach Acetate + Choline 6 Recycling of Choline
Cholinergic Antagonists (Parasympatholytics) SE: Alice in the wonderland Syndome A. Anti-muscarinic CNS-Acting (for Motion-sickness)
Scopolamine (Buscopan®, Transderm-Scop®)
aka Hyoscine alkaloid from henbase )Hyoscyamus niger) Anti-motion sickness via transdermal patch; sedative tertiary amine(exert CNS effects)
Anti-muscarinic CLINICAL USES: Mydriatic (cycloplegia)
Mx of Bradycardia Organophosphate overdose C
Glaucoma *Diphenoxylate addition to atropine to prevent addiction
Biperiden Akineton® Benztropine Cogentin® Trihexyphenidyl Artane® M
Atropine Anespin®, Isopto Atropine® DOC for cholinergic toxicity
aka Hyoscyamine prototype antimuscurinic
Effects: -Cycloplegia (Contraction of ciliary muscles) -Mydriasis (relaxation of the papillary constrictor
muscles) -Tachycardia (blockade of vagal slowing of the
Tropicamide
heart) Homatropine Lesopen®, Isopto Homatropine® Tropicamide + Phenylephrine Medriacyl®, Sanmyd-P® for ophthalmic examination Cyclop
Bronchodilator (Relaxant of Bronchial smooth muscles)
Ipratropium Br Atrovent® Oxytropium DOC bronchodilator for COPD (Chronic Obstructive Pulmonary Disease) Tiotropium Spiriva® M1-selective blocker (adjunct in hy
USE: Peptic disease (not available in USA)
Pirenzepine Gastrozepin® Telenzepine M3-blockers (useful for GIT & urinary bladder hyperactivity)
Hyosine-N-butylbromide Buscopan® Hyosine-N-butylbromide + Paracetamol Buscopan Venus® Dicycloverine Relestal® Glycopyrrolate Robinul® Clidini
Chlordiazepoxide Librax® Dicyclomine Bentyl® Methscopolamine Pamine® B. Anti-nicotinic
Neuromuscular Blockers /irreversible
Succinyl choline Depolarizing/ noncompetitive - Flaccid Paralysis Isoquinoline derivatives
Non-Depolarizing/ reversible - Fetanic Paralysis Atracurium Mivacurium
Atracor®. Tracrium®
CLINICAL USE: Skeletal muscle relaxants during surgey SE: Succinyl - rhabdomyolysis (massive release) S
Curare- cause anaphylactoid reaction (not IgE mediated) Pancuronium Pavulon® NA Vecuronium Norcuron®
*Succinylcholine - may cause malignant hyperthermia
Ganglionic Blockers
Hexamethonium Mecamylamine Inversine® for Nicotine Toxicity Trimethaphan camsylate Arfonad® expected to produce Hypotension Regenerator
Pralidoxime *Pralidoxime
*Diacetyl Monoxide *Atropine
DOC for organophosphate poisoning
II. AUTOCOIDS
stamine aka β-imidazolylethylamine; 1H-imidazole-4-ethenamine
Basophils & mast cell; ECL; (*Histidine major source of Histamine) H1: Physiologic antagonis: Epinephrine
Pharmacologic antagonist: H1-antihistamine Prototypic antagonist: Diphenhydramine
H2: Prototypic Antagonist: Cimetidine
Serotonin happy hormone; responsible for mood regulation
Tryptophan -decarboxylation -hydrolase 5HT

5HT1A Presynapse To inhibit further release 5HT1D Peripheral Blood Vessels Vasoconstriction 5HT2A Smooth Muscle vascular Uterine Contraction 5HT3 Chemorecepto

Emesis 5HT4 GIT Peristalsis Kalidin no agent, but its analogues/ drugs can mimic, block or modulate other autocoids Bradykinin function as an algesic Eicosanoids aka “Arachidon
Acid; 20-carbon polyunsaturated FA

Prostaglandin PG: PGE1, PGE2, PGF2 ; derivatives of Prostanoic Acid Leukotrienes LT: LTB, LTC, LTD ; for inflammation & bronchoconstriction Prostacyclin PGI2 Thromboxane

♥ Anti-histamines H1- Anti-histamines

MOA: Block H1 receptors especially in Mast Cells CLINICAL USES: allergic rhinitis
allergic contact dermatitis
Triple Response of Lewis following Intradermal Inj of Histamine:
-Sensory nerve ending stimulation
producing flare -Local flushing due to dilatation of
blood vessels -Endothelial cell contraction
leading to exudation of fluids
H1 receptor stimulation leads to:
- Extravascular smooth muscle contraction - Vascular smooth muscle relaxation - Endothelial cell contraction 1st G

MOA: Competitive pharmacologic block of peripheral and CNS H1 receptors plus - and M-receptor block.
Anti-motion sickness effect CLINICAL USES: Hay fever, angioedema, anti-motion sickness; used orally as OTC sleep aid; used parenterally for dystonias Ethanolamine most sedating
anticholinergic; used as sleeping pills; mx of EPS(atropine-like effects)
Diphenhydramine can block Na channel in excitable membranes bringing about a local anesthetics effect Diphenhydramine+ Calamine Benadryl®, Caladryl® Dimenhyd
Carbinoxamine Palgic® Doxylamine Unisom® Ethylenediamine (Ethylenediamine moiety contained in Piperazine, Imidazolines, & Phenothiazine-type)
Pyrilamine Tripelennamine Piperazine
Hydroxyzine Iterax® converted to Cetirizine(active metabolite) Meclizine Cyclizine Bonamine®, Valoid® Dizitab® Antimotion sickness Alkyl amines adjunct
Brompheniramine propylamine derivative Brompheniramine + Phenylephrine Dimetapp® Chlorpheniramine Antamin® result from the chlorination of pheniramine
phenyl ring Chlorpheniramine-containing Bioflu®, Neozep®, Sinutab®, Decolgen forte® Phenothiazine
Promethazine Phenargan®, Phenerzin®, Promet®, Zinmet® as anesthetic Cyproheptadine Periactin® for serotonin syndrome; has significant blocking effects on 5-
Generation/ Non-sedating
MOA: Competitive pharmacologic block of peripheral H1 receptors. No autonomic or anti-motion sickness effects CLINICAL USES: Hay fever, angioedema Less sedating
Cetirizne Alnix®, Zyrtec® Acrivastine Benadryl allergy relief® True non-sedating
Loratadine Allerta®, Claritin®, Clarihist®, Zylohist®,
Cardura ®, Lorid® Only antihistamines allowed for Pilots Fexofenadine Fenafex®, Telfast® Desloratadine Aerius® Levocetirizne Xyzal®
H2- Anti-histamines
MOA: Block H2 receptors especially in Parietal cells of the stomach CLINICAL USES: Alternative drug for PUD & GERD Potency: (most to least) Famotidine Nizatidine = Ranitidine Cim
H2 receptor stimulationj leads to:
- Gastric acid secretions
Cimetidine Tagamet® Ranitidine Zantac®, Ulcin® Famotidine H@ BLOC®, Hista-Bloc® Nizatidine Axid®, Nolcer® have an almost complete oral bioavailability
Products of Eicosanoids through Cyclooxygenase enzyme:
- Prostglandins -Prostacyclins -Thromboxanes

Serotonin & Related Drugs 5-HT1A Partial Agonist

Buspirone Buspar® anxiolytic 5-HT1D Full Agonist

Sumatriptan Sumigran®, Imigran® Naratriptan Naramig® Zolmitriptan Zomig® Rizatriptan Maxalt®
MOA: 5-HT1D agonist; causes vasoconstriction; modulates neurotransmitter release CLINICAL USES: Migraine and cluster headache(same w/ 5-HT1B) CI: Patient w/ Ischemi
because of their Vasospastic Effect

5-HT2A Agonist
Ergotamine Ergomar® Methylergometrine/ Methergine Methergin® Ergonovine Ergotrate® oxytoxic Dihydroegotamine Migrana® 5-HT2 Antagonist
MOA: Competitive 5-HT
Ketanserin 2 and 1
-receptor block
CLINICAL USE: Hypertension, carcinoid tumor (not available in United States) 5-HT3 Antagonist
MOA: Pharmacologic antagonist; blocks chemoreceptor trigger zone and enteric nervous system 5-HT
Granisetron Kytril®, Sancuso® 3 receptors Ondansetron Z

CLINICAL USE: Chemotherapy and Postoperative Vomiting 5-HT4 Partial Agonist

MOA: Partial agonist at 5-HT
Tegaserod Zelnorm® 4 receptors

CLINICAL USE: Constipation-dominant irritable bowel syndrome (restricted use) Toxicity: Diarrhea, Ischemic Colitis
♥ Prostaglandins & Other Eicosanoids
Leukotrienes
LTB4 MOA: Chemotactic factor in inflammation LTC4, LTD4 MOA: Bronchoconstrictors important in anaphylaxis; cause edema TOXICITY: Inflammatory Mediator Leukotriene
Zileuton
Lipoxygenase inhibitor
MOA: Blocks synthesis of leukotrienes
CLINICAL USE: Asthma prophylaxis TOXICITY: Liver enzyme elevation Leukotriene receptor in
Zafirlukast
MOA: Block CysLT
1 receptor; reduce bronchoconstriction in asthma CLINICAL USE: Asthma prophylaxis Toxicity: Liver enzyme elevation SE: Churg-Strauss Syndrome (a form of eosino
Thromboxane
MOA: Activates TP, receptors, causes platelet aggregation, vasoconstriction
TXA2
Prostacyclin
PGI2:
MOA: Activates IP receptors, causes vasodilation, reduces platelet aggregation
Epoprostenol Flolan®
CLINICAL USES: Vasodilator in pulmonary hypertension, antiplatelet agent in extracorporeal dialysis TOXICITY: Hypotension, Flushing, Headache *PGI2 analog, treprostinil: parenter
hypertension
Prostglandins
PGE1
Alprostadil Caverject®, Muse® injectable form for erectile dysfunction
MOA: Activates EP receptors, causes increased HCO3– and mucus sec
used as a palliative treatment to maintain neonates w/ ductus arteriosus Misoprostol Cytotec®
uterine contraction

CLINICAL USES: Protective agent in peptic ulcer disease; abortifacient ; Cytoprotectant TOXICITY: Diarrhea, Uterine Cramping PGE2
Dinoprostone Cerviprime® natural prostaglandin, used to terminate pregnancy from 12th week through the 2nd trimester.
MOA: Low concentrations contract, higher concentrations relax uterine and cervical smooth muscle CLINICAL USES: Abortifacient; for induction of labor-causes uterine contraction; cervical
Cramping, fetal trauma PGF2
MOA: Increases outflow of aqueous humor, reduces intraocular pressure
Latanoprost Xaltan®
CLINICAL USE/S: Glaucoma TOXICITY: Color change in iris
III. NSAIDS & related drugs
Cyclooxygenase inhibitors (NSAIDs) Nonselective COX-1, COX-2 inhibitors used as analgesic & anti-inflammatory
Salicylates
Aspirin Aspilet®
 325mg/day, 1st line in the primary & secondary prevention of acute thrombotic events absorbed in the stomach & in the small intestines in the unhydrolyze form EXCRETION:<600mg/d
0th order
(its excretion, enhance w/ alakalination of the urine; follows Michaelis Menten Elimination Kinetics) MOA: Irreversibly inhibits COX-1 and COX-2; reduce synthesis of prostaglandins/
Acetylation of COX-1 and COX-2 results in decreased prostaglandin synthesis CLINICAL USES: Analgesia, antipyretic(Inh. CNS response to Interleukin-1), anti-inflamma
Antithrombotic(irreversible acetylation of COX enzyme in platelets); prevention of colon cancer *3.2-4g/day usual adult dose of Aspirin for its Anti-Inflammatory Effect SE: GI discomfor
salicylism, vertigo, Hypersensitivity reaction=Reye’s Syndrom, Asthma
Reye’s Syndrome manifest as hepatic failure & encephalopathy
happen when there is a previous or current viral infection ADMINISTRATION: Must be given w/ or after heavy meal
Or take proton-pump inhibitor before taking aspirin RISK FACTORS: Taking multiple NSAIDS: causes Gastritis (blood in the stools)
Concurrent use of Glucocortcoids: Increase inhibition of cytoprotectant action of COX
TOXICITY: Gastrointestinal (GI)
toxicity, nephrotoxicity, and increased bleeding time at therapeutic levels; hypersensitivity reaction due to increased leukotrienes; tinnitus, hyperventilation metabolic acidosis, hyperthermia,
*Serum Salicylate Levels:
Low Toxic (50-80 mg/dL) -Hypeventilation -Respiratory Alkalosis -Tinnitus & Vertigo Moderate Toxic(80-110mg/dL)
-Metabolic Acidosis -Dehydration -Hyperthermia Py
Oxyphenbutazone
Phenylbutazone SE: Hematologi toxicities - Aplastic Anemia, Agranolocyte; ATN(Acute tubular necrosis)
CI: Drug allergy, Blood Dyscrasias, Hypertension Sulfinpyrazone Anturane® *Aromatic Hydroxylation involved in biotransformation of Phenylbutazone to Oxybutazone Indole der
Indomethacin Infree®, VI-Gel®
MOA: Inhibits COX1 than COX2(preferred for the mx of pain of an acute attacks of gout); Increase gastric ulcers BENEFICIAL: PDA/ Patent Ductus Artriosus failure to close ductus Pyro
derivatives
Tolmetin Tolectin® Oxicam derivatives
MOA: Inhibits COX1 than COX2 (represents a class of acidic inhibitors of prostaglandin synthetase, although it does not
Piroxicam Feldene®
antagonize PGE2 directly) Phenylaceticacid derivative
Sulindac Clinoril® sulfur-containing drugs
causes SJS (Steven Johnson Syndrome)
Indications: 0 Arthritis
Osteoarthritis Ankylosing Spondylitis Diclofenac Voltaren®, Cataflam®, Diclogen® Alclofenac Etodolac Etoflam® has minimal anti-inflammatory aactivity that are primarily
especially in Ketorolac replace morphine the mx of post-operative pain Nabumetone Relafen® *All known NSAIDs are weak acids, except Nabumetone Fenamates
Mefenamic Acid Dolfenal®, Gardan®, Ponsran® not anti-inflammatory
not antipyretic but only an analgesic
*must be given for not more than 5 says Flufenamic Acid
*never give it to children Meclofenamic Acid
*more toxic than aspirin Propionic Acid Derivative
Ibuprofen Advil®, Dolan FP®, Medicol®, Midol®, Nuprin®, Motrin®
is an arylacetic acid derivative appears comparable to aspirin In the tx of RA, with a lower incidence of side effects also been approved for use in primary dysmenorrheal prescribe
Patient for RA exists both as R- & S- enantiomers (S-enantiomer is the only active form) SE: Renal Failure Ibuprofen+Paracetamol Alaxan® Ketoprofen Orudis® Flurbiprofe
ophthalmic solution Naproxen Flanax®, Naprosyn® Selective COX-2 inhibitor
Meloxicam Mobic® Specific COX-2 inhibitor (Advantage: Less incidence of gastric irritation or ulceration)
MOA: Selectively reversibly inhibits COX-2
Celecoxib Celebrex®, Celcoxx® Eteroxib Arcoxia®
CLINICAL USE/S: Analgesia, antipyretic, and anti-inflammatory Toxicity: Nephrotoxicity; hypersensitivity due to increased leukotrienes; less risk of GI toxicity than nonselective
NSAIDs; greater risk of thrombosis than nonselective NSAIDs *Rofecoxib (Vioxx®) have been withdrawn from the market or are marketed w/ ―black box‖ warning because of
its increase risk of Thrombosis & cardiac death
*Aspirin, Other salicylates, Tolmetin contraindicated w/ GOUT (effect on urate levels: <2g/dL hyperuricemia/ >2g/dL uricosuric acid)
*COX-1 isozymes is widely distributed & constitutively expressed *COX-2 isozyme present only during inflammation upon stimulation by cytokines & growth factors, & by inflammatory &
♥ Disease-Modifying Anti-Rheumatic Drugs (DMARDs)
DMARDs alters/ slows down joint destruction
SAArTs (slow-acting antirheumatic drugs Methotrexate Zexate®, Alltrex® 1st line DMARDS in RA
Important to pyrimidine synthesis MOA: Cytotoxic to rapidly dividing immune cells due to inhibition of dihydrofolate reductase
Inhibit AICAR (aminoimidazole carboxanide tribonucleotide)
Inhibits DNA transcription CLINICAL USE/S: Anticancer, rheumatic disorders SE: Hepatotoxicity (*Folic Acid- hepatoprotectant) TOXICITY: Nausea, Mucosal Ulcers, Hematotoxicity, Hepato
ALTERNATIVE: Leflunamide Anti-Malarial Agents
Chloroquin Chloromax® Hydroxychloroquine Plaquenil
Auranofin Ridaura® Aurothiomalate Myochrysine® SE: hypersensitivity reaction Aurothioglucose Solganal® Sulfasalazine Azulfidine® has 2 metabolites:
Sulpapyridine I-aminosalicylate (
Inflximab Remicade®
Adalimumab Humiral® MAB (Monoclonal Antibodies) Etanercept Enbrel®
Inhibit TNF-α & also block inflammation. subjecting patients to inflammation Leflunomide Arava® alternative of Methotrexate Azathioprine Imuran® metabolize into 6-merca
Penicillamine Cuprimine® for copper toxicity/ Wlison’s Disease
alter the function of WBC for progressive rheumatoid Arthritis
is a degradation product of penicillin-type antibiotics also useful in treating Lead poisoning & RA
♥ Drugs for Gouty Arthritis
*Gout increase level of uric acid
 Deposition of uric acid in subcutaneous tissue Uric Acid strong negative birefringent needles of (MSU) - monosodium urate Formation of Uric Acid :
hypoxanthine -xo xanthine -xo uric acid
w/ allopurinol alloxanthine cannot be converted to uric acid Acute Gout
Colchicine Goutnil®, Rhea® 1st line treatment of acute gout (usual dose: 15mg once a week)
Microtubule assembly inhibitor (decreases macrophage migration and phagocytosi) MOA: Inhibitionof AICAR (aminoimidazolecarboxamide) CLINICAL USE/S: Chronic and acute gout, fa
fever TOXICITY: Diarrhea, Severe Liver & Kidney Damage in Overdose(mimimized w/ Leucovorin) NSAIDs Glucocorticoids (GC)
Methyl Prednisolone to inhibit inflammation
systemic management of RA,
Life threatening SLE (Systemic Lupus Erythematus) Intrasynovial Chronic Gout
Colchicine 1st line initial treatment of chronic gout
after 2-3 weeks MOA: Inhibits the synthesis of Microtubules Allopurinol Zyloprim®, Alpurase®, Allurase®, Purinase®, Lopric®, Loricid®
Drug of choice for chronic gout 1st line hypourecemic agent in chronic gout Xanthine oxidase inhibitors acts as suicide substrate MOA: Active metabolite irreversibly inhibits xanthine
production of uric acid CLINICAL USE/S: Chronic gout; Adjunct to cancer chemotherapy; Mx of recurrent renal urate stones TOXICITY: GI Upset, Hypersensitivity Reactions, Bone Marrow S
Probenecid Benuryl® Uricosurics (induce loss of uric acid in urine
*Sodium Bicarbonate to increase uric acid secretion MOA: Inhibition of renal reuptake of uric acid CLINICAL USE/S: Chronic gout, prolongation of antimicrobial drug action TOXICITY: Exa
hypersensitivity reactions,
inhibits renal tubular secretion of weak acids such as methotrexate Sulfinpyrazone Anturane® Uricosurics
Similar to probenecid Penicillamine Cuprimine®
IV. ANALGESICS
Non-Narcotic Analgesics
NSAIDs Acetaminophen/ Paracetamol /para-aminophenol
Biogesic®, MOA: Tylenol®, Calpol®, Tempra®, Kidilets®,
Selective, reversible inhibition of COX-2 results in decreased prostaglandin synthesis (weak inhibitor) CLINICAL USE/S: (Equivalent to Aspirin -Analgesia, Antipyretic) and (has non Anti-Infla
≥150mg/kg
Nephrotoxicity; hypersensitivity due to increased leukotrienes; less risk of GI toxicity than nonselective NSAIDs; greater risk of thrombosis than nonselective NSAIDs IMPORTANT TOXIC M
acetylparaquinone) Naprex®
ANTIDOTE: N-acetylcysteine Maximum Daily Dose for Adults: 4 grams
Opioids/ Opiates
*Opioids semi-synthetic or synthetic compunds *Opiates natural compound
Opioid Receptors: Mu (μ) dominant Receptor
responsible of most Opioid Effects Kappa(κ ) affords additional analgesia for women Delta (δ) additional analgesia Opioid Receptors are activat
peptides,
including endorphins such as:
β-endorphins -have affinity for μ receptor Enkephalins - for δ receptor Dynorphins - for κ receptor Uses: Pain States, Acute Pulmonary Edema(Conges
Adjunct, Antidiarrheal, Cough Suppresant, Antiemetics CI: Pregnancy, Partial Agonist,
History of Head Trauma or Increase Intracranial Pressure Narcotic Analgesics MOA: mimic or increase the release of endogenous opioid peptides. Natural opium
Morphine Morin®,
MST Continus®
Opioid Effects: Analgesic Euphoria Sedation Hypotension Respiratory Depression Bradycardia Vasodilation
Convulsion Constipation Mioisis
Other Effects: CNS-Tolerance Peripheral Effects: Vasodilation Biliary tree- contraction GIT-less of peristalsis -constipation Mast cells- release of histamine
(anaphylactoid reaction) Drugs dependence (addiction)
} are not observe in tolerance of opioids
*Tolerance developed in 2-3 weeks
is the standard by which you compare opioid activity (can tx acute pulmonary edema-reduce venous return) only 25% bioavailable (40 mg Oral Dose = 10 mg IV Dose) * Prescription Lim
3,000 mg Morphine Sulfate Codeine prodrug
has less activity compared to morphine USES: Antitussive, Mx for Moderate pain state Thebaine precursor substrate of Na
Heroin diacetyl morphine or diamorphine
diamorphine common drug of abuse Apomorphine Apokyn® non
Oxymorphone Opana®
USES: POD, emetic Hydromorphone Jurnista®
derivatives of morphine 10-12x more potent than morphine same efficacy w/ morphine Oxycodone Hydrocodone OxyContin®, O
same efficacy w/ codeine 8-10x more potent w/ codeine derivatives of codeine * Prescription Limit for Cancer Patients: 1,200 Oxycodone HCl S
Methadone same efficacy w/ morphine
has greater bioavalability(F), has longer duration of action, has less rapid development of tolerance than morphine USES: to wean-off patient addicted to Heroin or Morphine Mep
ADV: ha
has analgesia ( is not associated w/ Biliary Colic, Hypotension, Bradycardia) converted to normeperidine
Problem: can cross blood-brain barrier so it causes seizures as
Diphenoxylate + atropine Lomotil® other countries
convulsion Diphenoxylate Loperamide Diatabs®, Imodium®, Lomotil®
Sulfentanil Sufent
for diarrhea (antidiarrheals) *Diphenoxylate always given w/ Atropineto discourage the abuse of DIphenoxylate Alfentanil Alfenta®
same efficacy as morphine 100x more potent than morphine 100% bioavailability(F) Tramadol Tramal®, Ultram® Tramadol+P
 weak opioid agonist (synthetic analogue of Codeine) for mild pain states derivative of codeine only opioid that does not require S2 prescription Pentazocine
*Abstinence Syndrome is seen w/ abupt withdrawal of an opioid agonist in a patient taking the drug chronically, in newborn of a mother illicitly taking
heroin during pregnancy, & administration of Nalbuphine or Naloxone on a patient chronically taking on morphine
Opioids, Opioid Substitutes, & Opioid Antagonists
Subclass Mechanism of Action
(Receptors)
Clinical Applications Pharmacokinetics &
Interactions
Toxicities
Strong agonists Fentanyl Hydromorphone Meperidine Morphine Methadone Oxymorphone
Respiratory depression, constipation, addiction iability
Partial agonists Codeine Hydrocodone
Strong agonists; variable
Severe pain, anesthesia (adjunctive);
Hepatic metabolism; duration: and agonists
dependence maintenance (methadone)
1–4h (methadone 4–6 h)
As above, but lower affinity Mild-moderate pain; cough (codeine);
Genetic variations in
As above, but weaker analgesic combinations with NSAIDs

metabolism and acetaminophen Mixed agonist-antagonist Buprenorphine Partial agonist and

antagonist

Like strong agonists but can antagonize their effects Nalbuphin

antagonist
Moderate-severe pain; dependence
Long duration (buprenorphine); maintenance, reduces craving for
nalbuphine (parenteral only) alcohol (buprenorphine)
Has analagesic efficacy equivalent to Morphine Antagonists Naloxone Naltrexone Nalmefene
Rapid antagonism of all opioid actions
Antitussives Codeine Dextromethorphan
Antagonists at all receptors Opioid overdose; dependence
Duration: naloxone 2 h; maintenance (naltrexone)
naltrexone and nalmefene >10 h
Mechanism uncertain
Acute debilitating cough Duration: 0.5-1 h Reduce cough reflex; patrial agonists
toxic in overdose

Tramadol Weak agonist; inhibits

norepiniphrine and 5-HT transporters
Duration: 4-6 h Toxic in overdose
(seizures)
Drugs of Abuse
Signs and symptoms of overdose and withdrawal from selected drugs of abuse.
Drug Overdose Effects Withdrawal Symptoms Amphetamines, methylphenidate, cocainea Moderate pain; adjunctive to opioids in
chronic pain states
Agitation, hypertension, tachycardia, delusions, hallucinations, hyperthermia, seizures, death

Apathy, irritability, increased sleep time, disorientation, depression Barbiturates, benzodiazepines, ethanolb Slurred speech, "drunken" behavior, dilated pupils, we
pulse, clammy skin, shallow respiration, coma, death
Anxiety, insomnia, delirium, tremors, seizures, death

Heroin, other strong opioids Constricted pupils, clammy skin, nausea, drowsiness, respiratory
depression, coma, death
Nausea, chills, cramps, lacrimation, rhinorrhea, yawning, hyperpnea, tremor
Drugs Used to Treat Dependence and Addiction
SUBCLASS MOA EFFECTS CLINICAL APPLICATION Opioid antagonists Naloxone Naltrexone
Antagonists of
Reverse or block effects of opioids Naloxone: opioid overdose opioid receptors
Naltrexone: treatment of alcoholism Synthetic opioid
Methadone Slow-acting
agonist at opioid receptors
Substitution therapy for opioid addicts
Partial -receptor agonist
Buprenorphine Partial agonist at
opioid receptors
Acute effects like morphine
Toxicity: Like morphine re acute and chronic effects including withdrawal
Attenuates acute effects of morphine and other strong opioids Substitution therapy for opioid addicts
N-receptor partial agonist
Varenicline Agonist at ACh-N
receptor (22) subtype
Smoking cessation
Benzodiazepines Oxazepam Lorazepam
Blocks "rewarding" effects of nicotine
Toxicity: Nausea and vomiting, psychiatric changes, seizures in high dose
Modulators of

Enhance GABA functions in CNS; safest alternative for elderly Attenuate withdrawal symptoms GABAA receptors
including seizures from alcohol and other sedative-hypnotics NMDA r

Acamprosate Antagonist at
glutamate NMDA receptors
Treatment of alcoholism (in combination with counseling)
Cannabinoid receptor agonist
Rimonabant Agonist at CB1
receptors
May block synaptic plasticity
Toxicity: Allergies, arrhythmias, variable BP effects, headaches, and impotence; hallucinations in elderly
Decrease GABA and glutamate release in CNS
Treatment of obesity; off-label use for smoking cessation Toxicity: Major depressio

V. DRUGS FOR COAGULATION DISORDERS DRUGS FOR COAGULATION DISORDERS

Antithrombotic (Anticlotting drugs) Prothrombotic (drugs that facilitate clotting) Anticoagulants Replacement Fact
Antiplatelets Vitamins K Fibrinolytics/ Thrombolytics Antiplasmin drugs
Clot Formation: 1. Vascular event
Vasoconstriction Vasodilation 2.Cellular event/ types of Thrombosis
a. Platelet migration aggregation
Aggregation Adhesion Factors:
-Proaggregants (PLT) -Antiaggregants (endothelium)
Receptors: Glycoprotein IIb, IIIa b. Activation of Coagulation Cascade
*Glycoprotein IIb, IIIa
responsible for interplatelet binding *Glycoprotein Ia/ Ib
responsible for adhesion vascular surface Ia – bind w/ collagen Ib – bind w/ Von willebrand Factor *Red Thrombus - for after 6-12 hours formation of wh
Golden period of Coagulation Stimuli for Thrombosis
-endothelial injury -presence of foreign matter in the blood/ blood vessel -stasis of blood platelet plug final product
1° hemostasis White thrombosis temporary & unstable to make its stable, there will be an
Activation of Coagulation Cascade
Three factors that ingluence the formation of Pathologic Clot:
Virchow’s Triad:
- Abnormalities of Blood Flow - Abonormalities of Surface contact with Blood - Abnormalities of Clotting component
Embolus - small part of clot Thrombosis - formation of fibrin blood clot
Pro-aggregants:
Serotonin(5-HT) Thromboxin A2 (TXA2) ADP
Anti-aggregant:
Prostaglandin (PGI2) PGE1 cAMP
Replacement Factor Clotting factors
Factor VIII MOA: Key factor in the clotting cascade CLINICAL USES: Hemophilia A
Hemophilia A lack of Clotting factor VIII Hemophilia B lack of Clotting Factor IX
* Coagulation Cascade – “zymogen”
Coagulation Factor/
Clotting Factor
synthesis by liver synthesis to zymogen, as inactive factor I – XII Examples: Proth
Fibrinogen Fibrin
Intrinsic pathway Extrinsic Pathway
Va, VIIa
Factor X VIIIa
Factor Xa FII Prothrombin Factor IIa
Thrombin

Factor I Fibrinogen
Factor Ia
Fibrin
Fibrin form a mesh work over the white thrombus
(glue) attract cell (RBC)
product: Red Thrombus (secondary homeostasis) -stable & permanent -6-12 hours Regulatory Mechanisms: 1. Antithrombin endogenous anticoag
anticoagulant 3. Plasmin serine protease (enzyme aacting on protein)
produced as plasminogen, as inactive form activated by converting,
using TPA (Tissue-typePlasminogen Activator)
Plasminogen
Fibrinolytics
Plasmin
Thrombin Degradation Product
Antiplasmin Drugs
Fibrinogen Fibrin
Fibrin Split Products
Antithrombotic (Anticlotting drugs) Anticoagulant
Direct Thrombin Inhibitor: directly interfere with action/ destroy factor
Hirudin/
Lepirudin – DNA
recom. form of Hirudin
derive form medicinal leeches for the Mx of HIT (Heparin Induced Thrombocytopenia) MOA: Binds to thrombin's active site and inhibits its enzymatic action CLINICAL USE/S: Anticoa
heparin-induced thrombocytopenia (HIT) TOXICITY: Bleeding (monitor with aPTT); anaphylactic reactions Bivalirudin Angiomax® Given to patient post-PTCA to prevent thrombosis
transluminal coronary angioplasty) Argatroban alternative drug for Mx of HIT Indirect Thrombin Inhibitor: primarily affect the synthesis of thrombin or its form
Heparin - (mucopolysaccharide) Hemastat®, Heptin®
anticoagulant of choice(activates antithrombin III) initiating anticoagulant therapy also for long term use or extended anticoagulation therapy anticoagulation for pregnancy when u
there is no need to monitor activity in most cases SE: Bleeding, HIT (heparin-induced thrombocytopenia)-caused by idiopathic reaction against heparin,
alopecia, thrombocytopenia, osteoporosis with chronic use CLINICAL USE/S: Venous thrombosis/ deep vein thrombosis(DVT),pulmonary embolism, myocardial infarction,
unstable angina, adjuvant to percutaneous coronary intervention (PCI)/ acute coronary syndrome MONITORING PARAMETER: activated Partial Thromboplastin Time (aPTT) CI: Patients w
*Bleeding associated w/ the use of Heparin is best
managed w/ administration of Protamine Sulfate & stopping therapy
MOA: Forms an active complex w/ anti-thrombin III that inactivates factor IXa, Xa, XIa, XIIIa
Regular/ Unfractioned Heparin (IV, SQ) Low molecular weight / Fra
(SQ)
Enoxaparin Dalteparin Tinzaparin
MOA: Forms an active complex w/ anti-thrombin III that inactivates factor Xa *More selective anti-factor X activity, more reliable pharmacokinetics with renal elimination, protamine reversal o
less risk of thrombocytopenia
* Fondaparinux: Effects similar to LMW heparins
MOA: Inhibits vitamin K epoxide reductase (inactive from of Vitamin K) and thereby interferes with production
Warfarin Coumadin®, Zyparin®
of functional vitamin K-dependent clotting and anticlotting factors (II, VII, IX, X) TOXICITY: teratogen MONITORING PARAMETER: Prothrombin Time (PT) - (recommended PT: 3-4/ 2-3) A
Thromboxane synthesis Inhibitor: Aspirin
(<325mg/day) 1st line in the primary & secondary prevention of acute thrombotic events MOA: Nonselective, irreversible acetylation of COX in platelets CLINICAL USE/S: Prevention and
thrombosis TOXICITY: Gastrointestinal Toxicity, Nephrotoxicity; Hypersensitivity Reaction due to Increased Leukotrienes;
Tinnitus, Hyperventilation Metabolic Acidosis, Hyperthermia, Coma in Overdose ADP inhibitor :
MOA: Active metabolite irreversibly inhibits platelet ADP receptor(pro-aggregants)
Clopidogrel
CLINICAL USE/S: Acute coronary syndrome, prevention of restenosis after PCI, prevention and treatment of arterial thrombosis Ticlopidine Ticlid®, Tikpid® Older ADP receptor ant
toxicity,
MOA: Inh
particularly Leukopenia and Thrombotic Thrombocytopenic Purpural (weekly WBC monitoring is needed) Phosphodiesterase Inhibitors: Dipyridamole Persantin®
uptake and inhibits phosphodiesterase enzymes that degrade cyclic

nucleotides (cAMP, cGMP) -can cause Coronary steal phenomenon Glycoprotein IIb/ IIIa Inhibitors
MOA: Inhibits platelet aggregation by interfering with GPIIb/IIIa binding to fibrinogen and other ligands Tirofiban Aggrastan®
Abciximab Reopro® Eptifibatide
Integrilin®
CLINICAL USE/S: Used during PCI to prevent restenosis; acute coronary syndrome; post PTCA *Eptifibatide, tirofiban: Reversible GP IIb/IIIa inhibitors of smaller size than abciximab Fib
plaminogen to plasmin, a serine protease that catalyzes breakdown of fibrin & fribrinogen
Streptokinase comes from Streptococcus species of bacteria
can be given after 2 years from current administration enhances the conversion of plasminogen plasmin
* Bacterial protein that forms a complex with plasminogen that rapidly
converts plasminogen to plasmin. Subject to inactivating antibodies and allergic reactions Anisoylated Plasminogen – Streptokinase Activator Complex (APSAC) Tissue Plasm
PA
Recombinant: Reteplase, Tenecteplase
MOA: Converts plasminogen plasmin, which degrades the fibrin in thrombi
CLINICAL USE/S: Coronary artery thrombosis, ischemic stroke, pulmonary embolism; Thrombo
especially Cerebral Hemorrhage * Reteplase, Tenecteplase: Similar to alteplase but with a longer half-life Ur
Prothrombotic (drugs that facilitate clotting) Vitamin K
MOA: Increases supply of reduced vitamin K, which is required for synthesis of functional vitamin K-dependent clotting
Phytonadione (Vit. K1) Menaquinone (Vit.
(Vit. K3)
and anticlotting factors CLINICAL USE/S: Vitamin K deficiency, reversal of excessive warfarin anticlotting activity,
Prophylaxis against hemorrhagic disorder of Newborn Antiplasmin
MOA: Competitively inhibits plasminogen activation
Epsilon aminocaproic acid: Tranexamic Acid Hemostan®
(prevent conversion of plaminogen to plasmin) CLINICAL USE/S: for Excessive fibrinolysis, reduce the severity of hemarthroses
Minimize post-surgical/ post-dental procedur, TOXICITY: Thrombosis, Hypotension, Myopathy, Diarrhea
Acetanilide - Antifibrin
- Acetophenetidine - Phenacetin Phenprocoumon - limit its climincal use in the mx of t
primary drawback, its half-life.
VI. DRUGS FOR LIPID DISORDERS
Nieman- Pick Like
Enter the portal Transporter
circulation (NPC1 L1 Transporter)
(LIVER)
DRUGS FOR LIPID DISORDERS Statins 1st line in the Mx of Hypercholesterolemia
MOA: Inhibit HMG-CoA reductase
for coronary heart disease largest amount of evidence on the benefits of lipid-lowering therapy Short-acting
CLINICAL USE/S: Atherosclerotic vascular disease
(primary and secondary prevention); acute coronary syndromes Rhabdomyolysis TOXICITY/SE: Hepatoxicity (hepatic dysfunction),
Rhabdomyolysis/ Myopathy,teratogen INSTRUCTIONS: Take it Before Bedtime
Can be taken w/ or w/out meals
CHYLOMICRONS
Lipoprotein Lipase
(INCOMPLETE)
(COMPLETE) Blood vessel
VLDL repackaged Liver Monoglycerol + 2 fatty Acids
Glycerol or
Or
+ Systemic
Diglycerol + 1 fatty Acids
3 fatty Acids circulation
Lipoprotein
IDL Lipase
(Intermediate Density
LDL Lipoprotein)
Role of the Liver
*Liver only organ that metabolizes cholesterol
upon metabolizing cholesterol in Liver, it will be converted into Bile Acids maintains a certain amount of bile acid in the body. Sources of Cholesterol i
de novo synthesis of cholesterol (acetate mevalonate)
Normal Value Acetyl CoA HMG-CoA -HMG-CoA Reductase mevalonate Cholesterol Cyclopentanophenanthrene (CPPP)
Total Cholesterol 3.88 – 5.15 mmol/L
HDL <3.38 mmol/L LDL <1.04 mmol/L Secondary So
Triglycerides <2.82 mmol/L *increase or synthesis of hepatic LDL receptor
Hyperchlerolemia, Hypertriglyceridemia LDL bad cholesterol
may cause, primary role/function: brings cholesterol from the liver
*Atherosclerosis obstruction of blood flow to the systemic circulation HDL good cholesterol
Risk Factors: Female (age >55)
Male a (age >45) primary role/ function: sequester cholesterol from
Family History systemic circulation back to the liver
Obesity
*Lovastatin & Simvastatin - vulnerable to myositis Fluvastatin Lescol® Simvastatin Zocor® Lovastatin Long-acting
Statins & Fibric Acid Combination
-can increase the risk of myopathy & rhabdomyolysis - depend on P450-3A4 - active form: β-hydroxy acid *Pravastatin - doesn’t metabolized w/ P450-3A4 *Other Statin - have less
*Atorvastatin & Rosuvastatin - have long half-lives making A
bight dosing unecessary Rosuvastatin Crestor®
Fibrates 1st line in the Mx of Hypertriglyceridemia
(Fibric Acid Derivatives)
Gemfibrozil Lopid® Fenofibrate Clofibrate
Liphantyl®, Lofibra®
MOA:Stimulate lipoprotein lipase/ PPAR- agonists CLINICAL USE/S: to lowere VLDL, Hypertriglyceridemia, Low HDL cholestero SE: increase risk of Bile Stone or Gallstone formation cause
Increase incidence liver cancer w/ Clofibrate used Nicotinic Acid (Niacin) Vitamin B3
Niaspan® is associated w/ cutaneous vasodilation & sensation of warmth after an initial dose which may be reduced w/ the
use of 300mg dose Aspirin taken an hour before the dose is tolerated poorly because it induces Flushing(can be inhibited by Aspirin) MOA: Decreases VLDL synthesis and LDL cholester
increases HDL cholesterol CLINICAL USE/S: Low HDL cholesterol, elevated VLDL and LDL TOXICITY/SE: Hepatotoxicity, Gastrointestinal Irritation, Flushing, Hyperuricemia, may Reduce
Bile Acid binding resins add on treatment to statins for hypercholesrolemia
Cholestyramin Questran® anion-exchanger Colestipol Colestid®
MOA: Prevents reabsorption of bile acids from the gastrointestinal tract CLINICAL USE/S: Elevated LDL cholesterol, pruritus SE: Steatorrhea, Increase Gallstone Formation; Inhibit absorpti
subsatnces TOXICITY: Constipation, Bloating NPC1L1-like transportre inhibitors
MOA: Reduces intestinal uptake of cholesterol by inhibiting sterol transporter
Eztimibe Ezetrol®
CLINICAL USE/S: Elevated LDL cholesterol, phytosterolemia TOXICITY: Rarely, Hepatic Dysfunction, Myositis
VII. CARDIOVASCULAR DRUGS
Hypertension
Factors affect Blood Pressure BP Determinants: BP= CO X SVR – Systemic vascular Resistance
PVR – Peripheral Systemic Resistance TPR – Total Peripheral Resistance BP: Two Mechanism of BP regulation 1. Barorecepto
vasodilation vasoconstriction – (increase BP) *Barorecptors
Carotid arteries CVA (central vasomotor area)
sends sympathetic signals to the heart and to the bloodvessels: HR (vasoconstriction) Aortic arch detect P; vol (+) stretch 2. RAAS -
A
responsible for long term BP regulation *Renin is realsed in JG/ Juxtaglomerular (Kidney)
an enzyme released by the kidneys that breaks down proteins and helps regulate blood pressure -Renin is release: Stimulus: B activation
Renal Hypoperfussion Renal Hypotension *Angiotensinogen -renin Angiotensin I
Causes: Vasoconstriction
NE release aldosterone secretion NA & H2O retension K excretion Effect: elevation of BP *Angiotensin II - has 8 amino acids *Aldosterone (by A

SVR= Stroke Volume

amount of blood that
is pump out of the heart every bea
Application:
VasoC -Arteiolar - BP Vein - BP
β - (+)CC - BP
HR - BP
*Arteriolar vasodilators:
SE: Reflex tachycardia -Tx: β - blocker
-Tx: Diuretic
preloader
*ACE, ARBs
are preload &
afterload reducers/ unloaders
CO= HR X SV *HR- heart rate
SV – Stroke volume
volume of blood pump by the heart per beat CO – cardiac output
volume of blood pump by the heart per minute
SV = contributors of SV: CC Cardiac
Contractility ( CC, SV) V
cardiac preload end diastolic ventricular volume the amount of blood goes back to the heart during diastole VR = Factors of VR
VT – Venous Tone
VT: VasoC VT: VasoD VT: VR FC - Fluid Content
of Blood FC - VR FC- VR
SBP DBP Systolic heart contraction: the contraction of the heart, <120 <80 Normal
during which blood is pumped into the arteries 120-139 80-89 PreHypertension
Diastolic expansion of heart on each beat: the rhythmic 140-159 90-99 Stage 1
expansion of the chambers of the heart at each >160 >100 Stage 2
heartbeat, during which they fill with blood
Special Hypertension Conditions: a. HTN in pregnancy
Chronic Hypertension less than 20weeks gestation Gestational Hypertension greater the 20weeks of gestation Pre-eclampsia a gestational h
albuminuria Rclampsia a pre-eclampsia w/ seizure or convulsion
DOC : Magnesium Sulfate b. Hypertensive Crisis:
Hypertensive Urgency = 180/100 Hypertensive Emergency = Papilla edema
Acute hearing Failure Acute Renal Failure Encephalopathy
For Pregnancy Hypertensive:
Methyldopa Nefidipine Labetalol Hydralazine For Hyperte
Enalaprilat Diazoxide Sodium Nitroprusside
Sodium Nitroprusside - activation of Guanylyl
cyclase w/ increase in CGMP

♥Drugs Used in Hypertension Diuretics causes urinary loss of Na & H2O

Proximal convoluted : Carbonic Anhydrase inhibitors; Osmotic Diuretics Loop of Henle: Furosemide; Loop Diuretics early Loop of Henle: Osmotic Diretics Distal Convoluted Tubule: T
•Carbonic Anhydrase Inhibitors (-zolamide) 1st line Mx of Open-angle glaucoma
sulfonamide; sulfamoyl group responsible in invitro carbonic anhydrase inhibitory activity
& for the production of a diuresis in vivo. Acetazolamide Cetamid®,
Zolmide® Diamox®
MOA: Inhibits carbonic anhydrase in proximal convoluted tubule of the kidneys
& ciliary bodies of the eyes
* short-lived natriuretic & diuretic effect, don’t last for more that three days
Brinzolamide Azopt®
* increase aqueous humor production CLINICAL USE/S: Glaucoma; mountain sickness; edema with Metabolic A
Seizure disorder, especificcaly Metazolamid Dorzolamide + Timolol Dichlorphenamide
Trusopt®, Cosopt®
SE: Metabolic acidosis; sedation, paresthesias. Hyperammonemia in cirrhosis
Sulfa-associated side-effects: SJS, aplstic anemia, hemolytic anemia, hypersensitivity reaction CI: -COPD = Chronic Obstrcutive Pulmonary Disease (already has metabolic acidosis)
-chronic liver disease -patient w/ a history of TCA’s Hypersensitivity
*Acetazolamide is most useful for the mx of Nephrolithiasis due to idiopathic hypercalciuria
has been found to be useful for the management of catamenial seizures
(seizures during menses) use for Glaucoma to reduce reabsorption of hydrogen
MOA: Cretaes an osmotic gradient at the eater permeable regions of the renal tubule (PCT, early Loop of Henle)
•Osmotic Diuretics Mannitol
CLINICAL USE/S: Mx in increased Intracranial Pressure or Edema SE: Hyponatremia followed by hypernatremia; headache, nausea, vomiting; dehydration; Massive loss of wqter (hypovole
since doesn’t los sodium
•Loop Diuretics high ceiling, highly effective diuretics, most effective among diyretics
which ahave become preferred due to theior ability to increase sodium excretion by 20-25% of the filtered oad & to maintain their efficacy until
renal function is severely impaired sulfanamide = Frosemide, Bumetanide sulfonylurea = Torsemide Phenoxyacetate = Ethacrynic Acid (only loop diuretic does not contain Sulfur) Furo
Diuspec®, Fusemex® Bumetanide Burinex® Torsemide Ethacrynic Acid
MOA: Inhibit Na+
/K+/2Cl– transporter in thick ascending limb of loop of Henle.
Cause powerful diuresis and increased Ca2+ excretion CLINICAL USE/S: Heart failure, pulmonary edema, severe hypertension; other forms of edema;
Pulmonary congestion; oligoric/ aneuric/ acute renal failure; hyperkalemia; hypercalcemia; anion poisoning SE: Electrolyte Imbalance, Hyperglycemia, Dyslipidemia, Hyperuricemia,
Metabolic Hypokalemic Alkalosis; Ototoxicity; Hypovolemia CI: Gout *efficacy is reduced by nonsteroidal anti-inflammatory drugs. * Ethacrynic acid: Like furosemide but not a sulfonamide a
effect *Chem. Name of Furosemide: 4-chloro-N-furfuryl-5-sulfamoyl anthranilic acid
is useful as a rapid-acting intravenous agent in reversing acute pulmonary
edema ototoxic
•Thiazide Diuretics 1st line in Mx of HTN(as montherapy or combination therapy8) in nephrogenic diabetes insipidus
Structure: Benzothiadiazine-1,1-dioxide nucleus Benzothiazides (sulfur-containing)= HCTZ, Chlorthiazides Thiazide-like compound= Indapamide, Chlorthalidone, Metalazone Hydroc
Hydrochlorothiazide Hydrochlorothiazide Chlorothiazide
MOA: Inhibit Na+
(HCTZ) + Losartan + Valsartan /Cl– transporter in distal convoluted tubule.
Hytaz®, Combizar®, Hyzaar® Co-diovan®
Cause moderate diuresis and reduced excretion of calcium CLINICAL USE/S: Mx of nephrogenic diabetes insipidus SE:, Electrolyte imbalance; sulfonamide Effect;
metabolic Effects: Hyperglycemia, Hyperuricemia, Dyslipidemia CI: Gout
•Potassium-sparing diuretics
Aldosterone Antagonist = Spirinolactone, Eplerenone Direct Na-CL transporter = Amiloride, Triamterene Spirino
MOA: Steroid inhibitors of cytoplasmic aldosterone receptor in cortical collecting ducts; reduce K+
Aldactone® excretion
CLINICAL USE/S: Excessive K+ loss when using other diuretics; Aldosteronism; CHFw/ Conn’s Syndrome SE: Hyperkalemia; Gynecomastia (spironolactone only)/ Anti-Androgenic Effect A
Triamterene
MOA: Inhibitor of ENaC epithelial sodium channels in cortical collecting duct, reduces Na+
reabsorption and K+ excretion CLINICAL USE/S: Excessive K+ loss when using othe
combination with thiazides SE: Hyperkalemia *Triamterene is the primary compound selected from a host of pteridine analogues & resembles the structure of the folic acid & certain
dihydrofolate reductase inhibitors *MOA of Amiloride Pyrazinoyl Guanidine Diuretic that inhibits the electrogenic entry of 2% to 3% of the filtered load of Na into the
tubule cells
Sympathoplegics
Centrally-acting Anti-HTNsive
Clonidine Catapres®, Catapin®, Melzin® Methyldopa Aldomet®, Dopamet® is converted first to α-methyldopamine & α-methylnorepinphrine which stimulate central alph
SE: Sedation Guanfacine Guanabenz Peripheraly-acting sympathoplegics:
Reserpine Guanethidine Guanadrel Ganglionic Blockers Alpha Blockers Beta Blockers can actually worsen an Active Angina Pectoris
reduce myocardial oxygen demand by reducing myocardial contractility making them useful for Chronic Stable Angina Pectoris
Vasodilators for Hypertensive emergencies
Arteriolar Vasodilators
MOA: K+ channel opener in smooth muscle, secretory cells
Hydralazine Apresoline®, Aprezin® Minoxidil Diazoxide
Regrow®, Relive®, Minoxidil Isac®
CLINICAL USE/: Diazoxide - hypoglycemia due to insulin-secreting tumors
- pure arteriolar vasodilator SE: Hyperglycemia; edema, excessive hypotension; reflex tachycardia; peripheral edema
Minoxidil- hypertrichosis or hirsutism (extended use: hair growth stimulant)
-may minimize when combined w/Diuretic & β-blocker CI (hydralazine): Patient w/ Ischemic Heart Disease * Hydralazine - causes SLE-like symptoms Mixed Arteri
Na Nitroprusside Nipride® Nitrovasodilators/ Organic Nitrates (to be discussed in angina)
Na Nitroprusside (Fe, NO
2, CN) 1a st fast-acting line in HTNsive vasodilating emergencies agent also commonly used for sevrere deconsated congestive heart failure (CHF) MOA
(Releases NO from drug molecule) Special Precaution: Protect form sunlight, use freshly prepared preparations SE: Excessive hypotension; prolonged infusion may cause thiocyanate
Calcium Channel Blockers *all CCBs are Natriuretic & Diuretic
Drugs for Angina at rest. Intrinsically Short-acting Long-acting= amlodipine Modified long-acting= felodipine, Verapmil, Nefidipine Dihydropyridine (-dipine) close & open stat
MOA: block the L-type Ca channel in arteriolar smooth muscles
Nifedipine Adalat®, Adalat GITS®, Calcibloc®, Odipin® Nimodipine Nimotop® Amlodiipine Lo
Provasc®, Stamlo®, Vasalat®, Normasc®, Amvasc
CLINICAL USE/S: Hypertension, angina, arrhythmias SE: (Reflex Tachycardia)Excessive Cardiac Depression;
Peripheral Edema; Significant degree of Constipation Felodipine
Plendil®, Versant SR® Non-Dihydropyridine open state
Verapamil Calan® Verapamil + Trandolapril Isoptin®, IsoptinSR®, Tarka® Diltiazem Dilzem®, Dyalac®
MOA: block the L-type Ca channel in arteriolar smooth muscles and myocardium
SE: Bradycardia; Peripheral Edema *Verpamil has greater activity on Ca channel in myocard
Trandolapril (Isoptin®, IsoptinSR®, Tarka®) DOC for Prinzmetal Angina
Angiotensin Modifiers ACE Inhibitors (-pril) Base treatment of CHF
1st line Mx of HTN in CKD & DM 1st line for albuminuria inhibit kinin metabolism (in the lungs) Sulfhydryl = Captopril Phosphinyl = Fosinopril Carboxyl *active ACE: Captopril, Lisin
*Prodrug: Enalpril, Perindopril, Ramipril
Effects: 1. Decrease vasoconstriction
2. increase bradykinin (vasodilating effect)
reflex for cough reflex 3. increase prostaglandin CI: Bilateral renal artery stenosis; Hyperkalemia; Pregnancy
*NSAIDS reduce the efficacy of ACEi in the mx HTN
Captopril Fosinopril Lisinopril LIsonopril + Hydrochlorothiazide Capotec®, BPNorm
MOA: inhibit Angiotensin Converting ENzyme
Primace®, Prilat®, Tensoril®, Vasostad® CLINICAL USE/S: Hypertension, diabetic
renal disease, heart failure
Zestril®, Zestoretic®
SE: Hyperkalemia; Teratogen; Cough(Idiosyncratic Dry Cough);
Renal Failure in Infants Enalaprilat
Enalapril Perindropil
Renitec®, Hypace®, Vasopress®, Hypril®
*Enalapril exhibits pharmacodynamic interaction w/ the
Thiazide Diuretics leading to reduced diuretic effect Perindropil + Indapamide Conversyl®, Novaril®, Perigard-4®, Preterax® Angiotensin Receptor Block
MOA: Blocks AT1 receptors
Losartan Cozaar®, Hylos-50®, xartan®, Provisar®, Lifezar® Candesartan Candesartan + HCTZ Blopress®, Candez®, Blopres
Diovan®, Valsartan+ HCTZ Co-Diovan® Valsartan+ Amlodipine Exforge Renin Inhibitor
Aliskerin (Tekturna®,
Rasilez®)
MOA: Renin inhibitor; reduces angiotensin I synthesis /(binds to
CLINICAL USE/S: add-on to ACE-inhibitors or ARBs fro HTN rennin preventing interaction of rennin to angiotensin
SE: Angioedema, renal impairment, dry cough, rashes
♥Drugs for Angina Pectoris
Ischemia : decrease in Oxygen Infarction : no oxygen Determinants of Cardiac Oxygen Requirement
Diastolic Factor: Blood Volume Venous Tone Systolic Factor: Pe
Heart Rate Heart Force Ejection time Major determinant: Myocardial Fiber Tension *(the higher the tension, the greater the o
Nitrovasodilators
*Nitirc Oxide potent vasodilator Very short-acting: last only for 5-10 minutes
Amyl Nitrate (inhalational) for acute angina Short-acting: last 10-30minutes
Isosorbide Dinitrate Nitoglycerin SL Intermediate-acting: 5-8 hours ISDN PO, NTG-SR L
ISDN SR, ISMN
Primary MOA: Dentrification by glutathione S-transferase leads to
release of nitrite ion which is then converted to nitric oxide, a molecule that activates guanylyl cycles leading to increase cGMP
Uses: For mx of acute angina (sublingaual, inhalational)
Prinzmetal (type of chest pain)= DOC: CCBs For chronic For hypertensive emergencies For add-on CHF; ISDN+ hydralazine For Acute pulnmonary edemy Amyl Nitrite Isosorbide
Isodil®, Nitrosorbon®, Isoket spray®
Initial mx of CN poisoning: Amyl Nitrite Relief of Angina Pectoris MOA of NitroVasodialtors:
Reduction in Myocardial Nitroglycerin
Nitrostat®, Deponit NT,NItonal®, Transderm-Nitro 5 ®,
oxygen demand & cardiac Isosorbide Mononitrate Isomonit®, Isonate®, Monosorb®, Vasotrate®, Imdur®
preload
SE: Hypotension, Migraine-like HA, Tolerance(due to sulfhydryl
moieties)
*Veins the tissues exhibit the greatest sensitivity to
Nitrovasodilators at the lowest effective doses *Isosorbide Mononitrate does not undergo first-pass effect
(100 % bioavailability) *Amyl Nitrite for Cyanide Poisoning
=induce conversion of hemoglobin to
methemoglobin (methemoglobinemia) which can lead to cyanosis Beta Blockers DOC/ 1st line maintenance treatment for CSAP (Chronic Stable Angina Pectoris) Calcium Cha
DH
Long-acting – Alternative for CSAP Short-acting – for Prinzmetal Angina
♥Drugs for Heart Failure Inotropics
MOA: Blocks the Na-K ATPase thereby increasing intracellular sodium & preventing calcium
Cardiac Glycosides: Digoxin Lanoxin®, Lanox®, Cardioxin®
extrusion Primary Indications: Control the rate of Ventricular response in atrial fibrillation Useful in Pregnant patient w/ CHF Mechanical EFFECTS: (+) Inotropism(contaction of heart muscle
Intracellular Ca2x dromotism Decrease conduction velocity in the AV node Electrical EFFECTS: Decrease in the refractory period of atrial muscles
Increase in the refractory period of the AV node Increase in the automaticity of atrial tissues & the AV node Conditions that may augment the Effect
-Hypokalemia -Hypomagnesemia -Hypercalcemia (Concurrent administration of Calcium gluconate) -Hypoxia (Reduced oxygenation of myocardial tissues) SE: Heart: Bradycardia, Arrhythm
Non-Cardiac: Nausea, Vomiting, ophthalmic effect (blurring of vision) Pharmacokinetic Parameters: In about 10% of patients, use of antibiotics can lead to
increased oral bioavailability as the bacteria in the intestines normally reduce systemic absortion of Digoxin. Toxicity: Di
*Potassium Supplements - are given if the patient is hypokalemic *Cholestyramine - capable to binde to digitalis glycosides
- may also help prevent absorption & reabsorption of digitalis in
the bile *Fab-Fragment - for patient with very high serum digoxin levels
-for suicidal overdose w/ Digoxin * give Digibind®, Digifab® - antibody fragments that bind digitalis
Digoxin Digitoxin
F 70-75% ≥90% T1/2 36-40% Protein binding 20-40% ≥80% Vd 6.3L 6L Excretion renal hepatic * Toxic Plasma Concentration of Digoxin: 2ng/mL
* Quinidine decrease the renal clearance of Digoxin * Na-K pump affected by Digitalis Glycosides & Oabain
CLINICAL USE: Mx of acute heart failure or acute
B1 agonist Dobutamine Dobunex®, Cardomin® Dopamine Dopamax®, Dokard®, Cardiofast®, Myocar
exacerbation of a CHF Phosphodiesterase
MOA: Inhibits PDE enzyme (increase levels of cAMP) Milrinone
Amrinone
CLINICAL USE: mx of Acute Heart Failure or Exacerbation of CHF SE: Arrhythmia, Hypersensitivity, thrombocytopenia Unloaders
Preload first amount of the bloodgoes back to the heart Afterload systemic vascular resistance ACE inhibitors & Angiotensin Receptor Blockers (main treatment) very
heart failure: preload, afterload Diuretics preload unloader Vasodilators ISDN + hydralazine
ISDN - preload Hydralazine - afterload Beta Blockers: Metoprolol, Bsoprolol, Carvidilol only Brain natriuretic peptide (BNP) analogue: Nesiritide Na
-IV
Effect: Massive Vasodilation CLINICAL USE: Mx of AHF (acute heart Failure)
Dopamine exhibits a wide range of effects;
-Doses of 2-5 μg/kg/min - increases renal blood flow through its
dopaminergic effects. -Doses of 5-10 μg/kg/min - increase cardiac output through its β-adrenergic
stimulating effect - is seleted for its positive inotorpic effects on
treating the patient w/ HF -Doses of 10-20 μg/kg/min - increase peripheral vascular through α-
adrenergic stimulating effects.
Dopamine - 3,4-dihydroxyphenylethylamine
- acts directly as α & β resptors - biosynthetic precursor of norepinephrine & Epinephrine - used to treat Hypotension
♥Anti-Arrhythmic Drugs
Vaugh-williams Classification Class I (Na Channel Blockers)
Class Ia -prolong action potential work by blocking the rapid inward sodium current & thereby slow down the rate of rise of the cardiac tisue’s action
potential prolong the duration of the action potential & dissociates from the channel w/ Intermediate Kinetics Procainamide Pronestyl® causes SLE-like symptoms Quinidine Qu
Cinchonism (maniofestated by gastrointestinal disturbances. In severe cases, Nausea, Vomiting, Diarrhjea,

Headache, Confusion, Delirium, Photophobia, Diplopia, & psychosis may also occur)
Disopyramide Norpace® Class Ib - Shorten the duration of Action potential capable of shortening repolarization or the refractory period, as they weakly affect the repolari
Lidocaine DOC in the treatment in Ventricular Fibrillation
decrease efficacy over time
Metabolie: Xylidide competes Lidocaine fro binding LIdocaine + Epinephrine Xepacaine®, Xylocaine®, Nobucaine®, Enducaine®, Epicaine® Phenytoin Dilantin®
SE: Gingival Hyperplasia
Fenitin®
Nystagmus Tocainide
Tonocard® Mexiletine Mexitil® Class Ic - No effect on action potential strongly depress depolarization but have a negligible effect on the duration
dissociates from the channel w/ slow kinetics Profenone
Rythmol® Encainide Enkaid® Moricizine Ethmzine® Flecainide Tambocor® Class II (Beta Blockers)
Propanolol Inderal® Esmolol Brevibloc® Acebutolol Sectral® Class III (Potassium
Amiodarone Myodial®, Cordarone®, Arrythgo® 1st treatment in Ventricular Tachycardia/ Atrial Fibrillation
iodine-containing (32%) has a prolong action potential must be associated w/ ALT level measurement
SE: First two weeks: hypothyroidism
After two weeks: Hyperthyroidism

*Wolffe-Chaikoff Effect Bradycardia Important SE: Hepatotoxicity, Pulmonary Fibrosis Sotalol Betapace Bretylium Ibutelide Corvert SE: Torsade de pointes Dofetilide Tiko
(Calcium channel Blockers)
Verapamil - is primarily indicated for the tx of chronic paroxysmal Supraventricular Tachyaarhythmias
- only Ca channel blocker w/ proven clinical role in arrhythmia therapy Diltiazem Miscellaneous Agents:
Adenosine Cardiovert® 1st line treatment in acute episodes of Supraventtricular Tachycardia
5 seconds t1/2 SE: Bronchospasm Magnesium ion 1st line in the mx of Torsades de Pointes Potassium ion for Digitalis toxicity and other arrhythmias if serum K
VIII. DRUGS FOR THE RESPIRATORY SYSTEM
♥Drugs for Colds
*Viruses: Adenovirus
Coronavirus Rhinovirus (self limiting 5-7 day
Nasal Decongestants (local vasoconstrictors) fro 5 days only (if exceed, lead to tolerance)
Effect: Vasoconstrition; Urinary Retension Side Effect:
PO= exacerbation of HTN
Precipitate urinary retention in patient BPH T
Loss of responsiveness to a given dose of a drug Phenylephrine Cold medications:
Mydfrin®
*Phenylpropanolamine was out of the market increase hemorrhagic stroke Dextromethorphan + Paraceta
centrally acting sympathomimietic Chlorphenamine
Maleate + Paracetamol Decolgen Forte®, Bioflu® Phenyltoloxamine citrate + Paracetamol Sinutab PE®
Phenylpropanolamine+ Chlorphenamine + Paracetamol Sinutab Extra Strength
together with: Amphetamine
Methylphenidate Phentermine Phennetrazine Propylhexedrine Oxymetazoline A2 agonists: Colindine Apraclonidine Brimonidine Allergic Colds
Nasal decongestants H1-antihistamines
♥Drugs for Cough & Mucus Production Mucoregulators only produce a placebo-like effect
MOA: Increases the water portion of the mucus thus decreasing viscosity of mucus
Bromhexine Bisolvon® Carbocisteine Solmux® Ambroxol Mucosolvan® M
decrease the viscosity of bronchial secretions for easier expectoration
N-acetylcysteine Fluimucil®, Mucomyst®,
Hidonac®, Exflem®
MOA: Break sulfide linkages between mucus molecule *NAC has –SH, for formation of glutathione
to detoxify the paracetamol maetabolite that causes toxicity (NAPQI) Expectorants
MOA: Stimulate bronchial glands to secrete more of the water portion of the mucus
Guiafenesin (glycerol guiacolate) Robitussin
Expectorant: Mgt of chronic bronchitis
inflammation of bronchi & increase mucous production *COPD: Chronic bronchitis
Amphysema loss of decrease on elasticity of alveoli
there will be air trapping of carbon dioxide that lead to respiratory acidosis. CI with COPD patient: Diuretics (Carbonic Anhydrase inhibitors)
prevent reabsorption of Bicarbonate (bicarbonaturia)
lead to metabolic
acidosis Anti-tussive/ cough suppressant
MOA: Inhibit the cough center at the CNS Peripheral-acting
Butamirate citrate Sinecod® Peripheral-acting antitussive
MOA: decrease sensitivity of peripheral receptor Centrally-acting
Codeine Robitussin AC® Centrally-acting antitussive Noscapine Dextromethophan MOA: Hyperpolariztion of cough receptor
Robitussin DM®, Tuseran Forte®
*Narcotic codeine; noscapine *Non-narcotic dextromethrphan USES: Management of harmful cough (TB) – suffer from hemophy
Useful Cough (Iron-Productive) Excessive Cough
♥Drugs for Bronchospastic Disorders
Based on Effects:
Relievers management of acute exacerbation SABA Controllers prevention of acute exacerbation steroids; LABA Based on Mechanism of A
1. Bronchodilators 2. Mast cell Stabilizers 3. Anti-inflammatory
Brochodilators
β2 agonist
SABA (Short-acting) 1st line reliever in BA & alternative reliever in COPD SE: Tremors
Salbutamol Brecanyl® subcutaneously given as mx of acute episodes of bronchospasm Terbutaline subcutaneously given as mx of recalcitrant acute exacerbation of bronchial a
to increase heart rate in sympotomatic hypertension LABA (Long-acting) 1st line controller (w/ inhaled GC) for COPD
Salmeterenol is not suitable for acute breakthrough attacks of bronchospasm Formeterenol Bambuterenol Methylxanthine
MOA: Adenosine Antagonist;
Theophylline Theodor®, Asmalon® Aminophylline
PDE inhibitor;
Inhibit the late phase allergic reaction occurring 2-8 hrs after an acute attack CLINICAL USE: Alternative bronchodilator in severe BA attacks (reduce nocturnal attack
Respiratory Stimulant in COPD Neonatal Apnea
Tachycardia Arrhythm
-agitaion -confusion -seizure Diuresis (proximal renal tubule like osmotic diuretic, carbonic anhydrase inh. Anticholinergics 1st line bronchiodilator in COP
Oxytropium Tiotropium Ipratropium Ipratropium + Salbutamol Combivent®
Anticholinergics primary used as relievers (more effective in COPD than in Bronchial Asthma)

first line relivers of COPD altenative reliever of bronchial asthma can be safely given at high doses by inhalations SE: Alice in the Wonderland Syndrome Ipratropium + Te
Mast cell Stabilizer controllers only
MOA: Induce opening of inward Cl- channels leading to influx of Cl- into mast cells
Nedrocromil Cromolyn Sodium/ Na Cromoglycate
CLINICAL USE: Mx of allergic conditions SE: may induce bronchospam (given SABA to prevent bronchospasm) *Cromolyn Sodium - inhibit the degranulation of mast cells in asthmatic patie
the
release oof the chemical mediators of anaphylaxis Anti-inflammatory Agents
Leukotriene Modifiers:
Lipooxygenase Inhibitor Zileuton Zyflo® Leukotriene Receptor Blocker (LTD4 antagonist) Montelukast Montemax®, Singulair®
CLINICAL USE: alternative controllers in persistent bronchial asthma

Management of NSAIDs induced bronchial asthma SE: Unmask the symptoms of Churgg-Straus Syndrome (eosinophilic vasculitis)
can be treadted with steroids
Zafirlukast Accolate® Glucocorticoids
Budesonide Beclomethasone Fluticasone Triamcinolide
Locally-acting inhaled GC (Low dose) 1st
Pulmicort® line controllers for BA
Systemic GC(parenteral) 1st line in status asthamticus MOA: Inhibit the synthesis of phospholiase A2 Inhibit the late phase allergic reactions Inhibit the release of interleukin by the macro
Prednisolone Hydocortisone *Inhaled Corticoids adjunctive controllers; COPD
SE: oral candidiasis vocal cord nodules
Solucortef®
Oral thrush hoarseness Prevention of oral candidiasis: gargling (3-4x); use of spacers Methylprednis
*PO: Prednisone; Prednisolone
-are given not more thant 10days(if exceed, aderanl suppression) Short Course Therapy: Acute BA Exacerbation
Exacerbation: Early phase airway obstruction (brochodilation)
Late Phase 2-8hrs ; inflamation *IV: Methylprednisolone; Hydrocortisone
-management of severe acute asthma exacerbation
IX. DRUGS FOR GASTROINTESTINAL DISORDERS
♥Drugs for Peptic Ulcer Disease Antacids
MOA: Chemical Neutralization
Aluminum Hydroxide+ Magnesium Hydoxide Maalox® Aluminum Hydroxide+ Magnesium Hydoxide + Dimethicone Maal
IMPORTANT SE: Mg – Diarrhea, Al – constipation, Ca – renal stones Plus®
Aluminum Hydroxide+ Magnesium Hydoxide + Simethicone Kremil-S® Sodium Bicarbona
Carbonate+ Sodium Alginate Gaviscon® Sodium Bicarbonate Rhea® H2-receptor Antagonist Proton Pump Inhibitors (aka Benzimidazole)
MOA: Inhibit H-K ATPase pump
Omeprazole Losec®
USES: Mx of GERD (Gastrointestinal reflux disease)
Acid Peptic Disease Gastrtis (due to NSAIDs use) SE: Diarrhea
Vit B12 Deficiency
Gastric Infection NOTE: formulated as enteric coated tablets since they
get degrade in an acidic environment *Formulation: Acid –Labile enteric coated tablets
Intruction Before Use: ―Take this medication once a day
before Breakfats‖
*If Dopedogrel is given w/ PPI Lansoprazole Prevacid® Esomeprazole Nexium® Pantoprazole Pantoloc®
-the effect of Dopidogrel will decrease, since it blocks the CYP2C19 *ACS (Ac
tx: Clopedogrel+ PPI (Pantoprazole) Rabeprazole
-(to decrease risk of stress-
induced gastritis) ACS: Acute manifestation of CAD
Chest pain lasting for 20min & is not relieve by rest & nitrates Three conditions under ACS: -unstable angina -STEMI (st-elevation MI) -NSTEMI (non-ST elevation
PGE1 Analogue (cytoprotectant effect in the GI mucosa)
Misoprostol Cytotec® Mucosal Protectants
Colloidal Bismuth Subitrate
Sucralfate
MOA: forms a protective barrier between the acidic environment of the stomach the epithelium by lining the
Iselpin®
stomach wall * Sucralfate used as short term therapy of ulcers Triple Drug Therapy to Eradicate H. Pylori
Omeprazole + Clarithromycin + Metronidazole/Amoxicillin Bismuth subsalicylate + Metronidazole + Tetracylcine Ranitidine/ Bismuth subcitrate+ Tetr
Clarithromycin/ Metronidazole Quadruple Drug Therapy to Eradicate H. Pylori
Omeprazole + Bismuth subsalicylate + Metronidazole+ Tetracycline
GERD (Gastrointestinal Reflux Disease)
s/sx: -heartburn epigastric pain (4-6 weeks) Risk factors: Obesity, Tight Clothing, Food
GI intolerance hyperacidity
(-) mucosal damage Px: taking NSAIDs after a full meal GI ulcers
(+) mucosal damage Px: *PPI, H2 blockers, Misoprostol
PUD (Pepetic Ulcer Disease) Causes: Helicobacter pylori infection
Phase 1 tx: 4-6 weeks 1. Eradication by giving (PPI)Omeprazole + Clarithromycin + Metronidazole/Amoxicillin 2. Ulcer healing phase: PPI = 2-4 weeks R
NSAID-induced PUD disease
-old age -multiple NSAID used - dose NSAID -glucocorticoids
Magaldrate - used as gastric antacid & is
official as its oral suspension & tablets
Metronidazole - has activity against
anaerobic organism & against most protozoan
♥Drugs for Diarrhea Oral Rehydration Salts/ Oral Glucose-Electrolyte Solution (Oresol®) Antimotility agents(Opioids)
Diphenoxylate cross BBB Diphenoxylate + atropine Loperamide Imodium®, Diatabs® does not cross BBB; GI motility Paregoric Opium tincture Difenoxin A
Kaolin-Pectin mixture Polycarbophil Attapulgite (kaopectate) MOA: adsorbs H2O Antisecretory
 has antibacterial Effect (adsorbs bacterial toxins that cause diarrhea)
Bismuth Subsalicylate Peptobismol®
cause discoloration of stool (black) Enzymes Lactase® Bacterial replacement Lactobacillus® Octreotide
♥Drugs for Constipation Bulk-forming Laxatives
Fibers ( fruits, vegetable) MOA: adds bulk to the feces by absorbing water that causes the swelling of cellulose molecules *absorbs H2O swell distention of colon
Carboxy methylcellulose non-absorbable compounds
Oral Rehydration Powder
- is a dry mixture of Sodium
Chloride, Sodium Bicarbonate, or Sodium Citrate, Potassium Chloride & Dextrose - used to treat Chronic Diarrhea
Bran Methyl Cellulose Psyllium (C-lium®,
Metamucil®) Osmotic Laxatives (saline laxative)
Sorbitol
Lactulose (Lilac®)

create an osmotic gradient in the intestinal lumen prevent H2O reabsorption high consistency stools Magnesium hydroxide/ citrate/sulfate MOA: as an osmotic agent i
inviting water molecules into the lumen Glycerin(suppository) Stimulant Laxatives (irritant laxative) Bisacodyl Dulcolax® Phenolphthalein Cascara Sagrada Sen
irritate the GI tract leading to peristalsis
anthraquinone except CHrysarobin (Keratolytic) -senna
Melanosis Coli - a dark pigmentation of the colonic
Senokot®
MOA: stimulates mucosal nerves in the colon SE: may cause dependence o
mucosa that results from long-term use of Anthraquinone laxatives.
Castor Oil Stool Softeners/ Emollient Laxatives
-not good for acute constipation; good for patients who should not strain by passing a hard stool Docusate Na - (Stool Softener) Mineral Oil – (Emmolient)
MOA: surfactants which facilitates mixing of water & oily materials CLINICAL SE: prevent constipation in post MI patient & those who underwent rectal surgery
♥Drugs for Vomiting Dopamine Antagonist - may cause secondary
Chlorpromazine
Prochlorperazine Promethazine IMPORTANT SE: Extrapyramidal symptom, Sedation, Depression Metoclopromide Plasil®, Reglan® Selective Se
Inhibitors
Ondansetron Zofran®, Nozuka® Granisetron Kytril® Dolasetron Palonostron Antihistamine-Anitcholinergic Agents
Dimenhydrinate Gravol®, Dramamine® Diphenhydramine Benadryl® Meclizine Bonamine®, Dizitab® Scopolamine Cannabinoids: Marijuana, Nabilone,
Corticosteroids: Dexamethasone Benzodiazepines: Lorazepam Substance P/ Neurokinin 1 Receptor Antagonist: Aprepitant Pyridoxine
♥Inflammatory Bowel Disease: Ulcerative Colitis (patches in from the mouth to anus)
Colon) 1st : 5-aminosalicylate 2nd; Glucocorticoids 3rd: Biological
Agents (TNFα inh.): Adalimumab, Infliximab
Crohn’s Disease (there’s a patches
X. ENDOCRINE DRUGS
Links between hypothalamic, anterior pituitary, and target organ hormones or mediators
Anterior Pituitary Hormone Hypothalamic Hormone Target Organ Primary Target Organ Hormone(s) or
Mediator(s) Growth hormone (GH, somatotropin)
Growth hormone-releasing hormone (GHRH) (+) Somatostatin (–)
Liver, muscle, bone, kidney, and others
Insulin-like growth factor-1 (IGF-1)
Thyroid-stimulating hormone (TSH)
Thyrotropin-releasing hormone (TRH) (+) Thyroid Thyroxine, triiodothyronine
Adrenocorticotropin (ACTH) Corticotropin-releasing hormone (CRH) (+) Adrenal cortex Glucocorticoids, mineralocorticoids,
androgens Follicle-stimulating hormone (FSH) Luteinizing hormone (LH)
Gonadotropin-releasing hormone (GnRH) (+)b Gonads Estrogen, progesterone, testosterone
Prolactin (PRL) Dopamine (–) Breast —
♥Hypothalamic- Pituitary Hormone Hypothalamic
GnRH Agonist of the LH receptor
is released in pulses by the hypothalamus to induce secretion of FSH & LH by the pituitary Luteinizing hormone (LH) analogs
-Gonadorelin
CLINICAL USE: Stimulatory Dosing: Management of Hypothalamic Hypongonadism,
Inhibitory Dosing: Management of Hormone-sensitive disease SE: Male: femination; Female: Muscurization -Goserelin -Buserelin -Leuprolide
* Leuprolide a synthetic nonapeptide analogue of naturally occurring gonadotropin-releasing hormone, used for
palliative treatment of advanced prostatic cancer
Follitropin Gonal-F®, Puregon®
Follicle Stimulating Hormone
Growth hormone receptor antagonist MOA: Agonist of the follicle-stimulating hormone (FSH) receptor CLINICAL USE: Controlled ovulation hyperstimulation in women; infertility due to
MOA: mimics the hormone somatostatin which is an inhibitory hormone
Somatostatin
Agonists
-Octreotide
CLINICAL USE: Mx of acromegaly
Mx of Tumors associated with oversecretion of target hormones (Zollinger – Ellison Syndrome) Mx of carcinoid syndrome -Lanreotide
Mx of esophageal varice -Pasireotide
* deltasecrete somatostatin -Vapreotide Anterior Pituitary
ACTH release occurs in pulses that peak in the early morning hours & after meals
Agonists
CLINICAL USE: for growth
-Corticotrpin -Cosyntropin -Tetracosactide GH
-Somatropin -Sermorelin -Somatrem (recombinant) Genheal®,
*Prepuberty : dwarfism *Post puberty: risk of cardiac mortality Excess: Pre-puberty: Pituitarty Gigantism
Post Puberty: acromegaly Humatrope®, Norditropin®, Scitropin®
Features: Macrognathia (large jaws),Macroglossia (large tongue),

Wides space teeth, Broadened nose, Thickened Lips, Large Joints *pituitary adenoma (tumor pit. Gland) - secretion *pheochromacytoma - tumor/ hyperplasia in the adrenal medulla - NE

Thyrotropin Posterior Pituitary produced by hypothamlamus, stored in the posterior pituitary gland
Oxytocin PItocin®, Syntocin® -Carbetoxin
CLINICAL USE: Induction and augmentation of labor;
control of uterine hemorrhage after delivery; -Demoxytocin Antagonist: Atosiban
stimulate lactation as nasal spray mx of postpartum hemorrhage
Vasopressin Minirin® -Desmopressin (analogue)
antidiuretic hormone; Arginine Vasopressin (AVP)= V1(bloodvessels-vasoC); V2(Kidney-H@O reabsorption) CLINICAL USE: MX of Pituitary(central) diabetes insipidus; Hemophilia A and
EXCESS: cause SIADH (Syndrome of Inappropriate ADH Secretion : (malignancies-ccancer, CNS disorder)
most photosensitizing among tetracycline Antagonist: Conivaptan, Demeclocycline, Lixivaptan, Mozavaptan, Nelivaptan,
Tx: Demeclocycline (an example of tetracycline)
Satavaptan, Tolvaptan
Regulation: Circadian Rhythm/ Sleep-wake pattern
entrained to sleep
Peak during sleep: GH Peak durng waking up: ACTH, Cortisol
Chronic Gonadotropin - is a gonad-stimulating polypeptide hormone obtained from the urine of pregnant women
Pituitary-derived growth Hormone
- has been historitically associated w/ Creutzfeldt-jakob disease, a fatal neurogenerative disease caused by Prions.
Zones of Adrenal Cortex 1) Zona glomerulosa secretes mineralocorticoids 2) Zona fasciculate secretes glucocorticoids 3) Zona reticularis synthe
Mineralcorticoids (aldosterone) RAAS Angiotensin II
renin Angiotensiin I
ACE Angiotensin II
Aldosterone: Reabsorption: NA+/ H20/ HCO3 Excretion: K/Cl/H Hyperaldosteronism: Hypernatremia Hypervolemia Metabolic alkalosis (problem in
concentration HCO3) Hypokalemia HypoCl
USES: Corticoids
Rheumatologic Disorders
RA – given thru intasynovial
2-3x a yr, q 4-6 months SLE – life-threatening
Tx: Methylprednisolone IV infusion
1g OD x 3days, infused in 30 min-1hr Inflammatory bowel disease
-Sulfazalazine
*Sulfapyridine *5-amino salicylate *RA Dermatologic Disorder: Psoriasis, CA
Glucocortecoids (Cortisol) CRH ACTH Corisol
*morning: increase secretion of cortisol
before waking up: ACTH secretion upon waking up: peak of ACTH secretion
Start of cortisol secretion *2 hrs after peak of ACTH
Peak of cortisol Effects of Glucocorticoids: Physiologic
<10-20mg / day of cortisol metabolism of macromolecules increase vascular/ bronchial responsiveness to catecholamines Pharmacologic
>10-20 mg/day of cortisol anti-inflammatory immunosuppresant inhibition od cell division catabolism of bone / CHON
Cortisol - is capable of
targeting intranuclear receptors secondary to its ability to diffuse through lipid membranes
Adverse effects: 1. risk of infection 2. Cushing’s Syndrome
-Moon Face -Buffalo Hump -Truncal Obesity -Easy Bruising 3.Poor Wound Healing 4. Hyperglycemia 5. Proximal Myopathy 6.Adrenal Suppression If the
14 days
♥Adrenocortical Hormone Glucocorticoids CLINICAL USE: Inflammatory diseases
Short-acting
Cortisol/ Hydrocortisone Prednisone
All preparations w/ PRED
in their name except (Fulpred
 Transplant Rejection Inhibition Dermatologic Disease Hematologic Cancer Premature labor IMPORTANT SE: Cushing’s Syndrome (high levels of the hormone cortiso
Increased Risk of Infection Hyperglycemia
*Adrenal Suppression
- is expected to occur when
glucocorticosteroids therapy is extended beyond 2 weeks - requires very low dosage
Poor Wound Healing Adrenal Suppression
CI: Active Tuberculosis
reduction when the therapy is to stopped & when the dose reaches replacement l
- necessitates giving of Triamcinolone Paramethasone Long-acting
* Beclomethasone DOC for prophylaxis of Asthma * Hydrocortisone metabolize into Cortisone by Ketone Reduction * Hydrocortisone + Fludrocortisone is the appropriate maintenan
primary adrenal
insufficiency * Chronic Glucocorticoids therapy can cause: Hypertension, Osteoporosis, Glucose Intolerance * Dexamethasone Suppresion Test - is employed in the work-up of patients w/ C
diagnose the most probable etiology of the condition.
supplementary therapy at times of stress like surgery or trauma
Dexamethasone Betanethasone
Mineralcorticoid CLINICAL USE: Adrenal insufficiency (Addison's disease)
Desoxycorticosterone Fludrocortisone
* Fludrocortisone has the best mineralocorticoid effect Aldosterone
Equivalent Doses: Hydrocortisone 20mg = Prednisone 5mg = Dexamethasone 0.75mg
Physiologic Dose of Glucocorticosteroids: Hydrocortisone (Cortisol) dose less than 10-20 mg/day Pharmacologic (Supraphysiologic) Dose: Hydrocortison
greater than 10-20 mg/day
Thyroid Hormones
Thyroid Gland made up of multiple follicles/ follicular cells, parafollicular cells, calcitonin(calcium-controlling hormone)
Thyroglobulin the storage from of thyroid hormones.
Two Major Thyroid Hormones:
T3 (triiodothyronine) most active form
is better absorbed after oral administration than T4 T4 (thyroxine) longer t1/2
preferred oral replacement since its half0life is longer &
slower in onset. is deiodinated to T3 in the peripher
controlled by atropic hormone, Thyroid-stimulating Hormone (TSH; Thyrotropin) governed by hypothalamic Thyrotropin-
Releasing Hormone (TRH) action; mediated by cAMP & leads to stimulation of iodide uptake is the best monitoring guide for response to therapy
(Biochemical Goal of Therapy: To achieve a normal TSH) Biosynthesis of Thyroid Hormones: 1. Active Uptake of Iodide
▪ Amiodarone SE: Pulmonary fibrosis (pulmonary function test)
Hepatotoxicity (ALT) Thyroid abnormalities
- Hypothyroidism 1st 10-14 days - Hyperthyroidism beyond 14 days
▪Excess of Iodine inh. the uptake of iodide to follicular cell
- Wolff-chaikoff effect inh. organification 2. Peroxidase Mediated Steps
1. Peoxidation of iodide to iodine or iodides to peroxidate 2. Organification iodination of thyroxyl residues of thyroglobulin
TG- MIT monoiodotyrosyl TG-DIT diiodotyrosyl residue 3. Coupling: MIT+DIT T3 -TG DIT+MIT T
T4 -TG -protease T4 + TG T3 -TG -protease T3 + TG 4. Release of T4/T3 peripheral tissues 5. Peripheral conversion
T4 -5-iododinase T3
Calcium Homeostasis inh. the reabsorption of PO4
Ca; Po4
increase the absorption in GIT
Parathyroid Hormones
Vit D Ca;
Po4
deposition of CaPO4 in the bones
Calcitonin Ca;
Po4
Thyroid Hormone Deficiency
Hypothyroidism - T4, T3
TSH *Subclinical Hypothyroism: T4, T3
No symptoms Hypothyroidism hypometabolic state; hyposympathetic state
Weight gain (despite a low appetite) sleeping time Mental & Physical Slowing Poor ressistance to cold Bradycarida Children: Critinism, mental retardatio
CAUSES: Iodine Deficiency
Post-procedural: Radiactive Iodine Therapy
-Thyroidectomy Autoimmune Hashimoto’s Throiditis
Antibodies vs. own cells(peroxidase) Drug-induced Hyperthyroidism - T4, T3
TSH aka Thyrotoxicosis hypermetabolic state; hypersympathetic state SX: Tremors
Diaphoresis WeightLoss (despite increase appatite) Heat tolerance (increase Heat production) Tachycardia & cardiac arrhythmias Nervousness Palpiatat
CAUSES: Graves’s Disease
 -hyperthyroism, demopathy, ophthalmopathy Drug-induce : Amiodarone Solitary Hyperfuction ThyrotoxicosisFactitia
- T4, T3 –because of excessive intake of Levothyroxine/ Levothyronine
♥Drugs for Thyroid Disorders Hypothyroidism Levo-T4 (Levo-Thyroxine) Levothyroid®, Synthroid®, Eltroxin®,
Eltroxin®, Euthyrox®, Thyrax®
Levo-T4 (Levo-Thyroxine) 1st line hypothyroidism Levo-T3(Levo-Thyronine) 1st line in myedema coma Levo-T3(Levo-Thyronine) Liotrix T4/T3
MOA: Activation of nuclear receptors results in gene expression with
RNA formulation and protein synthesis PHARMACOKINETICS: T4 is converted to T3 in target cells, the liver,and the kidneys;
T3 is 10 x more potent than T4 *Sucralfate, Ferrous Sulfate & Aluminum hydroxide antacid
-may interfere w/ the absorption of Levothyroxine that patient must be
advised on the proper interval of intake these agents. Hyperthyroidism Thionamides 1st line drugs for hyperthyroidism
PTU safe for preganant
PTU- propylthiuracil Rhea® Methimazole Carbimazole Tapazole®
Neo- Mercazole®
MOA: Inhibit thyroid peroxidase reactions& the coupling of Iodotyrosine
Additional MOA (PTU): iodine organification, and peripheral conversion of T4 to T3 SE(both): Agranulocytosis : Granulocyte, Risk Of Infection (Fever, Sorethroat, Oral
*MX: Discotinue the Therapy
PTU Methimazole
Rapid onset Shorter duration of action Thyroid storm 10x PTU dose of methimazole SE: Hepatitis
Inorganic Anions
Perchlorate Perchlorate DOC in amoiodarone-induces hyperthyroidism
MOA: inhibit iodides uptake (compete with iodide transport into cells) CLINICAL USE: DOC in the managemebt of AMiodarone-induced Hyperthyroidism SE: Aplastic Anemia
Slow onset Longer duration of action Maintenance 10x more potent SE:Obstructive jaundice (icterus) Teratogenic
Thiocyanate (is not used anymore)
Iodides
SSKI (satutrated solution of Potassium Iodide)
MOA: Inhibit iodine organification and hormone release;
Inducing Wolff-chaikoff Effect Lugol’s Solution (strong Iodine Solution)
5% I2 (KI), H20
EFFECTS: reduce size and vascularity of thyroid gland CLINICAL USE: Initial Manangement of Throid storm; Preoperative control of hyperthyroidism CI: pregnant lead to fetal goiter
MOA: Radiation-induced destruction of
Breatfeeding (lactation) lead to goiter SE: Iodism: Conjunctivitis, Rhinitis, Sialadenitis Radioactive iodine (131I)
(emits β-radiation that destroys follicular cells of thyroid glands) -β-ray cause ablation of the thyroid gland CLINICAL USE: Preffered Tx fro most cases of hyperthyroidism except during pr
Hypothyroidism (80%)- 6-12 Hrs Quarantine: Patient within 72 hrs CI: Pregnancy, Lactation Radiocontrast dyes: Ipodate, Iopanoic acid Dexametasone inhibit the periph
Beta Blocker:
Propanolo(Inderal®)
most widely used in the terapy of Thyrotoxicosis MOA: Inhibition of receptors
Inhibition of peripheral conversion of T4 to T3 Control the sympathetic symptoms of Hyperthyroidism CLINICAL USE: Thyroid storm SE: Asthma, AV Blockade, Hypertension, Bradycardia
Consideration in Thyroid Hormone Replacement Therapy include: -Infants & children w/ congenital hypothyroidism require
higher dose per kilogram body weight than adults -Steady state levels of thyroxine takes about 6-8 weeks to
achieve after initiating therapy -Older adults & those w/ long-standing disease must be started
on lower than usual doses of levothyroxine
Types of Sex Hormones/ Sexogens: 1. Estrogen is essential for normal female reproductive development
responsible for estrus is responsible for the growth of the genital structures (vagina, uterus, and uterine tubes)
during childhood and for the appearance of secondary sexual characteristics and the growth spurt associated with puberty.
▪ Estradiol major ovarian estrogen in women; most potent estrogen produced & secreted by the ovary
principle estrogen in the premenopausal woman Metaboiltes of Estradiol: Estrone has approximately 1⁄2 the estrogenic potency of estradiol
primary circulatingestrogen after menopause Estriol is significantly less potent than estradiol
present during pregnancy, because it is the principal estrogen produce by placenta 2. Progesteron is the major progestin in humans produced in response to luteinizing hormone (L
males
-Females (secreted by the corpus luteum, primarily during second half of the menstrual cyle & the placenta) -Males (secreted by testes) also synthesized by the adrenal cortex in both sexe
responsible for thicking of endometrium lining that can accommodate implantation of a newly forming embryo
(gestational hormone)
▪Corpus luteus responsible for progesterone production in females 3. Androgen have anabolic &/or musculinizing effects in both males & females
▪ Testosterone most important androgen in humans
is synthesized by Leydig cells in the testes &,
in smaller amounts, by celss in the ovary of the female and by adrenal gland in both sexes responsible for the major changes in the male at puberty (growth of penis, larynx, and skeleton;
pubic, and axillary
hair; darkening of skin; enlargement of muscle mass). After puberty, testosterone acts to maintain secondary sex characteristics, fertility, and libido. It also acts on hair cells to cause male-p
Contraceptives decrease fertility by a number of different mechanisms,
such as preventing ovulation, imparing gametogenesis or gametematuration, or interfering with gestation Major Classes of Contraceptives: 1. Combination Oral Contace
contain Estrogen + Progesterone
* > 50mcg = risk for Thromboembolism SE: Thromboembolsm: myocardial infarction, stroke, deep vein thrombosis, pulmonary embolism CI: >35 yr old, Obese, Breast feeding, Smoke Mo
amount Biphasic D1 - D7; D8 - D14; D15 - D22 (three or more concentration/ pill) * Oral Contraceptives are avoided in females ab
D1 - D14; D15 - D28 (two concentraton/ pill) Triphasic
among chronic smokers due to a higher risk of stroke 2. Trandermal Patch: containing Ethinyl Estradiol + Progestin (Norelgestromin)
applied each week for 3 weeks to the abdomen, upper torso or buttock; week 4 is patch-free, & withdrawal bleeding occurs 3. Vaginal Ring : Ethinyl Estradiol + Etonogestrel; inserted
& week 4 is ring-free , & withdrawal bleeding occurs 4. Progestin-only pills: usually Norethindone or Norgestrel ( called a “mini-pill”) 5.Progestin Implants: Norplant 4cm caps
arm, q 3-5 yrs 6. Progestin Intrauterine Device (Impregnated IUD): Levorgestrel, q 1 yr 7.Post-coital Pills (Morning after pills): contain high dose of progesterone, within 36 ho
Depo-provera® ( Methoxy progesterone acetate), q 3months
♥Gonadal Hormones primary use is for CONTRACEPTION Estrogen
Natural Estrogen
Estradiol Estrone Estriol
MOA: Activation of estrogen receptors leads to changes in the rates of transcription of estrogen-regulated genes
(gene –activation) SE/ TOXICITY: -Moderate toxicity: Breakthrough bleeding, nausea, breast tenderness
-Serious toxicity: Thromboembolism, gallbladder disease, hypertriglyceridemia, migraine headache,
hypertension, depression Synthetic Estrogen
-Steroidal:
Ethinyl Estradiol -Non-Steoidal
DES (Diethylstilbestrol)
-In postmenopausal women: breast cancer, endometrial hyperplasia (unopposed estrogen) -Combination with cytochrome P450 inducer can lead to breakthrough bleeding and reduced con
DES (Diethylstilbestrol) clear cell carcinoma of the vaginal/ cervix *Mestranol: A prodrug that is converted to ethinyl estradiol, contained in some contraceptives *Estrogen Esters (eg, Estr
acting estrogens administered IM and used for hypogonadism in young females Progestins
Norgestrel Derivative: Hydoxyprogesterone caproate Medroxyprogesterone acetate (Provera®) Megestrol Acetate
can promote appetite MOA: Activation of progesterone receptors leads to changes in the rates of transcription of
progesterone-regulated genes SE: Weight gain, reversible decrease in bone mineral density (high doses)
*Breakthrough Bleeding - most common problem encountered in female patients using progestin-only oral
contraceptive pills Androgens
Testosterone Methyltestosterone Danazol Menotropins
MOA: Androgen receptor agonist
CLINICAL USE: Male hypogonadism; weight gain in patients with wasting syndromes
Androgen replacement; GYnecollogic Disoreders such as endometrial bleeding, refractory anemia, osteoporosis SE: -NA & H2O retention, CHolestatic Jaundice
-In females, Virilization In men, High Doses can cause Gynecomastia, Testicular Shrinkage, Infertility
MOA CLINICAL USES SE/ TOXICITY Antiestrogens
-SERMS Tamoxifen Estrogen antagonist actions in breast
tissue and CNS; estrogen agonist effects in liver and bone
Prevention and adjuvant treatment of hormone-responsive breast cancer
Hot flushes, thromboembolism, endometrial hyperplasia
Toremifene: Similar to tamoxifen Raloxifene: Approved for osteoporosis and prevention of breast cancer in selected patients; antagonist effects in breast,
endometrium and agonist effects in the liver Clomiphene: Used for ovulation induction; antagonist effect in pituitary increases gonadotropin secretion
-Receptor antagonist Fulvestrant Estrogen receptor antagonist in all
tissues
Adjuvant treatment of hormone-responsive breast cancer that is resistant to first-line antiestrogen therapy
Hot flushes, headache, injection site reactions

-Aromatase inhibitors Anastrozole Reduces estrogen synthesis by

inhibiting aromatase enzyme
Adjuvant treatment of hormone-responsive breast cancer
Hot flushes, musculoskeletal disorders, reduced bone mineral density Letrozole: S
adjuvant therapy for hormone-sensitive breast cancer Exemestane: Irreversible aromatase inhibitor (steroidal hormone agent, usefull in mx of advanced
unresponsiveness to Tamoxifen)
-GnRH agonist - Leuprolide GnRH receptor antagonist - Ganirelix, cetrorelix -Other Danazol Weak cytochrome P450 inhibitor and
partial agonist of progestin and androgen receptors
Endometriosis, fibrocystic breast disease Acne, hirsutism, weight gain, menstrual
disturbances, hepatic dysfunction
Antiprogestin
Mifepristone Progestin and glucocorticoid receptor
antagonist
Used in combination with a prostaglandin (eg, misoprostol) for medical abortion
Gastrointestinal disturbances (mostly due to coadministration of misoprostol); vaginal bleeding, atypical infecti

5-reductase inhibitors Finasteride Inhibition of 5-reductase enzyme that

converts testosterone to dihydrotestosterone
Benign prostatic hyperplasia (BPH), male- pattern hair loss
Rarely, impotence, gynecomastia

Dutasteride: Similar to finasteride Receptor antagonists Flutamide Competitive inhibition of androgen

receptor
Advanced prostate cancer Gynecomastia, hot flushes, impotence,
hepatoxicity Bicalutamide,
nilutamide: Similar to flutamide but lower risk of hepatotoxicity Spironolactone: Mineralocorticoid receptor antagonist used mainly
sparing diuretic (see Chapter 15); also has androgen-receptor antagonist activity, used for the treatment of hirsutism
GnRH agonist - Leuprolide GnRH receptor antagonist - Abarelix, degarelix Synthesis inhibitor Ketoconazole Inhibition of cytochrome P450 enzymes
involved in androgen synthesis
Advanced prostate cancer that is resistant to first-line antiandrogen drugs
Interferes with synthesis of other steroids; many drug interactions due to cytochrome
Diabetes Mellitus chronic hyperglycemia
Type 1 DM absolute lack of insulin; early onset (below 30 yrs old)
autoimmune condition destruction of β-cells of pancreas
-β-cells (Produces insulin)
Islets of Langerhans TX: Insulin Type 2 DM relative lack of insulin; late onset (above 30 yrs old)
1. secretion of insulin by the β-cells of pancreas 2. Insulin resistance (decrease sensitivity of insulin receptors) 3. Increase gluconeogenesis
*gluconeogenesis formation of glucose
from non-carbohydrate sources such as Fatty Acids TX: Oral Antidiabetic Agents causes
▪Insulin Secretagogues
-Sulfonylureas -Meglitinides
Type 1 Type 2 Age of Onset Usually during
childhood or puberty
Frequently over age 35 Nutritional st
Frequently undernourished
Obesity usually present Prevalence 5
diabetics
90-95% of diagnosed diabetics Genetic predisposition
Moderate Very Strong
Defect or Deficiency β cells are destroyed,
eliminating the production of insulin
Inability of β cells to produce appropriate quantities of Insulin; Insulin Resistance; other defects
INSULIN
▪ β cells ( Islets of Langerhans)
▪ Type 3 receptor (enzyme-linked)
-tyrosine kinase Effects: Translocation of glucose transporter in the cell membrane
Anabolism promotes: Lipogenesis
Protein Synthesis Gluconeogenesi
Tipodystrophy prevented by rotation of injection sites
*Immune Insulin Resistance - is said to be due to production of low levels of
what type of insulin antibodies
*Insulin - produce by using non-disease producing strain of E.coli by Eli lily company as the first commercial application of the technique in Pharmacogno
Chromium
Diagnosis: 1. FBS (Fasting Blood sugar)/ FPG ( Fasting Plasma Glucose)
a person must not to eat for 12 to 14 hours. Diagnosis categories:
Hypoglycemia: < 70 mg/dL normal range: 70 mg/dL to 99 mg/dL prediabetes: 100 mg/dL to126 mg/dL Diabetes: ≥ 126 mg/dL OGTT (Oral Glucose
is a lab test to check how your body
breaks down sugar. most common glucose tolerance test
-cannot eat or drink anything after midnight
before the test/ (8-10 hours before the test) -For the test, you will be asked to drink a liquid
containing a certain amount of glucose. - blood will be taken every 30 to 60 minutes - test takes up to 3 hours. Diagnosis categories:
▪ For a 50-gram oral glucose tolerance test
used to screen for gestational diabetes 1 hour: ≤ 140 mg/dL
▪ For a 75-gram oral glucose tolerance test
Normal: Fasting: 60 -100 mg/dL
1 hour: less than 200 mg/dL 2 hours: less than 140 mg/dL. Prediabetes: 140 - 200 mg/dL Diabetes M
▪ For the 100-gram oral glucose tolerance test:
Fasting: > 95 mg/dL 1 hour: > 180 mg/dL 2 hours: > 155 mg/dL 3 hours: > 140 mg/dL *Intravenous Glucose Tolerance Test (IGTT) rarely used 2. RBS
Sugar) aka casual blood glucose test
is a blood sugar test taken from a non-fasting subject can be used in symptomatic diabetic patient
-Polyuria -Polydipsia -Weight Loss D
normal range: 80 - 140 mg/dl prediabetes: 140 - 200 mg/dl diabetes: ≥ 200 mg/dl 3. HBA1C (gly
monitor the control of the patient’s blood sugar
for the past 3-4 months Diagnosis categories:
Normal: < 5.7% Pre-diabetes: 5.7% to 6.4% Diabetes: ≥ 6.5% 4. Platelet : Aspirin 7-10d
Drugs that may reduce the effects of sulfonylureas, leading to loss of glucose control:
• Atypical antipsychotics
• Corticosteroids
• Diuretics
• Niacin
• Phenothiazines
• Sympathomimetics
Drugs that may potentiate the effects of sulfonylureas, leading to hypoglycemia:
• Allopurinol
• Azole antifungals
• Chloramphenicol
• Clarithromycin
• Monoamine oxidase inhibitors
• Probenecid
• Salicylates
• Sulfonamides
♥Drugs for Diabetes Mellitus
Insulin - MOA: Activate insulin receptor
* Zinc - improves stability & shelf life of insulin in commercial insulin preparations Rapid acting insulin:
Insulin Lispro Insulin Aspart Insulin Glulisine
SQ; 5 min before meals Rapid onset of action in 5-15 minutes
Short-acting insulin:
Regular Insulin (Humulin-R®)
SQ/IV; 20 min before meals USES:To prevent Postprandial Hyperglycemia
*Target Postprandial Glucose = < 180mh/dL
Target Preprandial Glucose = 90-130 mg/dL Target HbA1C = < 7% Interme
Isophane Insuin/ NPH (neutral protamine Hagedorn)
/Humulin N,/Insulatard, /Novolin N, /Novolin NPH, /NPH
USES: Insulin basal insulin secretion DOSE: BID: AM - 2/3 of the dose
PM - 1/3 of the dose *Lente Insulin - prepared by mixing 30% Semilente & 70% Ultralente Insulin
Long-acting insulin: Insulin Glargine Insulin Detemir Insulin Levemir
SQ, OD USES: Provide basal insulin requirement
.
*Insulin Glargine (―peak-less insulin‖) - has a character release pattern that shows no peak & a plateau serum insulin level that is maintained for about 24 hours
Insulin Secretagogues known to induce Hypoglycemia among diabetic & euglycemic individuals.
promote release of insulin by the remaining functional beta-cells of the pancreas Sulfonylureas - MOA: block outward K+ channel lead to to depolarization of β cells to release Insu
CI: Liver disease, Renal Disease Common SE: Hypoglycemia, Weigh
Chlorpropamide longest t1/2 Tolbutamide most cardiotoxic Acetahexamide Tolazamide safest for elderly
-2nd generation Less Potent,
Glibenclamide(Euglucon®) More side effects
Glipizide (Minidiab®) SE: Disulfiram-like reaction
Gliclazide (Diamicron®) Glimepiride (Solosa®)
More potent,
Less side effect
Meglitinides
Repaglitide (Prandin®, Novonorm®) Nateglitide (Starlix®)
Short-Acting CLINICAL USE: Control 2hr post prandial Hyperglycemia SE: Hypoglycemia
Insulin Sensitizers
Biguanides
Metformin (Gucophage®) very low risk of lactic acidosis Phenformin high risk of lactic acidosi ( out in the market)
*Metformin 1st line initial treatment of type 2 DM esp. among obees patients SE: Diarrhea, Weight Loss, Lactic Acidosi MOA: UNKNOWN - Still not understood but possibly
enhances fatty acid oxidation (decreased hepatic gluconeogenesis)/ decreased endogenous glucose production CLINICAL USE: 1st line tx of type 2 DM especially among obese Px. CI: C
Failure, Hepatitis Thiazolidinedione must not be given to patient
Rosiglitazone (Avandia®) risk of cardiovascular mortality Pioglitazone (Actos®) bladder cancer Troglitazone
MOA: Regulates gene expression by binding to PPAR- γ /
Activate PPAR ( Peroxisome Proliferator-acting receptor ) Gamma SE: Hepatotoxicity
Alpha-glucosidase Inhibitors
Acarbose (Glucobay®, Gluconase®) Voglibose (Basen®) Miglitol (Glyset®)
may be given to Type 1 DM patients as a combnation therapy with Insulin Alpha-glucosidase Inhibitors important in conversion of
*Complex Carbohydrate Simple Carbohydrate (absorbable) MOA: Inhibit intestinal α-glucosidases
Inhibit a variety of enzymes present in the brush-border of the mucosa of the wall intestine that are
responsible for the breakdown of complex polysaccharides & sucrose into asbsorbable monosaccharides SE: Flatulence, Hepatotoxicity (Acarbose) ADMINISTRATION: After 1st bite of food
Incretin-acting drugs NOTE: can cause weight loss
insulin secretion; glucagon secretion; GI motility; Gastric Emptying Time GLP-1 analogue (Glucagon-like peptide-1)
Exenatide (Byetta®)
risk hypoglycemia ADMINISTRATION: Parenteral (SQ) MOA: Analog of glucagon-like peptide-1 (GLP-1) activates GLP-1 receptors SE: GI disturbances, headache, pancrea
(Dip
Sitagliptin (Januvia®)
responsible in metabolizing GLP- 1 to active ones ADMINISTRATION: Oral MOA: Inhibitor of the dipeptidyl peptidase-4 (DPP-4) that degrades GLP-1 and other incretins SE: Rhinitis, upp
rare allergic reactions Amylin Analogue
Pramlitide
given SQ cosecreted w/ insulin enhances the effect of insulin
MOA: Analog of amylin activates amylin receptors CLINICAL USE: Type 1 and type 2 diabetes SE: risk of hypoglycemis Glucagon parenteral useful for reversing the cardiac effe
blocking agents because of its ability to increase cAMP
production in the heart. MOA: Activates glucagon receptors CLINICAL USE/S: Severe hypoglycemia(not responding well to glucose),
β -blocker overdose(by increasing cAMP Levels as it binds to Glucagons Receptors in the Heart) SE: GI Disturbances, Hypotension, Flatulence (most common)
XI. DRUGS FOR OSTEOPOROSIS
Calcium Carbonate salt of choice (highest elemental Ca) NOTE: should be taken with meals
Biphosphonate
SE: Constipation, Flatulence
Alendronate (Fosamax®) Risedronate (Actonel®) Ibandronate
MOA: Bind to hydroxyapatite in bones & inhibits osteoclast adherence NOTE: Taken at morning with plain tap water 30 minutes before meals
& Should remain upright for 30 minutes SE: Nausea, Abdominal Pain, Dyspepsia, GI Irritation, Ulcers,
Osteonecrosuis of the Jaw Selective Estrogen Receptor Modulator (SERMs)
Raloxifene
MOA: Decreases bone resorption (2nd
MOA: estrogen agonist at bones but anatagonist in the breast & uterus NOTE: Decreases breast CA risk like Tamoxifen Calcitonin
MOA: Decrea
Hormonal Therapy
Inhibits PTH (parathyroid hormone), Increase Vitamin D & calcium absorption, Decrease calcium excretion Phytoestrogens - isofalvonoids from soy beans & lignans from flax seeds
alone) Testosterone
Oral Methyltestosterone Testosterone Implants P
Terparatide
NOTE: Given SubQ every 28 days, should not be used with Bisphosphonates (Antagonistic Effect)