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University of San Agustin

College of Health and Allied Medical Professions


Bachelor of Medical Laboratory Science
Pharma 1: Basic Pharmacology
Pharmacology- Study of substances that interact with living systems through
chemical processes, especially by binding to regulatory molecules and activating or
inhibiting normal body processes.
Medical pharmacology- science of substances used to prevent, diagnose and
treat disease.
Toxicology- branch of pharmacology that deals with the undesirable effects of
chemicals on living systems, from individual cells to humans to complex
ecosystems.
Receptors- Selective, modifiable proteins or non- protein macromolecules in the
human cells where interactions of the body with the drug occur.
Recognition site- Specific binding region of receptors that initially and directly
comes into contact with drugs.
The interaction of a drug with its specific recognition site is the fundamental event
that initiates the action of such drug.
Inert binding sites- Macromolecules that bind drugs but without initiating the
events leading to any of the drugs effects.
Prodrugs- precursor drugs that are inactive after preparation and must be
converted first into its active form before exerting its effect on the body.
Pharmacokinetics- The actions of the body on the drugs. Processes involved
govern the absorption, distribution, and elimination of drugs and are of great
practical importance in the choice and administration of a particular drug for a
particular patient.
Pharmacodynamics- The actions of the drug on the body. The properties involved
determine the group in which the drug is classified, and they play the major role in
deciding whether that group is appropriate therapy for a particular symptom or
disease.
Loading dose- Amount of drug given if it is necessary to achieve the drugs target
plasma level rapidly.
Maintenance dose- Amount of drug given when it is needed to maintain the drug
plasma concentration
within a specified range over long periods of therapy.
TD50- Median toxic dose. The dose required to produce a particular toxic effect
in 50% of individuals. The concentration/dose that produces 50% of the maximum
dose that is toxic to the body.
LD50- Median lethal dose- dose required to produce a particular lethal(death)
effect in 50% of individuals. The concentration/dose that produces 50% of the
maximum dose that is lethal to the body.
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Therapeutic index- The ratio of the dose of a drug required to produce a desired
effect to that which produces an undesired effect.
Therapeutic index = Median Lethal dose
Median Effective dose
Therapeutic window - Dosage range between the minimum effective therapeutic
dose/ concentration and the minimum toxic dose/concentration .
Example: Therapeutic window of Aspirin = 80 300 mgs
Potency- Denotes the amount of drug needed to produce a given effect.
First pass elimination- Process wherein a fraction of a drug in plasma is removed
by an organ as it passes through that organ.
Absorption- Delivery or transfer of drug molecules from the site of administration
to the bloodstream.
Distribution- Transfer of rug molecules from the bloodstream to the different parts
of the body and into the target organs.
Well- perfused organs like the heart and kidneys often achieve higher tissue
concentrations of the drugs administered as compared to poorly-perfused organs
like bones and fat.
Permeation- Transfer of drug molecules from the bloodstream/plasma into the
target organs traversing a barrier.
Excretion- Actual clearance or passage out of drug molecules from the body.
Elimination- Disappearance/ clearance
of
active drug molecules from the
bloodstream.
First order elimination- The rate of drug elimination is proportionate to the drug
concentration.
Zero- order elimination- The rate of elimination is constant regardless of
concentration.
Half- life- The time it takes for the amount / concentration of a drug to fall to 50%
of an earlier measurement.
Volume of distribution- The ratio of the amount of a drug in the body to its
plasma concentration.
Minimum effective concentration-Plasma concentration below which a patients
response is too
small
for therapeutic benefit.
Median effective dose- dose at which 50% of individuals exhibit a specified
quantal/beneficial effect of a drug.
Effectors- Molecules that translate the drug- receptor interaction into a change in
cellular activity.

Agonists- Substances that bind to and activate the receptors in some fashion
which directly or indirectly brings about the effects. (Example: Epinephrine acts as
alpha & beta receptor agonist which brings about vasoconstriction.)
Full Agonist- A drug capable of fully activating the effector system when it binds to
the receptor.
Partial Agonist- A drug capable of binding to the same receptors as full agonists
but do not evoke as great a response no matter how high the concentration.
Inverse agonists- Drugs that bind to the same receptors as other agonists but
produce
effects
that are
the opposite of what those conventional agonists offer.
Antagonists-

synonymous

with

Reversible

competitive pharmacologic
antagonists)
Drugs that by binding to receptors, compete with and prevent binding by other
molecules to those
receptors.
Physiologic antagonist - A drug that binds to a different receptor producing an
effect opposite to
that
produced by the drug it is antagonizing.( example: Salbutamol as a beta receptor
agonist produces
bronchodilation which is antagonistic to the bronchoconstricting effects of Histamine
in patients with
severe allergies and asthma. )
Chemical antagonist- A drug that interacts directly with the agonists to inhibit
their
effects.
(Example:
Antidotes like Dimercaprol which directly inactivates and neutralize poisons like
Lead.)
Bioavailability- the fraction of unchanged drug reaching the systemic circulation
following
administration by any route.= Amount of Drug Absorbed
X 100%
Amount of Drug Administered
The Physical Nature of Drugs:
1. Solid ( Tablets, capsules, powdered forms)
2. Liquid ( Syrup, Suspension)
3. Gas ( Nitrous oxide as anesthetic agents)
Drug size:
Smallest- Lithium ( MW 7)
Large- Alteplase (MW 59,050)
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Most drugs with MW of 100 1000


Drug- Receptor Bonds:
1. Covalent- strongest, often irreversible
2. Electrostatic- affected by electrical charges
3. Hydrophobic- Weakest bond, easily disrupted by water molecules.
Drug Shape:
Follows a Lock and Key principle on interaction with specific receptors.
Most have Chirality or Stereoisomerism.
Determinants of drug distribution to tissues / Target organs:
1. Binding capacity
2. Solubility of drug molecules
3. Blood flow to target organs
4. Size of drug molecules
The rate and efficiency of absorption differ depending on the drugs route of
administration
Common Routes of Drug Administration:
1. Intravenous ( antibiotics, Paracetamol)
2. Intramuscular ( Vaccines, Hyoscine)
3. Oral ( Antibiotic Tablets, Analgesics)
4. Sublingual ( Clonidine, Nitrate tablets)
5. Subcutaneous ( Insulin, Erythropoietin)
6. Rectal ( Bisacodyl, Paracetamol)
7. Topical ( Creams, Ointments)
8. Transdermal ( Nitrate patch)
9. Inhalation ( Salbutamol, Inhaled steroids)
Ficks Law of Diffusion: Predicts the rate of movement of drug molecules across a
barrier.
Rate of Diffusion=

(C1- C2) X Area x Permeability coefficient


Thickness

C1- Higher concentration


C2- Lower concentration
Area- Cross- sectional area of the diffusion path
Permeability coefficient- Measure of the mobility of the drug molecules in the
medium of the diffusion path
Thickness- Length/ Thickness of the barrier/ diffusion path.
Permeation- Transfer of drug molecules from the bloodstream/plasma into the
target organs traversing a barrier. Also refers to the movement of drug molecules
into and within the biologic environment.
Types of Permeation:
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1. Aqueous diffusion- Transport of drug molecules through watery compartments


of the body.
Governed by Ficks law. A Passive type of Diffusion.
2. Lipid diffusion- Transport of drug molecules through lipid barriers (cell
membranes) of the body.
Governed by Ficks law. A Passive type of Diffusion.
3. Use of special carriers- Employment of macromolecules ( like Albumin) as
transport mechanisms for drug transfer or carrying endogenous substances.
Capacity- limited. Not governed by Ficks Law.
4. Endocytosis/ Exocytosis- Engulfment and release of drug molecules by
vacuoles. Not governed by Ficks Law.
Idiosyncratic drug response- Reaction or response to a drug that is infrequently /
unusually observed in most patients. Usually caused by genetic differences in
metabolism of the drug or by immunologic mechanisms, including allergic reactions.
Hypersensitivity- refers to allergic or other immunologic responses to drugs.
Tolerance- decreasing responsiveness during the course of therapy as a
consequence of continued drug administration.
Tachyphylaxis- response characterized by a rapidly diminishing responsiveness
after administration of a drug.
Medical pharmacology- also known as Therapeutics. The science of substances
used to prevent, diagnose and treat disease. Its ultimate goal is to achieve a desired
beneficial effect with minimal adverse effects.
Pharmacodynamics- governs the concentration-effect part of the drug- body
interaction.
Pharmacokinetics- deals with the dose- concentration part of the drug-body
interaction.
The Pharmacokinetic processes:
1. Absorption

2. Distribution3. Metabolism

4. Elimination

The 2 Basic Parameters essential in Drug- Dosage Adjustments:


1. Clearance- the measure of the ability of the body to eliminate the drug.
Clearance: Rate of elimination
Concentration
2. Volume of distribution- the measure of the apparent space in the body
available to contain the drug.
V:

Amount of drug in the body


Concentration

Definition of Basic terms used in Pharmacodynamics:

1. Receptors- specific molecular components of a biologic system with which drugs


interact to produce changes in the function of the system.
Characteristics:
a. Selective/ Specific
b. Modifiable
c. Proteins
d. Macromolecules
The interaction of a drug with its receptor/ recognition site is the fundamental
event that initiates the actions of such drug.
2. Effectors- molecules that translate the drug- receptor interaction into a change
in cellular activity. Mostl are enzymes.
3. Full Agonist- A drug capable of fully activating the effector system when it
binds to the receptor.
4. Partial agonist- a drug which produces less- than- the- full effect even when
it has saturated the receptors. It acts on the same receptor as that with a full
agonist. In the presence of a full agonist, a partial agonist acts as an Inhibitor.
5. Efficacy- a.k.a the maximal efficacy- the maximal effect (Emax) an agonist can
produce if the dose is taken to very high levels.
6. Potency- denotes the amount of drug needed to produce a given effect .
7. Spare receptors- receptors which exist if the maximal drug response is
obtained at less than the maximal occupation of the receptors.
8. Inert binding sites- components of endogenous molecules that bind a drug
without initiating the events leading to any of the drugs effects.
9. Antagonist- A drug whose effects are opposite with that of the agonist.
a. Reversible competitive pharmacologic antagonist- drugs that bind to
the same receptors (with that of an agonist) in a reversible way without activating
the effector system for that receptor. In its presence, the dose of agonists is shifted
to higher doses to bring about the same maximal effect.The effects of reversible
competitive pharmacologic antagonists can be overcome by adding more agonists.
b. Irreversible pharmacologic antagonist- drugs that bind to the same
receptors (with that of an agonist) which cause a downward shift of the maximum
agonist effect. The effects of Irreversible pharmacologic antagonists can not be
overcome by adding more agonists.
c. Physiologic antagonist- a drug that binds to a different receptor
producing an effect opposite to that produced by the drug it is antagonizing. ( Ex.
Epinephrine binding to receptors causing effects opposite with that caused by
Histamine receptors after binding with histamine in allergic reactions. )

d. Chemical antagonist- a drug that interacts directly with the drug being
antagonized to remove it or to prevent it from reaching its target. It does not
depend on interaction with the agonists receptor.
(E. Dimercaprol chelating lead in cases of lead poisoning)
10. TD50- (Median toxic dose)- The concentration or dose that produces 50% of the
maximum dose that is toxic to the body.
11. LD50- (Median lethal dose)- The concentration or dose that produces 50% of
the maximum dose that is lethal to the body.
12. ED50- (Median effective dose)- The concentration or dose that produces 50% of
the dose that is effective to the body.
13. Therapeutic index (T.I.) - The ratio of either the TD50 or LD50 to the ED50. It
represents an estimate of the safety of the drug. A safe drug should have a large
toxic dose and a small effective dose.
LD50 or TD50
Ex ED50 is 3 mgs; LD50 is 150 mgs; thus
T.I. is 150/3 = 50
ED50
14. Therapeutic window (T.W.) the dosage range between the minimum effective
therapeutic concentration or dose and the minimum toxic concentration or dose.
Ex. Minimum therapeutic plasma concentration= 8 mgs.
Minimum toxic plasma concentration= 18 mgs
Therapeutic window= 8 18 mgs.

Definition of Basic terms used in Pharmacokinetics:


1. Effective drug concentration- The concentration of a drug at the receptor site
which is often proportionate to the drugs concentration in the plasma. It is a
function of:
a.) Rate of Absorption.
b.) Rate of distribution to the target organs.
c.) Rate of elimination and excretion.
2. The 2 basic parameters of PharmacokineticsA. ) Volume of distribution (Vd)- the ratio of the amount of drug in the body to its
concentration in the plasma or blood. It is a measure of the apparent space in the
body available to contain the drug.
Amount of drug in the body
Plasma drug concentration
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B.) Clearance- the ratio of the rate of elimination of a drug to its concentration in
the plasma or blood. It is a measure of the ability of the body to eliminate the drug.
Rate of drug elimination
Plasma drug concentration
3. Half- life- The time it takes for the amount or concentration of a drug to fall to
50% of an earlier measurement.
4. Area under the curve- the graphic area under a plot of drug concentration in
plasma vs. time after a single dose of a drug or during a single dosing interval. It is
important for calculating the bioavailability of a drug given by any route other than
intravenously.
5. Bioavailability- the percentage or fraction of the administered dose of a drug
that reaches the systemic circulation.
6. Minimum effective concentration (MEC)- the plasma concentration below
which a patients response is too small for therapeutic benefit.
7. Extraction- the process by which a fraction of a drug in the plasma is removed
by an organ as it passes through that organ.
8. Bioequivalence- The equivalence of blood concentrations of two preparations of
the same drug measured over time. If the concentration- time plots for the two
preparations are nearly superimposable, the preparations are said to be
bioequivalent- meaning, one preparation may be safely substituted for the other.
9. Dosage regimen- a plan for drug administration over a period of time. An
appropriate dosage regimen results in the achievement of therapeutic levels of the
drug in the blood without exceeding the minimum toxic concentration.
A.) Loading dose- drug concentration given if it is necessary to achieve the
target plasma levels rapidly.
B.) Maintenance dose- drug concentration given if it is necessary to
maintain the plasma concentration within a specified range over long periods of
therapy.

I. Cardiovascular Drugs

Hypertension - Blood pressure greater than 130/80 mm Hg; usually > or equal
to 140/90 mm Hg in repeated readings.

Stroke volume
Cardiac output
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Heart rate
Arterial pressure
Vascular structure
Peripheral resistance
Vascular function
Common causes of Hypertension:
1. Genetic predisposition
2. Hyperthyroidism
3. Pheochromocytoma- Adrenal gland tumor
4. OSA- Obstructive Sleep Apnea
5. Lifestyle
Drugs to treat Hypertension
1.) Diuretics- lower blood pressure by reducing blood volume (diuresis), increasing
renal sodium excretion (natriuresis) and via a direct vascular effect.
A. Thiazides (Hydrochlorothiazide)- inhibit the Na+/ Cl- pump in the distal
convoluted tubules .
- also act as vasodilators.
B. Loop diuretic ( Furosemide)- acts on the Na+K+Cl- cotransporter in the
thick ascending loop of Henle.
Adverse effects :
1. Hypokalemia
2. Hyperlipidemia
3. Hyperuricemia
4. Hyperglycemia
5. Impotence
2.) Sympathoplegic agents (Blockers)- lower blood pressure by interfering with
sympathetic nerve function thus reducing peripheral vascular resistance, inhibiting
cardiac function, increasing venous pooling in capacitance vessels and reducing
cardiac output.
A. Alpha- 1 selective blockers (Prazosin)
B. Beta- blockers (Metoprolol, Propranolol, Atenolol)

Adverse effects:
1. Asthma attack (Beta- blocker)
2. Hyperlipidemia (Both)
3. Bradycardia (Beta blocker)
4. Sedation (Both)
5. Impotence (Both)
C. CNS active agents
Alpha- 2 selective agonists (Clonidine, Methyldopa)- decrease
sympathetic outflow by activating the alpha- 2 receptors in the CNS.

Adverse effects:
1. Sedation
2. Hemolytic anemia
3. Rebound hypertension
3.) Vasodilators- Dilate blood vessels by acting directly on smooth muscle cells.
- Release Nitric oxide
- Open K+ channels
- Block Ca++ channels
A. Hydralazine- Releases Nitric oxide (major mechanism)
Adverse effects:
1. Tachycardia
2. Salt and water retention
B. Minoxidil- A Prodrug which is converted to Minoxidil Sulfate (its active
metabolite)
- Opens K+ channels causing hyperpolarization and relaxation of vascular
smooth muscles.
Adverse effects:
1. Tachycardia
2. Salt and water retention
3. Hirsutism- overgrowth of hair
C. Calcium channel blockers ( Amlodipine, Felodipine, Nifedipine, Diltizem,
Verapamil)- Block voltage- dependent Ca++ channels which are most important in
cardiac and smooth muscle contraction.
- Decrease Calcium influx during action potentials thus reducing intracellular
calcium concentration and muscle contractility.
- Relax blood vessels, uterus, bronchi and GIT.
Adverse effects:
1. Constipation
2. Edema
3. Nausea
4. Vomiting
5. Dizziness and Flushing
D. Parenteral vasodilators- used to lower blood pressure fast in
Hypertensive Emergencies
- Hypertensive emergency- Elevated blood pressure with signs of end- organ
damage
a. Brain- Stroke
b. Heart- Myocardial infarction
c. Kidneys- Renal failure
d. Nerves- Neuropathies
e. Eyes- Retinopathies
f. Liver- Hepatic failure
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1. Nitroprusside- Causes release of Nitric oxide which stimulates Guanylyl


cyclase and subsequent increase in cGMP concentration in smooth muscles which
brings about vasodilation.
Adverse effects:
1. Hypotension
2. Reflex Tachycardia
2. Diazoxide- Opens K+ channels thus hyperpolarizing and relaxing smooth
muscle cells.
- Reduces insulin release.
Adverse effects:
1. Hypotension
2. Hyperglycemia

4.) Angiotensin antagonists- block the production of /or action of angiotensin


thereby reducing peripheral vascular resistance.
Kidneys
Renin
Receptor = Decreased

Angiotensinogen
BP

Angiotensin I

ACE

Angiotensin II

Decreased
Aldosterone

A. Angiotensin Converting Enzyme (ACE) Inhibitor


Lisinopril)- inhibits ACE
- reduces Angotensin II and Aldosterone production

(Captopril, Enalapril,

Adverse effects:
1. Cough
2. Renal damage in fetus
B. Angiotensin II Receptor Blockers (A2RB) ( Losartan, Telmisartan,
Valsartan)- competitively inhibit Angiotensin II at its receptor site
- reduces Aldosterone production.
Adverse effects:
1. Renal damage in fetus
2. Hyperkalemia
3. Renal damage to patients with pre- existing renal defects.

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Angina- condition in which a patient experiences chest pain (crushing, strangling,

pressing)associated with coronary vasospasm or coronary artery disease.


Types:
1. Classic angina- Angina of effort, Atherosclerotic angina, Stable angina
- precipitated by physical exertion which causes increased Oxygen demand
by the heart that can not be met because of partial atherosclerotic obstruction of
the coronary arteries. When cardiac work increases, the obstruction of flow results
in the accumulation of acidic metabolites and ischemic changes which stimulate
myocardial pain- mediating nerve endings.
- relieved by rest.
2. Unstable angina- Crescendo angina
- rapidly progressing increase in frequency and severity of angina attacks
especially noted at rest caused by diminished coronary flow that results from a
combination of atherosclerotic plaques, platelet aggregation ( at fractured plaques)
and vasospasm.
3. Prinzmetals angina Vasospastic angina, Variant angina
- precipitated by reversible spasm of the coronary vessels usually at the site
of an atherosclerotic plaque.
- spasms may occur anytime even during sleep.
- may deteriorate into unstable angina.
Factors that contribute to myocardial oxygen requirement:
1. Preload- Venous or Diastolic filling pressure
- a function of blood volume and venous tone.
- Venous tone is mainly controlled by sympathetic outflow.
2. Afterload- Arterial blood pressure
- also depends on the peripheral vascular resistance which is determined by
sympathetic outflow to the arteriolar vessels.
3. Heart rate- The faster the heart rate, the stronger is the myocardial contractility
and the shorter is the time available for coronary flow.
4. Cardiac contractility- controlled mainly by sympathetic outflow to the heart.
Drugs to treat Angina:
1. Nitrates- Nitroglycerin- the most important type.
- Releases Nitric oxide which stimulates Guanylyl cyclase and subsequent
increase in cGMP concentration in smooth muscles which brings about vasodilation,
decrease in preload pressure, reduced cardiac contractility, cardiac size and cardiac
output.
- Reduces platelet aggregation.
- Relaxes the smooth muscles of the bronchi, GIT and GU tract.
Forms:
a. Nitroglycerin patch- used transdermally
b. Isosorbide mononitrate/ dinitrate- used orally and sublingually
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c. Amyl nitrite- used via inhalation


Adverse effects:
1. Tachycardia
2. Hypotension
3. Headache
4. Methemoglobinemia
5. Monday disease- loss of tolerance to nitrates during work- free days
leading to severe vasodilatory effects on the day of first reexposure.
2. Calcium channel blockers- ( Amlodipine, Felodipine, Nifedipine, Diltiazem,
Verapamil)- Block voltage- dependent Ca++ channels which are most important in
cardiac and smooth muscle contraction.
- Decrease Calcium influx during action potentials thus reducing intracellular
calcium concentration and muscle contractility.
- Relax blood vessels, uterus, bronchi and GIT.
Adverse effects:
1. Constipation
2. Edema
3. Nausea
4. Vomiting
5. Dizziness and Flushing
6. Hypotension
3. Beta- blockers- (Metoprolol, Propranolol, Atenolol)
-Block beta- adrenoreceptors by acting as competitive pharmacologic
antagonists to these receptors.
- Decreases cardiac rate
- Decreases cardiac contractility
- Decreases blood pressure
Adverse effects:
1. Bradycardia
2. Bronchoconstriction
3. Atrioventricular heart blockade

Introduction to Antimicrobial agents


Antibiotic stewardship- judicious, rational and proper use of antibiotics in proper
situations.
Questions to consider before starting on antibiotics:
1. Is it truly indicated on basis of clinical findings?
2. Have appropriate clinical specimens been obtained?
3. What are the likely etiologic agents for the patients illness?
4. What measures should be taken to protect individuals exposed to the index case?
5. Is there clinical evidence that antimicrobial therapy will confer clinical benefit and
safety for the patient?
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Types of Antibiotic s according to range of Activity:


a. Narrow- spectrum- indicated to act upon a single type of microorganism.
b. Broad spectrum- indicated to act on multiple types of microorganisms.
Empirical antimicrobial therapy- Presumptive therapy without yet the benefits
offered by diagnostic test results.
Types of Antibiotics according to specific actions:
a. Bactericidal- kills microorganisms
b. Bacteriostatic- suppresses the growth of microorganisms.
Synergism- Occurs when the inhibitory or killing effects of 2 or more antimicrobials
used together are significantly greater than expected from their effects when used
individually.
Antagonism- Occurs when the combined inhibitory or killing effects of 2 or more
antimicrobials used together are significantly less than expected from their effects
when used individually.

Chemotherapeutic / Antimicrobial agents


Types of Antibiotic s according to range of Activity:
a. Narrow- spectrum- indicated to act upon a single type of microorganism.
b. Broad spectrum- indicated to act on multiple types of microorganisms.
Empirical antimicrobial therapy- Presumptive therapy without yet the benefits
offered by diagnostic test results.
Types of Antibiotics according to specific actions:
a. Bactericidal- kills microorganisms
b. Bacteriostatic- suppresses the growth of microorganisms.
Synergism- Occurs when the inhibitory or killing effects of 2 or more antimicrobials
used together are significantly greater than expected from their effects when used
individually.
Antagonism- Occurs when the combined inhibitory or killing effects of 2 or more
antimicrobials used together are significantly less than expected from their effects
when used individually.

Antibacterial Drugs
Beta- lactam & other cell wall & cell- membrane active antibiotics:
Mode of action: Inhibits cell wall synthesis by interfering in the
transpeptidation reaction of bacterial cell wall
I.
Penicillins

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1. Penicillins ( Pen G)- gram + organisms; gram cocci; non- Beta


lactamase producing anaerobes. Little activity vs gram - rods
2. Antistaphylococcal penicillins ( Nafcillin)- Resistant to Staphylococcal Blactamases; active Staphylococci & Streptococci but not vs
enterococci; Anaerobic bacteria, gram cocci & rods.
3. Extended spectrum penicillins ( Ampicillin)- Retain the antibacterial
activity of Penicillin & have improved activity vs gram negative
organisms. Susceptible to hydrolysis by B- lactamases.
II.
Cephalosporins
st
1. 1 generation- Cephalexin; Cefazolin
2. 2nd generation- Cefuroxime; Cefoxitin
3. 3rd generation- Ceftriaxone; Ceftazidime
4. 4th generation- Cefepime
III.
Monobactams- Aztreonam
- Limited soectrum of activity to aerobic gram rods including
Pseudomonas.
IV.
Beta- lactamase inhibitors
Clavulanic acid; Sulbactam; Tazobactam
V.
Carbapenems
Doripenem; Ertapenem; Imipenem; Meropenem

Glycopeptide Antibiotics
Vancomycin- produced by Streptococcus orientalis; active only vs Gram positive
bacteria
- Inhibits cell wall synthesis by binding firmly to the D- Ala- - Ala terminus of
nascent peptidoglycan pentapeptide
- Adverse reaction: Red man or Red neck syndrome

Aminoglycosides
- Irreversible inhibitors of bacterial protein synthesis
- Streptomycin, Gentamycin, Amikacin
Sulfonamides & Trimethoprim
- Inhibit dihydropteroate synthase & folate production essential for bacterial
nucleic acid synthesis

Fluoroquinolones
- Block bacterial DNA synthesis by inhibiting bacterial topoisomerase II (DNA
gyrase) anf Topoisomerase IV

Antimycobacterial Drugs
1. Isoniazid
2. Rifampin/ Rifampicin
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3. Pyrazinamide
4. Ethambutol
5. Streptomycin- now used as second line drug

Antiprotozoal Drugs
Malaria- the most important parasitic disease of humans (caused by
Plasmodium species: falciparum, vivax, malariae, ovale and knowlesi)
Anti- Malarial drugs
Tissue schizonticides- eliminate developing or dormant liver forms
Blood schizonticides- act on erythrocytic parasites
Gametocides- kill sexual stages and prevent transmission to mosquitoes
Causal Prophylactic drugs- capable of preventing erythrocytic infection.
Chemoprophylaxis :
- Measures to prevent mosquitoe bites ( repellents, insecticides and bed
nets)
- CDC (Center for Disease Control and Prevention) recommends the ff
drugs:
1. Chloroquine- for few areas infested by only chloroquine-sensitive
malarial parasites (Caribbean and Central America west of Panama canal)
2. Doxycycline- for areas with very high prevalence of multidrug- resistant
falciparum malaria (border areas of Thailand)

Treatment:
1. Chloroquine- drug of choice for both treatment & chemoprophylaxis of
malaria since 1940s.
- synthetic 4- aminoquinoline; rapidly & almost completely absorbed
from the G.I. tract, reaches maximum concentration in about 3 hours and
rapidly distributed to tissues. It has large Vd and principally excreted in the
urine.
- a highly effective blood schizonticide. Moderately effective against
gametocytes of P. vivax, P. ovale and P. malariae but not against those of P.
falciparum.
- not active against liver stage parasites.
- Acts by concentrating in parasite food vacuoles, preventing the
biocrystallization of the hemoglobin breakdown product, heme, into
hemozoin and thus eliciting parasite toxicity due to the buildup of free heme.

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- Mutations in the transporter PfCRT have been correlated with


resistance (which could be reversed by certain agents like Verapamil &
Desipramine)
- Rapidly terminates fever (in 24- 48 hours) and clears parasitemia in
48-72 hours.
-Does not eliminate dormant liver forms of P. vivax and P. ovale ( and
so Primaquine must be added for the radical cure of these species).
- Adverse effects (also applicable to the other antimalarial drugs):
Pruritus, nausea and vomiting, abdominal pain, headache, anorexia,
urticaria, blurring of vision.
2. Artemisinin & its derivatives- a sesquiterpene lactone endoperoxide,
the active component of an herbal medicine that has ben used as an
antipyretic in China for over 2000 years.
- Derivatives: Artesunate, Artemether and Dihdroartemisinin
-Blood schizonticides which act by production of free radicals that
follows the iron- catalyzed cleavage of the artemisinin endoperoxide bridge
in the parasite food vacuole or from inhibition of a parasite calcium ATPase.
3. Quinine and Quinidine- derived from the bark of the Cinchona tree, a
traditional remedy for intermittent fevers from South America.
- Mechanism of action: Unknown
- Parenteral Treatment of choice for severe Falciparum malaria.
- Not generally used in chemoprophylaxis owing to its cardiac toxicity
and cinchonism adverse effects ( tinnitus, headache, nausea, dizziness,
flushing & visual disturbances). Blackwater fever- a rare severe illness due
to marked hemolysis and hemoglobinuria in the setting of quinine therapy
due to hypersensitivity reaction.
4. Primaquine- the drug of choice for the eradication of dormant hypnozoite
liver forms of P. vivax and P. ovale
- a synthetic 8- aminoquinoline derivative active against hepatic stages
of all human malaria parasites. Also acts against erythrocytic stage
parasites.
- Mechanism of action: Unknown

Amebiasis
Treatment of specific forms of Amebiasis:
A. Asymptomatic Intestinal infection- generally not treated in endemic areas.,
but in nonendemic areas, they are treated with a luminal
amebicide( Diloxanide furoate, iodoquinol).
B. Amebic colitis- Metronidazole plus a luminal amebicide is the treatment of
choice.
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C. Extraintestinal infections- Metronidazole plus a luminal amebicide is the


treatment of choice.
1.Metronidazole- a nitroimidazole, is the drug of choice in the treatment of
extraluminal amebiasis. It kills trophozoites but not cysts of Entamoeba
histolytica and effectively eradicates intestinal and extraintestinal tissue
infections.
- Readily absorbed and permeate all tissues by simple diffusion.
- The nitro group is chemically reduced in anaerobic bacteria and
sensitive ptotozoans. Reactive reduction products appear to be responsible
for antimicrobial activity.
- Also a treatment of choice for Giardiasis and Trichomoniasis.
- Adverse effects: Nausea, headache, G.I. discomfort, dry mouth &
metallic taste
2. Diloxanide furoate a dichloroacetamide derivative effective as luminal
amebicide but is not active against tissue trophozoites.
- In the gut, it is split into diloxanide and furoic acid; about 90% of the
diloxanide is rapidly absorbed and then conjugated to form the glucoronide
which is promptly excreted in the urine. The unasorbed diloxanide is the
active antiamebic substance.
-The mechanism of action is unknown.
- Does not produce serious adverse effects but flatulence is common
with occasional nausea, abdominal cramps and rashes. Not recommended
for pregnancy.
Other Antiprotozoal drugs:
Pentamidine- an aromatic diamidine formulated as an isethionate salt. Only
administered parenterally.
- Clinically
used
to
treat
Pneumocystosis
(Pulmonary
and
extrapulmonary) infections caused by Pneumocystis jiroveci; African
Trypanosomiasis (Sleeping sickness); and Leishmaniasis.
- Highly toxic drug which may cause severe hypotension, tachycardia
and dyspnea if intravenously given; and severe pain with possible
sterile abscesses if given IM.
Sodium stibogluconate- pentavalent antimonials are generally considered
first line agents (IV or IM) for cutaneous and visceral leishmaniais (excpt in
most parts of India).
- Mechanism of action: Unknown
- Adverse effects: G.I. symptoms, fever, headache, myalgias, arthralgias
AntiHelminthic Drugs

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1.
Albendazole/
Mebendazoledrug
of
choice
for
helminth
infections( pinworm, hookworm, ascaris, trichuris, strongyloides infections
and cysticercosis)
- A benzimidazole carbamate. Undergoes 1st pass metabolism in the
liver & is converted to the active metabolite albendazole sulfoxide.
- Inhibits microtubule synthesis in nematodes and have larvicidal
effects in hydatid disease, cysticercosis, ascariasis and hookworm infections;
and ovicidal effects in ascariasis, ancylostomiasis and trichuriasis.
2. Praziquantel- synthetic isoquinoline- pyrazine derivative which is effective
in the treatment of schistosome infections, and most other trematode and
cestode infections including cysticercosis.
- Increases the permeability of trematode & cestode cell membranes to
calcium, resulting in paralysis, dislodgement and death.
3. Diethylcarbamazine citrate- a synthetic piperazine derivative which is the
drug of choice in the treatment of filariasis( Wuchereria bancrofti, Brugia
malayi, Brugia timori) & loiasis (loa loa).
-Immobilizes microfilariae and alters their surface structure, displacing
them from tissues & making them more susceptible to destruction by host
defense mechanisms. The mode of action against adult worms is unknown.
Antiviral agents
Agents to treat Herpes Simplex Virus (HSV) & Varicella zoster virus
(VZV) infections:
Acyclovir( Valacyclovir and Famciclovir)- Acyclic guanosine derivative with
clinical activity against HSV-1, HSV-2 and VZV.
- Requires 3 phosphorylation steps for activation: ( Converted to
Monophosphate by virus thymidine kinase; & then to the di- &
triphosphate compounds by host cell enzymes).
- It inhibits viral DNA synthesis by 2 mechanisms: Competition with
deoxyGTP for the viral DNA polymerase, resulting in binding to the DNA
template as an irreversible complex; and chain termination following
incorporation into the viral DNA.
Agents to treat Cytomegalovirus (CMV) Infections:
Ganciclovir- an acyclic guanosine analog that requires activation by
triphosphorylation before inhibiting viral DNA polymerase.
- Phosphorylation is catalyzed by the virus- specified protein kinase
phosphotransferase UL97 in CMV- infected cells. The activated
compound competitively inhibits viral DNA polymerase & causes
termination of viral DNA elongation.
- Most common adverse effect: Myelosuppression. Nausea, diarrhea,
rash, fever, insomnia & peripheral neuropathy.
Antiretroviral agents
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Zidovudine- (Azidothymidine) a deoxythymidine analog that has been shown


to decrease the rate of clinical disease progression and prolong survival in
HIV- infected individuals.
- Acts by competitive inhibition of HIV-1 reverse transcriptase;
incorporation into the growing viral DNA chain causes premature chain
termination due to inhibition of binding with the incoming nucleotide.
- Most common adverse effect: Myelosuppression resulting in macrocytic
anemia or neutropenia. G.I. intolerance, headaches and insomnia.
AntiHepatitis Agents
Interferon alfa- Induces intracellular signals following binding to specific
cell membrane receptors, resulting in inhibition of viral penetration,
translation, transcription, protein processing, maturation and release; as well
as increased host expression of major histocompatibility complex antigens,
enhanced phagocytic activity of macrophages & augmentation of the
proliferation and survival of cytotoxic T cells.
LamivudineInhibits HBV DNA polymerase and HIV reverse transcriptase by competing
with deoxycytidine triphosphate for incorporation into the viral DNA,
resulting in chain termination.
Anti- influenza Agents
Oseltamivir- Neuraminidase inhibitor, an analog of sialic acid, interferes
with release of progeny influenza virus from infected host cells, thus halting
the spread of infection within the respiratory tract.
-Competitively and reversibly interacts with the active enzyme site to
inhibit viral neuraminidase activity at low nanomolar concentrations.
Inhibition of viral neuraminidase results in clumping of newly released
influenza virions to each other and to the membrane of the infected cell.
- Adverse effects: Transient nasal and throat discomfort, cough,
bronchospasm.
Antifungal agents
Amphotericin B- forms pores in fungal membranes which contain
ergosterol
Azoles- Blocks fungal P450 enzymes & interferes with Ergosterol synthesis
Echinocandins- Blocks B- glucan synthase

EnD

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