Introduction to the pharmacology and pharmaco therapy

Prof. M Aris Widodo Department pharmacology and Therapeutics

SCOPE PHARMACOLOGY BASIC PHARMACOLOGY CLINICAL PHARMACOLOGY CLINICAL TOXICOLOGY SOCIAL PHARMACOLOGY PHARMACO ECONOMIC PHARMACO GENETIC

Why you have to study pharmacology As a physician you will give a prescription explaining the administration, caution and warning of drug/s

To give medicine to the patients you have to consider proper diagnoses of the disease symptom and complain knowledge of pathofisiology of the disease laboratory result (renal, liver, heart function,others) pharmacodynami knowledge Pharmacokinetic knowlwdge

To make decision of medication

To give medicine to the patients you have to consider side effect of the drugs drugs and drugs interaction food and drugs interaction interaction of disease and drugs

EXPLAINING TO THE PATIENT

HOW MUCH HOW OFTEN WHAT FORM

Many entirely new class of drugs have bee introduced More than 20 molecules are invented every year as a Candidate for drugs / medication and approved by FDA Total expenditure of medication are increasing every year Self medication, by purchasing (prescription drugs) as OTC drugs 64 % antibiotics in the ward may be unnecessary Understanding patophisiology of disease and molecular Mechanism of the drugs Medication are more complex then before

Adverse drug reation are increase with increasing number of Drugs administered 15% of hospitalized patients experiene On adverse drug reaction 5% admission to hospitals are to manage adverse drug Reaction (ADR) Elderly patient may be especialy prone to develop ADR The effect of nutrient, polutant on human gen makes Different effect of drugs on ceretain indvidual /population Drugs nutrient interaction become importan to medical Services Drug may interact with alternative medicine (like herbal, Acupuncture, Massage, rubbing )

The progresive mprovment of patients diagnose capability doesnt seem to be match by improvement in therapeutic decision The therapeutic decision appear to be guided by personal impresion, tradition sentiment uncritial acceptance of advertising claim .

Irrational therapeutic decision

Need practicing therapeutic skill during Studying in medical school and after doing Practising as physician

Drugs therapy must consider efficacy suitability safety cost Medication / drugs therapy as a basic for rationale therpeutics

Rationale therapeutics means pecribing drugs to maximize the Chance of efficacy and minimize drug induce illness

Basic Pharmacological Concepts

Pharmacology = The study of the interaction between chemicals and a biological system. Pharmacodynamics = study of the biochemical and physiological effects of drugs and their mechanisms of action (the effects of the drug on the body)

Pharmacokinetics = deals with absorption, distribution, biotransformation and excretion of drugs (the way the body affects the drug with time)

Pharmacodynamics

Mechanisms of drug action

Non-specific drug action

general anaesthetics, osmotic diuretics, antacids

Alter transport systems

Ca antagonists, local anaesthetics, cardiac glycosides

Alter enzyme function

COX inhibitors, MAO inhibitors, AChE inhibitors

Act on receptors

Synaptic transmitter substances, hormones

Receptors

Proteins

Cell membranes Intracellular

4 main types:

Agonist gated transmembrane channels G-protein coupled Nuclear receptors that regulate gene transcription Linked directly to tyrosine kinase

Agonist

= a drug that is able to alter the conformation of a receptor in such a way that it elicits a response in the system Full Partial

Antagonist

= a drug that binds to a receptor but does not elicit a response from the system

Competitive

Irreversible

Transport Systems
Lipid cell membrane
barrier to hydrophyllic molecules transport in /out cell

Ion channels
voltage gated ligand gated

Active transport processes

Na+ pump Noradrenaline transport

Ion channels
Voltage and transmitter gated

Ca2+ channels in heart Na+, K+, Ca2+ - same basic structure Subtypes of each exist Examples:

Voltage gated

calcium antagonists local anaesthetics anticonvulsants antiarhythmics

Ca2+ in VSM & heart Na+ in nerves Na+ Na+

Transport systems

Active transport processes

transport substances against concentration gradient special carrier molecules require metabolic energy

Sodium Pump
expel Na+ ions Na+/K+ ATPase

cardiac glycosides some diuretics tricyclic antidepressants block reuptake

Transport systems

Noradrenaline transport

Enzymes
Catalytic proteins that increase the rate of chemical reactions Drug examples
Anticholinesterases Carbonic anhydrase inhibitors Monoamine oxidase inhibitors Cyclo-oxygenase inhibitors

 Agonist gated channels

receptors

Voltage gated channels

Transport systems

 G-protein coupled

receptors

G-protein coupled receptors

 Nuclear receptors that regulate gene transcriptio n

receptors

 Linked directly to tyrosine kinase

Receptor acts as an enzyme

receptors

Speed of responses

DRUG RECEPTOR INTERACTIONS

Intermolecular forces
- (40-110kcal/mol) - long lasting

Covalent bonds - two atoms share an electron

- desirable?
e.g. Alkylating agents (e.g. anticancer nitrogen mustards)

Ionic bonds - electrostatic attraction between

oppositely charged ions
- much weaker than covalent bonds (10 kcal/mol) - reversible

Hydrogen bonds - electrostatic attraction between

hydrogen atom and electronegative atom
- relatively stable (1-7 kcal/mol) reversible -

Affinity

measure of how avidly a drug binds to its receptor

Equilibrium constant KD KA concentration of drug that produses 50% of response

Intrinsic activity

Ability of a drug to elicit a response from a receptor

Agonist

= a drug that is able to alter the conformation of a receptor in such a way that it elicits a response in the system Full Partial

Antagonist

= a drug that binds to a receptor but does not elicit a response from the system

Competitive

Irreversible

Agonist vs antagonist
A g

K+1 R K-1

A g

Response

Ant

K+1

K-1

Ant

One tissue/organ can yield the full response range

Full agonist
Response

Graded dose-responses

Partial agonist

Agonist concentration [A]

Log dose-response curve

Full agonist

Response

Partial agonist

Log concentration [A]

Emax & ED50

Emax
Response

Emax

ED50

Log concentration [A]

I ED100

Effect of competitive antagonists

Agonist alone

Response

Increasing concentrations of competitive antagonist

Log [A]

Effect of irreversible antagonists

Agonist alone Low dose

Response

High dose

Log [A]