Pharmacodynamics

Pharmacodynamics Important Notes

1. Therapeutic index
   • Therapeutic index helps in the assessment of the safety of drugs
   • The larger the therapeutic index, the safer the drug
   • Penicillin has a larger therapeutic index
2. Affinity
   • Affinity is the ability of the drug to bind to a receptor
3. Agonist
   • A drug that initiates pharmacological reaction after combining with receptors
   • Agonist has
     • More affinity
     • High intrinsic activity
4. Antagonist
   • A drug that bonds to receptors but it is not capable to produce any action
   • Antagonist produces receptor blockade
   • Antagonist has
     • Affinity same as an agonist
     • Poor intrinsic activity
5. Partial agonist
   • A drug with
     • Affinity equal to agonist
     • Less intrinsic activity
6. Additive effect
   • Two drugs with the same effect produce an effect that is equal to the sum of the effects of individual drug
   • Example: ephedrine+aminophylline in bronchial asthma
7. Synergism
   • Two drugs with the same effect produce an effect that is greater than the sum of the effects of individual drug
   • Example: procaine + adrenaline
8. Antagonism

Read And Learn More: Pharmacology Question and Answers

Pharmacodynamics Long Essays

Question 1. Describe the principles & mechanism of action of drugs with examples. Add a note of enzyme induction.

Answer:

Principle:

• Drugs produce their effects by interacting with the physiological systems of the organisms.
• By such interactions, drugs modify the rate of functions of various systems but do not change the basic functions.

Types of Drug Action:

Mechanism of drug action:

• Physical action.
  • Glucocorticoids
    • The action of drug results from its physical properties.
    • Adsorption-activated charcoal in poisoning.
    • Mass of the drug – bulk laxatives like psyllium.
    • Osmotic property – osmotic diuretics, mannitol.
    • Radioactivity – Radioiodine 1131
• Chemical action.
  • Drugs interact according to simple chemical reactions.

• Through enzymes:
  • Drugs can either increase/stimulate or decrease/inhibit enzymatic action.

• Through receptors.
  • Drugs may act by interacting with receptors in the body.
  • Receptors have specificity & selectivity.
  • Similarly, drugs are relatively selective.
  • Receptors may be present in the cell membrane, in the cytoplasm or in the nucleus.
  • Example: Adrenaline binds at adrenergic receptors.
• Through ion channels.
  • Drugs may interfere with the movement of ions across specific channels
  • Example: calcium channel blockers.
• By altering metabolic processes.
  • Drugs may alter the metabolic pathway in the mi- cro-organism resulting in the destruction of the micro-organisms.
  • Example: Sulphonamides interfere with bacterial folic acid synthesis.

Enzyme induction:

• The synthesis of microsomal enzymes, mainly cytochrome P450 can be enhanced by certain drugs & environmental pollutants.
• This is called enzyme induction.
• It speeds up the biotransformation of the inducing drug.
  • Example: phenobarbital, rifampicin, and alcohol.
• It involves microsomal enzymes in the liver as well as other organs.
• Increase the rate of metabolism by 2-4 fold.
• Induction takes 4-14 days to reach the peak.

Enzyme induction Consequences:

• Decreased intensity of action of drugs that are inactivated by metabolism.
• Increased intensity of action of drugs that are activated by metabolism.
• Development of tolerance to drugs.
• May result in toxicity & therapeutic failure.
• May result in diseases
  • Example: Antiepileptics enhance the breakdown of Vit. D – re- sulting in osteomalacia.
• Intermittent use of an inducer may interfere with the adjustment of the dose of another drug.
• Some endogenous substrates are metabolized faster.

Enzyme induction Uses:

• Congenital nonhemolytic jaundice.
• Cushing’s syndrome.
• Chronic poisoning.
• Liver disease.

Question 2. Discuss factors modifying drug action with examples.

Answer:

Factors Modifying Drug Action:

• Drug Factors:

1. Route of administration.

• It may modify the speed & intensity of drug response.
• Example: Magnesium sulfate.

2. Presence of another drug.

• Drugs may interact with each other & modify the response.
  • Example: Hydralazine + propranolol used in hypertension.
• Succinylcholine – induces arrhythmias in digitalized patients.

3. Cumulation.

• When the rate of elimination of the drug is slower than the rate of administration, the drug gets cumulated in the body.
  • Example: Digoxin cumulates & results in toxicity.
• Chloroquine cumulate & cause retinal damage.

4. Dose.

• The dose of the drug can modify the drug response.
• An increase in dose increases drug response but only till the maximum is reached.
• Further increase in dose may lead to adverse effects.
• Example: Neostigmine.
  • Therapeutic doses-enhances muscle power
  • Higher doses cause muscle paralysis.

2. Sex.

• Smaller body size & hormonal effects in females may influence drug action.
• Example: Some antihypertensive drugs like clonidine may interfere with sexual functions in males but not in females.
• Some drugs are prohibited in pregnancy and lactation.

3. Species & race.

• Different response to drugs occurs in different species & races.

Drug Action Examples:

• Rabbits are resistant to atropine.
• Blacks require a high dose while mangoes require a low dose of atropine to dilate their pupils.

4. Body weight.

• It influences the concentration of the drug attained at the site of action.
• Accordingly, the dose is calculated as follows.

\(\text { Dose }=\frac{\text { Body weight }(\text { in } \mathrm{kg})}{70} \times \text { average adult dose }\)

. Drug Action Environment.

• Exposure to insecticides, carcinogens, and tobacco smoke induces drug metabolism.
• Food interferes with the absorption of drugs.
• Example: Tetracycline forms complexes with calcium. Present in food & are poorly absorbed.

6. Drug Action Genetic factors.

• Drug response is mediated genetically.
• It occurs due to variations in the amount of drug-metabolizing enzymes.
  • Example: Acetylation of drugs like INH, and hydralazine.
• Their acetylation differs in fast and slow acetylators.
• Slow acetylators may develop lupus erythematosus with hydralazine.

7. Emotional/psychological states.

• Doctor-patient relationship influences the drug response.
• Example: Use of placebo.

8. Pathological state.

• The presence of certain diseases influences drug response.

9. Tolerance.

• It refers to the requirement of a higher dose of a drug to produce a given response.
• It may be natural or acquired.
• Example: Tolerance develops to the sedative action of chlorpromazine.

10. Drug dependence.

• It is a drug response that always includes a compulsion to take a drug on a continuous or periodic basis in order to experience its psychic effects & sometimes to avoid the discomfort of its absence.
• Example: Alcohol, barbiturates.

Pharmacodynamics Short Essays

Question 1. Pharmacodynamics.

Answer:

Pharmacodynamics Definition:

Pharmacodynamics is the study of the actions of drugs on the body and their mechanisms of action.

Question 2. Placebo.

Answer:

Placebo is the inert dosage form with no specific biological activity.

• It is a dummy preparation
• It is a Latin word that means “I will please”.
• It may induce physiological responses.
  • Example: Placebo can release endorphins in the brain causing analgesia.
• It supplements pharmacological effects.
• Placebo effects are variable.
• Example: Placebo may induce sleep on the first night but not subsequently.

Placebo Uses:

• In clinical trials to minimize bias.
• To relieve subjective symptoms.

Factors Influencing it:

1. Patient factor.
   • Patients with neurotic symptoms respond well.
2. Drug factor.
   • The response can be affected by the drug presentation or route of administration.
   • Example: the color of the drug, injections.
3. Doctor factors.
   • The doctor’s personality and doctor-patient relationship may affect the response.
   • Example: Lactose, sucrose, injections of distilled water.

Question 3. Drug antagonism.

Answer:

Drug antagonism Definition:

One drug decreasing or inhibiting the action of another drug is called antagonism.

Drug antagonism Types:

Question 4. Drug Synergism.

Answer:

• When the action of one drug is increased or facilitated by another drug the combination is synergistic

Drug Synergism Types:

1. Additive
   • Effect of two drugs are in same direction Side effects of each may be different
   • But the combination is better-tolerated Effect of A + B = effect of A+ effect of B
   • Example: aspirin + Paracetamol- used as analgesic
2. Supra additive
   • The effect of the combination is greater than the individual effects
   • Effect of A+ B> effect of A+ effect of B
   • One component given alone is inactive
   • Example: acetylcholine + physostigmine

Pharmacodynamics Short Answers

Question 1. Drug synergism.

Answer:

When the action of one drug is increased or facilitated by another drug, the combination is synergistic.

Drug synergism Types:

1. Additive.
   • The effect of the two drugs is in the same direction.
   • Effect of A + B = effect of A+ effect of B.
     • Example: Aspirin + paracetamol – used as analgesic.
2. Supra-additive (potentiation)
   • The effect of the combination is greater than the individual effects.
   • Effects of A+B > effect of A+ effect of B.
     • Example: Acetylcholine + physostigmine.

Question 2. Drug antagonism.

Answer:

Drug antagonism Types:

1. Physical antagonism.
2. Chemical antagonism.
3. Physiological antagonism.
4. Antagonism at the receptor level.
   • Reversible.
   • Irreversible.
5. Non-competitive antagonism.

Question 3. Tachyphylaxis.

Answer:

Tachyphylaxis is the rapid development of tolerance.

• When a drug is given repeatedly at short intervals, tolerance develops & is known as tachyphylaxis.
• These drugs act by displacing noradrenaline from sympathetic nerve endings.
• There may be slow dissociation of the drug from the receptor, thereby blocking the receptor.
• Other mechanisms involve the internalization of receptors, homeostatic adaptation, etc.
• Example: Epinephrine given repeatedly in bronchial asthma may not give desired response.

Question 4. Bioassay.

Answer:

Bioassay is the determination of the amount of biological activity in a unit’s quality of preparation.

Bioassay Indications:

• When the chemical composition of a substance is not known.
• When the chemical assay method is too complex.
• When drugs differ in composition but have the same action.
• When the active principle is unknown.

Bioassay Methods:

• Direct comparison on the same tissues.
• Direct assay on several animals.
• Indirect assays.

Viva Voice:

1. The larger the therapeutic index the safer the drug
2. Drug efficacy refers to the maximal response that can be elicited by the drug
3. Drug potency refers to the amount of drug needed to produce a certain response