Pharmacology Lecture: Pharmacodynamics

Study Notes

Pharmacodynamics examines how drugs exert their therapeutic effects through interactions with receptors, enzymes, and proteins.
Mechanisms of action include receptor-mediated and non-receptor-mediated actions.

Non-receptor mediated actions:
- Physical Action: Involves physical processes like adsorption (e.g., activated charcoal treating diarrhea).
- Chemical Action: Involves chemical reactions such as neutralizing gastric acid with antacids.
- Enzymatic Action: Drugs can affect enzyme activity (e.g., Neostigmine inhibits acetylcholinesterase).
Receptor-mediated actions:
- Receptors are macromolecules that selectively bind ligands (drugs) and initiate cellular responses.
- Drug-receptor interactions follow a "lock and key" model based on affinity and intrinsic activity.

Membrane Receptors:
- Ligand-gated ion channels: Open in response to ligand binding; regulate ion flow (e.g., nicotinic acetylcholine receptors).
- G Protein-Coupled Receptors (GPCRs): Activate G proteins to trigger intracellular signaling pathways (e.g., β1 receptors).
- Enzyme-linked receptors: Include protein tyrosine kinases that influence cellular functions (e.g., insulin receptors).
Intracellular Receptors:
- Located in the cytoplasm; require lipid-soluble ligands that enter the cell (e.g., steroid hormone receptors).

Agonists: Bind to receptors producing a biological response; characterized by both affinity and intrinsic activity.
- Full Agonist: Produces maximal response.
- Partial Agonist: Generates a lesser effect than a full agonist at maximum dosage.
Antagonists: Bind to receptors but do not activate them, preventing agonist actions.
- Reversible (Competitive): Competes with agonist for binding; can be overcome with increased agonist concentration.
- Irreversible (Non-competitive): Binds covalently, preventing agonist action permanently.

Synergism: Combined effect of drugs is greater than their individual effects.
Additive Effect: The total effect is the sum of individual actions.
Antagonism: One drug counteracts the action of another.

Quantal Dose-Response Curve:
- Plots dose against percentage of subjects responding, identifying metrics like ED50 and LD50.
- Therapeutic Index (TI): Indicates drug safety; TI = LD50 / ED50.
Graded Dose Response Curve:
- Shows the relationship between drug dose and pharmacological response, culminating in maximum efficacy (Emax).

Potency: Refers to the dose required to elicit a response (e.g., 1 mg of bumetanide vs. 50 mg of frusemide).
Efficacy: Reflects a drug's ability to produce a response upon receptor binding.

Individual Factors: Body weight, age, sex, species/race, diet/environment, genetic factors.
Administration Variables: Route of administration and dose impact drug effects.
Repeated Dosing Effects:
- Cumulation: Accumulation of drugs leading to toxicity (e.g., digoxin).
- Tolerance: Increasing doses required for the same effect due to repeated use.
  - Natural Tolerance: Species-level insensitivity (e.g., rabbits and atropine).
  - Acquired Tolerance: Develops with continuous exposure (e.g., barbiturate tolerance).
- Tachyphylaxis: Rapid onset of tolerance (e.g., ephedrine after repeated doses).