Pharmacodynamics Overview

Pharmacodynamics

• Pharmacodynamics studies how drugs interact with the body to produce their effects.
• Drugs act through either receptor or non-receptor mechanisms.

Receptor-mediated Mechanism

• Receptors are specific cellular structures that interact with drugs to cause a pharmacological effect.
• Drugs acting on receptors can be agonists or antagonists.
• Agonists: bind to the receptor, have affinity, and produce an effect (efficacy).
• Antagonists: bind to the receptor, block the effect of agonists, and do not produce their own effect.

Types of Agonists

• Full agonists: produce maximal efficacy.
• Partial agonists: produce less than maximal efficacy and block the effects of full agonists.
• Inverse agonists: bind to the receptor to decrease the constitutive activity (negative efficacy).

Types of Antagonists

• Pharmacological antagonists: bind to the receptor without activating it, preventing agonist activation.
  • Competitive: bind reversibly; can be displaced by increasing agonist concentration. Duration depends on relative concentration of agonist and antagonist.
  • Irreversible: bind irreversibly; cannot be displaced by increasing agonist concentration. Duration depends on the rate of new receptor synthesis.
• Physiological antagonists: bind to different receptors, causing opposing effects.
• Chemical antagonists: bind to the agonist drug itself.

Signal Transduction Systems

• Ligand-gated ion channel receptor: drug binding to the ion channel receptor causes ion flux.
• G-protein-coupled receptor: agonist binding activates a G protein which produces a response.
• Catalytic receptor (enzyme-linked receptor): e.g., insulin receptor; binding to the extracellular component stimulates the intracellular component and tyrosine kinase enzymes.
• Intracellular receptor: e.g., corticosteroids; the drug crosses the cell membrane and binds to a cytoplasmic receptor.

Non-receptor Mediated Mechanism

• Drugs act directly on enzymes (e.g., choline esterase inhibitors).
• Drugs act on plasma membranes (e.g., digoxin inhibiting Na+-K+ ATPase).
• Drugs act through physical means (e.g., lubricants).
• Drugs act through chemical mechanisms (e.g., antacids neutralizing HCl).

Dose-response Relationship

• Efficacy: the ability of the drug-receptor complex to produce a response.
• Maximal efficacy: the maximum response a drug can produce.
• Potency: the amount of drug needed to produce a specific effect.
• ED50: the dose that cures 50% of cases.
• LD50: the dose that kills 50% of animals (measures toxicity).

Therapeutic Index

• The ratio between LD50 and ED50.
• A larger therapeutic index indicates greater safety—the drug is less toxic.
• Drugs with a narrow therapeutic index need careful dosing.

Therapeutic Window

• The safe dosage range between the minimum effective therapeutic dose and the minimum toxic dose.
• Used to determine acceptable plasma levels for drug regimens.

Adverse Drug Reactions

• Classified into types based on their characteristics.
  • Type A are dose related, associated with the pharmacological action, predictable, and often low mortality.
  • Type B reactions are non-dose related, not associated with pharmacology, unpredictable, and often have high mortality.
  • Type C are chronic effects, dose-related, and time-related.
  • Type D are delayed reactions, time-related.
  • Type E occur after the drug is discontinued, and are called withdrawal effects.

Drug Allergy

• Classifies drug allergies based on immune response types. The three types of immune-mediated drug allergy are Type I, Type II, and Type III. There is no Type IV drug allergy.