Pharmacodynamics I and II Quiz

Objectives of Pharmacodynamics

• Define receptors and interaction of drugs with target cell molecules.
• Outline receptor-mediated signal transduction mechanisms.
• Explain drug dose-response relationships through graded and quantal curves.
• Differentiate between potency, efficacy, and affinity; illustrate these on dose-response curves.
• Distinguish full, partial, and inverse agonists.
• Clarify concepts of synergism, potentiation, and additive effects.
• Differentiate competitive and non-competitive antagonists.
• Define TD50, LD50, ED50 and the relationship between ED50 and EC50.
• Conceptualize therapeutic window; calculate therapeutic index.
• Define desensitization, tolerance, and receptor regulation (up/down regulation).

Receptors and Drug Interaction

• Receptors mediate therapeutic and toxic drug effects by interacting with endogenous molecules.
• Drug-receptor binding alters cellular and organ function; receptors are specific cellular components.
• Ligands interacting with receptors include neurotransmitters, ions, hormones, and drugs.

Affinity and KD

• KD represents the ligand concentration for 50% receptor occupancy; lower KD indicates higher affinity.
• Intrinsic activity measures a drug's ability to generate a cellular response upon receptor binding.

Receptor Properties

• Receptors are physiological control points, regulated by endogenous molecules.
• Drugs cannot create new cellular functions; they modify existing physiological processes.
• Drugs synthesize with aims to influence biological processes via receptor interaction.

Drug-Receptor Interaction

• Full agonists produce maximum response (100% intrinsic activity).
• Partial agonists bind strongly but elicit weaker responses than full agonists.
• Antagonists block receptor activation, showing low to no intrinsic activity.

Dose-Response Relationships

• Drug response increases incrementally with low doses; higher doses plateau at a maximum response.
• Graded response curves demonstrate a dose-dependent relationship, with a defined threshold and ceiling effect.

Two-State Receptor Theory

• Proposes that ligand binding changes receptor state from inactive to active, eliciting biological responses.
• Agonists and inverse agonists selectively bind to receptor states, generating different cellular effects.

Efficacy and Potency

• Efficacy refers to the maximum effect achievable by a drug regardless of dosage.
• Potency is the required dosage to produce a specified effect (e.g., ED50 for 50% response).

Competitive vs Non-Competitive Antagonism

• Competitive antagonism involves agonist-antagonist competition for the same binding site, shifting response curves to the right.
• Non-competitive antagonism occurs when antagonists bind irreversibly, reducing the maximum response achievable.

Therapeutic Index

• Therapeutic index (TI) is the ratio of LD50 (median lethal dose) to ED50 (median effective dose).
• A higher TI indicates a safer drug; a gap between therapeutic effect and toxic effect is crucial for safety.

Regulation of Receptors

• Regulation involves synthesis, degradation, covalent modifications, and interactions with other proteins.
• Receptor desensitization leads to reduced responsiveness after continued stimulation (tachyphylaxis).
• Upregulation occurs with reduced agonist presence or prolonged antagonist use; downregulation follows overstimulation.

Drug Interactions

• Synergism: Combined effects of two drugs exceed their individual effects.
• Additive effects: Combined effects equal the sum of individual drug effects.
• Potentiation: One drug enhances the effect of another without eliciting a response alone.