Receptor Concept & Drug-Receptor Interaction

Receptor Concept & Drug-Receptor Interaction

1. Pharmacodynamics — definition and scope

• Pharmacodynamics is the study of the biochemical, cellular and physiological actions of drugs, including the molecular mechanisms by which these actions are achieved — "what the drug does to the body" (G&G 14e Ch.3, p.43; KDT 8e Ch.4, p.45).
• Pharmacodynamics encompasses the complete action→effect sequence, the dose–effect relationship, and the modification of one drug's action by another (drug interactions, synergism, antagonism) (KDT 8e Ch.4, p.45).
• The emergence of pharmacology as a science dated from the shift from describing what drugs do to explaining how they work — credited to Paul Ehrlich, who insisted drug action is explicable by conventional chemical interactions, dispelling "vital forces" (R&D 10e Ch.2, p.1).
• Ehrlich's dictum: "Corpora non agunt nisi fixata" — "a drug will not work unless it is bound." Pharmacological effects require non-uniform (bound) distribution of the drug; if randomly distributed, the chance of interaction with any specific cellular molecule would be negligible (R&D 10e Ch.2, p.2).
• Even very low concentrations involve enormous molecular numbers — one drop at 10^-10 mol/L still contains ~3 × 10⁹ molecules; some toxins (e.g. diphtheria toxin) act with such precision that a single molecule taken up by a cell can kill it (R&D 10e Ch.2, p.2).
• Basic tenet: drugs (except gene-based therapies) do not impart new functions; they only alter the pace (rate or magnitude) of ongoing physiological/biochemical processes (KDT 8e Ch.4, p.45; G&G 14e Ch.3, p.43).

Basic types of drug action (KDT framework)

• Stimulation — selective enhancement of activity of specialised cells (e.g. adrenaline stimulates heart; pilocarpine stimulates salivary glands). Excessive stimulation is often followed by depression (e.g. picrotoxin → convulsions then coma) (KDT 8e Ch.4, p.45).
• Depression — selective diminution of activity (e.g. barbiturates depress CNS; quinidine depresses heart; omeprazole depresses gastric acid secretion). Many drugs stimulate one cell type but depress another (e.g. ACh stimulates intestinal smooth muscle but depresses SA node) — so most drugs cannot be simply labelled stimulant or depressant (KDT 8e Ch.4, p.45).
• Irritation — nonselective, often noxious effect on less specialised cells; strong irritation → inflammation, corrosion, necrosis (KDT 8e Ch.4, p.45).
• Replacement — use of natural metabolites/hormones/congeners in deficiency states (e.g. levodopa in parkinsonism, insulin in diabetes, iron in anaemia) (KDT 8e Ch.4, p.45).
• Cytotoxic action — selective toxicity on parasites/cancer cells, sparing host cells (e.g. penicillin, chloroquine, zidovudine, cyclophosphamide) (KDT 8e Ch.4, p.45).