dynamics & kinetics
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| pharmacodynamics | actions of drug on body; receptors are inactive until ligand (proteins, DNA, enzymes) binds; high and selective affinity needed
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| more pharmacodynamics | drug + receptor --> drug-receptor complex -->effect
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| 4 types of receptors | ligand gated ion channels; g-protein coupled receptors; enzyme linked; intracellular
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| Ligand-gated ion channels | change in concentration of some types of ions; ex: cholinergic nicotinic receptors
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| G protein coupled receptors | spans membranes 7X, binds GDP or GTP-large protein family; ex: alpha and beta adrenoreceptors; protein phosphorylation
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| Enzyme-lined receptors | ex: insulin receptors; protein and receptor phosphorylation
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| Intracellular receptors | Ex: steroid receptors; altered gene expression
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| Effectors | molecules that translate the drug-receptor interaction into a change in cellular activity; enzymes (adenylyl cyclase, PLC) or the receptor itself
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| Second messengers | cAMP (protein phosphorylation); IP3 (regulates Ca2+ concentration); DAG (regulates Ca & activates PKC); they work once they are phosphorilated
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| Gs proteins | stimulates adenylyl cyclase & Ca channels
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| Gp proteins | activates phospholipase & signals transduction pathways
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| Gi proteins | inhibitory; inactivates adenylyl cyclase
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| Drug-receptor binding | measures the fraction of receptors bound against drug concentration; affinity of drug (Kd) & number of receptors in system (B max)
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| Dose-response relationship | measures drug response against increasing concentrations of drug; efficacy (E max), potency (EC50), median effective dose (ED 50), and median lethal dose (LD 50)
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| Occupancy theory | the study of pharmacodynamics is based on the concept of drug-receptor binding
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| Potency | amount of drug needed to produce given effect; compare the dose that causes 50% of max effect (EC 50)-the lower the EC 50 the more potent the drug
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| Efficacy | max effect of a drug; depends on number of drug receptor complexes formed
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| Antagonists | favor inactive formation when bound; competitive-irreversibly bound, affects POTENCY, not efficacy; noncompetitive-binds to an allosteric site-reduces EFFICACY, not potency
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| Quantal dose-response curve | demonstrates average effect of a drug as a function of its concentration in a population of individuals; ED50, TD50, LD50
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| Therpeutic Index | safety of the drug; = TD50/ED50; the narrower the distance between 2 curves, the smaller the therapeutic window
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| Effectiveness of drug therapy factors | concentration of drug, metabolic rate, frequency of dosing, food-drug interactions, drug-drug interactions, absorption rate, genetics, excretion rate, half-life of drug, changing medical conditions
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