How Drugs Act I

 Definitions of pharmacology and drug.

 Financial considerations of pharmacology.
 Types of drugs such as sport enhancement and recreational.
 A drug is a chemical applied to a physiological system that affects its function in a specific
way.
 Drugs target proteins such as a receptor, enzymes, carriers and ion channels.
 Receptors as drug targets.
 Specificity- drugs bind to only certain targets.
 No drugs are completely specific in their actions- can lead to side effects.
 Dug targets- non-receptor- alcohol, ammonium hydroxide and plant sterols, receptors-
salbutamol, sildenafil and ibuprofen.
 Choosing the receptor allows drugs to target specific tissues.
 Specificity is due to drug binding to receptor- specific shapes.
 Lock and key- complementary shapes.
 Timecourse- the time drugs take to reach a receptor, binding rate constants,
activation/inactivation of receptor and time for drug to be removed from tissues.
 Drug-receptor interactions are dynamic.
 Definitions of specificity, affinity, dissociation constant.
 The study of drug-receptor interactions is called pharmacodynamics.
 Abbreviations and law of mass action and equilibrium equation for equilibrium dissociation
contact.
 Binding is not All specific- semilog plot.
 Definitions of agonist, antagonist, inverse agonist, efficacy and potency.
 Drug effect on spectrum.
 Agonism- if binding is linearly proportional to effect 50% = 50% binding- Kd.
 Competitive antagonism, non-competitive, inverse agonism,
 Reverse binding model.
 Responses are receptor dependent.
 Four main types of effector systems- ligand-gated ion channels, G-protein coupled receptors,
kinase-linked receptors and nuclear receptors.
 Responses are receptor dependent.
 Structure of ligand hated ion channels and electrochemical equilibrium (Nerst equation).
 Multiple drug binding sites within an ion channel.
 Multiple GPCR subtypes- Family, receptors and structural features. Family- rhodopsin,
secretin/glucagon receptor and metabolic glutamate receptor/calcium sensor.
 Alpha sub units and beta of G proteins.
 Effector cascades:
 Convergence- multiple G-proteins affect one target.
 Divergence- single G-proteins affect multiple targets.
 Example 1: beta adrenoreceptor (GalphaS).
 Summary of kinase receptors- mainly involved in growth differentiation and homeostasis.
 The MAP kinase pathway.
 Summary of nuclear receptors- cytoplasmic and nuclear.
 48 soluble receptors that sense lipid and hormonal signals and modulate gene transcription.
 Tachyphylaxis- short timecourse.
 Tolerance- long timecourse.
 The roles of drugs in altering gene expression.
 Tolerance and dependence- linked with drug effect.
 Treatment of dependence- cues associated with drug withdrawal and cues associated with
drug taking.
 Classification of ADR (adverse drug reactions)- maybe be related or unrelated to
pharmacological property.
 Type A: augmented adverse reactions related to dose and susceptibility, often dose
dependent, may be reversed by dose reduction and drug toxicity may be due to synergistic
effect with a co-administered drug.
 Examples of ADR related to pharmacological property- all antibiotics and antiglycaemic
(insulin).
 Type B- bizarre reaction with side effects and could be due to an enzyme
inhibition/activation.
 Examples of ADR unrelated to pharmacological property- analgesic like paracetamol
(hepatotoxic) and antibiotics such as penicillin (anaphylaxis).