Pharmacology intro key principles.pdf

Itrlab.com Pharmacology Dr Sarah Trinder [email protected] 30AY04 Outline ▪ What is pharmacology? ▪ Key principles for pharmacology – how drugs work! ▪ Types of drugs ▪ How drugs interact with receptors Pharmacycol.org What is pharmacology? ▪ The study of medicines and drugs, including their ac...

Itrlab.com Pharmacology Dr Sarah Trinder [email protected] 30AY04 Outline ▪ What is pharmacology? ▪ Key principles for pharmacology – how drugs work! ▪ Types of drugs ▪ How drugs interact with receptors Pharmacycol.org What is pharmacology? ▪ The study of medicines and drugs, including their action, their use, and their effects on living systems. ▪ Pharmacodynamics – ‘branch of pharmacology concerned with the action of drugs on the physiology or pathology of the body’ ▪ Pharmacokinetics – ‘branch of pharmacology concerned with movement of drugs within the body’ “But, will it cure me?” ▪ Therapy ▪ A drug that attempts to remediate a condition. ▪ Many do not rectify the underlying physiological cause. ▪ Diuretic for hypertension ▪ Insulin for diabetes ▪ Cure ▪ A drug which removes the underlying physiological cause of a condition. ▪ Anti-biotic, anti-fungal ▪ What about anti-cancer agents? Drug names ▪ Always us the generic name ▪ Ibuprofen, paracetamol (lowercase unless start of a sentence!) ▪ Do not use brand names ▪ Neurofen®, Panadol® ▪ Do not use chemical names ▪ (RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid How do drugs work? ▪ Bind to biological molecules ▪ Proteins – most common target ▪ Receptors ▪ Enzymes ▪ Ion channels ▪ Protein carriers ▪ Lipids – lipoprotein targets in viral infections ▪ Nucleic acids – anti cancer agents Drug binding ▪ Agonist – a molecule that can bind and activate receptor, eliciting a response ▪ Antagonist – a molecule that can bind to a receptor but cannot activate it. ▪ Affinity – attraction ▪ Efficacy – ability to produced a desired result Rang & Dale’s Pharmacology, 8th Ed Drug targets Salbutamol – β2 agonist Atenolol – β1 antagonist Nifedipine – Ca2+ channel antagonist Benzodiazepines Rang & Dale’s Pharmacology, 8th Ed Ion channel receptors Nifedipine – calcium channel blocker for hypertension Nitrazepam – benzodiazepine GABA receptor modulator G protein coupled receptors Phenylephrine - 𝝰1 adrenoceptor agonist - decongestant localized vasodilation Propranolol – β adrenoceptor antagonist - treatment of hypertension To look up types of GPCRs Rang & Dale’s Pharmacology 9th Ed Enzyme linked receptors Insulin and cytokines given as therapy for conditions. Nuclear receptors Steroid hormones and glitazone drugs, eg rosiglitazone (oral hypoglycaemic) Drug targets Captopril – ACE inhibitor Flurouracil – replaces uracil – anti-cancer L-dopa – converted to dopamine SSRI – inhibits reuptake of 5-HT Lithium (Li+) – mood stabiliser Rang & Dale’s Pharmacology, 8th Ed Definitions ▪ Emax – maximal response a drug can produce ▪ EC50 – concentration of drug required to produce 50% of maximal response ▪ ED50 – dose of drug required to produce 50% of maximal response ▪ Kd – dissociation constant = concentration of ligand at 50% of receptor occupancy ▪ Kd = [drug][receptor] [drug/receptor complex] Concentration-response curve Emax EC50 of histamine on GP heart = 9x10-7 mol/l = 900nM EC50 of ACh on frog rectus muscle = 1x10-5 mol/l = 10μM Rang & Dale’s Pharmacology, 8th Ed Types of antagonists Type of antagonist – competitive, reversible Rang & Dale’s Pharmacology, 8th Ed Type of antagonist – competitive, irreversible Type of antagonist – non-competitive Type of antagonist – competitive, irreversible Rang & Dale’s Pharmacology, 8th Ed Allosteric modulation Rang & Dale’s Pharmacology, 8th Ed Types of allosteric modulation Rang & Dale’s Pharmacology, 8th Ed Glutaminase GlnT Gln Glu GAD Benzodiazepines (BDZ) GAT1 GABA GABAergic neuron GABA BDZ α2 γ2 α2 β2 Clα2 β2 α2 γ2 β2 Cl- Cl Cl- β2 GABA α2 ClCl- ClClClCl- γ2 Cl- β2 α2 β2 GABA + BDZ Partial agonist - efficacy In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. Inverse agonist- the effects Inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agonist but can block the activity of either. Learning outcomes ▪ Explain what a drug is. ▪ Appropriately use the terms affinity & efficacy ▪ List some potential drug targets. ▪ Identify the Emax & EC50 from a concentration response curve. ▪ Compare and contrast competitive vs non-competitive and reversible vs non-reversible antagonism. ▪ Explain the different types of allosteric modulation.