Pharmacodynamics is the study of how drugs affect the body. Drugs bind to their target to elicit a response, common targets include: Ion channels: e.g., calcium channel blockers prevent calcium entry into excitable cells Enzymes: enzyme inducers and inhibitors lead to many clinically significant drug interactions Receptors: e.g., beta blockers block β1-adrenoceptors in the heart, preventing binding of adrenaline and noradrenaline Transporters: e.g., amiodarone strongly inhibits P-glycoprotein (P-gp), a transmembrane efflux pump. Inhibition increases serum concentrations of P-gp substrates such as apixaban. Ion channels Ion channels facilitate flow of ions across lipophilic cell membranes, performing essential functions such as neurotransmitter release, hormone secretion and maintaining electrolyte balance. Ion channels can be: Ligand gaged Mechanically gated Voltage gated Always open Example: Amlodipine is a calcium channel blocker (CCB). CCBs inhibit the transmembrane influx of calcium ions into cardiac and vascular smooth muscle through blockade of voltage-dependent L-type calcium channels, leading to vasodilation. Created in BioRender. Boucher, M. (2025) https://BioRender.com/lbx91kq Fig 1: Types of ion channels Enzymes Enzymes are proteins which catalyse the conversion of substrates into products. Example: Ramipril, an angiotensin converting enzyme (ACE) inhibitor, blocks the conversion of angiotensin I to angiotensin II. Since angiotensin II is a potent vasoconstrictor, ACE inhibition results in vasodilation. Drug metabolising enzymes The cytochrome P450 (CYP450) system is the most important enzyme group for drug metabolism. CYP3A4 is the most common isoenzyme. Inducers increase enzyme activity → increased metabolism of substrates. Example: rifampicin induces CYP 1A2, 2B6, 2C8, 2C9, 2C19, and 3A4. The combined oral contraceptive (COC) is a substrate for CYP3A4 and levels of COCs are reduced with concomitant therapy. Patients on oral contraceptives should be advised to use alternative, non-hormonal methods of birth control during rifampicin therapy. Inhibitors decrease enzyme activity → reduced metabolism of substrates. Example: Clopidogrel (a prodrug) is metabolised by CYP2C19. Use of strong or moderate CYP2C19 inhibitors (e.g., omeprazole, fluconazole) may result in reduced drug levels of the active metabolite and therefore is discouraged. Created in BioRender. Boucher, M. (2025) https://BioRender.com/e2uqnxw Fig 2: Inhibitors and inducers of CYP450 Receptors Receptors recognise and bind to ligands, leading to a conformational change in the receptor followed by a series of biochemical reactions. Only substances that fit the receptor can bind to it, often described as the “lock and key” analogy, ligands are the keys and the receptors are the locks. Ligands can be exogenous (drugs) or endogenous (hormones and neurotransmitters). When drugs bind a receptor they can elicit different responses: Agonists: activate receptors (full, partial, or inverse). Full agonist: maximum response (e.g., salbutamol at β2 receptors). Partial agonist: weaker response (e.g., buprenorphine at μ-opioid receptors). Inverse agonist: opposite effect to agonist. Antagonists: block receptor function Competitive (reversible): competes for the binding site with the agonist and can be overcome with high levels of agonist. (e.g., naloxone treats opioid toxicity by binding opioid receptors, preventing opioids from binding) Non competitive (irreversible): alteration of binding site means that agonist can no longer bind (e.g. ketamine alters the binding site at NMDA receptors so glutamate cannot bind, leading to blockade of pain signals) Created in BioRender. Boucher, M. (2025) https://BioRender.com/ogu6i8u Fig 3: Ligands and receptors Transporters Transporters are proteins which translocate exogenous (drugs) and endogenous compounds across membranes. Some drugs target specific transporters in the body to elicit their pharmacological effect. Example: Selective serotonin reuptake inhibitors (SSRIs) (e.g. fluoxetine) inhibit presynaptic reuptake of serotonin at the serotonin transporter, increasing the amount of serotonin in the synaptic cleft to bind to serotonin receptors at postsynaptic neurons The P-glycoprotein (p-gp) efflux pump is an ATP-dependent drug efflux pump which reduces drug accumulation in cells and is clinically significant in drug interactions. Drugs can be P-gp pump substrates, as well as inhibitors or inducers of the P-gp pump. Induction reduces drug concentrations of substrates Inhibition increases drug concentrations of substrates Common inducers and inhibitors of the P-gp pump include: Example: digoxin is a P-gp substrate. P-gp inhibitors increase digoxin concentrations raising the risk of toxicity. Created in BioRender. Boucher, M. (2025) https://BioRender.com/26hngd5 Fig 4: Inhibitors and inducers of P-gp References Gudin J, Fudin J. A Narrative Pharmacological Review of Buprenorphine: A Unique Opioid for the Treatment of Chronic Pain. Pain Ther. 2020 Jun;9(1):41-54. doi: 10.1007/s40122-019-00143-6. Epub 2020 Jan 28. PMID: 31994020; PMCID: PMC7203271. Rifampicin 300 mg Capsules – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 11/10/24 Inhibitors and inducers of P-glycoprotein drug efflux – UpToDate Digoxin 0.125 Tablets – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 14/10/24 Do you think you’re ready? Take the quiz below Pro Feature - Quiz Pharmacodynamics Question 1 of 3 Submitting... 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