Pharmacokinetics, adverse drug reactions, drug interactions, prescribing in special populations, and toxicology essentials.
ACE inhibitors (ramipril, enalapril, lisinopril) and ARBs (losartan, candesartan, valsartan) inhibit the renin-angiotensin-aldosterone system. First-line for hypertension in <55 years/non-Black, heart failure (mortality benefit), diabetic nephropathy, and post-MI. ACE-i cause dry cough in ~10–15%; ARBs are the alternative. Both are teratogenic. Key trials: HOPE, SOLVD, ONTARGET.
Unwanted or harmful effects caused by medication at normal therapeutic doses. ADRs cause ~6.5% of UK hospital admissions and are the fourth leading cause of death in developed countries. Classified as Type A (dose-dependent, predictable) or Type B (idiosyncratic, unpredictable). MHRA Yellow Card scheme is the UK reporting system. NICE CG183 covers drug allergy management.
Pain management follows the WHO analgesic ladder (paracetamol → weak opioid → strong opioid) with adjuvants at each step. Neuropathic pain requires specific agents (amitriptyline, gabapentin, pregabalin per NICE CG173). Multimodal analgesia combining different mechanisms is preferred. The UK faces an opioid prescribing crisis requiring careful risk-benefit assessment and regular review.
Antimicrobial agents used to treat bacterial infections. UK prescribing is guided by NICE guidelines, local antimicrobial formularies, and the 'Start Smart — Then Focus' antimicrobial stewardship toolkit. Key classes include penicillins, cephalosporins, macrolides, tetracyclines, fluoroquinolones, and aminoglycosides. Antimicrobial resistance is a global threat; rational prescribing is essential.
Drugs that inhibit the coagulation cascade to prevent and treat thromboembolic disease. Key classes include heparins (unfractionated and LMWH), vitamin K antagonists (warfarin), and direct oral anticoagulants (DOACs — apixaban, rivaroxaban, edoxaban, dabigatran). DOACs are now first-line for most indications in the UK per NICE guidelines. Bleeding is the major complication; reversal agents are available.
Drugs used to treat depression, anxiety disorders, OCD, PTSD, and neuropathic pain. SSRIs (sertraline, fluoxetine, citalopram) are first-line per NICE CG90/NG222. Other classes include SNRIs (venlafaxine, duloxetine), TCAs (amitriptyline), MAOIs (phenelzine), and mirtazapine. Take 4–6 weeks for therapeutic effect. Discontinuation syndrome is common — taper gradually. Risk of serotonin syndrome with combinations.
Pharmacological agents for type 2 diabetes. Metformin remains first-line. NICE NG28 recommends a stepwise approach: metformin → dual therapy (add SGLT2 inhibitor, DPP-4 inhibitor, sulfonylurea, or pioglitazone) → triple therapy → insulin. SGLT2 inhibitors (empagliflozin, dapagliflozin) have cardiovascular and renal benefits beyond glycaemic control. GLP-1 receptor agonists (semaglutide, liraglutide) promote weight loss and reduce CV events.
Drugs used to prevent seizures in epilepsy and related conditions. Choice depends on seizure type: sodium valproate or lamotrigine for generalised; carbamazepine or lamotrigine for focal. NICE NG217 provides UK guidance. Valproate is highly teratogenic (MHRA Pregnancy Prevention Programme). Drug interactions via CYP450 enzymes are clinically important. Switching formulations should be avoided for narrow TI AEDs.
Drugs used to treat fungal infections ranging from superficial dermatophyte and candidal infections to life-threatening invasive mycoses. Key classes include azoles (fluconazole, itraconazole, voriconazole), polyenes (amphotericin B), echinocandins (caspofungin), and allylamines (terbinafine). Drug interactions (CYP450), hepatotoxicity, and nephrotoxicity are major prescribing considerations.
Drugs used to lower blood pressure and reduce cardiovascular risk. NICE NG136 provides a stepwise approach: Step 1 — ACE inhibitor/ARB (or CCB if >55 or Black African/Caribbean); Step 2 — ACE-i/ARB + CCB; Step 3 — add thiazide-like diuretic; Step 4 (resistant HTN) — add spironolactone. Target BP <140/90 mmHg (clinic) or <135/85 (ABPM/HBPM).
Drugs that inhibit platelet activation and aggregation, used primarily in cardiovascular disease prevention. Aspirin irreversibly inhibits COX-1 (thromboxane A2 synthesis); clopidogrel, prasugrel, and ticagrelor inhibit P2Y12 ADP receptors. Dual antiplatelet therapy (DAPT) is standard after ACS and PCI. Key considerations include bleeding risk, interaction with PPIs (clopidogrel), and duration of therapy.
Drugs primarily used in schizophrenia and other psychotic disorders, also for bipolar disorder, severe agitation, and antiemesis. Classified as first-generation/typical (haloperidol, chlorpromazine) or second-generation/atypical (olanzapine, quetiapine, risperidone, aripiprazole, clozapine). Block dopamine D2 receptors. Major side effects include extrapyramidal symptoms, metabolic syndrome, QT prolongation, and neuroleptic malignant syndrome. Clozapine is reserved for treatment-resistant schizophrenia.
Drugs that inhibit viral replication at various stages of the viral life cycle. Key agents include aciclovir (herpes viruses), oseltamivir (influenza), direct-acting antivirals for hepatitis C (sofosbuvir, ledipasvir), and antiretrovirals for HIV. Unlike antibiotics, most antivirals are virostatic rather than viricidal. Drug interactions and resistance are important prescribing considerations.
Competitive antagonists at beta-adrenoceptors that reduce heart rate, contractility, and renin release. Used in heart failure (bisoprolol, carvedilol), angina, post-MI, arrhythmias, thyrotoxicosis, and migraine prophylaxis. No longer first-line for hypertension (NICE NG136). Contraindicated in asthma (non-selective) and decompensated heart failure. Key agents: bisoprolol (beta-1 selective), propranolol (non-selective), atenolol, carvedilol.
Bronchodilators are medications that relax airway smooth muscle, used in asthma and COPD. They include beta-2 agonists, antimuscarinics, and methylxanthines.
Drugs that block L-type voltage-gated calcium channels in cardiac and smooth muscle. Two main subclasses: dihydropyridines (amlodipine, nifedipine — vascular selectivity, vasodilation) and non-dihydropyridines (verapamil, diltiazem — cardiac selectivity, rate control). First-line for hypertension in patients ≥55 or of Black African/Caribbean heritage (NICE NG136). Also used in angina and arrhythmias.
Chemotherapy uses cytotoxic drugs to treat cancer by disrupting cell division. Understanding drug classes, mechanisms, and toxicity profiles is essential for safe prescribing.
Synthetic analogues of cortisol with potent anti-inflammatory and immunosuppressive effects. Used in asthma, COPD exacerbations, autoimmune diseases, inflammatory conditions, and adrenal insufficiency. Major long-term side effects include osteoporosis, diabetes, adrenal suppression, infections, and Cushing's syndrome. Gradual tapering is essential after prolonged courses to avoid adrenal crisis.
Drugs that increase urine output by acting on the nephron. Key classes: loop diuretics (furosemide), thiazide-like (indapamide, chlortalidone), potassium-sparing (spironolactone, amiloride), and osmotic (mannitol). Used in hypertension, heart failure, oedema, and ascites. Major side effects include electrolyte disturbances (hypokalaemia, hyponatraemia), dehydration, and metabolic effects (gout, hyperglycaemia).
An immune-mediated adverse drug reaction involving specific immunological mechanisms (Types I–IV hypersensitivity). Most commonly caused by penicillins, NSAIDs, and neuromuscular blocking agents. True allergy must be distinguished from non-allergic ADRs. NICE CG183 provides guidance on diagnosis, documentation, and management. Specialist allergy assessment can confirm or exclude allergy safely.
Clinically significant modifications of drug effect caused by co-administration of another drug, food, or herbal product. Classified as pharmacokinetic (ADME) or pharmacodynamic (additive/synergistic/antagonistic effects at receptors). Drug interactions are a major cause of adverse drug events, particularly in elderly patients with polypharmacy. BNF interactions checker is the key UK prescribing resource.
Drug metabolism occurs predominantly in the liver via Phase I (oxidation/reduction — mainly CYP450 enzymes) and Phase II (conjugation) reactions. The cytochrome P450 system is the most important drug-metabolising enzyme family. CYP3A4 metabolises ~50% of drugs. Enzyme induction and inhibition are the most common causes of pharmacokinetic drug interactions.
Drug overdose and poisoning are common emergency presentations. Knowledge of specific antidotes, risk assessment tools, and management protocols is essential for safe clinical practice.
Drugs that suppress the immune system, used in organ transplantation, autoimmune diseases, and inflammatory conditions. Key agents include azathioprine, methotrexate, mycophenolate, ciclosporin, tacrolimus, and biologic therapies. Require careful monitoring due to infection risk, bone marrow suppression, hepatotoxicity, and nephrotoxicity. TPMT testing is mandatory before azathioprine.
Inhaled corticosteroids (ICS) are the mainstay anti-inflammatory therapy in asthma and are used in combination with bronchodilators in COPD with eosinophilic features.
Exogenous insulin is essential in type 1 diabetes and used in advanced type 2 diabetes when oral/injectable agents are insufficient. Classified by onset and duration: rapid-acting (insulin aspart, lispro), short-acting (Actrapid), intermediate (isophane/NPH), long-acting (glargine, detemir, degludec). Basal-bolus regimen is standard for T1DM. Hypoglycaemia is the most dangerous complication. NICE NG17 (T1DM) and NG28 (T2DM) provide UK guidance.
Medication errors are preventable events that may cause patient harm at any stage of the medicines pathway. They are a major patient safety concern in the NHS.
Medicines reconciliation is the process of creating an accurate list of a patient's medications at every care transition, identifying and resolving discrepancies to prevent errors.
The most widely used analgesic and antipyretic in the UK. Mechanism involves central COX inhibition and endocannabinoid modulation. Safe at therapeutic doses but paracetamol overdose is the leading cause of acute liver failure in the UK. N-acetylcysteine (NAC) is the antidote. The Rumack-Matthew nomogram guides treatment decisions. Maximum dose 4 g/day in healthy adults; reduce in liver disease, low body weight, and chronic alcohol use.
The study of the biochemical and physiological effects of drugs on the body ('what the drug does to the body'). Encompasses receptor theory, dose-response relationships, agonism, antagonism, and signal transduction. Key concepts include efficacy, potency, therapeutic index, and receptor types. Underpins rational drug selection and understanding of drug effects and side effects.
The study of drug absorption, distribution, metabolism, and excretion (ADME). Determines the time course of drug concentration in the body. Key concepts include bioavailability, volume of distribution, clearance, half-life, and steady state. Essential for rational prescribing, dose adjustment in organ impairment, and understanding drug interactions.
The concurrent use of multiple medications, typically defined as ≥5 drugs. Affects ~30% of adults >65 years in the UK. Associated with increased risk of adverse drug reactions, drug interactions, falls, hospitalisation, and mortality. Structured medication review and deprescribing are the cornerstones of management. NICE NG5 provides guidance on medicines optimisation.
Most drugs are excreted into breast milk to some degree, but the infant dose is usually <1–2% of the maternal dose and clinically insignificant. The benefits of breastfeeding usually outweigh the risks of maternal medication. Key drugs to avoid include cytotoxics, amiodarone, lithium (relative), and radioactive iodine. The BNF, UKTIS, and LactMed database provide guidance.
Liver disease significantly alters drug pharmacokinetics through reduced metabolism (Phase I > Phase II), decreased protein synthesis (reduced albumin → increased free drug), altered volume of distribution (ascites), and portal-systemic shunting. The Child-Pugh score guides prescribing. Hepatotoxic drugs must be avoided or used with extreme caution. No single liver test reliably predicts drug-metabolising capacity.
Drug prescribing in pregnancy requires balancing the risk of teratogenicity and fetal harm against the risk of untreated maternal disease. Most drugs cross the placenta. Key teratogens include valproate, methotrexate, ACE inhibitors, warfarin, retinoids, and lithium. The BNF and UK Teratology Information Service (UKTIS) provide guidance. Folate supplementation (400 mcg–5 mg daily) reduces neural tube defect risk.
Renal impairment significantly affects drug pharmacokinetics, requiring dose adjustment for renally cleared drugs. Key considerations include reduced drug clearance, altered protein binding, and increased sensitivity to nephrotoxic drugs. The BNF renal appendix provides dose guidance based on eGFR or creatinine clearance. Essential drugs to adjust include metformin, DOACs, digoxin, gentamicin, and lithium.
Elderly patients (≥65 years) are at increased risk of adverse drug reactions due to altered pharmacokinetics, pharmacodynamics, multi-morbidity, polypharmacy, and frailty. ADRs cause ~10% of hospital admissions in the elderly. Key principles: 'start low, go slow', regular medication review, use STOPP/START criteria, and deprescribe where appropriate. NICE NG5 and NG56 provide guidance.
Proton pump inhibitors (PPIs) irreversibly inhibit the gastric H+/K+ ATPase, potently suppressing acid secretion. They are widely prescribed for GORD, peptic ulcers, and dyspepsia.
Targeted therapies are drugs designed to interfere with specific molecular targets involved in tumour growth, offering improved selectivity over conventional chemotherapy.
Therapeutic drug monitoring (TDM) involves measuring drug levels to optimise dosing for drugs with narrow therapeutic indices, ensuring efficacy while minimising toxicity.