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Core Pharmacology Diuretics: remove sodium and water safely—treat congestion without causing collapse Diuretics increase renal sodium excretion (natriuresis); water follows sodium, producing diuresis. They rapidly relieve oedema and pulmonary congestion, but they do not replace disease-modifying heart-failure therapy. Correct class selection, fluid assessment and electrolyte monitoring are what make them safe. 1. The renal map: where each class acts Nephron site Drug class Target Key effect Proximal tubule Carbonic anhydrase inhibitor Carbonic anhydrase Bicarbonate-rich urine; weak diuresis Thick ascending limb Loop diuretic Na-K-2Cl cotransporter (NKCC2) Most powerful natriuresis; calcium and magnesium loss Early distal tubule Thiazide/thiazide-like Na-Cl cotransporter (NCC) Moderate diuresis; calcium retention Collecting duct Potassium-sparing Aldosterone receptor or ENaC Mild diuresis; potassium retention Whole nephron Osmotic Filtered osmoles Water loss; expands extracellular fluid first Core principle: where sodium goes, water follows. A diuretic is therefore mainly a sodium-management drug, not simply a “urine-making” drug. 2. Classification and quick selection Loop diuretics Furosemide, bumetanide, torsemide. Best for acute pulmonary oedema, significant heart-failure congestion, severe oedema, and low eGFR states. Thiazides Hydrochlorothiazide, chlorthalidone, indapamide. Important for hypertension; add-on to loops for resistant oedema. Mineralocorticoid receptor antagonists Spironolactone, eplerenone. Potassium-sparing and disease-modifying in eligible HFrEF—not merely “weak diuretics.” Other potassium-sparing Amiloride and triamterene block ENaC; useful with potassium-wasting drugs and selected specific conditions. 3. Loop diuretics: furosemide is the acute-congestion workhorse Mechanism: blockade of NKCC2 in the thick ascending limb prevents sodium, potassium and chloride reabsorption. Loops are “high-ceiling”: larger doses can create greater natriuresis, but safety limits remain. Common use Typical adult approach* Expected problems Bedside priority Acute pulmonary oedema/acute HF congestion Furosemide 20–40 mg IV in diuretic-naïve adults; dose/route must be individualised Hypotension, AKI/azotaemia, low K/Mg/Na, alkalosis, gout, ototoxicity Monitor response early: breathlessness, urine output, weight, BP, renal function and electrolytes Chronic oedema Oral furosemide, bumetanide or torsemide; lowest dose that maintains euvolaemia Over-diuresis, adherence problems, interactions Teach daily weights, sick-day review and when to seek help *Educational examples only; use local protocols, product information and prescriber review. Excessive furosemide can cause profound water/electrolyte depletion. Rapid IV administration, high doses and renal impairment increase the risk of tinnitus/hearing injury. Important: a rise in creatinine during effective decongestion requires clinical interpretation. Look at BP, perfusion, congestion, urine output and trend—do not reflexively stop a lifesaving decongestion plan or ignore hypotension/true volume depletion. 4. Thiazide and thiazide-like diuretics Mechanism: inhibit NCC in the early distal convoluted tubule. They lower blood pressure initially through sodium/water loss and later through reduced peripheral resistance. Examples are hydrochlorothiazide, chlorthalidone and indapamide. Best uses: hypertension, mild oedema, nephrogenic diabetes insipidus, prevention of calcium renal stones in hypercalciuria, and add-on “sequential nephron blockade” when loop response is poor. Adverse effects: hypokalaemia, hyponatraemia, hypomagnesaemia, dehydration, hyperuricaemia/gout, hyperglycaemia, photosensitivity and erectile dysfunction. Calcium: thiazides reduce urinary calcium, unlike loops. This helps distinguish the classes. Safety: severe hyponatraemia can present with confusion, seizure or collapse—check sodium urgently in an unwell patient. 5. Potassium-sparing diuretics: do not overlook hyperkalaemia Subgroup Examples Mechanism Major caution Aldosterone antagonist (MRA) Spironolactone, eplerenone Blocks mineralocorticoid receptor Hyperkalaemia, renal impairment; spironolactone can cause gynaecomastia ENaC blocker Amiloride, triamterene Blocks epithelial sodium channel Hyperkalaemia; avoid unsafe combinations MRAs improve outcomes in appropriately selected HFrEF patients. Before starting or increasing, check potassium and renal function; repeat testing after initiation and dose changes. Combining an MRA with ACE inhibitor/ARB/ARNI or potassium supplements may be appropriate only with deliberate monitoring—not by accident. 6. Less common but examinable classes Acetazolamide: carbonic anhydrase inhibitor; causes bicarbonate loss and metabolic acidosis. Uses include glaucoma, acute mountain sickness, selected metabolic alkalosis and adjunctive decongestion. Can cause paraesthesia, renal stones and sulfonamide-related reactions. Mannitol: osmotic diuretic used to reduce raised intracranial/intraocular pressure in selected patients. It initially expands intravascular volume and may worsen pulmonary oedema; avoid in anuria, severe dehydration or uncontrolled HF/pulmonary congestion. Vaptans: vasopressin antagonists produce aquaresis (water loss more than sodium loss); specialist use in selected hyponatraemia settings. 7. Diuretics in heart failure: a safe practical sequence Confirm congestion: dyspnoea, orthopnoea, raised JVP, oedema, crackles, weight gain, hepatomegaly or pulmonary oedema. Check perfusion and BP. Cold/hypotensive patients may have cardiogenic shock and need urgent escalation—not just escalating diuretic doses. Give loop diuretic for fluid overload, reassess urine output and symptoms, and monitor fluid balance/weight. If response is inadequate, review dose, adherence, absorption, renal function, salt intake, NSAIDs and diagnosis. Sequential nephron blockade may be prescribed by an experienced clinician, with closer electrolyte checks. Once euvolaemic, use the lowest maintenance loop dose and optimise disease-modifying HFrEF therapy where indicated. Diuretics mainly improve symptoms and prevent congestion-related admission; they do not by themselves reverse the underlying cardiomyopathy. 8. Nursing monitoring and patient education Monitor Why it matters Escalate urgently if BP, pulse, postural symptoms Over-diuresis causes hypotension/falls Syncope, shock, symptomatic hypotension Input/output, daily weight, oedema, lungs Measures decongestion better than one urine measurement Worsening breathlessness/pulmonary oedema or very low urine output Na, K, Mg, creatinine/eGFR, bicarbonate Detects electrolyte and renal injury Severe K/Na disturbance, arrhythmia, confusion or seizure Hearing (high-dose/rapid IV loop) Early ototoxicity detection Tinnitus or sudden hearing change Give oral doses early in the day when possible; explain nocturia if a late dose is unavoidable. Daily weight is more useful than guessing fluid retention. Agree a local action plan for rapid gain, worsening oedema or breathlessness. Avoid self-medicating with NSAIDs: they can blunt diuretic effect and worsen renal function. Do not advise potassium supplements or salt substitutes containing potassium without prescriber direction. 9. High-yield comparisons and cases Loop vs thiazide Loop: strongest, loses calcium, preferred for major HF congestion. Thiazide: excellent antihypertensive, retains calcium, more likely to cause hyponatraemia. Case: spironolactone HFrEF patient on ACE inhibitor develops weakness and K 6.2 mmol/L. Answer: urgent assessment for hyperkalaemia/ECG changes; withhold relevant drugs as directed and treat using local emergency protocol. Case: furosemide After IV furosemide a patient becomes dizzy, hypotensive and dry with low K. Answer: suspect over-diuresis; assess perfusion, hold/reduce under prescriber direction and correct fluid/electrolytes. References Supplied class reference: Diuretics (SlideShare). 2022 AHA/ACC/HFSA Heart Failure Guideline; 2021 ESC Heart Failure Guideline.

Core Pharmacology Inotropic agents: raise cardiac output only when low output is causing harm Positive inotropes increase the force of myocardial contraction. In modern practice they are mainly short-term, closely monitored IV medicines for cardiogenic shock or acute heart failure with hypotension and hypoperfusion—not routine treatment for a congested but adequately perfused patient. They can restore perfusion, but can also cause tachyarrhythmia, myocardial ischaemia and excess mortality if used unnecessarily or for too long. This lesson connects the pharmacology to bedside decisions: identify low output, treat the cause, select the least harmful haemodynamic support, monitor continuously, and wean as soon as perfusion is stable. 1. Meaning, terminology and the clinical goal Inotropy is the strength of cardiac contraction. A positive inotrope increases intracellular calcium availability or the contractile apparatus response to calcium, increasing stroke volume and cardiac output. Chronotropy changes heart rate; dromotropy changes conduction; lusitropy improves relaxation. Term What it does Example Clinical warning Inotrope Increases contractility and cardiac output Dobutamine, milrinone, digoxin May provoke ischaemia/arrhythmia Inodilator Inotropy plus arterial/venous vasodilation Milrinone, levosimendan Can lower blood pressure Vasopressor Raises vascular tone and blood pressure Norepinephrine Does not by itself fix poor contractility Chronotrope Changes heart rate Isoprenaline Increased rate may raise oxygen demand 2. First decide: does the patient truly need an inotrope? Use an inotrope when there is evidence of low cardiac output with end-organ hypoperfusion, especially if accompanied by hypotension, despite correcting immediately reversible problems. Warning signs include cold clammy peripheries, oliguria, altered mental state, rising lactate/metabolic acidosis, narrow pulse pressure, weak pulses and pulmonary oedema with a low-output state. Before starting: treat the cause in parallel Secure airway, oxygenation/ventilation and IV access; obtain ECG, blood pressure, urine output, glucose, electrolytes, renal function and lactate where available. Look for acute coronary syndrome, serious arrhythmia, mechanical complication, sepsis, pulmonary embolism, tamponade, acute valvular disease, severe anaemia, drug toxicity or fluid loss. Assess volume status. A hypotensive patient may need cautious fluid if genuinely hypovolaemic; fluid overload needs decongestion, not repeated blind boluses. In cardiogenic shock with marked hypotension, a vasopressor—often norepinephrine—may be needed to maintain perfusion pressure while an inotrope supports cardiac output. Do not use an inotrope simply because the ejection fraction is low. A warm, adequately perfused patient with chronic HFrEF should receive guideline-directed therapy and diuretics as indicated, not continuous inotropic stimulation. 3. How contraction is increased: the calcium map Action potential opens L-type calcium channels during phase 2. Small calcium influx triggers larger calcium release from the sarcoplasmic reticulum (calcium-induced calcium release). Calcium binds troponin C, allowing actin–myosin cross-bridge cycling and contraction. Relaxation requires calcium reuptake into sarcoplasmic reticulum (SERCA) and extrusion via the Na+/Ca2+ exchanger. Drugs increase contractility by one of four broad strategies: beta1 stimulation (dobutamine), PDE-3 inhibition (milrinone), Na+/K+-ATPase inhibition (digoxin), or calcium sensitisation (levosimendan). More calcium or cyclic AMP can improve output—but also increases arrhythmogenic risk and myocardial oxygen consumption. 4. Classification at a glance Cardiac glycoside Digoxin: positive inotrope, vagotonic AV-node slowing; long half-life and narrow therapeutic index. Beta-adrenergic agonists Dobutamine (mainly beta1), dopamine and adrenaline/epinephrine: rapid IV catecholamine support. PDE-3 inhibitor Milrinone: inodilator; useful when beta-blockade limits catecholamine response, but hypotension and renal accumulation matter. Calcium sensitiser Levosimendan: availability varies; an inodilator used in some settings with specialist monitoring. 5. Dobutamine Mechanism: predominantly beta1-receptor agonism increases cAMP, calcium entry and contractility. It has some beta2/alpha effects, so the blood-pressure response is variable. It starts quickly and has a very short half-life; it is given by controlled IV infusion. Use Typical adult ICU approach* Important adverse effects Practical point Low-output acute HF/cardiogenic shock with adequate or supported BP; post-cardiac surgery; stress echo Start low and titrate to perfusion, often 2–20 micrograms/kg/min IV infusion Tachycardia, atrial/ventricular arrhythmias, hypertension or hypotension, angina/ischaemia, hypokalaemia Response may be blunted by beta blockers; do not use as a routine long-term HF drug *Dose ranges are educational examples only: prescribe through local adult/paediatric protocols and use an infusion pump. Monitor ECG, heart rate, rhythm, BP, urine output, mental status and peripheral perfusion. The product label warns that marked increases in heart rate or systolic BP can occur; reducing the rate usually reverses the effect. Avoid or use specialist judgement in obstructive hypertrophic cardiomyopathy, uncontrolled tachyarrhythmia, active ischaemia, severe hypovolaemia or uncorrected obstruction to outflow. Treat new tachyarrhythmia or ischaemic pain urgently; reduce/stop the infusion and call senior/critical-care support. 6. Milrinone: the classic inodilator Mechanism: selective PDE-3 inhibition prevents cAMP breakdown in myocardium and vascular smooth muscle. The result is stronger contraction plus vasodilation, with reduced systemic/pulmonary vascular resistance and filling pressures. Unlike dobutamine, its action is not directly dependent on beta receptors. When milrinone may be considered Acute decompensated HFrEF or low-output states where an inodilator is appropriate, particularly when a patient is receiving beta blockade or has pulmonary hypertension/right-ventricular failure. It is not automatically safer than dobutamine: its vasodilation can worsen hypotension and it accumulates in renal impairment. Typical adult regimen: loading dose 50 micrograms/kg IV over 10 minutes may be used in some protocols, followed by 0.375–0.75 micrograms/kg/min infusion. Many unstable patients are started without a loading dose. Reduce maintenance dosing in renal impairment. Adverse effects: hypotension, ventricular/supraventricular arrhythmias, headache, thrombocytopenia and hypokalaemia. Never use as chronic oral “heart-strengthening” therapy: long-term oral PDE-3 inhibition increased mortality. Nursing alert: a falling BP after milrinone may reflect vasodilation; do not automatically increase the dose. Reassess perfusion, volume status and need for vasopressor support. 7. Digoxin: an inotrope with a different bedside role Mechanism: digoxin inhibits the Na+/K+-ATPase. Intracellular sodium rises, reducing sodium–calcium exchange, so intracellular calcium rises and contraction strengthens. It also increases vagal tone and slows AV-node conduction. Useful role Not the role Key monitoring Rate control in chronic atrial fibrillation, especially with HFrEF or sedentary patients; selected symptomatic HFrEF patients despite standard therapy Rapid rescue drug for cardiogenic shock; first-line treatment for sinus rhythm HFrEF; rate control in AF with WPW/accessory pathway Apical pulse/ECG, renal function, potassium, magnesium, calcium, interacting drugs and serum digoxin level when clinically indicated Safe use: dose is

Core Pharmacology Other antihypertensive agents: choose the class that fits the patient Blood pressure is determined mainly by cardiac output × systemic vascular resistance. Antihypertensive medicines lower blood pressure by reducing salt and water, relaxing arterioles, suppressing the renin–angiotensin system, reducing sympathetic tone, or combining these effects. This lesson complements the separate ACE inhibitor and beta-blocker lessons. The practical priorities are correct indication, contraindication screening, safe combination therapy, laboratory monitoring and recognition of hypertensive emergency. 1. First-line treatment framework For adults who need drug treatment, WHO recommends a medicine from one of three major classes: thiazide/thiazide-like diuretics, ACE inhibitor/ARB, or long-acting dihydropyridine calcium-channel blocker. The best first choice depends on age, pregnancy potential, kidney function, albuminuria, heart failure, ischaemic disease, diabetes, pulse, electrolytes, availability and cost. Class Primary action Common examples High-yield caution Thiazide / thiazide-like diuretic Promotes sodium excretion; later reduces vascular resistance Hydrochlorothiazide, chlorthalidone, indapamide Hypokalaemia, hyponatraemia, gout, glucose rise Dihydropyridine CCB Arteriolar calcium-channel blockade and vasodilation Amlodipine, nifedipine LA, felodipine Peripheral oedema, flushing, headache ARB Blocks AT1 receptor Losartan, valsartan, telmisartan, candesartan Pregnancy, hyperkalaemia, renal monitoring Mineralocorticoid antagonist Blocks aldosterone receptor Spironolactone, eplerenone Hyperkalaemia; spironolactone gynaecomastia Central sympatholytic Reduces sympathetic outflow Methyldopa, clonidine Rebound hypertension with abrupt clonidine withdrawal 2. Diuretics Thiazide and thiazide-like diuretics These block sodium–chloride reabsorption in the early distal convoluted tubule. Early BP lowering comes from reduced extracellular volume and cardiac output; with continued use, peripheral vascular resistance falls. Chlorthalidone and indapamide are longer acting; local formularies determine preferred choice. Uses: uncomplicated hypertension; combination treatment; selected older patients and salt-sensitive hypertension. Adverse effects: hypokalaemia, hyponatraemia, hypomagnesaemia, dehydration, hyperuricaemia/gout, hyperglycaemia, photosensitivity and erectile dysfunction. Monitoring: BP, sodium, potassium, creatinine/eGFR, uric acid where relevant, glucose in at-risk patients and symptoms of dehydration. Interactions: NSAIDs reduce effect and increase renal risk; digoxin toxicity risk increases with hypokalaemia; lithium levels may rise. Loop diuretics Furosemide and torsemide act in the thick ascending limb of the loop of Henle. They are powerful diuretics but are not routine first-line treatment for uncomplicated hypertension. Use mainly for oedema, heart failure, advanced CKD with fluid overload, or when thiazides are ineffective at low eGFR. They can cause marked volume depletion, hypokalaemia, hypomagnesaemia and ototoxicity at high IV doses. Potassium-sparing diuretics and aldosterone antagonists Spironolactone and eplerenone antagonise the mineralocorticoid receptor; amiloride blocks epithelial sodium channels. Spironolactone is a key add-on for resistant hypertension and has major benefit in HFrEF, but check potassium and renal function. Spironolactone may cause gynaecomastia, menstrual disturbance and sexual adverse effects; eplerenone is more selective but often more costly. 3. Calcium-channel blockers (CCBs) CCBs block L-type calcium channels. Their clinical effect depends on whether they act mainly on vascular smooth muscle or also on cardiac tissue. DihydropyridinesAmlodipine, nifedipine LA, felodipine Act mainly on arterioles, causing vasodilation and lowering BP. Amlodipine is long acting and commonly once daily. Typical effects are dose-related ankle oedema, flushing, headache, dizziness, palpitations and gingival hyperplasia. The ankle oedema is due to precapillary dilation—not necessarily fluid overload—so adding a loop diuretic may not solve it. Non-dihydropyridinesVerapamil and diltiazem Also depress sinus rate, AV conduction and contractility. Useful for selected rate-control and angina patients but not routine first-line BP medicines. Avoid or use extreme caution with beta blockers because the combination can cause severe bradycardia, AV block and heart failure worsening. Clinical safety Immediate-release nifedipine is not used to rapidly “crash” BP Rapid, uncontrolled BP reduction can cause cerebral, myocardial or renal hypoperfusion. Hypertensive emergencies require monitored IV therapy and management of the underlying target-organ injury; asymptomatic severe BP elevation is reduced gradually with oral treatment and close follow-up. 4. Angiotensin-receptor blockers (ARBs) and aliskiren ARBs block the angiotensin-II AT1 receptor. They provide RAAS blockade without substantially increasing bradykinin, so cough is less common than with ACE inhibitors. They are used for hypertension, albuminuric CKD, HFrEF when appropriate, and ACE-inhibitor intolerance. Examples: losartan, candesartan, valsartan, telmisartan, irbesartan, olmesartan. Adverse effects: hypotension, hyperkalaemia and creatinine rise. Angioedema is less frequent but still possible. Contraindications: pregnancy and major RAAS-related safety concerns similar to ACE inhibitors. Never routinely combine: ACE inhibitor + ARB, or ARB + aliskiren, because of hypotension, hyperkalaemia and kidney injury. Aliskiren directly inhibits renin. It is not commonly first choice; avoid inappropriate dual RAAS blockade, particularly in diabetes or renal impairment. 5. Sympatholytics and alpha blockers Central agents Methyldopa: converted centrally to an alpha2 agonist, reducing sympathetic outflow. It has a long history in pregnancy hypertension. Adverse effects include sedation, dry mouth, depression, hepatitis, positive Coombs test and rarely haemolytic anaemia; monitor according to protocol. Clonidine: central alpha2 agonist that lowers sympathetic tone. It can cause dry mouth, sedation, constipation and bradycardia. Never stop abruptly: rebound sympathetic activity may cause severe hypertension, tachycardia and headache. Alpha1 blockers Prazosin, doxazosin and terazosin relax arterioles and veins. They can improve lower-urinary-tract symptoms from benign prostatic enlargement but are usually not first-line antihypertensives. The important adverse effect is first-dose postural syncope; start low, often at bedtime, and counsel patients to rise slowly. Alpha + beta blockers Labetalol and carvedilol produce both alpha1 vasodilation and beta blockade. Labetalol is important in selected acute and pregnancy-related hypertension protocols. Carvedilol is particularly valuable in stable HFrEF. 6. Direct vasodilators Medicine Role Important adverse effects / precautions Hydralazine Direct arteriolar dilator; selected resistant hypertension, pregnancy protocols, and with nitrates in some HFrEF patients Reflex tachycardia, fluid retention, headache, lupus-like syndrome, peripheral neuropathy Minoxidil Potent arteriolar K+-channel opener for severe resistant hypertension Fluid retention and tachycardia—usually needs loop diuretic + beta blocker; hypertrichosis; rare pericardial effusion Sodium nitroprusside Rapid IV arterial and venous dilator in selected ICU hypertensive emergencies Requires invasive/continuous monitoring; cyanide/thiocyanate toxicity risk with prolonged/high-dose use or renal/hepatic dysfunction IV nitroglycerin Mainly venodilator; useful when emergency hypertension accompanies acute pulmonary oedema or myocardial ischaemia Headache, hypotension, tolerance; avoid with PDE-5 inhibitors 7. Resistant hypertension and combination therapy Resistant hypertension means BP remains above target despite adherence to an appropriate three-drug regimen at tolerated doses, commonly including a RAAS blocker, long-acting dihydropyridine CCB and diuretic—or BP is controlled only

Core Pharmacology Beta blockers: reduce harmful sympathetic stimulation of the heart Beta-adrenergic blockers (beta blockers or β-blockers) competitively antagonise beta-adrenoceptors. Their most important cardiovascular effects are slowing sinus rate, slowing atrioventricular-node conduction, reducing myocardial contractility and reducing renin release. Used correctly, they improve angina, control many tachyarrhythmias, reduce aortic-wall stress, and improve survival in stable HFrEF with selected agents. Critical distinction: beta blockers are not interchangeable. The beta blocker chosen must match the indication, receptor profile, route, comorbidity and evidence base. In HFrEF, the evidence-based agents are bisoprolol, carvedilol and metoprolol succinate (extended release)—not simply any beta blocker. 1. Sympathetic physiology: what beta receptors normally do The sympathetic nervous system releases noradrenaline from nerve terminals and adrenaline from the adrenal medulla. These catecholamines bind adrenergic receptors on cell membranes. Beta blockers prevent catecholamine stimulation at beta receptors; their effects are most visible when sympathetic drive is high, such as exercise, pain, anxiety, thyrotoxicosis, acute coronary syndrome or heart failure. Receptor Main sites Normal stimulation effect Effect of blockade β1 Heart, juxtaglomerular cells of kidney ↑ heart rate, ↑ contractility, ↑ AV conduction, ↑ renin release ↓ rate, ↓ contractility, ↓ AV conduction, ↓ renin β2 Bronchi, vascular smooth muscle, uterus, liver, skeletal muscle Bronchodilation, vasodilation in some beds, uterine relaxation, glycogenolysis Bronchoconstriction risk, cold extremities, reduced glycogenolysis, may oppose β2-agonists β3 Adipose tissue, bladder detrusor Lipolysis and detrusor relaxation Limited routine relevance for conventional beta blockers 2. How beta blockers work Cardiac effects Negative chronotropy: reduce sinoatrial-node automaticity, lowering heart rate. Negative dromotropy: slow AV-node conduction and increase AV-node refractoriness. This is why they control ventricular rate in atrial fibrillation/flutter and terminate or prevent some AV-node-dependent supraventricular tachycardias. Negative inotropy: reduce contractile force and myocardial oxygen demand. This relieves effort angina but can acutely worsen decompensated heart failure. Antiarrhythmic action: they are Class II antiarrhythmics: they suppress catecholamine-driven ectopic activity, reduce automaticity and limit post-MI ventricular arrhythmia risk in appropriate patients. Blood-pressure effects Initially, cardiac output falls; with chronic use, peripheral resistance adapts downward. β1 blockade in the kidney reduces renin, decreasing angiotensin II and aldosterone activity. Some agents add vasodilation: carvedilol and labetalol block α1 receptors; nebivolol promotes nitric-oxide-mediated vasodilation. Why beta blockers relieve angina Myocardial oxygen demand rises with heart rate, wall stress, contractility and blood pressure. Beta blockers reduce all four major demand determinants. A slower heart rate also prolongs diastole, improving coronary perfusion time. They are useful in stable exertional angina, but non-selective beta blockade may aggravate vasospastic (Prinzmetal) angina because it can leave alpha-mediated coronary vasoconstriction unopposed. 3. Classification of beta blockers Non-selective β1 + β2 Propranolol, nadolol, timolol, pindolol, sotalol Block both β1 and β2. Useful for conditions such as essential tremor, migraine prophylaxis, portal hypertension, thyrotoxicosis and glaucoma depending on the agent. They have greater risk of bronchospasm and interference with hypoglycaemia recovery. Relatively β1-selective Metoprolol, bisoprolol, atenolol, esmolol, nebivolol Often called cardioselective. At higher doses, selectivity diminishes. They are generally preferred when bronchospasm risk, diabetes or peripheral vascular symptoms make β2 blockade undesirable, but asthma still requires caution. β + α1 blockade Carvedilol and labetalol Add α1-mediated vasodilation. Carvedilol is evidence-based for stable HFrEF. Labetalol is widely used for hypertension, including pregnancy-related hypertensive emergencies where clinically indicated by local protocol. Intrinsic sympathomimetic activity (ISA) Pindolol, acebutolol Partially stimulate while blocking beta receptors. They tend to cause less resting bradycardia but are not preferred after MI or in HFrEF, where full beta blockade with evidence-based medicines is desired. Ultra-short acting Esmolol Intravenous, β1-selective and rapidly metabolised by red-blood-cell esterases. Its very short action makes it valuable when rapid titration and rapid reversal are needed, for example selected perioperative tachycardia, SVT, thyrotoxicosis or acute aortic syndromes. Additional antiarrhythmic action Sotalol Non-selective beta blocker with Class III potassium-channel-blocking activity. It prolongs repolarisation and QT interval, so it can cause torsades de pointes; initiation and monitoring require specific expertise. 4. Important medicines compared Drug Receptor profile / special feature High-yield uses Key caution Propranolol Non-selective; lipophilic Essential tremor, performance anxiety, migraine prevention, thyrotoxicosis symptoms, portal hypertension, some arrhythmias Bronchospasm, CNS effects, hypoglycaemia masking Metoprolol β1-selective; tartrate is immediate-release, succinate is extended-release Angina, rate control, hypertension; succinate for evidence-based HFrEF Do not assume tartrate and succinate are interchangeable in HFrEF Bisoprolol Highly β1-selective, once daily HFrEF, angina, hypertension, rate control Bradycardia/AV block; selectivity is dose dependent Carvedilol β1, β2 and α1 blockade; antioxidant properties Evidence-based HFrEF, hypertension Postural hypotension and bronchospasm risk Atenolol β1-selective; hydrophilic; renal excretion Hypertension, angina, some rate-control settings Adjust in renal impairment; not one of the three evidence-based HFrEF agents Nebivolol β1-selective with nitric-oxide-mediated vasodilation Hypertension; selected heart-failure populations according to local guidance Cost/availability and bradycardia Labetalol β blockade + α1 blockade Hypertension; IV use in selected acute settings; pregnancy hypertension protocols Postural hypotension; avoid in asthma/heart block Timolol Non-selective; topical preparations reduce aqueous-humour production Glaucoma Eye drops can still cause systemic bradycardia and bronchospasm 5. Evidence-based clinical uses Hypertension Beta blockers lower BP but are not generally first-line for uncomplicated hypertension in current WHO-style primary hypertension treatment because other classes have broader first-line evidence. They are particularly useful when hypertension coexists with a compelling indication: angina, previous MI with reduced ejection fraction, certain tachyarrhythmias, HFrEF, aortic disease, hyperthyroidism or pregnancy-related hypertension where the local guideline recommends labetalol. Stable angina and ischaemic heart disease By reducing heart rate and contractility, beta blockers reduce exertional angina and improve exercise tolerance. Avoid initiating or escalating during cardiogenic shock, severe bradycardia or acute decompensated HF. In modern post-MI care, ongoing beta-blocker benefit is clearest in patients with reduced LVEF or heart failure; duration in patients with preserved LVEF should follow current cardiology guidance rather than an automatic lifelong rule. Heart failure with reduced ejection fraction Chronic sympathetic activation is toxic to failing myocardium. When the patient is euvolaemic and clinically stable, beta blockers started at a low dose and titrated slowly improve survival, reduce hospitalisation and improve ventricular function over time. Use only one evidence-based agent: bisoprolol, carvedilol or metoprolol succinate extended release. Do not

Antiparkinsonism drugs: replace dopamine, mimic it, or reduce its breakdown Parkinson disease causes bradykinesia plus tremor and/or rigidity, with non-motor symptoms also common. Medicines improve symptoms but do not replace exercise, physiotherapy, falls prevention, speech/swallow support and assessment for depression, dementia and autonomic dysfunction. Treatment is individualised to age, functional impairment, cognition and risk of dyskinesia or impulse-control disorder. Never stop dopaminergic therapy abruptly Sudden withdrawal can cause severe rigidity, fever, autonomic instability and a neuroleptic-malignant-like syndrome. If a patient is nil by mouth, vomiting or admitted for surgery, get urgent specialist/pharmacy advice on an alternative route. 1. Drug classes Class Examples Use and major issue Levodopa + decarboxylase inhibitor Levodopa/carbidopa; levodopa/benserazide Most effective symptomatic therapy; later motor fluctuations/dyskinesia may occur. Dopamine agonists Pramipexole, ropinirole, rotigotine Can reduce off time but cause sleepiness, hallucinations, oedema and impulse-control disorders. MAO-B inhibitors Selegiline, rasagiline Reduce dopamine metabolism; review serotonergic and sympathomimetic interactions. COMT inhibitors Entacapone, opicapone Extend levodopa effect; can worsen dyskinesia and cause diarrhoea/discolouration of urine. Antimuscarinics Trihexyphenidyl, benztropine Occasional tremor role in younger people; avoid in older adults/cognitive impairment because confusion, urinary retention and constipation are common. Amantadine Amantadine May help dyskinesia; adjust in renal impairment and monitor hallucinations/livedo oedema. 2. Dose-titration examples Medicine Indicative adult starting approach Monitor Carbidopa/levodopa immediate release 25/100 mg One tablet orally three times daily is a common label-based initial regimen; increase gradually to response. Product labels may allow up to eight 25/100 tablets/day, but specialist titration is usual. Nausea, postural hypotension, hallucinations, dyskinesia, wearing off; timing with protein-rich meals may matter. Pramipexole Start low and titrate gradually; regimen differs by indication/formulation and renal function. Sleep attacks, hallucinations, oedema and new gambling, shopping, hypersexuality or binge eating. Entacapone Given with individual levodopa doses in protocol-directed regimens; do not add it without reviewing total levodopa exposure. Dyskinesia (often requires levodopa reduction), diarrhoea and interactions. 3. Managing wearing off and dyskinesia Wearing off is predictable return of symptoms before the next levodopa dose; dyskinesia is excessive involuntary movement, often at peak dose. First obtain a timed symptom/medicine diary. Check adherence, constipation/absorption issues and interacting dopamine blockers. Adjusting dose interval, formulation or adding an adjunct must be specialist-guided; simply escalating every dose can worsen dyskinesia and hallucinations. 4. Safety and OSCE Ask about falls, BP lying/standing, swallowing, constipation, urinary symptoms, sleep attacks, hallucinations, cognition and impulse-control behaviour. Review all antiemetics/antipsychotics: dopamine-blocking medicines may worsen Parkinsonism. Counsel the patient and family to seek help for sudden confusion, dangerous sleepiness, compulsive behaviour, severe vomiting or inability to take regular dopaminergic medicine. Further study Antiparkinsonism drugs — supplied slides Carbidopa/levodopa prescribing information

Anti-vertigo drugs: relieve symptoms, but do not miss the cause Vertigo is an illusion of movement, usually spinning. Medicines can reduce severe acute nausea and vestibular symptoms, but they do not replace diagnosis, repositioning manoeuvres, vestibular rehabilitation or treatment of a central cause. Long-term vestibular suppression can delay central compensation and may worsen falls. Red flags: do not simply prescribe an antiemetic New focal weakness/numbness, dysarthria, diplopia, severe gait ataxia, sudden severe headache, new central-pattern nystagmus, chest pain/syncope, acute deafness, persistent inability to walk, trauma or severe dehydration requires urgent assessment for stroke or another serious cause. 1. Think syndrome first Pattern Likely approach Role of medicines Brief positional attacks (BPPV) Positional examination and canalith repositioning manoeuvre. Medicines rarely solve BPPV; avoid prolonged vestibular suppressants. Acute vestibular syndrome (neuritis/labyrinthitis after central cause excluded) Hydration, short-term symptom control, early mobilization/vestibular rehabilitation. Short course only for severe vertigo/nausea. Ménière-type episodes ENT review, audiology and disease-specific plan. Betahistine is used in some settings; evidence and local availability vary. Central vertigo/stroke concern Urgent neurologic evaluation. Symptom relief must never delay imaging/referral where indicated. 2. Medicines and indicative adult doses Medicine Usual role / common adult regimen Key cautions Prochlorperazine Vestibular nausea/acute vertigo; common oral regimens are 5 mg three times daily or 5–10 mg as directed by local product guidance. Drowsiness, dystonia/EPS, hypotension, QT risk; avoid/seek advice in Parkinsonism and with other dopamine blockers. Cinnarizine Short-term vestibular suppression; commonly 15–30 mg up to three times daily depending on local formulation. Sedation, anticholinergic effects and parkinsonism risk; avoid driving and avoid prolonged use. Meclizine/cyclizine/promethazine Antihistamine options for nausea and motion-related vestibular symptoms; product-specific regimens vary. Anticholinergic burden, blurred vision, urinary retention, confusion and falls—especially in older adults. Betahistine Used in some protocols for Ménière-related vertigo; a common regimen is 16 mg three times daily initially, then maintenance in divided doses. Not a treatment for generic imbalance. Use caution in asthma and peptic-ulcer disease; efficacy varies. Diazepam Occasional specialist-directed rescue vestibular suppressant only. Dependence, falls and respiratory depression; avoid routine/long-term use and avoid with alcohol/opioids. Duration matters: use vestibular suppressants only for the shortest severe acute period, then reduce them and encourage mobilization/rehabilitation as clinically appropriate. Continuing a sedating medicine because the patient still feels “off balance” may increase falls without treating the cause. 3. Safe assessment and follow-up Confirm true vertigo versus presyncope, disequilibrium, anxiety or medication-related dizziness. Check onset, trigger, hearing loss/tinnitus, headache, neurologic symptoms, infection, trauma, cardiovascular symptoms and medicines. Assess gait, eye movements/nystagmus, hydration, blood pressure including postural measurements when relevant, glucose and focused neurologic signs. Review sedation, falls, anticholinergic burden, QT-risk drugs and ability to drive/work safely. Give a time-limited plan and explicit safety net; arrange repositioning/rehabilitation or referral where indicated. OSCE point Say: “I will first exclude stroke or another central cause. If this is a peripheral acute vestibular syndrome, I will use a short course of an antiemetic/vestibular suppressant only when symptoms are severe, then stop it early and support vestibular rehabilitation.” Further study Pharmacotherapy of vertigo — supplied slides Vertigo and dizziness guidance

Anticonvulsants (antiseizure medicines): prescribe for the seizure type Antiseizure medicines (ASMs) reduce seizure recurrence; they do not cure every cause of a seizure. Safe treatment begins with classification of seizure type, exclusion of acute symptomatic causes, counselling about adherence and safety, and one clear plan for titration and review. Choose monotherapy when possible and do not stop an effective ASM suddenly. Urgent rule A convulsive seizure lasting ≥5 minutes, repeated seizures without recovery, respiratory compromise, pregnancy-related seizure, serious injury or persistent altered consciousness is an emergency. Give ABCDE care and follow the local status-epilepticus protocol; this article is not a substitute for emergency orders. 1. Mechanisms and matching drug to syndrome Mechanistic group Examples Clinical point Sodium-channel modulation Carbamazepine, phenytoin, lamotrigine Often useful in focal-onset seizures; some may worsen particular generalised seizure types. Enhance GABA activity Benzodiazepines, phenobarbital, valproate Useful in acute seizures or selected long-term settings; sedation/respiratory depression matter. SV2A modulation Levetiracetam Few interactions but may cause irritability, agitation or mood change; renal clearance needs attention. Calcium-channel effects Ethosuximide, valproate Ethosuximide is mainly for absence seizures, not broad “convulsion treatment.” WHO recommends lamotrigine or levetiracetam as first-line monotherapy for focal-onset seizures; for generalised onset seizures, lamotrigine, levetiracetam or valproate may be options in men/boys and women/girls not of childbearing potential. In women and girls who may become pregnant, lamotrigine or levetiracetam are preferred first-line options because valproate carries substantial fetal risk. 2. Common maintenance doses: adult teaching table Medicine Typical initiation / titration Key monitoring and warnings Levetiracetam Common adult start 500 mg orally twice daily; increase gradually (often by 500 mg twice daily every 2 weeks) to response. Typical maximum 1,500 mg twice daily in many labels. Adjust for renal impairment. Ask about irritability, depression, aggression and suicidal thinking. Lamotrigine Must be titrated slowly; schedule depends on whether valproate or enzyme-inducing ASMs are also used. Stop and assess urgently for rash, mucosal lesions, fever or systemic symptoms (SJS/TEN risk). Never use a generic fast titration schedule when interactions differ. Carbamazepine Common adult start 100–200 mg once or twice daily; increase gradually. Maintenance often 800–1,200 mg/day in divided doses, product/indication dependent. FBC, LFT and sodium; rash/SJS, leucopenia, hyponatraemia. Strong enzyme inducer—review contraception, anticoagulants and many other drugs. Sodium valproate Dose is weight- and formulation-dependent; common adult total maintenance range is about 600–2,000 mg/day in divided or modified-release dosing. Major teratogenic/neurodevelopmental risk; avoid in pregnancy potential unless no suitable alternative and a formal risk-prevention pathway is used. Monitor LFT/FBC; watch weight, tremor, thrombocytopenia, pancreatitis. Phenytoin Maintenance often around 300 mg/day but has nonlinear kinetics; dose changes must be small and guided by clinical response/levels where used. Check interactions, albumin/renal context when interpreting levels, gingival hyperplasia, ataxia, rash and bone health. Phenobarbital Maintenance is protocol- and weight-dependent. Sedation, cognitive effects, respiratory depression, dependence and enzyme induction; do not stop abruptly. Medication-reconciliation pearl: record dose in mg, formulation, timing, adherence, recent vomiting/diarrhoea, new medicines and pregnancy potential before calling “treatment failure.” 3. Status epilepticus: the treatment sequence 0–5 minutes: ABCDE, protect from injury, time the seizure, check glucose, oxygen/suction, IV/IO access, pregnancy and cause. At 5 minutes: give a benzodiazepine by local protocol and monitor ventilation continuously. Persistent seizures: give a protocol-directed second-line loading ASM (such as levetiracetam, fosphenytoin/phenytoin or valproate depending on patient factors and local availability). Refractory seizures: anaesthesia/critical-care management, EEG where available and urgent search for cause. Do not copy a loading dose from a maintenance table. Emergency loading depends on weight, route, age, pregnancy, organ function, ECG/respiratory monitoring and the local protocol. 4. Pregnancy, contraception and long-term care Discuss pregnancy before initiation and at every review. Valproate is a particularly high-risk medicine in pregnancy. Enzyme-inducing ASMs can reduce hormonal-contraception effectiveness; provide a method-specific plan. Prescribe folate according to local guidance, but do not imply it removes ASM fetal risk. Encourage seizure diary, adherence, sleep regularity, avoidance of alcohol/recreational drugs, and advice about bathing, heights, driving, cooking and occupational risks. 5. Adverse effects and withdrawal All ASMs can cause dizziness, diplopia, sedation, ataxia and falls. New rash, fever, jaundice, severe abdominal pain, easy bruising, suicidal thoughts or marked behavioural change requires prompt review. Abrupt withdrawal can trigger rebound seizures/status epilepticus. If seizure-free and considering withdrawal, involve an experienced clinician and taper gradually with an individual risk discussion. OSCE checklist Identify the seizure phenotype; confirm adherence and exact formulation; screen for pregnancy/contraception and interactions; review adverse effects; document renal/liver tests where relevant; give a seizure-safety plan; and state when emergency help is needed. Explain why a seizure medicine cannot be selected from a “one drug for all seizures” list. Further study Anticonvulsants — supplied slides WHO antiseizure-medicine guidance

Sedative–hypnotics: useful medicines with a narrow safety margin Sedatives reduce anxiety or agitation; hypnotics promote sleep. Many agents do both depending on dose. They are useful for carefully selected short-term indications, but can impair breathing, cognition, balance and driving—and can cause dependence or dangerous withdrawal. Non-drug sleep treatment and treatment of the cause of insomnia should come first whenever possible. Learning outcomes: compare the major classes; select a short, safe course when indicated; state common adult dose ranges; recognise overdose and withdrawal; and avoid hazardous combinations. Essential dose warning Use current local guidance and the exact product label. The table gives common adult teaching doses, not a prescription. Older/frail adults, hepatic disease, respiratory disease, pregnancy, concurrent opioids/alcohol and sleep apnoea often require a different choice or no sedative at all. 1. Classes and mechanisms Class Examples Main action Clinical implication Benzodiazepines Diazepam, lorazepam, temazepam, midazolam Positive allosteric modulators at GABAA; increase the frequency of chloride-channel opening in the presence of GABA. Anxiolysis, sedation, anticonvulsant and muscle-relaxant effects; dependence and respiratory depression are major concerns. Z-drugs Zolpidem, zopiclone Act at GABAA benzodiazepine receptor sites with relative hypnotic selectivity. Short-term insomnia treatment; still cause falls, next-day impairment, complex sleep behaviours and dependence. Barbiturates Phenobarbital, thiopental At GABAA, prolong chloride-channel opening; at high concentration can directly depress CNS activity. Greater overdose danger and enzyme induction; limited routine hypnotic role but important in seizures/anaesthesia. Other sedating medicines Antihistamines, antipsychotics, melatonin agonists Different mechanisms. “Non-benzodiazepine” does not mean harmless; assess anticholinergic, metabolic, cardiovascular and fall risks. 2. Rational indications First assess duration, sleep pattern, caffeine/stimulant use, depression/mania, pain, withdrawal, thyroid disease, depression, trauma, domestic safety and obstructive sleep apnoea. For insomnia, use stimulus control, a regular wake time, exercise, reduction of late caffeine/alcohol and cognitive behavioural therapy for insomnia where available. A hypnotic should be short-term, goal-directed and reviewed early. Acute severe insomnia: a short course only after addressing precipitating causes. Acute seizures/status epilepticus: benzodiazepines are emergency medicines, used by protocol with airway and respiratory monitoring. Alcohol withdrawal, procedural sedation, acute severe agitation: specialist/protocol-directed use; these are not routine “sleep tablet” situations. 3. Common adult dosing examples Medicine / use Teaching dose range Critical safety point Temazepam for short-term insomnia Common usual adult dose 15 mg orally at bedtime; some need 7.5 mg and some labels allow 30 mg. In adults ≥65 years, 7.5 mg is a common cautious starting dose. Use the lowest effective dose and a short course. Do not combine with alcohol, opioids or other sedatives without specialist risk assessment. Zolpidem immediate-release for sleep-onset insomnia Take once immediately before bedtime only when 7–8 hours remain for sleep. Many labels start women at 5 mg, men at 5–10 mg; maximum 10 mg/night. No repeat dose during the same night. Next-day impairment and complex sleep behaviours can occur; avoid driving if impaired. Diazepam for selected acute anxiety/muscle spasm/withdrawal indications Regimens vary greatly by indication and patient. Use local protocol; avoid teaching it as a routine long-term anxiety medicine. Long half-life and active metabolites: accumulation, falls and prolonged sedation are common in older adults and liver disease. Lorazepam for acute seizures/agitation Emergency dose, route and repeat-dose limit must follow the local resuscitation/status epilepticus protocol. Give only where airway, oxygenation and ventilation can be monitored; respiratory depression may be delayed when other depressants are present. Phenobarbital Use only for a clearly defined indication and protocol-directed loading/maintenance plan. Major CNS/respiratory depression, enzyme induction and long half-life make casual dosing unsafe. Do not confuse the numbers: a bedtime dose for insomnia is not an emergency seizure dose, and oral formulations are not interchangeable with IV preparations. Always state the indication, route, formulation and monitoring environment. 4. High-risk groups and interactions Situation Why risk rises Practical response Opioids, alcohol, gabapentinoids or other sedatives Additive respiratory and CNS depression. Avoid combinations where possible; if unavoidable, document rationale, use the minimum dose and arrange close monitoring. Older/frail patient, falls, delirium or dementia Ataxia, confusion and cognitive impairment increase injury risk. Prefer non-drug approaches; if used, start lower, prescribe briefly and review urgently. Obstructive sleep apnoea, COPD or hypoventilation Reduced respiratory reserve; sedatives can worsen nocturnal hypoxaemia. Usually avoid or seek specialist advice; never use an unsupervised dose to “treat” breathlessness. Pregnancy/lactation Fetal/newborn sedation and withdrawal issues vary by medicine and timing. Use specialist obstetric/psychiatric guidance. Liver impairment Reduced metabolism and accumulation, especially with long-acting agents. Choose carefully, lower dose where appropriate and reassess frequently. 5. Dependence and withdrawal Regular benzodiazepine or Z-drug exposure can lead to tolerance and dependence. Abrupt cessation may cause rebound insomnia/anxiety, tremor, sweating, perceptual disturbance, agitation, seizures or delirium. Do not simply stop long-term therapy. Make an individualised, slow taper with one prescriber, regular review and psychological/non-drug support. The taper rate must respond to dose, duration, comorbidity and withdrawal symptoms. Overdose: do not be falsely reassured by sleepiness Assess ABCDE, respiratory rate, oxygen saturation, consciousness, glucose, temperature and co-ingestants. Give oxygen/ventilatory support as needed and seek toxicology/critical-care input. Flumazenil can precipitate seizures and withdrawal in dependent patients or mixed overdoses; it is not a routine “wake-up” antidote. Supportive care and airway protection are often the correct priorities. 6. Counselling checklist Use only the prescribed dose, at the prescribed time; never “top up” after a poor night. Do not drink alcohol or use recreational drugs; check cough/cold and pain medicines for sedatives. Do not drive, operate machinery or make safety-critical decisions while drowsy or the next day if impaired. Keep treatment short and attend review; report falls, memory problems, unusual sleep behaviours, low mood or breathing problems. Do not stop a regular long-term sedative abruptly without a taper plan. 7. OSCE station For a patient requesting “sleeping tablets,” ask about insomnia duration, sleep routine, caffeine/energy drinks, alcohol and drugs, pain, depression/mania, suicidality, snoring/apnoea, pregnancy, driving and existing sedatives. Explain non-drug treatment first. If a short course is justified, state the exact bedtime plan, duration, no-alcohol/no-opioid rule, driving advice and early review. Further study Sedatives and hypnotics — supplied slides Temazepam prescribing information

Cholinesterase inhibitors: symptomatic treatment in dementia Donepezil, rivastigmine and galantamine inhibit acetylcholinesterase, increasing acetylcholine at synapses. They may offer modest symptomatic benefit for cognition/function in selected people with Alzheimer disease and, for rivastigmine, Parkinson disease dementia. They do not reverse neurodegeneration. Good care also needs diagnosis, carer support, vascular-risk management, delirium prevention and realistic treatment goals. Before prescribing Check pulse, syncope/falls, conduction disease, asthma/COPD, weight loss, peptic-ulcer/GI-bleed risk, bladder outflow obstruction, seizures and anticholinergic medicines. Cholinergic effects can cause bradycardia, vomiting, fainting and weight loss. 1. Drug comparison and dose titration Medicine Typical adult initiation Titration and monitoring Donepezil 5 mg orally once daily, often at night (move to morning if vivid dreams/insomnia). After at least 4–6 weeks, increase to 10 mg once daily if tolerated. Typical maximum for mild–moderate disease is 10 mg/day; 23 mg is a specialist/product-specific option for selected severe disease after stable 10 mg treatment. Rivastigmine oral 1.5 mg twice daily with food. Increase slowly, commonly at ≥2-week intervals, to tolerance. GI adverse effects are common; stop and reassess significant vomiting/weight loss. Rivastigmine patch 4.6 mg/24 h patch once daily on intact skin. Increase after at least 4 weeks if tolerated (often to 9.5 mg/24 h; selected patients to 13.3 mg/24 h). Apply only one patch; remove the old patch first. If interrupted >3 days, restart at 4.6 mg/24 h and retitrate. Galantamine Formulation-dependent; commonly 4 mg twice daily immediate-release or 8 mg daily modified-release. Titrate slowly with food and hydration; check renal/hepatic suitability and CYP interactions. Assessment target: record baseline cognition, activities of daily living, behaviour, weight, pulse and carer observations. At review, continue only if benefit/tolerability and the person’s goals justify treatment. 2. Adverse effects and interactions Expected cholinergic effects include nausea, vomiting, diarrhoea, anorexia, weight loss, sweating, vivid dreams and muscle cramps. Serious concerns include bradycardia, heart block, syncope, falls, GI bleeding, bronchospasm and seizures. Review beta-blockers, digoxin and other rate-slowing medicines; also review anticholinergic drugs, which can oppose cognitive benefit and worsen confusion. 3. Patch and oral-medicine counselling For a patch: remove yesterday’s patch before applying one new patch; rotate sites; avoid damaged skin and external heat; seek help for severe rash. Take oral agents with food where advised; report persistent vomiting, black stool, fainting or markedly reduced intake. Do not use the medicine as a substitute for supervision, falls prevention, driving review, carer support or assessment of acute confusion. New confusion over hours/days is delirium until proven otherwise—look for infection, medicines, dehydration, pain, constipation and metabolic causes. 4. Cholinesterase inhibitors beyond dementia Neostigmine and pyridostigmine are also acetylcholinesterase inhibitors, used in different clinical contexts such as myasthenia gravis or reversal of non-depolarising neuromuscular blockade. They are not interchangeable with donepezil/rivastigmine. Excess cholinergic effect can produce salivation, sweating, bronchospasm, bradycardia, abdominal cramps, diarrhoea, miosis and weakness; emergency treatment is protocol- and cause-specific. OSCE checklist Confirm dementia subtype and treatment goal; obtain collateral history; check pulse, weight, falls/syncope, GI and respiratory history; review rate-slowing and anticholinergic medicines; explain slow titration and the expected modest symptomatic role; give patch-specific instructions where relevant; agree a review date and carer safety-net. Further study Acetylcholinesterase inhibitors — supplied slides Donepezil prescribing information