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Anti-Inflammatory Agents NSAIDs: relieve inflammatory pain, but prescription safety is part of the treatment Non-steroidal anti-inflammatory drugs (NSAIDs) are chemically diverse medicines that reduce pain, fever and inflammation mainly by reducing prostaglandin synthesis through cyclo-oxygenase (COX) inhibition. They are particularly useful for inflammatory nociceptive pain, but they can cause peptic ulcer/bleeding, acute kidney injury, fluid retention, hypertension, heart failure decompensation and cardiovascular events. Choosing an NSAID therefore means choosing the least-risk option for this patient, at the lowest effective dose for the shortest necessary duration. Do not prescribe before this safety screen Ask about ulcer or GI bleed, kidney disease/eGFR, dehydration, heart failure/ischaemic heart disease/stroke, hypertension, asthma triggered by aspirin/NSAIDs, pregnancy, anticoagulants/antiplatelets, corticosteroids, SSRIs/SNRIs, diuretics and ACE inhibitors/ARBs. Do not combine two systemic NSAIDs. A “painkiller” bought over the counter may already contain one. Lesson map 1. FoundationsArachidonic acid, COX-1/COX-2 and prostanoids. 2. ClassificationTraditional, preferential and selective COX-2 drugs. 3. Individual medicinesAspirin, ibuprofen, naproxen, diclofenac, indomethacin, ketorolac, mefenamic acid, piroxicam and coxibs. 4. Clinical usePain, fever, rheumatic disease, dysmenorrhoea, gout and PDA. 5. SafetyGI, renal, CV, pregnancy, interactions and monitoring. 1. What makes an NSAID different from an opioid or paracetamol? NSAIDs: analgesic, antipyretic and (at adequate doses) anti-inflammatory; no opioid receptor action, no euphoria, no physical dependence. Best for inflammatory/nociceptive pain. Opioids: act mainly in CNS at opioid receptors; can treat severe pain but have sedation, respiratory depression, tolerance and dependence risks. Paracetamol (acetaminophen): analgesic-antipyretic with negligible peripheral anti-inflammatory effect. It is not a classic NSAID and does not substitute for an anti-inflammatory drug in active inflammatory arthritis. Neuropathic pain: burning/electric/shooting pain from nerve lesion often responds poorly to NSAIDs; identify the mechanism rather than escalating an NSAID. NSAIDs reduce prostaglandin-mediated peripheral nociceptor sensitisation. They are therefore more effective for toothache, dysmenorrhoea, sprain, inflammatory arthritis, gout and postoperative inflammatory pain than for pure visceral colic, ischaemic pain or neuropathic pain. 2. Arachidonic-acid pathway and COX isoenzymes Pathway component Normal/clinical role What inhibition explains Phospholipase A2 Releases arachidonic acid from membrane phospholipid. Glucocorticoids act upstream here; NSAIDs do not block all inflammatory mediators. COX-1 Constitutive “housekeeping” prostanoids in gastric mucosa, platelets and kidney. Loss of mucus/bicarbonate and mucosal blood flow → ulcer/bleeding; loss of TXA2 → platelet effects; reduced renal perfusion reserve. COX-2 Induced at inflammation; also constitutive in kidney, brain, vascular/endothelial and reproductive sites. Analgesia, antipyresis and anti-inflammatory effect; COX-2 selectivity does not eliminate renal/CV risk. PGE2/PGI2 Vasodilation, pain sensitisation, fever set-point, gastric/renal protection; PGI2 opposes platelet aggregation. Less pain/fever/swelling but GI injury, reduced renal blood flow, salt-water retention and possible CV risk. TXA2 Platelet aggregation and vasoconstriction. Aspirin’s irreversible platelet COX-1 inhibition produces sustained antiplatelet effect. Mechanism summary: most NSAIDs reversibly inhibit COX-1 and COX-2. Aspirin irreversibly acetylates both, so the antiplatelet effect outlasts the drug concentration because platelets cannot synthesize new COX. Selective COX-2 drugs spare platelet COX-1 but reduce endothelial PGI2, which helps explain their prothrombotic concern. 3. Pharmacological actions Action Mechanism Clinical consequence Analgesic Less PGE2/PGI2 sensitisation of nociceptors; some central spinal effect. Relieves inflammatory mild-moderate pain; ceiling effect occurs. Antipyretic Less hypothalamic PGE2 resets a raised fever set-point. Lowers fever, not normal temperature; does not treat heat stroke—use cooling/supportive care. Anti-inflammatory Less prostaglandin-mediated vasodilation, oedema and inflammatory-cell effects. Reduces pain, tenderness, swelling and stiffness but does not cure RA or prevent structural disease progression. Antiplatelet Reduced TXA2; sustained only with aspirin. Low-dose aspirin has a distinct cardiovascular indication; other NSAIDs are not substitutes. Ductus closure Reduced PGE2/PGI2 maintains less ductal patency. Indomethacin/ibuprofen may close PDA under neonatal protocol; late-pregnancy exposure can close it prematurely. 4. Classification: learn by COX selectivity and by chemical family Group Examples High-yield point Salicylate Aspirin Unique irreversible COX inhibition; antiplatelet use and salicylate toxicity/Reye syndrome. Propionic-acid derivatives Ibuprofen, naproxen, ketoprofen, flurbiprofen Common oral agents; ibuprofen short acting, naproxen longer acting. Acetic-acid/indole derivatives Diclofenac, aceclofenac, indomethacin, sulindac, ketorolac Diclofenac widely used but CV risk matters; indomethacin potent but CNS/GI toxicity; ketorolac short-term only. Fenamate Mefenamic acid Often taught for dysmenorrhoea; GI upset/diarrhoea prominent. Oxicam Piroxicam, tenoxicam, meloxicam Long half-life; prolonged exposure also prolongs adverse effects. Preferential COX-2 Meloxicam, etodolac; diclofenac has relative COX-2 preference Not equivalent to complete GI or CV safety. Selective COX-2 (coxibs) Celecoxib, etoricoxib, parecoxib Less endoscopic GI injury/platelet effect, but CV, BP, fluid and renal risks remain. 5. Individual-drug profiles Aspirin (acetylsalicylic acid) The prototype NSAID and the only commonly used irreversible COX inhibitor. At low dose it preferentially blocks platelet TXA2 and is used for antiplatelet indications; at analgesic/anti-inflammatory dose it has the familiar NSAID actions and risks. Do not confuse low-dose cardiovascular aspirin with analgesic aspirin. Uses: antiplatelet secondary prevention/ACS where indicated; pain/fever and inflammatory conditions are now less common uses because safer alternatives are often available. Do not give for viral illness in children/adolescents: association with Reye syndrome (acute hepatic encephalopathy). Adverse effects: dyspepsia, ulcer/bleeding, bronchospasm in susceptible asthma, hypersensitivity, renal fluid retention, salicylism and overdose. Salicylism: tinnitus, reduced hearing, dizziness, nausea/vomiting, sweating and hyperventilation. Acute salicylate poisoning: early respiratory alkalosis, then high-anion-gap metabolic acidosis in severe toxicity; assess urgently and manage with toxicology/emergency protocol (including alkalinisation and dialysis when indicated). Ibuprofen, naproxen and mefenamic acid Ibuprofen: short-acting propionic-acid NSAID; common for brief musculoskeletal/dental pain, dysmenorrhoea and fever. Still carries GI/renal/CV risk and can interfere with aspirin’s antiplatelet action depending on timing. Naproxen: longer half-life and good anti-inflammatory effect; often used for inflammatory arthropathy, acute gout or dysmenorrhoea. Its risk profile must still be individualised. Mefenamic acid: fenamate used in some settings for dysmenorrhoea/short-term pain; diarrhoea and GI intolerance are notable. Avoid casual repeated courses without diagnosis of abnormal uterine bleeding. Diclofenac, indomethacin, ketorolac and piroxicam Diclofenac: potent analgesic/anti-inflammatory with good synovial penetration; used for acute musculoskeletal, dental, postoperative and rheumatic pain. Review CV risk carefully. Indomethacin: potent anti-inflammatory; useful in selected acute gout, spondyloarthropathy and PDA protocols. Headache, dizziness, confusion and GI toxicity make it a poor casual choice, especially in older people. Ketorolac: potent short-term analgesic for acute moderate pain; its GI/renal/bleeding toxicity limits duration. It is not a chronic-pain

Blood-Modifying Drugs Antifibrinolytics: stabilise fibrin clots when excessive fibrinolysis is causing harm Antifibrinolytic medicines reduce fibrin breakdown by inhibiting plasminogen activation or plasmin activity. They stabilise haemostatic clots; they do not replace resuscitation, source control, blood products, uterotonics or surgery when these are required. Correct indication, timing, thrombosis risk and renal function determine safe use. Safety first In major trauma and postpartum haemorrhage (PPH), tranexamic acid is time-critical and adjunctive. Activate the emergency/major-haemorrhage pathway, treat the bleeding source and follow the current local protocol. Do not use a general learning page to choose emergency doses. Lesson map MechanismPreserve fibrin by limiting plasmin activity. DrugsTranexamic acid, aminocaproic acid, aprotinin. UsesPPH, trauma, surgery and heavy menstrual bleeding. SafetyThrombosis, renal impairment, seizures and haematuria. 1. Fibrinolysis and the drug target After a fibrin clot has achieved haemostasis, tissue plasminogen activator (tPA) and urokinase convert plasminogen to plasmin. Plasmin degrades fibrin into soluble degradation products. This normal process limits unnecessary clot persistence; it becomes harmful when premature or excessive fibrinolysis worsens bleeding. Component Function Drug relevance tPA/uPA Activate plasminogen. TXA and aminocaproic acid competitively reduce plasminogen binding/activation at fibrin. Plasmin Breaks down fibrin and, systemically, can reduce fibrinogen. Inhibition preserves clot stability when clinically appropriate. PAI and α2-antiplasmin Natural inhibitors of fibrinolysis. Antifibrinolytics reinforce this direction; excessive treatment may favour thrombosis. 2. Classification and pharmacology Medicine Mechanism Key point Tranexamic acid (TXA) Synthetic lysine analogue; blocks lysine-binding sites on plasminogen/plasmin and reduces fibrin breakdown. Main commonly used agent; oral and IV pathways differ. Renal excretion means protocol-led dose adjustment in renal impairment. Aminocaproic acid Lysine analogue with similar inhibition of plasminogen activation/fibrin binding. Used in selected specialist perioperative/haematology settings. Aprotinin Serine protease inhibitor that inhibits plasmin and other proteases. Restricted/specialist use; not a routine first-line substitute for TXA. 3. Clinical indications Situation Role Clinical rule PPH Early IV TXA is part of WHO-recommended care for clinically diagnosed PPH, ideally within 3 hours of birth. Give alongside uterine massage, uterotonics, IV fluids, examination/source control and escalation. Major trauma with significant bleeding Early TXA may reduce bleeding-related mortality in protocolled trauma care. Record injury time and manage ABCDE/major haemorrhage; TXA is adjunctive to blood products and surgery. Surgery May reduce perioperative blood loss/transfusion in selected operations. Use surgical/anaesthetic protocol and review thrombosis history and renal function. Heavy menstrual bleeding Oral TXA is a non-hormonal option for some patients. Assess pregnancy, anaemia and cause of bleeding; consider personal thrombosis risk. Haemophilia/dental or mucosal bleeding Adjunct to factor replacement and local measures in selected pathways. Follow haematology/dental protocol. 4. Pre-treatment checklist Confirm the bleeding source and whether excessive fibrinolysis is plausible. For trauma/PPH, identify onset time and start definitive bleeding management immediately. Ask about DVT/PE/arterial thrombosis, thrombophilia, seizures, renal disease and allergy. Review anticoagulants, antiplatelets and other pro-thrombotic medicines. Check renal function and, in major bleeding, FBC/coagulation/fibrinogen and group-and-save/crossmatch as the protocol directs. In haematuria, seek senior/urology advice: clots can obstruct the urinary tract, especially with upper-tract bleeding. 5. Contraindications, cautions and adverse effects Haemostasis is not the same as thrombosis Avoid or seek specialist direction in active thromboembolic disease, uncontrolled DIC, significant renal impairment, unexplained upper urinary-tract haematuria and situations where clot extension could cause harm. Exact exclusions vary by product and indication. Thromboembolism: assess new unilateral leg swelling, pleuritic chest pain, sudden dyspnoea and focal neurological symptoms. Renal impairment: accumulation can raise adverse-effect risk; adjust treatment by protocol. Seizures: particularly reported with high-dose IV surgical use; monitor neurological status in high-risk settings. Visual symptoms: altered colour vision or visual disturbance requires prompt assessment. Common effects: nausea, vomiting, diarrhoea, dizziness and headache. 6. Monitoring and counselling In acute bleeding, monitor pulse, BP, ongoing blood loss, urine output, mental state and response to definitive treatment. Trend FBC, coagulation/fibrinogen and renal function as directed; a laboratory value alone does not prove haemostasis. Administer IV TXA at the prescribed rate; rapid administration can cause hypotension. For heavy periods, explain that TXA reduces bleeding but does not remove the underlying cause. Seek urgent help for chest pain, dyspnoea, new leg swelling, focal neurological symptoms, visual disturbance or persistent/severe bleeding. 7. Antifibrinolytics versus thrombolytics Feature Thrombolytics Antifibrinolytics Action Activate plasmin and dissolve fibrin clot. Inhibit plasminogen/plasmin action and preserve fibrin. Typical emergency role Selected STEMI, ischaemic stroke, massive PE. PPH, trauma, surgical/mucosal bleeding reduction. Main danger Major bleeding/intracranial haemorrhage. Potential thrombosis or inappropriate clot persistence. High-yield cases and OSCE points PPHCall for help, commence the full first-response bundle and give protocolled early TXA without delaying source control. Major traumaRecord injury time; manage ABCDE and major haemorrhage. TXA is time-sensitive and adjunctive. Heavy periods + prior PEDo not issue TXA casually; assess thrombosis history and obtain prescriber review. HaematuriaIdentify source and escalate rather than routinely giving an antifibrinolytic. Define antifibrinolytic and name TXA as the common lysine analogue. State the WHO PPH principle: early IV TXA within 3 hours of birth, alongside standard care. List thrombosis risk, renal impairment, seizures, visual symptoms and haematuria as core safety checks. Further study Course reference: Fibrinolytics and Antifibrinolytics—SlideShare. Review the WHO PPH TXA recommendation, NICE heavy menstrual bleeding guidance and MedlinePlus TXA safety information. Local protocols determine emergency dose, route and exclusions.

Blood-Modifying Drugs Thrombolytics: dissolve an established fibrin clot when time matters Thrombolytic (fibrinolytic) drugs activate plasminogen to plasmin, which breaks down fibrin within an existing thrombus. They can rapidly restore perfusion in selected, time-critical emergencies, but may cause catastrophic bleeding. Their use is hospital-based, protocol-led and never a substitute for diagnostic confirmation, contraindication screening or mechanical reperfusion where that is indicated and available. Emergency safety rule Before thrombolysis, exclude haemorrhage and actively search for contraindications. Suspected aortic dissection, active internal bleeding, intracranial haemorrhage, recent high-risk surgery/trauma, severe uncontrolled hypertension or a major bleeding diathesis can make treatment dangerous. For suspected stroke, urgent brain imaging is required to distinguish ischaemic from haemorrhagic stroke. Lesson map MechanismPlasminogen → plasmin → fibrin degradation. DrugsStreptokinase, urokinase and tissue plasminogen activators. UsesSTEMI, acute ischaemic stroke, massive PE and selected catheter occlusion. SafetyTime window, imaging, bleeding, monitoring and rescue. 1. Physiological fibrinolysis and mechanism Haemostasis forms a fibrin mesh to stabilise the platelet plug. The endogenous fibrinolytic system limits clot growth: plasminogen is incorporated into the clot and, when activated to plasmin, degrades fibrin into soluble fibrin-degradation products. Plasmin can also reduce circulating fibrinogen and other coagulation proteins, which explains the systemic bleeding risk of less fibrin-selective agents. Step Key event Clinical implication Clot formation Fibrin stabilises a platelet plug. Antiplatelets and anticoagulants prevent extension/new clot formation; they do not directly lyse an established clot. Drug activation Thrombolytic converts plasminogen to plasmin. Fibrin is degraded, potentially restoring blood flow. Reperfusion Occluded vessel may reopen. Benefit decreases with delay; treat only within the appropriate indication-specific window. Re-occlusion prevention Platelets and coagulation can re-form thrombus. Antiplatelet/anticoagulant therapy may be prescribed as part of a defined pathway, but adds bleeding risk. 2. Classification Group Examples Key pharmacology Non-fibrin-specific activators Streptokinase, urokinase, anistreplase Activate circulating and clot-bound plasminogen; more systemic fibrinolysis. Streptokinase is antigenic because it is streptococcal-derived. Fibrin-enhanced tissue plasminogen activators (tPA) Alteplase, reteplase, tenecteplase Preferential activity at fibrin-rich clot; recombinant products. Fibrin selectivity does not eliminate major bleeding risk. Adjunct/reversal concepts Antifibrinolytics: tranexamic acid, aminocaproic acid Inhibit plasminogen activation/fibrinolysis. They may be considered in serious bleeding only under specialist, indication-specific guidance. 3. Drug profiles Drug Important features High-yield safety point Streptokinase Indirect plasminogen activator forming a streptokinase–plasminogen complex; inexpensive and non-fibrin-specific. Fever, hypotension, allergy/anaphylaxis and neutralising antibodies can occur. Avoid repeat exposure or recent streptococcal infection according to protocol. Urokinase Direct plasminogen activator; non-antigenic. Systemic bleeding remains the principal hazard; specialist use varies by availability and indication. Alteplase Recombinant tPA with short half-life; commonly administered in a protocolised bolus/infusion regimen. Used in selected acute ischaemic stroke and other thrombotic emergencies; careful timing and imaging are essential. Reteplase Modified tPA with longer half-life than alteplase. Often given in protocolled bolus dosing for selected myocardial infarction pathways. Tenecteplase Genetically modified tPA with higher fibrin specificity and longer half-life; convenient single-bolus administration. Current stroke guidance in several settings supports tenecteplase as an alternative to alteplase for eligible acute ischaemic stroke patients; follow local protocol. 4. Indications: match the drug to the emergency Thrombolysis is not “one treatment for all clots.” Eligibility depends on the diagnosis, onset time, imaging, severity, available reperfusion service, comorbidities and bleeding risk. Condition Role of thrombolysis Key decision Acute ischaemic stroke IV thrombolysis may improve outcome in eligible patients within the local time window; many guidelines use up to 4.5 hours from known onset in selected adults. Establish last-known-well time, perform urgent brain imaging, assess severity/BP/glucose/anticoagulant exposure and follow stroke-team protocol. Do not thrombolyse haemorrhagic stroke. ST-elevation MI (STEMI) Fibrinolysis may be used when timely primary PCI cannot be delivered and no contraindication exists. ECG diagnosis, symptom timing and transfer/PCI pathway determine choice. PCI remains preferred where promptly available. Massive/high-risk pulmonary embolism May be considered for PE with haemodynamic instability/shock. Balance life-threatening obstructive shock against bleeding; involve senior/emergency/critical-care team. Acute limb-threatening arterial occlusion or catheter occlusion Catheter-directed/local thrombolysis may be used in selected specialist settings. Vascular/interventional radiology assessment is required; not routine self-directed systemic therapy. 5. Pre-thrombolysis checklist Confirm diagnosis and timing: symptom onset/last-known-well; ECG or imaging as required. In stroke, check non-contrast brain imaging first. Establish baseline: ABCDE assessment, neurological findings where relevant, weight, blood pressure, blood glucose, FBC/platelets, coagulation tests and renal function as the protocol requires. Ask specifically about bleeding risk: previous intracranial haemorrhage, recent stroke/head injury/neurosurgery, known intracranial lesion, active bleeding, recent major surgery/trauma, peptic ulcer and pregnancy/postpartum state. Review antithrombotics: anticoagulants (including DOAC timing), heparin, warfarin/INR and antiplatelets. These can change eligibility. Exclude mimics/alternative catastrophes: haemorrhagic stroke, aortic dissection, severe uncontrolled hypertension and hypoglycaemia in suspected stroke. Explain and document: benefit, serious bleeding risk, consent/emergency decision process, exact drug/time, checks and escalation plan. 6. Contraindications and cautions Absolute or major exclusions are indication-specific Use the current local protocol; lists differ slightly between stroke, STEMI and PE. The following are major red flags that require senior review and usually exclude systemic thrombolysis. Active internal bleeding or known serious bleeding disorder. Current or previous intracranial haemorrhage; suspected subarachnoid haemorrhage; significant intracranial tumour, arteriovenous malformation or aneurysm according to protocol. Recent significant head trauma, intracranial/intraspinal surgery or recent major surgery/trauma. Severe uncontrolled hypertension; in stroke pathways BP must be within the protocol threshold before treatment. Marked thrombocytopenia or clinically important abnormal coagulation from anticoagulants. Suspected aortic dissection, active infective endocarditis, recent GI/GU bleeding or active peptic ulcer—assess the specific guideline. Pregnancy, early postpartum period, diabetic proliferative retinopathy and recent invasive/traumatic puncture are important relative-risk discussions, not automatic shortcuts. 7. Administration and monitoring principles Thrombolytics are administered only in a setting equipped for immediate resuscitation, serial assessment and management of intracranial or major extracranial bleeding. Never memorise one dose across all conditions. Drug, dose, bolus/infusion method and weight limit differ by agent and indication. During treatment Why it matters Frequent vital signs, consciousness/neuro checks and bleeding inspection Early recognition of intracranial haemorrhage, shock, allergy or reperfusion complication. Avoid unnecessary IM injections, arterial punctures, urinary catheterisation and traumatic procedures Puncture sites can become major bleeding sources; if necessary, use the safest approach and prolonged compression. Monitor

Blood-Modifying Drugs Antiplatelet drugs: prevent platelet-rich arterial thrombosis Antiplatelet drugs reduce platelet activation, adhesion and aggregation; they do not dissolve an established clot. They are central to secondary prevention after arterial events (myocardial infarction, ischaemic stroke/TIA and peripheral arterial disease) and to acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). Prescribing always balances thrombosis prevention against bleeding risk, diagnosis, renal/hepatic function, interacting medicines and the planned duration. Safety first Do not stop aspirin, clopidogrel, prasugrel or ticagrelor after an ACS or coronary stent without the treating cardiology/medical team. Premature interruption can cause stent thrombosis, myocardial infarction or death. Active major bleeding, suspected intracranial bleeding, haemodynamic instability, or urgent surgery requires immediate senior assessment and protocol-led management. Lesson map 1. PhysiologyPrimary haemostasis and platelet plug formation. 2. ClassesCOX-1, P2Y12, PDE and GP IIb/IIIa inhibitors. 3. UsesACS/PCI, secondary prevention, stroke and PAD. 4. SafetyBleeding, interactions, procedures and counselling. 1. Why antiplatelet drugs work: primary haemostasis Stage What happens Drug relevance Vessel injury Collagen and von Willebrand factor (vWF) become exposed; platelets adhere through surface glycoproteins. Antiplatelets chiefly target the platelet response, not fibrin production. Activation Platelets change shape and release ADP, thromboxane A2 (TXA2), serotonin and other mediators. Aspirin reduces TXA2; P2Y12 inhibitors block ADP signalling. Aggregation Activated GP IIb/IIIa binds fibrinogen, cross-linking platelets into a platelet plug. GP IIb/IIIa inhibitors block this final common pathway. Secondary haemostasis Thrombin generates fibrin to stabilise the clot. Anticoagulants mainly act here; combination therapy substantially increases bleeding risk. Clinical distinction: platelet-rich “white” thrombi are typical of high-shear arterial disease (coronary, cerebral and peripheral arteries); fibrin-rich venous thrombi are principally managed with anticoagulants. The distinction is useful, but real patients may need both drug groups for separate indications. 2. Classification and key mechanisms Class Examples Mechanism and practical point COX-1 inhibitor Aspirin Irreversibly acetylates platelet COX-1, reducing TXA2. Effect lasts for the affected platelet’s lifespan. P2Y12 receptor inhibitors Clopidogrel, prasugrel, ticagrelor; IV cangrelor Block ADP-dependent platelet activation and GP IIb/IIIa activation. Clopidogrel/prasugrel are prodrugs; ticagrelor is direct and reversible. Phosphodiesterase/adenosine pathway agents Dipyridamole; cilostazol Increase platelet cAMP and reduce aggregation. Indication varies; cilostazol is avoided in heart failure. GP IIb/IIIa inhibitors Abciximab, eptifibatide, tirofiban IV specialist drugs blocking fibrinogen-mediated platelet cross-linking; used selectively around high-risk PCI/ACS. PAR-1 antagonist Vorapaxar Blocks thrombin-mediated platelet activation; specialist use only because of serious bleeding risk. 3. Aspirin Mechanism and uses At antiplatelet doses, aspirin irreversibly suppresses platelet TXA2 production. Platelets cannot replace COX-1, whereas endothelial cells can resynthesise it. Aspirin is commonly used for secondary prevention of myocardial infarction, ischaemic stroke/TIA and peripheral arterial disease, and as one component of dual antiplatelet therapy (DAPT) for appropriate ACS/PCI patients. It is not a routine self-started medicine for everyone: primary-prevention benefit must be weighed against bleeding. Important adverse effects: dyspepsia, gastritis/ulceration, gastrointestinal bleeding, bruising, hypersensitivity/bronchospasm and rarely intracranial bleeding. Major cautions: active bleeding, previous serious aspirin hypersensitivity, peptic ulcer disease, asthma with NSAID sensitivity, severe liver disease and concurrent medicines that increase bleeding. Children and adolescents: avoid aspirin in viral illness unless a specialist indication exists because of Reye syndrome risk. Interaction pearl: ibuprofen and other NSAIDs can increase gastrointestinal bleeding; avoid self-medication and follow local advice on timing/alternatives. 4. P2Y12 inhibitors Medicine High-yield pharmacology Safety detail Clopidogrel Irreversible thienopyridine prodrug activated mainly through CYP2C19. Used alone when aspirin is unsuitable and with aspirin when DAPT is indicated. Bleeding, GI upset/rash; rare thrombotic thrombocytopenic purpura/neutropenia. Omeprazole and esomeprazole may reduce activation—use a prescriber/pharmacist-approved gastroprotection plan. Prasugrel Irreversible thienopyridine with rapid, potent platelet inhibition; specialist ACS/PCI use. Higher bleeding risk; generally contraindicated with prior stroke/TIA and used cautiously in older or low-weight patients under cardiology guidance. Ticagrelor Direct, reversible oral P2Y12 inhibitor, usually taken more than once daily according to the prescribed regimen. Bleeding, dyspnoea and bradyarrhythmia can occur; review CYP3A interactions and adherence carefully. Cangrelor Rapid-onset, reversible IV P2Y12 inhibition. Used in monitored specialist/PCI settings; bleeding is the key toxicity. Do not interchange P2Y12 agents or change their dose/duration casually. The indication, timing of ACS/PCI, bleeding risk, previous stroke/TIA, drug interactions and local protocol determine the choice. 5. Other antiplatelet agents Dipyridamole: increases extracellular adenosine and platelet cAMP. In some settings it is combined with aspirin for selected secondary stroke-prevention regimens. Headache, flushing and hypotension limit use; confirm the indication locally. Cilostazol: PDE-3 inhibitor with antiplatelet and vasodilator actions, used in selected intermittent claudication pathways. Avoid in heart failure. GP IIb/IIIa inhibitors: powerful IV agents used by specialist teams in selected high-risk PCI/ACS cases. Monitor for bleeding and acute thrombocytopenia; renal adjustment applies to some agents. 6. Core clinical indications Situation Usual principle Critical caution Acute coronary syndrome Aspirin plus a P2Y12 inhibitor is a major component of care alongside reperfusion/anticoagulation decisions. Agent and duration are guideline-, procedure- and bleeding-risk-specific. PCI/coronary stent DAPT reduces stent thrombosis and recurrent MI. Never stop either component early without the treating cardiology team. Prior MI/PAD Long-term single antiplatelet therapy is often used for secondary prevention. Confirm diagnosis, bleeding history and concurrent anticoagulation. Ischaemic stroke/TIA Antiplatelet treatment is used for non-cardioembolic disease; short-course DAPT may be used in selected acute pathways. Atrial fibrillation-related stroke prevention usually requires anticoagulation, not antiplatelet substitution. Mechanical/prosthetic valve or VTE Antiplatelets may occasionally have a specific additional role. They do not replace required anticoagulation; specialist direction is essential. DAPT rule DAPT means aspirin + a P2Y12 inhibitor. It is not automatically lifelong and it is not interchangeable with anticoagulation. Duration must be documented, reviewed and individualised by the relevant guideline/team. Adding an anticoagulant (triple therapy) markedly increases bleeding risk and should follow a defined specialist plan. 7. Pre-treatment and follow-up checklist Confirm the indication: ACS, PCI/stent, secondary prevention, stroke/TIA or PAD. Record bleeding history: previous GI or intracranial bleed, ulcer disease, anaemia, thrombocytopenia, liver disease, alcohol excess and recent surgery. Review all medicines: anticoagulants, NSAIDs, corticosteroids, SSRIs/SNRIs, other antiplatelets, herbal products and PPI selection with clopidogrel. Check baseline FBC/platelets; consider renal/liver function and pregnancy status where clinically relevant. Document the drug, reason, intended duration, review date and stop plan. For

Blood-Modifying Drugs Anticoagulants: prevent or treat thrombosis while actively managing bleeding risk Anticoagulants reduce formation and extension of fibrin-rich clots; they do not “dissolve” an established clot. Their benefit can be lifesaving in venous thromboembolism (VTE), atrial fibrillation and selected cardiac/prosthetic-valve settings, but every prescription must balance thrombosis risk against bleeding risk, renal function, drug interactions, pregnancy status and planned procedures. Safety first Major bleeding, haemodynamic instability, suspected intracranial bleeding, spinal/epidural haematoma, or urgent surgery requires emergency assessment and protocol-led reversal. Do not improvise anticoagulant doses, bridging or reversal from a summary page. 1. Haemostasis and where the drugs act Stage Key event Drug relevance Primary haemostasis Platelet adhesion/aggregation creates initial plug Mainly targeted by antiplatelet drugs, not the focus here. Secondary haemostasis Coagulation cascade generates thrombin; thrombin turns fibrinogen into fibrin Heparins, warfarin and DOACs reduce thrombin or factor Xa activity. Fibrinolysis Plasmin breaks down fibrin Thrombolytics act here; anticoagulants prevent clot propagation rather than lyse clot. 2. Core classification Unfractionated heparin (UFH) Parenteral indirect anticoagulant. Potentiates antithrombin, inhibiting IIa (thrombin) and Xa. Rapid onset/offset; adjustable infusion; monitored with aPTT or anti-Xa per protocol. Low-molecular-weight heparin (LMWH) Enoxaparin, dalteparin. More anti-Xa than anti-IIa activity, predictable SC effect and usually no routine laboratory monitoring. Renal function and body weight matter. Vitamin-K antagonist Warfarin inhibits vitamin-K recycling, reducing synthesis of II, VII, IX and X and proteins C/S. Delayed onset; requires INR monitoring and has many interactions. DOACs Apixaban/rivaroxaban/edoxaban inhibit factor Xa; dabigatran directly inhibits thrombin. Fixed-dose regimens are common, but renal function, indication and interactions still determine suitability. 3. Indications: ask “which clot, which patient, which duration?” Treatment and secondary prevention of DVT and pulmonary embolism. Prevention of embolic stroke in eligible atrial fibrillation. Mechanical heart valves and selected valvular disease—warfarin remains important; DOAC suitability must be checked carefully. Perioperative, hospital or obstetric thromboprophylaxis in selected high-risk patients. Acute coronary and procedural settings with specialist protocols. Anticoagulant choice is indication-specific. A drug appropriate for non-valvular AF may be wrong for mechanical valves, severe renal impairment, pregnancy or antiphospholipid syndrome. “Blood thinner” is not an adequate prescription category. 4. Mechanism, onset and monitoring table Group Main target Onset/monitor Important practical point UFH Antithrombin → IIa and Xa Immediate IV; aPTT/anti-Xa according to protocol Preferred in some unstable, high-bleeding-risk or rapidly reversible situations; monitor platelets for HIT. LMWH Antithrombin → Xa > IIa SC; routine anti-Xa not usually needed Adjust/avoid according to renal function and indication; weight-based treatment dosing is common. Warfarin Vitamin-K epoxide reductase Delayed; PT/INR Early protein-C reduction can create transient hypercoagulability; some acute indications need heparin overlap. Factor-Xa DOACs Xa Rapid oral effect; no routine INR Assess renal/hepatic function, adherence and interacting P-gp/CYP3A4 medicines. Dabigatran Direct thrombin (IIa) Rapid oral effect; no routine INR Renal clearance is important; check product instructions and local protocol. 5. Before starting: the anticoagulation safety checklist Confirm the indication, intended dose and duration; distinguish prophylaxis from treatment. Document weight, age, pregnancy possibility, renal function, liver disease, previous bleeding, falls risk, alcohol use and adherence ability. Baseline tests as relevant: FBC/platelets, creatinine/eGFR, liver tests, PT/INR/aPTT; pregnancy testing where clinically appropriate. Review every medicine: NSAIDs, aspirin/antiplatelets, SSRIs, antibiotics/antifungals, antiepileptics, herbal products and other anticoagulants. Ask about planned dental, surgical, spinal/epidural or invasive procedures before the first dose. 6. Warfarin: the exam and ward essential Warfarin’s effect is measured by INR. For many indications the target is 2.0–3.0, but targets differ (for example, certain mechanical valves), so use the documented indication-specific range. Dose changes must be guided by a monitored protocol. Warfarin interacts with many medicines and with inconsistent vitamin-K intake. Counsel a consistent dietary pattern rather than telling patients to avoid all green vegetables. Warfarin counselling Take at the same time each day; never double a missed dose without advice. Attend INR tests and carry anticoagulant identification. Tell every clinician/dentist/pharmacist before new medicines or procedures. Report bleeding, pregnancy, illness with poor intake/diarrhoea, or major diet/alcohol change. 7. Heparin and HIT Heparin-induced thrombocytopenia (HIT) is an immune, prothrombotic complication—platelets fall but thrombosis risk rises. Suspect it with a significant platelet fall or new thrombosis after heparin exposure. Stop all heparin and obtain urgent senior/specialist guidance; do not simply “give platelets” or switch casually to LMWH because cross-reactivity may occur. UFH is reversed with protamine. Protamine partly reverses LMWH; follow the local emergency protocol. 8. DOACs: simple dosing does not mean zero monitoring DOACs have predictable pharmacokinetics and do not need routine INR testing, but patients still need periodic renal function, liver function, FBC, adherence and interaction review. Their anticoagulant effect can decline within about 12–24 hours after the last dose, so missed doses matter. Do not use INR to measure their activity or use a normal INR as proof that there is no clinically important DOAC effect. Procedure and neuraxial safety Timing of interruption/restart depends on the drug, renal function, bleeding risk and procedure. Spinal/epidural procedures carry a rare but devastating haematoma risk. Liaise with anaesthesia/surgery and follow the local peri-procedural anticoagulation protocol. 9. Bleeding: immediate structured response Step Action 1. Stabilise ABC assessment, haemodynamics, IV access, blood group/crossmatch and resuscitation as needed. 2. Identify drug/timing Name, last dose, indication, renal function, co-medications and any overdose. 3. Stop contributing agents Withhold anticoagulant; review antiplatelets/NSAIDs and local haemostatic measures. 4. Laboratory/imaging FBC, renal/liver function, coagulation tests; targeted DOAC assays if available; urgent CT when intracranial bleeding suspected. 5. Reverse protocol-led Warfarin: vitamin K plus PCC for major bleeding in many protocols. Dabigatran: idarucizumab where available. Xa inhibitors: andexanet alfa or PCC according to local availability/protocol. Never delay emergency referral while searching for a perfect reversal agent. Reversal is reserved for life-threatening/uncontrolled major bleeding or truly urgent procedures and must weigh thrombosis risk. 10. Red flags patients must know Vomiting blood/coffee-ground material, black tarry stool, rectal bleeding or heavy unexplained vaginal bleeding. Red/brown urine, severe persistent headache, collapse, new weakness/speech change, head injury or severe back pain with leg weakness after spinal procedures. Large unexplained bruises, prolonged nosebleed, breathlessness, chest pain, swollen painful leg, or missed doses with

Haematinics • Cobalamin Vitamin B12: treat deficiency early—neurological injury can occur even without anaemia Vitamin B12 (cobalamin) is essential for DNA synthesis, myelin integrity and red-cell maturation. Deficiency may cause megaloblastic anaemia, glossitis and neuropsychiatric disease. The defining clinical difference from folate deficiency is that B12 deficiency can cause progressive neuropathy and spinal-cord injury; never wait for macrocytosis before considering it. Learning outcomes Explain intrinsic-factor dependent absorption, identify dietary and malabsorptive causes, distinguish B12 from folate deficiency, interpret the core investigation pathway, choose oral versus parenteral replacement principles, and monitor neurological recovery safely. 1. The one-minute clinical map Question Answer What is B12? A water-soluble cobalamin obtained from animal-source foods or supplements; body stores can delay presentation for years. Where is it absorbed? Terminal ileum after binding to intrinsic factor produced by gastric parietal cells. Why does it matter? DNA synthesis, methionine synthase, methylmalonyl-CoA metabolism and neurological myelin maintenance. Key danger? Neurological damage—paresthesia, sensory ataxia, gait or cognitive change—may occur with a normal Hb/MCV. Core treatment principle? Replace promptly using a cause-appropriate oral or IM regimen; manage the underlying cause and monitor response. 2. Absorption and pharmacology Release and binding Food B12 is released in the stomach, binds salivary haptocorrin, then after pancreatic digestion binds intrinsic factor (IF). Terminal ileum The IF–B12 complex is taken up in the terminal ileum. It travels in blood on transcobalamin to tissues and is stored mainly in liver. Metabolic reactions B12 supports methionine synthase (folate recycling/homocysteine metabolism) and methylmalonyl-CoA mutase. Deficiency raises homocysteine and methylmalonic acid (MMA). Clinical link: autoimmune destruction of parietal cells or intrinsic factor causes pernicious anaemia; ileal disease/resection prevents normal uptake. In these situations diet alone will not correct the problem. 3. Causes and risk groups Cause Examples Clinical implication Autoimmune malabsorption Pernicious anaemia/autoimmune gastritis Intrinsic-factor failure; usually long-term replacement and review for associated autoimmune disease as locally indicated. Gastric causes Gastrectomy, bariatric surgery, chronic atrophic gastritis Reduced acid/IF handling; assess lifelong risk. Ileal/pancreatic causes Crohn disease, terminal-ileal resection, coeliac disease, bacterial overgrowth, pancreatic insufficiency Absorption may be unreliable; parenteral therapy may be required. Low intake Strict vegan diet without supplementation, food insecurity, frailty Dietary replacement may succeed if absorption is intact, but assess severity and adherence. Medicine-related Metformin, acid-suppressing therapy and others in susceptible patients Review duration, symptoms and alternative causes; do not stop essential medicines without a clinician. 4. Presentation: anaemia plus the nervous system Haematological: fatigue, pallor, exertional dyspnoea, macrocytosis, glossitis, mouth ulcers; severe cases may have leukopenia or thrombocytopenia. Neurological: numbness/tingling, loss of vibration or position sense, gait imbalance, weakness, visual change and subacute combined cord disease. Neuropsychiatric: poor concentration, memory change, depression, irritability, psychosis or cognitive decline. Paediatric: poor growth, developmental delay or regression in severe deficiency. B12 versus folate deficiency Both cause megaloblastic anaemia and high homocysteine. MMA rises in B12 deficiency, not isolated folate deficiency. Folate can improve the blood count in a B12-deficient patient but cannot protect the nervous system—so test and treat B12 when there is uncertainty. 5. Diagnosis: tests and interpretation Assessment Use FBC and film Macrocytosis, macro-ovalocytes, hypersegmented neutrophils; a normal MCV does not exclude B12 deficiency if iron deficiency or thalassaemia coexist. Serum B12 Initial biochemical test; interpret borderline values with symptoms, medicines and assay limitations. MMA ± homocysteine Helpful for uncertain cases. MMA is more specific for B12 deficiency but can be raised in renal impairment. Anti-intrinsic-factor antibodies Supports pernicious anaemia/autoimmune cause when clinically appropriate. Cause investigation Diet, alcohol, drug and surgical history; assess gastric/ileal disease, coeliac disease and other malabsorption risks. Urgent escalation: new gait disorder, rapidly progressive sensory loss, severe weakness, cognitive change, severe anaemia or pancytopenia needs urgent senior/specialist assessment and prompt replacement—not routine delayed follow-up. 6. Replacement: formulation and route principles Oral cyanocobalamin Can be appropriate for dietary deficiency and selected patients with intact or sufficient absorption, using the local guideline and reliable follow-up. High oral doses may still be absorbed passively in some malabsorptive states, but this is a cause-specific clinical decision. IM hydroxocobalamin Commonly used where deficiency is due to malabsorption, pernicious anaemia, significant symptoms or neurological involvement. Loading and maintenance schedules vary by guideline, product and cause. NICE-based pathways commonly use 1 mg IM three times weekly for two weeks when no neurological involvement; neurological symptoms require more urgent/specialist-led regimens. Do not copy a schedule blindly—apply the local protocol. Maintenance Non-diet-related irreversible malabsorption often needs lifelong replacement; diet-related deficiency may allow oral maintenance after stores are restored. Review the cause before deciding that injections can stop. 7. Monitoring and expected response Stage Check Interpretation Baseline Symptoms, neurological examination, FBC, B12 ± MMA, cause assessment Record deficits before treatment; do not let a single normal-looking MCV overrule the story. Early response Reticulocyte response and symptomatic change may be seen within days to weeks Failure suggests wrong diagnosis, mixed deficiency, non-adherence, wrong route or ongoing pathology. Follow-up FBC/MCV recovery and neurological review Haematology often corrects before nerves; neurological recovery may be incomplete if treatment is late. Long-term Adherence, injection schedule/oral supply, recurrent symptoms and cause-specific review Lifelong risk requires a clear follow-up plan. 8. Adverse effects and counselling Vitamin B12 replacement is usually well tolerated. Injection-site reactions, headache, nausea, rash or rarely hypersensitivity can occur. Explain that hydroxocobalamin may discolour urine pink/red temporarily. Counsel patients to report worsening weakness, gait change, numbness, breathlessness, chest pain or severe allergic symptoms. Dietary improvement is valuable, but it cannot replace injections where intrinsic factor or ileal absorption is absent. 9. Cases for exams and wards Case 1 — “normal Hb” does not rule it out A patient with metformin exposure reports progressive tingling and impaired vibration sense; Hb and MCV are normal. B12 deficiency remains possible. Investigate and treat promptly if confirmed; do not wait for macrocytic anaemia. Case 2 — pernicious anaemia A patient has macrocytosis, low B12 and positive intrinsic-factor antibody. Explain the absorption defect, initiate cause-appropriate replacement, record neurological status and plan long-term maintenance rather than repeated short courses. Case 3 — folate trap A macrocytic patient was given folic acid

Haematinics • Vitamin B9 Folic acid: essential for one-carbon transfer, DNA synthesis and fetal neural-tube development—never give it blindly in unexplained macrocytic anaemia Folate (vitamin B9) is needed for DNA synthesis, cell division and red-cell maturation. Folic acid is the stable synthetic form used in supplements and fortified foods. Deficiency produces ineffective DNA synthesis, causing megaloblastic anaemia. The major safety rule is simple: correct folate deficiency, but exclude or treat vitamin B12 deficiency first, because folic acid can improve the blood count while B12-related neurological injury continues. Learning outcomes Explain folate/folic-acid terminology, link tetrahydrofolate to DNA synthesis, recognise folate deficiency, distinguish it from B12 deficiency, apply periconceptional prevention guidance, identify important antifolate medicines, and monitor treatment safely. 1. The clinical map Question High-yield answer What is folate? Vitamin B9 from foods; it participates as tetrahydrofolate (THF) in one-carbon transfer reactions. What is folic acid? The synthetic, oxidised form used in supplements and fortified foods. It is converted to active folate coenzymes. Deficiency pattern? Megaloblastic macrocytic anaemia, glossitis, fatigue and raised homocysteine; fetal neural-tube defects are a key periconceptional risk. Most important safety check? Assess vitamin B12 before high-dose folic acid in unexplained macrocytosis/megaloblastic anaemia. Routine prevention around conception? WHO recommends 400 micrograms daily from when pregnancy is being attempted until 12 weeks’ gestation. Is folic acid the same as folinic acid? No. Folinic acid (leucovorin) is a reduced folate used in selected antifolate-toxicity/rescue protocols; it is not a substitute to improvise. 2. Terminology students must keep separate Folate The collective term for naturally occurring B9 forms in food and body tissues. Rich sources include dark green leafy vegetables, legumes, liver and fortified grains; cooking and storage can reduce food folate. Folic acid The synthetic form in tablets and fortified foods. It is well absorbed and used for prevention and treatment under clinical guidance. THF and methyl-THF Active coenzyme forms that carry one-carbon units. They support purine synthesis, thymidylate synthesis and methionine/homocysteine metabolism. Folinic acid A reduced folate (leucovorin). Its role in methotrexate rescue or selected toxicities belongs to a specific protocol and specialist decision. 3. Pharmacology: why deficiency causes macrocytosis Folic acid is reduced to dihydrofolate then tetrahydrofolate (THF). THF derivatives accept and donate one-carbon groups. This chemistry is essential for synthesis of purines and thymidylate—building blocks for DNA. When folate is insufficient, nuclear DNA maturation lags behind cytoplasmic maturation. Rapidly dividing tissues are affected most, producing large immature erythroid precursors (megaloblasts) and macro-ovalocytes in peripheral blood. Folate–B12 partnership: the methyl-folate trap Vitamin B12 is required for methionine synthase to transfer a methyl group from 5-methyl-THF to homocysteine. In B12 deficiency, folate becomes metabolically trapped as 5-methyl-THF, creating functional folate deficiency for DNA synthesis. Both deficiencies can therefore cause megaloblastic anaemia and raised homocysteine—but only B12 deficiency typically causes progressive neurological disease. 4. Causes and risk groups for folate deficiency Mechanism Examples Clinical response Low intake Food insecurity, restrictive diet, alcohol use disorder, prolonged overcooking, poor dietary diversity Nutrition history and practical dietary support alongside treatment. Increased requirement Pregnancy, breastfeeding, infancy/adolescence, chronic haemolysis, exfoliative skin disease, malignancy Prevent or replace under the relevant obstetric/medical protocol. Malabsorption Coeliac disease, inflammatory bowel disease, extensive small-bowel disease/resection Investigate the cause; oral absorption is often still possible, but treatment must be individualised. Drug-related interference Methotrexate, trimethoprim, pyrimethamine, some antiseizure medicines, sulfasalazine and other antifolate pathways Do not stop essential treatment casually; review with the prescriber/pharmacist. Loss/dialysis Some patients receiving dialysis or prolonged nutritional support Follow renal/nutrition-specific guidance. 5. Clinical features and differential diagnosis Suggestive features Fatigue, weakness, exertional breathlessness, palpitations, pallor. Glossitis, sore mouth or oral ulcers; anorexia, nausea, diarrhoea or weight loss may occur. Macrocytosis may precede overt anaemia. In pregnancy, folate deficiency is clinically important because early neural-tube closure occurs before many people realise they are pregnant. Folate versus B12 deficiency Both can cause macrocytosis, hypersegmented neutrophils, megaloblastic marrow and elevated homocysteine. Peripheral neuropathy, loss of vibration/proprioception, gait change, cognitive change or subacute combined cord features should make you think urgently of B12 deficiency. Their absence does not prove B12 is normal. Serum B12 and the clinical context determine safe treatment; methylmalonic acid is more specifically raised in B12 deficiency when available. Do not assume macrocytosis equals folate deficiency. Consider alcohol/liver disease, hypothyroidism, reticulocytosis, myelodysplasia, medicines and B12 deficiency. A mixed iron-and-folate/B12 deficiency may even give a normal MCV. 6. Investigation before treatment Test/assessment What it contributes Full blood count and film Hb, MCV, RDW, leucocytes/platelets; macro-ovalocytes and hypersegmented neutrophils support megaloblastic change. Serum B12 and folate Interpret with clinical context and local laboratory ranges; test B12 before giving high-dose folic acid when possible. Reticulocyte count, bilirubin/LDH May support ineffective erythropoiesis or alternative diagnoses. Homocysteine ± methylmalonic acid Homocysteine rises in folate and B12 deficiency; methylmalonic acid preferentially rises in B12 deficiency. Cause-directed work-up Diet/alcohol assessment, pregnancy history, medication review, coeliac/GI assessment, thyroid/liver/renal tests as indicated. 7. Uses and dosing principles Prevention of neural-tube defects WHO: people planning pregnancy should take 400 micrograms (0.4 mg) folic acid daily from the time they begin trying to conceive until 12 completed weeks of gestation. This is a prevention recommendation, not a replacement for booking early for antenatal care. Those with a previous neural-tube-defect-affected pregnancy, certain antiseizure medicines, malabsorption or other high-risk factors may require a different regimen (often higher dose): use the current local obstetric protocol rather than guessing. Treatment of confirmed folate deficiency Use a local formulary/clinician-directed dose and duration. Many clinical protocols use a therapeutic daily dose for several months while the cause is corrected, but the exact regimen varies by country, preparation, age, pregnancy status and coexisting disease. Never let a standard folic-acid dose delay assessment of possible B12 deficiency. Pregnancy and anaemia programmes Daily iron–folic-acid supplementation is commonly used in antenatal prevention programmes. WHO recommends 30–60 mg elemental iron plus 400 micrograms folic acid daily during pregnancy to prevent maternal anaemia and adverse outcomes. Follow the national ANC guideline for the individual patient and distinguish prophylaxis from treatment of established anaemia. 8. Monitoring response and recognising failure When Expected

Haematinics • Core Pharmacology Ferrous sulphate: replace iron only after you have identified iron deficiency—and find out why it occurred Ferrous sulphate is an oral ferrous (Fe²⁺) salt used to prevent or treat iron deficiency. It supplies elemental iron for haemoglobin synthesis and repletion of body iron stores. It is excellent therapy for confirmed or strongly suspected iron deficiency anaemia (IDA), but it is not a treatment for every low haemoglobin. The safest clinical sequence is: recognise anaemia → confirm iron deficiency where possible → look for the cause → choose and monitor iron therapy. Learning outcomes By the end, you should be able to explain iron handling, interpret the core tests for IDA, convert a ferrous-sulphate strength to elemental iron, give practical oral-iron instructions, detect non-response or toxicity, and distinguish cases that need investigation, referral or intravenous iron. 1. The one-minute clinical map Clinical question High-yield answer What does it treat? Iron deficiency with or without anaemia; prevention only in selected groups following local/WHO protocols. What matters on the packet? Elemental iron, not just the mass of the salt. Check the local formulation and label. What usually confirms depleted stores? Low serum ferritin in an appropriate clinical context. Ferritin rises with inflammation, infection and liver disease, so a “normal” ferritin may mislead. What is the main error? Giving iron indefinitely without investigating blood loss, poor intake, malabsorption, inflammation or another cause of anaemia. Most common adverse effects? Nausea, epigastric discomfort, constipation or diarrhoea; dark stools are common. Danger signal? Iron overdose in a child is an emergency. Keep all iron products locked away and seek urgent help after a suspected ingestion. 2. Why the body needs iron Transport and storage Most functional iron is in haemoglobin; it carries oxygen. Iron is also in myoglobin and iron-containing enzymes. Circulating iron is carried by transferrin; reserve iron is mainly stored as ferritin. Absorption Non-haem iron is absorbed mainly in the duodenum and proximal jejunum. Ferrous iron is generally absorbed more readily than ferric iron. Acidic conditions and vitamin-C-containing food can favour absorption; several foods and medicines reduce it. Hepcidin Hepcidin reduces intestinal iron export and macrophage iron release. It rises with inflammation and can make oral iron less effective even when total-body iron is present. 3. Do not call every anaemia “iron deficiency” Anaemia is a finding, not a diagnosis. IDA is common, but microcytosis may also occur with thalassaemia traits, anaemia of inflammation and other disorders. Macrocytosis suggests a different pathway such as folate/B12 deficiency, medicines, liver disease or marrow disease. A normocytic anaemia may be early iron deficiency, blood loss, renal disease, inflammation or haemolysis. Core pre-treatment assessment History: fatigue, dyspnoea, pica, diet, pregnancy, menstrual loss, post-partum bleeding, GI symptoms, melena, medicines (including NSAIDs), previous surgery, malabsorption risk, deworming/parasite exposure and family history. Examination: pallor, pulse, heart-failure signs, glossitis/cheilitis, abdominal findings and signs of ongoing bleeding or systemic disease. Tests when available: full blood count (Hb, MCV, MCH, RDW), ferritin, peripheral film; add transferrin saturation/CRP where inflammation is likely. Reticulocyte count, renal profile, B12/folate, stool/GI work-up or haemoglobinopathy testing are directed by the case. Important: in adult men and post-menopausal women, IDA commonly requires evaluation for gastrointestinal blood loss unless there is an obvious alternative explanation. In menstruating patients and pregnancy, do not simply assume the cause—assess the bleeding, diet and clinical context. 4. Ferrous sulphate and elemental-iron mathematics Ferrous sulphate is a salt; the therapeutic component is elemental iron. Common preparations differ in hydration, coating and local strength. A frequently encountered example is 325 mg ferrous sulphate ≈ 65 mg elemental iron, but this is not universal. Always read the product label or formulary before prescribing, dispensing or teaching a dose. Oral iron salt What students must compare Practical point Ferrous sulphate Salt strength, elemental iron per tablet/5 mL, release formulation Widely available and inexpensive; GI intolerance often limits adherence. Ferrous fumarate Usually more elemental iron per mass of salt Not automatically “stronger” clinically; compare elemental iron and tolerance. Ferrous gluconate/other ferrous salts Elemental iron per unit and dosing schedule May be selected for formulation or tolerance; evidence of benefit depends on adherence and absorption. 5. Oral treatment: dosing principles, not a one-size-fits-all prescription For established IDA, prescribe in elemental iron and follow the local guideline/formulary. Many adult regimens use a single daily dose of a ferrous salt; some patients are managed on alternate days or with a lower dose to improve tolerance and adherence. More tablets are not always better: unabsorbed iron increases gastrointestinal adverse effects and hepcidin biology may limit absorption. Do not confuse prevention with treatment. WHO recommends daily oral iron plus folic acid in pregnancy for prevention in relevant settings (30–60 mg elemental iron with 400 micrograms folic acid daily); treat confirmed anaemia using the applicable ANC/clinical protocol. Children: use weight-based elemental-iron dosing under paediatric/local guidance; avoid “adult tablet fractions” without checking the product and the protocol. Severe symptomatic anaemia, haemodynamic compromise, active bleeding, chest pain, syncope or heart failure signs: this is urgent clinical assessment, not routine outpatient iron counselling. 6. How to take ferrous sulphate well Timing Absorption is usually best away from food, but take with a small meal if nausea or pain would otherwise make adherence impossible. Do not stop treatment silently because of side effects—adjust the plan with a clinician. What to separate Ask specifically about antacids, calcium, tea/coffee, dairy, tetracyclines, quinolones, levothyroxine and other medicines. Spacing requirements vary: check the product and medicine-specific advice. Levothyroxine and iron are commonly separated by at least four hours. Liquid preparations They can stain teeth. Dilute as directed, use a straw where appropriate and rinse/brush after the dose. Keep the bottle closed and out of a child’s reach. Counselling sentence for exams: “Take exactly as prescribed; empty stomach improves absorption but food is acceptable for troublesome GI effects. Keep it separate from absorption-interfering products. Expect darker stools, but seek assessment for sticky tarry stools, faintness, severe abdominal pain or suspected bleeding.” 7. Expected response and how to monitor it Time point

Core Pharmacology Fibrates: lower triglycerides to reduce pancreatitis risk—use them deliberately and safely Fibrates are PPAR-α agonists. They accelerate triglyceride-rich lipoprotein metabolism, reduce VLDL production and increase lipoprotein-lipase activity. Their main effect is a marked fall in triglycerides, with a modest rise in HDL and variable LDL effect. They are not routine substitutes for statins when the main goal is ASCVD prevention. Learning outcomes Explain the PPAR-α mechanism, identify the hypertriglyceridaemia patterns that need urgent attention, distinguish fenofibrate from gemfibrozil, recognise renal/hepatic/gallbladder contraindications, prevent statin-related muscle toxicity, and give safe monitoring and counselling. 1. The clinical map: which lipid problem are we treating? Problem Immediate priority Where fibrates fit Raised LDL-C / established ASCVD Lower atherogenic LDL and prevent MI/stroke. Statins are first-line when cardiovascular risk reduction is the principal goal. A fibrate is not an automatic add-on. Triglycerides 150–499 mg/dL(~1.7–5.6 mmol/L) Address obesity, alcohol, refined carbohydrate intake, diabetes, thyroid/renal disease and medicines; assess ASCVD risk. Statin-based ASCVD therapy and lifestyle are usually prioritised in high-risk patients; fibrate use is individualised. Severe triglycerides ≥500 mg/dL(≥5.6 mmol/L) Reduce acute pancreatitis risk and find secondary causes. Fenofibrate or other triglyceride-lowering therapy may be used with a very-low-fat diet and metabolic correction, according to local protocol. Very severe ≥1,000 mg/dL(≥11.3 mmol/L) or abdominal pain Urgent pancreatitis assessment; rapid dietary/metabolic intervention. Do not simply issue a routine prescription and wait. Escalate clinically; fibrate/omega-3 therapy is part of a broader urgent plan. Exam anchor: high LDL → think statin for ASCVD prevention. very high triglycerides → think pancreatitis prevention, secondary causes, diet and possible fibrate. One lipid drug does not solve every dyslipidaemia pattern. 2. Drugs in the class Agent Key feature Practical implication Fenofibrate Commonly used; a prodrug converted to fenofibric acid. Renal dose adjustment is required. Generally preferred if a fibrate must be combined with a statin, but the combination still requires a clear indication and monitoring. Gemfibrozil More problematic statin interaction; inhibits pathways that increase some statin concentrations. Avoid with statins whenever possible because myopathy/rhabdomyolysis risk is higher. Clofibrate Older agent with adverse-effect limitations. Rarely used in contemporary practice in many settings. Bezafibrate/ciprofibrate Availability varies by country. Use local formulary, renal dosing and product information—not a copied dose from another formulation. 3. Mechanism: PPAR-α changes triglyceride handling PPAR-α activation Fibrates activate the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-α), altering transcription of lipid-metabolism genes. More clearance They increase lipoprotein-lipase activity and reduce apoC-III influence, improving clearance of triglyceride-rich VLDL/chylomicron remnants. Less VLDL output Hepatic fatty-acid oxidation rises and VLDL triglyceride production falls. Net lipid effect Triglycerides commonly fall about 30–50%; HDL often rises modestly; LDL response is variable and may rise when baseline TG is extremely high as VLDL is cleared. 4. Indications and decision-making Before prescribing, identify the cause Metabolic: poorly controlled diabetes, obesity/metabolic syndrome, alcohol excess, high-refined-carbohydrate intake. Endocrine/renal/hepatic: hypothyroidism, pregnancy, nephrotic syndrome, CKD, cholestatic disease. Medicines: oestrogens, corticosteroids, thiazides, beta blockers in selected settings, retinoids, antipsychotics, protease inhibitors and others. Genetic: familial chylomicronaemia or combined dyslipidaemia, especially when triglycerides are extreme/recurrent from a young age. Correcting diabetes, alcohol intake, dietary fat/refined carbohydrate excess or hypothyroidism can lower triglycerides dramatically. A fibrate does not replace this search. Clinical situation Fibrate role Key caution Severe hypertriglyceridaemia Adjunct to dietary/metabolic therapy to lower TG and reduce pancreatitis risk. Assess abdominal pain, vomiting, pancreatitis and precipitating factors; urgent cases need escalation. Mixed dyslipidaemia with high TG/low HDL May be considered after individual ASCVD-risk and statin assessment. Do not promise cardiovascular-event benefit solely from an improved TG number. Statin intolerance / selected LDL indication Fenofibrate may be used only within a defined lipid-management plan when appropriate. Non-statin LDL therapies such as ezetimibe/PCSK9-directed therapy/bempedoic acid may better match the LDL problem. Diabetes Selected phenotype-based use, especially marked TG elevation. Optimise glycaemia first and monitor renal function carefully. 5. Dosing principles—formulation and renal function matter Fenofibrate tablets/capsules are not dose-for-dose interchangeable; bioavailability and food instructions differ. Use the product available in your setting. Start with the formulation-specific recommended dose, reassess fasting/non-fasting lipids after the recommended interval (often 4–8 weeks), and use the lowest effective dose. Mild–moderate renal impairment: start at a reduced formulation-specific dose and increase only after renal function and lipid response are reviewed. Severe renal impairment (eGFR <30 mL/min/1.73m²), ESRD or dialysis: fenofibrate is contraindicated/should be avoided according to current labels. Do not prescribe a “standard fibrate dose” from memory—check the exact brand/formulation and renal advice. 6. Adverse effects: know what can harm the patient Muscle toxicity Myalgia, myopathy and rare rhabdomyolysis. Risk rises with older age, diabetes, renal impairment, hypothyroidism and statin co-therapy. Renal change Fenofibrate can raise serum creatinine, often reversibly. It still demands renal monitoring and dose review. Hepatic effects Transaminase elevations and rare clinically significant liver injury can occur; investigate jaundice, dark urine, persistent nausea or RUQ pain. Biliary/GI effects Dyspepsia, abdominal pain, nausea and gallstone/cholelithiasis risk. New biliary-type pain needs review. Recognising possible rhabdomyolysis Red flags: diffuse or proximal muscle pain, marked weakness, tenderness, fever/malaise, tea-coloured urine, oliguria or rising creatinine. Stop the suspected myotoxic medicine, check CK, creatinine/electrolytes and urinalysis, and arrange urgent assessment. This is especially important when a fibrate was added to a statin. 7. Contraindications and high-risk situations Condition Why it matters Action Severe renal impairment / dialysis Drug accumulation and toxicity. Do not use fenofibrate; follow product-specific contraindications. Active liver disease or unexplained persistent LFT abnormality Potential hepatotoxicity and impaired handling. Avoid/initiate specialist evaluation rather than starting empirically. Pre-existing gallbladder disease Fibrates can increase biliary cholesterol excretion and gallstone risk. Contraindicated in many fenofibrate labels; choose an alternative plan. Pregnancy/breastfeeding Limited safety data; severe hypertriglyceridaemia requires specialist risk–benefit management. Do not self-start; use specialist/local protocol. Hypothyroidism, frailty, diabetes, alcohol excess Raises risk of muscle/liver toxicity or drives the TG elevation. Correct/assess the cause and monitor closely. 8. Interactions: the fibrate–statin safety trap Gemfibrozil + statin Avoid this combination whenever possible. Gemfibrozil can substantially increase exposure to several statins, markedly increasing myopathy and rhabdomyolysis risk. “Both lower lipids” is not a reason to use them

Core Pharmacology Statins: lower LDL cholesterol, stabilise plaque and prevent cardiovascular events Statins inhibit hepatic HMG-CoA reductase. The fall in hepatic cholesterol up-regulates LDL receptors, clearing more LDL cholesterol from the blood. Their value is not simply “a better lipid result”: in the right patient they lower the risk of myocardial infarction, ischaemic stroke and cardiovascular death. They are foundational therapy for established atherosclerotic cardiovascular disease (ASCVD) and are selected for primary prevention according to total risk. Learning outcomes Explain lipoprotein transport and the statin mechanism; classify statin intensity; choose appropriate prevention contexts; identify adverse effects and interactions; investigate muscle symptoms safely; and counsel patients on adherence, pregnancy and lifestyle. 1. Start with the lipid map Particle Main cargo / origin Clinical meaning Chylomicron Dietary triglyceride from intestine Very high triglycerides raise pancreatitis risk; chylomicron remnants carry cholesterol back to the liver. VLDL → IDL Triglyceride-rich particles made by liver VLDL is progressively triglyceride-depleted to IDL, then LDL. LDL Cholesterol delivered to peripheral tissues The main atherogenic target in most patients. Cumulative LDL exposure drives plaque formation. HDL Reverse cholesterol transport Low HDL can mark risk, but drugs are not prescribed merely to “raise HDL.” Treat the whole risk profile. Lipoprotein(a) Genetically determined LDL-like particle A risk enhancer; consider measurement where guidance/resources support it, especially with premature ASCVD or family history. Atherosclerosis in one line ApoB-containing particles—especially LDL—enter and are retained in the arterial wall. Inflammation, oxidation, foam-cell formation and fibrous plaque follow. Plaque rupture with thrombosis produces acute MI or ischaemic stroke. Statins lower circulating LDL and also improve plaque stability. 2. Mechanism of action: why blocking synthesis lowers blood LDL 1. Competitive inhibition Statins competitively and reversibly inhibit HMG-CoA reductase, the rate-limiting enzyme converting HMG-CoA to mevalonate in cholesterol synthesis. 2. Less hepatic cholesterol Hepatocytes sense a lower intracellular cholesterol pool. 3. More LDL receptors The liver up-regulates LDL receptors on its surface and removes more circulating LDL particles. 4. Clinical benefit LDL-C falls substantially; triglycerides often fall modestly and HDL may rise slightly. Event reduction follows sustained use in appropriate-risk patients. Exam distinction: statins do not “dissolve an acute clot.” They reduce atherosclerotic risk and are central to secondary prevention after ACS/MI, alongside antiplatelet therapy, BP/diabetes management, smoking cessation, rehabilitation and revascularisation when indicated. 3. The drugs: potency and intensity Intensity (approximate LDL-C reduction) Common examples Use concept High intensity (≥50%) Atorvastatin 40–80 mg; rosuvastatin 20–40 mg Usually preferred in many adults with clinical ASCVD if tolerated; use current local guidance and product labelling. Moderate intensity (30–49%) Atorvastatin 10–20 mg; rosuvastatin 5–10 mg; simvastatin 20–40 mg; pravastatin 40–80 mg Chosen when risk/age/comorbidity or tolerance makes high intensity unsuitable, and in many primary-prevention plans. Low intensity (<30%) Simvastatin 10 mg; pravastatin 10–20 mg Less common when meaningful LDL reduction is required; consider only within an individualised plan. Important pharmacokinetic comparison Atorvastatin, simvastatin and lovastatin: important CYP3A4 interaction potential. Rosuvastatin and pravastatin: less CYP3A4 dependence, but still have clinically relevant transporter/drug interactions. Simvastatin: has more dose-related interaction restrictions; check the specific co-prescription rather than assuming all statins behave alike. 4. Indications: primary versus secondary prevention Situation Statin role Clinical reasoning Established ASCVDprior MI/ACS, angina with coronary disease, ischaemic stroke/TIA, symptomatic peripheral arterial disease Secondary prevention—usually a maximally tolerated high-intensity statin unless contraindicated. Risk of recurrent event is high; treatment aims for large LDL reduction and addition of non-statin therapy may be considered if response is inadequate. Diabetes mellitus Risk-based primary prevention; intensity depends on age, risk factors, duration/organ damage and guideline assessment. Diabetes substantially increases ASCVD risk, but treatment should remain individualised. Familial hypercholesterolaemia (FH) Early high-potency therapy and specialist pathway. Consider very high baseline LDL-C, family cascade screening, and need for combination treatment. No established ASCVD Primary prevention after formal cardiovascular-risk assessment and shared decision-making. Do not prescribe from a total-cholesterol number alone. Include BP, smoking, diabetes, kidney disease, age, family history and local risk tool. Severe hypertriglyceridaemia Statins may address ASCVD risk but are not the sole urgent strategy. Identify secondary causes and treat pancreatitis risk with appropriate diet/diabetes/alcohol review and triglyceride-directed therapy where indicated. Before starting: look for secondary causes and risk amplifiers Check for hypothyroidism, uncontrolled diabetes, nephrotic syndrome/CKD, excess alcohol, obesity, cholestatic liver disease and relevant drugs. Untreated hypothyroidism can both worsen lipids and increase muscle-toxicity risk. Obtain a careful family history of premature ASCVD and extreme cholesterol because it may signal FH. 5. Baseline assessment and follow-up When Assess Why Before therapy Lipid profile; ASCVD risk; BP, glucose/diabetes status; adherence barriers; interacting medicines; alcohol/liver history; pregnancy/breastfeeding status where relevant. Defines indication, expected response and safety risks. Baseline tests ALT/liver enzymes before initiation; HbA1c/glucose when clinically indicated; TSH if hypothyroidism is suspected. Baseline CK is not routine for everyone, but is reasonable with prior muscle disease/symptoms, interacting drugs, renal impairment or high risk. Allows rational interpretation of later abnormalities and avoids missing reversible causes. After starting or dose change Repeat lipid profile at the interval specified by local guidance (often 4–12 weeks) to assess adherence and percentage LDL response. Do not label treatment a failure until adherence, dose, secondary causes and interactions are reviewed. Symptom-triggered review CK for significant unexplained muscle symptoms; liver enzymes if symptoms/signs of liver injury; renal function and urine assessment if severe muscle injury is suspected. Routine serial CK and LFT “screening” in a well patient is usually not required; investigate clinically meaningful symptoms. 6. Adverse effects: separate common symptoms from rare emergencies Muscle symptoms Myalgia (pain/aches without major CK rise) is reported commonly. Assess timing, bilateral proximal pattern, exertion, thyroid disease, vitamin deficiency, infection and interacting drugs; not every ache is caused by the statin. Myopathy / rhabdomyolysis Rare but serious. Severe pain, weakness, marked CK elevation, dark/tea-coloured urine or reduced urine output demand urgent review and stopping the suspected drug. Hepatic effects Small transaminase rises can occur. Serious liver injury is rare; jaundice, dark urine, persistent nausea, right-upper-quadrant pain or marked fatigue require evaluation. Other Dyspepsia, headache and a small increase in glucose/diabetes risk in susceptible people