PH4.1-11 | Cardiovascular and Blood Pharmacology — Glossary

Carboxypeptidase concentrated in pulmonary and renal endothelium; converts Ang I → Ang II; also degrades bradykinin to inactive fragments. Blocked by ACE inhibitors.

Spectrum of myocardial ischaemia caused by coronary plaque rupture and thrombosis: includes STEMI (ST-elevation MI — complete occlusion), NSTEMI (non-ST-elevation MI — partial occlusion + troponin rise), and unstable angina (partial occlusion, no troponin rise).

Endogenous nucleoside antiarrhythmic; activates A1 receptors → hyperpolarises AV node → transient AV block; terminates AV-node-dependent SVTs in seconds; half-life ~10 seconds; given as rapid IV bolus.

Dose- and duration-dependent adverse effect of amiodarone in 5–10% of long-term users; presents as progressive dyspnoea, cough, and new pulmonary infiltrates; can progress to fibrosis; requires drug discontinuation.

Chest pain due to myocardial ischaemia — episodic, typically effort-related, relieved by rest or nitrate; caused by inadequate coronary blood flow relative to demand.

The primary active effector of the RAAS — an octapeptide produced from Ang I by ACE; causes vasoconstriction, aldosterone release, and cardiac/vascular remodelling via AT1 receptors.

Plasma serine protease inhibitor that inactivates thrombin (IIa) and Xa; heparin binding increases its activity ~1000-fold — this is the basis of heparin anticoagulation.

Water channel in principal cells of the collecting duct; inserted into the apical membrane by ADH/vasopressin V2 receptor signalling (via cAMP); mediates water reabsorption.

Excretion of electrolyte-free water without proportional sodium loss — the mechanism of vaptans (V2 antagonists); distinguished from diuresis (water + sodium loss).

Atherosclerotic cardiovascular disease — encompasses coronary artery disease, ischaemic stroke, and peripheral arterial disease due to atherosclerosis.

Angiotensin II receptor subtype mediating vasoconstriction, aldosterone secretion, and remodelling; the target of ARBs and the downstream effector blocked by ACEi.

Angiotensin II receptor subtype with vasodilatory, anti-proliferative, and anti-fibrotic effects — generally counterbalances AT1; stimulated by the Ang II that 'escapes' AT1 blockade by ARBs.

Narrowing of both renal arteries; GFR is maintained by Ang II-driven efferent vasoconstriction; ACEi/ARB remove this compensation → acute kidney injury. Absolute contraindication to RAAS blockade.

Cholesterol-lowering resin (cholestyramine, colestipol, colesevelam) that binds bile acids in the gut lumen, interrupting enterohepatic circulation and diverting hepatic cholesterol to new bile-acid synthesis; not systemically absorbed.

Vasodilatory peptide that also stimulates pain and cough reflexes; degraded by ACE and neprilysin; accumulates with ACEi therapy → dry cough and angioedema.

Structural and functional changes in the heart under chronic neurohormonal stress — myocyte hypertrophy, apoptosis, interstitial fibrosis, ventricular dilatation; reversed by ACEi/ARNI, beta-blockers, MRA, and SGLT2i.

Preferential blockade of β1-adrenergic receptors over β2 at therapeutic doses; reduces cardiac effects (HR, contractility) with less impact on bronchospasm and peripheral vasodilation; examples: atenolol, bisoprolol, metoprolol.

Cardiac Arrhythmia Suppression Trial — landmark RCT showing Class Ic drugs (flecainide, encainide) increased mortality in post-MI patients with asymptomatic VPBs; established pro-arrhythmia as a class-wide danger of Class Ic drugs in structural heart disease.

PDE3 inhibitor used for peripheral arterial disease (claudication); reduces platelet aggregation and promotes vasodilation; contraindicated in heart failure.

Combination of aspirin + a P2Y12 inhibitor; standard for 12 months after ACS or coronary stent placement to prevent stent thrombosis and recurrent events.

Synthetic V2-selective vasopressin analogue; lacks V1a-mediated vasoconstriction; used for central diabetes insipidus, nocturnal enuresis, and haemophilia A/vWD type 1.

Digoxin-specific antibody fragments; used for severe digoxin toxicity (life-threatening arrhythmias or haemodynamic compromise); each vial binds ~0.5 mg digoxin.

Calcium channel blocker with preferential vascular smooth muscle selectivity (e.g., amlodipine, nifedipine); minimal cardiac effect; used for hypertension and angina.

Class of oral anticoagulants acting directly on Factor IIa (dabigatran) or Factor Xa (rivaroxaban, apixaban, edoxaban) without requiring antithrombin III; predictable pharmacokinetics; no routine monitoring required.

Abnormal levels of lipids or lipoproteins in blood — includes elevated LDL-C, elevated TG, low HDL-C, or combinations; a major modifiable risk factor for ASCVD.

Epithelial sodium channel — apical Na-entry channel in principal cells of the cortical collecting duct; regulated by aldosterone (upregulated) and blocked directly by amiloride/triamterene.

Primary hypertension without an identifiable cause; accounts for 90–95% of all hypertension; multifactorial (genetic, sympathetic, RAAS, dietary).

Autosomal dominant disorder caused by loss-of-function LDL-R mutations (most common), APOB mutations, or gain-of-function PCSK9 mutations; heterozygous FH presents with LDL-C 190–350 mg/dL and premature CVD.

Fibrinolytic that preferentially activates plasminogen bound to fibrin on clots, producing localised clot dissolution with less systemic plasminaemia; e.g., alteplase, tenecteplase; contrast with streptokinase (non-fibrin-specific).

Immune complication of heparin — antibodies form against PF4-heparin complexes; activate platelets → thrombocytopenia + paradoxical thrombosis; stop all heparin, switch to argatroban/fondaparinux.

Heart failure with preserved ejection fraction — LVEF ≥50%; characterised by diastolic dysfunction; only empagliflozin has proven benefit; treat comorbidities and congestion.

Heart failure with reduced ejection fraction — LVEF <40%; characterised by systolic dysfunction; responds to the four-pillar survival drugs.

Statin therapy expected to lower LDL-C by ≥50%: atorvastatin 40–80 mg/day or rosuvastatin 20–40 mg/day.

Hepatic enzyme catalysing the rate-limiting step of cholesterol synthesis (HMG-CoA → mevalonate); the molecular target of statins.

BP ≥180/120 mmHg with evidence of acute target-organ damage (encephalopathy, aortic dissection, acute MI, acute pulmonary oedema, eclampsia); requires IV antihypertensives with controlled, gradual BP reduction.

BP ≥180/120 mmHg WITHOUT target-organ damage; managed with oral antihypertensives and gradual BP reduction over 24–48 hours; IV treatment not required.

Humanised monoclonal antibody fragment specific for dabigatran; immediate reversal of dabigatran anticoagulation; indicated for life-threatening bleeding or emergency surgery in patients on dabigatran.

Autoimmune disorder with antibodies against platelet surface glycoproteins (GPIIb/IIIa, GPIb); treated with corticosteroids (first-line), IVIg (acute), splenectomy or TPO agonists (chronic).

Standardised measure of warfarin anticoagulant effect; normalised PT ratio; target 2.0–3.0 for AF and VTE; 2.5–3.5 for mechanical heart valves.

Glycoprotein secreted by gastric parietal cells; essential for vitamin B12 absorption in the terminal ileum; absent in pernicious anaemia (autoimmune parietal cell destruction) — requires parenteral B12 supplementation.

Selective I(f) funny-current inhibitor in the SA node; reduces heart rate without negative inotropy or blood pressure effect; indicated in HFrEF with sinus rhythm and HR ≥70 bpm on maximum beta-blocker (SHIFT trial).

Hypothesis that excessively low treated diastolic BP (<70 mmHg) may worsen coronary perfusion in patients with established coronary artery disease; consideration for elderly patients with isolated systolic hypertension.

Hepatocyte surface receptor mediating clearance of circulating LDL particles; upregulated by statins and PCSK9 inhibitors, degraded by PCSK9.

Failure of adequate natriuresis despite escalating loop diuretic doses; caused by excessive dietary sodium, NSAID use, hypoalbuminaemia, or compensatory distal nephron sodium reabsorption.

Central α2-agonist that reduces sympathetic outflow; drug of choice for oral antihypertensive therapy during pregnancy due to its established safety record in multiple trials.

Metoprolol succinate (extended-release, XL/CR) has proven HFrEF mortality benefit (MERIT-HF); metoprolol tartrate (immediate-release) does NOT — the formulation distinction is clinically critical.

Nuclear receptor for aldosterone in the collecting duct; when activated, upregulates ENaC and Na-K-ATPase → Na retention and K secretion; blocked by spironolactone and eplerenone.

Drug class (spironolactone, eplerenone) blocking aldosterone at the MR in the collecting duct and cardiac fibroblasts; reduces Na retention, K excretion, and cardiac fibrosis; mortality-reducing in HFrEF (RALES, EMPHASIS-HF).

Drug-induced muscle disease on the spectrum from asymptomatic CK elevation → myalgia (pain without CK rise) → myositis (pain + CK elevation <10× ULN) → rhabdomyolysis (CK >10× ULN + myoglobinuria).

Na-Cl cotransporter — apical transporter in the early distal convoluted tubule; co-transports Na and Cl; the target of thiazide diuretics.

Endopeptidase that degrades natriuretic peptides (ANP, BNP) and bradykinin; inhibited by sacubitril (the 'N' in ARNI) → elevated ANP/BNP → vasodilation, natriuresis.

The theory that sustained RAAS, SNS, and aldosterone activation in HFrEF is the primary driver of cardiac remodelling and mortality — providing the rationale for the four-pillar drug classes that block these pathways.

Attenuation of nitrate vasodilatory effects with continuous use, occurring within 24 hours; prevented by a daily nitrate-free interval of 8–12 hours.

Na-K-2Cl cotransporter — apical transporter in the thick ascending limb of Henle's loop; co-transports 1 Na, 1 K, and 2 Cl ions into tubular cells; the target of loop diuretics.

Calcium channel blocker that also blocks cardiac calcium channels (verapamil, diltiazem); negative chronotropy, dromotropy, and inotropy; used for arrhythmias and angina; contraindicated in HFrEF.

Niemann-Pick C1-Like 1 protein — intestinal cholesterol transporter inhibited by ezetimibe, reducing dietary and biliary cholesterol absorption.

Vasodilatory drug that releases nitric oxide → cGMP → smooth muscle relaxation; GTN is the prototype; reduces preload and afterload; prone to tolerance with continuous use.

Neurological injury caused by overly rapid correction of chronic hyponatraemia (>6–8 mEq/L per 24h); presents as pseudobulbar palsy, quadriplegia, and altered consciousness; potentially irreversible.

ADP receptor on platelets; when activated by ADP, promotes platelet shape change and GP IIb/IIIa expression → aggregation; the target of clopidogrel, ticagrelor, and prasugrel.

Landmark RCT (8,442 patients) comparing sacubitril/valsartan vs enalapril in HFrEF (LVEF ≤40%); sacubitril/valsartan reduced CV death + HF hospitalisation by 20% — established ARNI as first-line in HFrEF.

Proprotein convertase subtilisin/kexin type 9 — a serine protease that binds LDL-R and routes it for lysosomal degradation, reducing hepatic LDL clearance.

Megaloblastic anaemia caused by autoimmune gastritis → absent intrinsic factor → B12 malabsorption; treated with lifelong IM hydroxocobalamin; untreated causes subacute combined degeneration of the spinal cord.

Statin effects beyond LDL-C lowering — include endothelial function improvement, anti-inflammatory action (reduced hsCRP), plaque stabilisation, and antithrombotic effects.

Peroxisome proliferator-activated receptor alpha — nuclear receptor activated by fibrates; increases lipoprotein lipase activity and reduces hepatic VLDL synthesis, lowering triglycerides.

Hypertension (≥140/90 mmHg) after 20 weeks gestation with proteinuria and/or end-organ dysfunction (pre-eclampsia); seizures develop in eclampsia. Managed with antihypertensives (labetalol, hydralazine) + MgSO4 for seizure prophylaxis.

The paradoxical property of antiarrhythmic drugs to cause new arrhythmias or worsen existing ones; exemplified by Class Ic flecainide increasing mortality in post-MI patients (CAST trial).

An inactive drug form that requires metabolic conversion to the active compound; most ACEi (enalapril→enalaprilat, ramipril→ramiprilat) are prodrugs requiring hepatic esterase activation.

The most common mechanism of sustained tachyarrhythmias; requires two pathways with different conduction velocities and refractory periods forming a circular electrical loop; interrupted by drugs that slow conduction (Class I) or increase refractoriness (Class III).

Compensatory rise in plasma renin during RAAS blocker therapy; occurs because Ang II (which normally suppresses renin release via negative feedback) is reduced; pharmacologically expected and does not indicate treatment failure.

Severe skeletal muscle breakdown with release of myoglobin; presents as muscle pain + brown urine + markedly elevated CK + acute kidney injury; the most serious statin ADR.

Combination of two diuretics acting at different nephron sites (e.g., furosemide + metolazone) to achieve synergistic natriuresis in refractory oedema.

Beyond glucose lowering: SGLT2i cause osmotic diuresis + natriuresis (↓preload), reduce inflammation and cardiac fibrosis, improve mitochondrial function, and provide nephroprotection — explaining their HF and CKD benefits independent of diabetes status.

IV direct NO donor; balanced arterial and venous vasodilator; fastest-acting antihypertensive for hypertensive emergency; metabolised to cyanide — monitor if used >48 hours.

Bacterial fibrinolytic protein (from Streptococcus); non-fibrin-specific; forms antibodies after first use — cannot be re-administered; 1.5 MIU IV over 60 min.

Drug class (eltrombopag oral, romiplostim SC) stimulating the c-Mpl thrombopoietin receptor on megakaryocytes → increased platelet production; used for chronic ITP and aplastic anaemia.

Polymorphic ventricular tachycardia occurring in the context of QT prolongation; caused by early after-depolarisations (EADs) triggered by Class Ia/III drugs, hypokalaemia, or hypomagnesaemia; treated with IV MgSO4.

Antifibrinolytic agent — lysine analogue that blocks plasminogen lysine-binding sites, preventing plasmin formation; used in trauma (CRASH-2), surgery, heavy menstrual bleeding, and obstetric haemorrhage.

Property of Class I and III antiarrhythmics to block more effectively at faster heart rates (more frequent channel activation means more channel visits per unit time → more drug binding); contributes to both efficacy and pro-arrhythmic risk.

System classifying antiarrhythmic drugs into four classes based on their primary electrophysiological mechanism: I (Na-channel block), II (beta-adrenergic block), III (K-channel block/APD prolongation), IV (Ca-channel block in nodal tissue).

Wolff-Parkinson-White syndrome — presence of an accessory atrioventricular conduction pathway (Bundle of Kent) that bypasses the AV node; manifests as delta wave and short PR on ECG; can conduct AF at extremely rapid rates to ventricles → VF.