PH4.1-11 | Cardiovascular and Blood Pharmacology — Practice Quiz

ACE inhibitors (e.g., enalapril, ramipril) are the preferred first-line agents in diabetic nephropathy. They reduce intraglomerular pressure by dilating the efferent arteriole via Ang II blockade, slowing the progression of proteinuria and CKD independently of their blood pressure–lowering effect.

In diabetic nephropathy with microalbuminuria, the goal is dual: BP control AND renoprotection. ACEi/ARBs provide both. Avoid ACEi+ARB combination due to additive hyperkalemia/AKI risk. Monitor K+ and creatinine at 1-2 weeks after initiation.

While other agents lower blood pressure, they lack the renoprotective benefit of RAAS blockade in diabetic nephropathy. Thiazides and CCBs do not reduce proteinuria; beta-blockers may mask hypoglycaemia symptoms.

The four pillars of GDMT for HFrEF are: (1) ACEi or ARNI (sacubitril/valsartan), (2) beta-blocker (carvedilol, metoprolol succinate, or bisoprolol), (3) mineralocorticoid receptor antagonist (spironolactone/eplerenone), and (4) SGLT2 inhibitor (dapagliflozin or empagliflozin). Each independently reduces CV mortality.

HFrEF management = neurohormonal blockade (four pillars) + symptom control (diuretics). Do not confuse symptom management with mortality-reducing therapy. The four pillars are initiated and up-titrated simultaneously, not sequentially.

Furosemide relieves symptoms but does not reduce mortality. Amlodipine is not proven to reduce HF mortality. Digoxin reduces hospitalisations but not mortality. Hydralazine+isosorbide is reserved for ACEi/ARB-intolerant Black patients.

Amiodarone is the most effective antiarrhythmic for ventricular arrhythmias in structurally abnormal hearts. It has multi-class activity (I, II, III, IV) and does not worsen cardiac function, unlike Class Ic agents. It is the drug of choice for VT in patients with reduced EF.

The CAST trial (1989) remains the cardinal lesson: Class Ic agents (flecainide, encainide) suppress VT in post-MI patients but increase sudden cardiac death. Never use Class Ic in structural heart disease. Amiodarone is the safest effective option in reduced EF.

Flecainide (Class Ic) is absolutely contraindicated in structural heart disease or post-MI (CAST trial — increased mortality). Verapamil (Class IV) is for SVTs, not VT. Lignocaine is used for acute VT in ICU but not for long-term suppression.

CK elevation <5× ULN with symptoms warrants dose reduction and monitoring, not immediate discontinuation. High-intensity statins (atorvastatin 80 mg) carry higher myopathy risk. Dose reduction preserves lipid-lowering benefit while reducing muscular adverse effects.

Statin myopathy threshold: myalgia without CK rise = continue and reassess; CK 3-10× ULN with symptoms = reduce dose or switch to alternate statin; CK >10× ULN = stop immediately. Risk factors: high dose, concurrent gemfibrozil/amiodarone/CYP3A4 inhibitors, hypothyroidism, renal impairment.

Stopping immediately is appropriate only if CK >10× ULN or rhabdomyolysis is suspected. Switching to simvastatin is not appropriate — simvastatin has more DDIs (CYP3A4) and higher myopathy risk than atorvastatin at equivalent doses. Ignoring symptomatic CK elevation risks progression to rhabdomyolysis.

Statements a, b, and d are correct. Beta-blockers must be initiated in a euvolaemic state (acute decompensation is a contraindication to STARTING, though existing therapy is continued). Only carvedilol, metoprolol succinate (not tartrate), and bisoprolol have landmark trial evidence (MERIT-HF, CIBIS-II, COPERNICUS). Their mechanism is suppressing chronic SNS activation.

The rule: Start low, go slow, and only when dry. Up-titrate to target doses over weeks-months. In acute decompensation, HOLD new initiation; CONTINUE but REDUCE existing beta-blocker only if haemodynamics demand it. Never abruptly stop — rebound tachycardia can destabilise HF.

Statement c is wrong — acute decompensation is a contraindication to initiating (not to continuing) beta-blockers. Statement e is wrong — atenolol lacks mortality benefit in HFrEF (not studied in landmark trials; beta-1 selective without additional vasodilatory/anti-oxidant properties of carvedilol).

Both statements are correct, and the reason directly explains the assertion. Heparin's high molecular weight (~15,000 Da for UFH; ~4,500 Da for LMWH) and high negative charge prevent placental transfer. Warfarin (a small lipophilic molecule, MW ~330 Da) crosses the placenta and causes: (1) warfarin embryopathy (nasal hypoplasia, stippled epiphyses) in T1; (2) fetal haemorrhage in T3.

Pregnancy anticoagulation rule: Heparin only. Warfarin is teratogenic (T1) and causes fetal intracranial haemorrhage (T3). DOACs are not established as safe. LMWH (enoxaparin) is preferred over UFH for ease of dosing. Switch to UFH near delivery (easier reversal with protamine).

The reason is the actual mechanism. The assertion is also fully correct — both UFH and LMWH are safe throughout pregnancy. DOACs (dabigatran, rivaroxaban) are also contraindicated — they cross the placenta and their safety is not established.

The standard pharmacological reperfusion strategy when PCI is unavailable: (1) Aspirin 325 mg loading (then 75-100 mg daily); (2) Clopidogrel 300 mg loading (preferred P2Y12 over ticagrelor with thrombolytics due to increased intracranial haemorrhage risk with newer agents); (3) Fibrinolytic — tenecteplase (weight-based, single bolus, lower bleeding than streptokinase, no antigenicity); (4) Anticoagulant — UFH or enoxaparin.

Streptokinase is associated with allergic reactions and antigenicity on re-exposure; clopidogrel is preferred over ticagrelor/prasugrel with thrombolytics. Prasugrel + ticagrelor together is contraindicated — dual P2Y12 is never used.

Post-STEMI secondary prevention with reduced EF includes: (1) DAPT — aspirin + P2Y12 (ticagrelor preferred post-ACS, 12 months); (2) ACEi (ramipril — proven post-MI, reduces LV remodelling, AIRE trial); (3) High-intensity statin (atorvastatin 80 mg, PROVE-IT trial); (4) Beta-blocker (carvedilol — HFrEF with EF 38%). This is the complete evidence-based bundle.

Amlodipine does not reduce mortality post-MI. Digoxin has no role in post-STEMI without AF. Warfarin without a specific indication (LV thrombus, AF) increases bleeding without added benefit over DAPT.

IV furosemide is the diuretic of choice in acute pulmonary oedema. Its rapid venodilatory effect (within 5 minutes of IV administration, before diuresis begins) relieves preload and reduces pulmonary capillary pressure. Diuresis follows within 30-60 minutes. Onset is more rapid and reliable than oral administration.

IV furosemide has two distinct pharmacodynamic phases in acute pulmonary oedema: (1) Immediate (5 min): venodilation via PGE2 release → ↓preload; (2) Delayed (30-60 min): diuresis via NKCC2 block → further ↓preload. This dual action makes it the cornerstone of acute HF treatment.

Thiazides (HCTZ) are less potent and oral — inappropriate for acute emergency. Spironolactone acts via aldosterone blockade with delayed onset (days) and is used for chronic HF mortality reduction, not acute decompensation. Acetazolamide is used for glaucoma and altitude sickness.

Clopidogrel is a prodrug converted by CYP2C19 to its active metabolite which irreversibly alkylates the P2Y12 ADP receptor. Platelet inhibition persists for the lifetime of the platelet (7-10 days). This irreversibility requires stopping clopidogrel 5-7 days before elective surgery.

Antiplatelet mechanisms and reversibility: Aspirin = irreversible COX-1; Clopidogrel/prasugrel = irreversible P2Y12; Ticagrelor = reversible P2Y12; GP IIb/IIIa inhibitors = IV use only, ACS. The irreversibility of clopidogrel explains why 5-7 days washout is needed pre-surgery. CYP2C19 poor metabolisers may have reduced clopidogrel efficacy (pharmacogenomics).

COX-1 inhibition is aspirin's mechanism. Reversible P2Y12 block describes ticagrelor (and cangrelor IV). GPIIb/IIIa inhibition describes abciximab, eptifibatide, tirofiban.

For supratherapeutic INR with minor bleeding (haematuria, stable haemodynamics): withhold warfarin and give low-dose oral vitamin K (2.5-5 mg). This reverses INR within 24-48 hours without making the patient over-anticoagulated and refractory to warfarin. FFP is reserved for major bleeding or emergency surgery.

Warfarin reversal algorithm: INR >3 without bleeding → reduce dose; INR 3-5 without bleeding → may withhold 1-2 doses; INR 5-9 with minor bleeding → withhold + oral vitamin K 2.5-5 mg; INR >9 or any major bleeding → IV vitamin K 5-10 mg + FFP or PCC (4-factor prothrombin complex concentrate). Protamine reverses heparin, not warfarin.

FFP is not needed for minor bleeding — it has volume and infection risk. Continuing warfarin with INR 8.2 carries serious bleeding risk. Switching to LMWH does not reduce immediate bleeding risk.

ACEi-induced cough is caused by bradykinin accumulation (ACE also degrades bradykinin). It occurs in 5-20% of patients (more frequent in Asian/Indian populations — up to 30-40%). The cough is class-effect — dose reduction does not help. ARBs block the AT1 receptor without affecting bradykinin breakdown, providing equivalent renoprotection without cough.

ACEi cough vs angio-oedema: both are bradykinin-mediated but cough is benign and reversible; angio-oedema is rare (0.1-0.5%) but potentially life-threatening. For cough → switch to ARB (same RAAS benefit, no bradykinin accumulation). For angio-oedema → stop ACEi permanently; ARBs carry small cross-risk (1-2%), so use with caution.

Dose reduction will not resolve ACEi cough as it is a class effect, not dose-dependent. Cough suppressants mask but do not treat the cause. Amlodipine lacks the renoprotective RAAS blockade needed in diabetic nephropathy.

For uncomplicated iron deficiency anaemia in pregnancy without GI malabsorption, oral ferrous sulphate is first-line. Lower doses (e.g., 100 mg/day, or alternate-day dosing) have equivalent efficacy to higher doses with fewer GI side effects and better compliance. Vitamin C (ascorbic acid) reduces ferric to ferrous form, enhancing non-haem iron absorption. IV iron is reserved for intolerance or malabsorption.

Oral iron absorption: ferrous (Fe2+) > ferric (Fe3+) — absorbed from duodenum/upper jejunum. Take on empty stomach for maximum absorption; GI side effects (nausea, constipation) are dose-dependent. Lower, once-daily dosing with vitamin C improves compliance. Monitor Hb response in 4-6 weeks (expected rise: 1-2 g/dL/month). Continue for 3 months after Hb normalisation to replenish stores.

IV iron (ferric carboxymaltose) is reserved for: GI intolerance, malabsorption, third trimester urgency, or failure of oral therapy — not first-line. High-dose TDS regimens (200 mg × 3 = 600 mg/day) have more GI side effects without proportionally greater absorption. Ferric salts have lower bioavailability than ferrous salts.