Year 3 · Semester 1

Faculty of Medicine · Peradeniya

Cardiovascular
Pharmacology

Welcome! This is your complete guide to CV drugs — taught as Dr. Amiyangoda would explain it to you from scratch. We start with why the heart needs these drugs, then learn each drug family using the exam formula.

🔑

The Formula — Learn This First

⚙️

Mechanism

How does it work at the molecular level?

✅

Uses

When do you give it? Which disease?

⚠️

Adverse Effects

What goes wrong? What to monitor?

🚫

Why NOT

Contraindications — the exam loves this!

What You'll Master

🩸

Vascular Tone Drugs

ACE inhibitors, ARBs, Calcium channel blockers, Nitrates, Catecholamines, ARNIs

Hypertension Heart failure Angina

⚡

Antiarrhythmics

Vaughan-Williams Classes 0–4 with key drugs: amiodarone, lidocaine, digoxin, adenosine

AF VT SVT

💪

Inotropes

Digoxin, dobutamine, PDE inhibitors, levosimendan — for failing hearts

Heart failure Shock

🩹

Coagulation Drugs

Anticoagulants (heparin, warfarin, DOACs) + antiplatelets + thrombolytics

DVT MI Stroke

💧

Diuretics

Loop, thiazide, K⁺-sparing, osmotic, carbonic anhydrase inhibitors — where each works in the nephron

Oedema HTN

🏥

Clinical Scenarios

Real patient cases — choose the right drug and explain why. Exam-style practice.

Exam prep Clinical reasoning

Begin with Chapter 01: Vascular Tone

Chapter 01

Drugs Influencing Vascular Tone

Vascular tone = how tight or relaxed your blood vessels are. It determines blood pressure and how hard the heart works. These drugs are the backbone of hypertension and heart failure treatment.

🧠 The Big Picture First

Vascular smooth muscle contracts when Ca²⁺ enters → activates MLCK → myosin phosphorylation → contraction. It relaxes when cGMP/cAMP increases or Ca²⁺ is blocked.

AT-I

→ ACE →

AT-II

→ AT₁ receptor →

↑Ca²⁺

→

VASOCONSTRICTION

👆 This is what ACE inhibitors and ARBs block. Block different steps, same result: vasodilation.

Drug Families

⚙️

Mechanism

ACE inhibitors block the Angiotensin Converting Enzyme — the enzyme that converts AT-I → AT-II. Less AT-II means:

✓Less vasoconstriction → lower blood pressure
✓Less aldosterone → less Na⁺/water retention
✓More bradykinin (not broken down) → extra vasodilation
⚠That same bradykinin causes the infamous dry cough

💊

Key Drugs

Captopril

Short-acting · needs 2-3x daily dosing

Short

Enalapril / Ramipril / Lisinopril

Long-acting · once daily · most commonly used

Long

✅

Uses

Hypertension

Heart failure

Post-MI remodeling

Diabetic nephropathy

🚫

Adverse Effects & Why NOT

✕Dry cough — bradykinin accumulation (switch to ARB)

✕Angioedema — rare but life-threatening

✕First dose hypotension — start low, go slow

✕Pregnancy — absolutely contraindicated (fetal renal damage)

✕Bilateral renal artery stenosis — causes AKI

⚠Hyperkalaemia — monitor K⁺ (don't combine with K⁺-sparing diuretics carelessly)

Three Classes — VERY Different Effects!

Class	Drug	Where it acts	Key use
Phenylalkylamines	Verapamil	Cardiac ≫ Vascular	SVT, rate control
Benzothiazepines	Diltiazem	Cardiac > Vascular	SVT, angina
Dihydropyridines	Nifedipine, Amlodipine, Felodipine	Vascular ≫ Cardiac	HTN, angina

⚙️ Mechanism

Block L-type voltage-gated Ca²⁺ channels. Less Ca²⁺ entry → less MLCK activation → smooth muscle relaxes → vasodilation. In heart: also reduces contractility and slows conduction.

🚫 Key Contraindications

✕ Verapamil/Diltiazem + β-blockers = severe bradycardia/heart block
✕ Heart failure with reduced EF (negative inotropes)
⚠ Ankle oedema (common with DHPs)
⚠ Reflex tachycardia with short-acting nifedipine

Catecholamine Receptor Actions

Drug	α₁	β₁	β₂	Net effect
Noradrenaline	++++	++	+	Vasoconstriction, ↑BP
Adrenaline	++++	+++	++	↑HR, ↑BP, bronchodilation
Dopamine	++	+++	+	Dose-dependent (renal at low dose)
Phenylephrine	++++	—	—	Pure vasoconstriction (eye drops, hypotension)

💡 Clinical Pearl: In anaphylaxis, you give adrenaline (epinephrine) IM because it does everything at once — vasoconstriction (α₁), ↑cardiac output (β₁), bronchodilation (β₂).

📊 Quick Reference: All Vascular Tone Drugs

Drug class	Mechanism	Main use	Key adverse effect / CI
ACE inhibitors	Block ACE → ↓AT-II	HTN, HF, post-MI, DM nephropathy	Dry cough, angioedema, pregnancy CI
ARBs	Block AT₁ receptor	Same as ACEi (no cough)	Pregnancy CI, hyperkalaemia
CCB (DHP)	Block L-type Ca²⁺ (vascular)	HTN, stable angina	Ankle oedema, flushing, reflex tachycardia
CCB (non-DHP)	Block Ca²⁺ (cardiac + vascular)	SVT, rate control in AF	Bradycardia, heart block — NEVER with β-blockers
Nitrates	→ NO → ↑cGMP → venodilation	Angina (acute & prophylaxis)	Nitrate tolerance, CI with PDE5 inhibitors
ARNI	Neprilysin inh + ARB	HFrEF (replaces ACEi)	CI: with ACEi (↑↑angioedema risk)

Chapter 02

Antiarrhythmic Drugs

Arrhythmias = abnormal heart rhythms. These drugs work by modifying ion channel activity to restore normal rhythm. The Vaughan-Williams classification is the key you need.

🧠 Why do arrhythmias happen?

Normal cardiac rhythm depends on precise ion flow. Arrhythmias occur due to: (1) Abnormal automaticity — cells firing when they shouldn't, (2) Re-entry circuits — impulse going round in circles, (3) Triggered activity — afterdepolarisations.

Phase 0: Na⁺ influx (fast) Phase 2: Ca²⁺ influx (plateau) Phase 3: K⁺ efflux (repolarisation) Phase 4: Pacemaker current (HCN)

Vaughan-Williams Classification

0

Class 0 — HCN Channel Blockers

Ivabradine

Blocks the funny current (If) in the SA node → slows pacemaker rate. Reduces heart rate WITHOUT affecting contractility. Used in stable angina/heart failure when β-blockers can't be used.

⚠ CI: bradycardia, sick sinus syndrome, severe hepatic impairment

1

Class 1 — Na⁺ Channel Blockers

1a — Intermediate

Quinidine, Disopyramide, Procainamide

Also block K⁺ → ↑QT (torsades risk)

1b — Fast binding

Lignocaine (lidocaine), Mexiletine

IV for VT after MI. Short-acting. CNS toxicity (seizures).

1c — Slow binding

Flecainide, Propafenone

Potent. CI post-MI (proarrhythmic in structural disease)

2

Class 2 — Autonomic Modulators

2a: β-blockers (Bisoprolol, Metoprolol, Carvedilol)

Block β₁ → ↓SA node rate, ↓AV conduction. Used for AF rate control, post-MI, heart failure (chronic). CI: asthma (use cardioselective), decompensated HF

2d: Digoxin · 2e: Adenosine

Digoxin: vagal → ↓AV conduction, used for AF rate control. Adenosine: IV bolus → transiently blocks AV node, diagnosis/termination of SVT. Very short half-life (10s).

3

Class 3 — K⁺ Channel Blockers (Amiodarone — learn this well!)

Amiodarone — The Drug of Multiple Actions

Na⁺ block

K⁺ block

Ca²⁺ block

α, β block

✓ Used for SVT, VT, AF cardioversion
✓ Highly lipophilic → huge volume of distribution
✓ Half-life up to 5 MONTHS (amiodarone lasts forever!)
✕ Toxicity: pulmonary fibrosis, thyroid dysfunction (both hyper/hypo), liver damage, corneal deposits, photosensitivity
✕ Monitor: TFTs, LFTs, PFTs, CXR, eye exam

4

Class 4 — Ca²⁺ Channel Blockers (cardiac)

Verapamil & Diltiazem — block L-type Ca²⁺ in SA/AV nodes → ↓heart rate, ↓AV conduction. Used for SVT, AF rate control.

🚫 NEVER combine with β-blockers — risk of complete heart block and cardiac arrest

🔬 Digoxin — The Classic Drug

Mechanism

Inhibits Na⁺/K⁺-ATPase pump
↑ intracellular Na⁺ → less Ca²⁺ expelled
↑ intracellular Ca²⁺ → stronger contraction (positive inotrope)
Also increases vagal tone → ↓ AV conduction (rate control in AF)

Toxicity (very important!)

• Nausea, vomiting, visual disturbances (yellow halos)
• Arrhythmias (bradycardia, heart block, VT)
• Hypokalaemia WORSENS toxicity (diuretics + digoxin = dangerous!)
• Narrow therapeutic window — monitor drug levels
• Antidote: Digibind (anti-digoxin antibody fragments)

Chapter 03

Inotropic Drugs

These drugs increase myocardial contractility — the force of the heartbeat. Used when the heart can't pump adequately (heart failure, cardiogenic shock).

🧠 One Principle: Increase Intracellular Ca²⁺

All inotropes work by getting more Ca²⁺ available to cardiac myofilaments. They do this through different routes:

β₁ stimulation

↑cAMP → PKA → ↑Ca²⁺ release

Dobutamine, adrenaline

PDE inhibition

↑cAMP (less breakdown)

Milrinone, enoximone

Na/K pump block

↑Na⁺ → ↑Ca²⁺

Digoxin

💊 Dobutamine

Class: Synthetic catecholamine, β₁ agonist
Route: IV infusion only
Use: Acute decompensated heart failure, cardiogenic shock
Caution: Causes tachycardia and arrhythmias at high doses
CI: Hypertrophic obstructive cardiomyopathy

💊 PDE Inhibitors (Milrinone, Enoximone)

Mechanism: Inhibit phosphodiesterase 3 → ↑cAMP → ↑contractility + vasodilation ("inodilatators")
Use: Short-term acute HF
Key point: Long-term use increases mortality — only for bridge therapy
AE: Hypotension, arrhythmias

💊 Levosimendan — The Modern Inotrope

Mechanism: Ca²⁺ sensitiser — makes myofilaments more sensitive to Ca²⁺ (doesn't increase Ca²⁺ itself)
Also: Opens K-ATP channels → vasodilation (lusitropic effect)
Advantage: Doesn't increase O₂ demand as much as catecholamines

Use: Acute decompensated HF where dobutamine insufficient
Route: IV infusion, single dose (24h) — effects last days due to active metabolite
AE: Hypotension, headache, tachycardia

Chapter 04

Drugs Used in Coagulation

Three groups: Anticoagulants (prevent clot formation), Antiplatelets (prevent platelet aggregation), Thrombolytics/Fibrinolytics (dissolve existing clots).

1. Anticoagulants

The Big 3: Heparin vs Warfarin vs DOACs

Property	Heparin (UFH)	LMWH (Enoxaparin)	Warfarin	DOACs
Mechanism	Activates antithrombin → inhibits IIa + Xa	Activates antithrombin → mainly Xa	Inhibits Vit K epoxide reductase → ↓II, VII, IX, X	Direct Xa (rivaroxaban) or IIa (dabigatran)
Route	IV / SC	SC (once daily)	Oral	Oral
Monitoring	aPTT	Anti-Xa (usually not needed)	INR (target 2-3)	Usually not needed
Reversal	Protamine sulphate	Protamine (partial)	Vitamin K + FFP/PCC	Idarucizumab (dabigatran); Andexanet alfa (Xa)
Pregnancy?	✓ Safe (doesn't cross placenta)	✓ Safe	✕ Teratogenic in T1, bleeding T3	✕ Avoid

2. Antiplatelet Drugs

Aspirin

Irreversibly inhibits COX-1 → ↓TXA₂ (platelet aggregant). Low dose (75mg) for antiplatelet effect.

✓ ACS, stroke prevention, post-stent

✕ Peptic ulcer, asthma (aspirin-induced)

⚠ GI bleeding — give with PPI

Clopidogrel (P2Y12 blocker)

Irreversibly blocks ADP receptor (P2Y12) on platelets. Prodrug — requires CYP450 activation (genetic variability!).

✓ ACS, PCI, peripheral vascular disease

⚠ Effect lasts 7-10 days (platelet lifetime)

ℹ Dual antiplatelet = aspirin + clopidogrel

GP IIb/IIIa Antagonists

Block the final common pathway of platelet aggregation (fibrinogen bridge). Most potent antiplatelets. IV only.

✓ High-risk PCI, NSTEMI

Abciximab, Tirofiban, Eptifibatide

✕ Thrombocytopenia risk

3. Thrombolytics (Fibrinolytics)

These drugs activate plasminogen → plasmin → dissolves fibrin clot. They break down existing clots — unlike anticoagulants which prevent new ones.

Drugs

Streptokinase — bacterial protein, allergic reactions possible, cheaper
tPA (Alteplase) — fibrin-specific, preferred in stroke
Tenecteplase — single IV bolus, used in STEMI

Uses & Contraindications

✓ STEMI (<12h), ischaemic stroke (<4.5h), massive PE

✕ Recent surgery/trauma, active bleeding, haemorrhagic stroke, severe HTN

Chapter 05

Diuretics & Fluid Replacement

Diuretics increase urine output by blocking Na⁺ reabsorption at different points in the nephron. The key is knowing WHERE each drug acts.

🗺️ Where Each Drug Acts in the Nephron

PCT

Carbonic anhydrase inhibitors

Acetazolamide

Also: Osmotic (PCT + descending limb)

Loop of Henle

Loop diuretics

Furosemide, Bumetanide

Highest efficacy — 20-30% Na⁺

DCT

Thiazides

HCTZ, Indapamide

Moderate — 8% Na⁺

CD

K⁺-sparing

Spironolactone, Amiloride

Weak — 2% Na⁺

🔵 Loop Diuretics — Furosemide

Mechanism: Block NKCC2 cotransporter in thick ascending limb
Effect: Also lose Ca²⁺, Mg²⁺ (lose everything with the loop!)
✓ Pulmonary oedema (IV — fast), chronic HF, hypertension
✓ Hypercalcaemia (force Ca²⁺ excretion — with IV saline)
✕ Hypokalaemia, hypomagnesaemia, gout, ototoxicity (high IV dose)

🟡 Thiazides — HCTZ, Indapamide

Mechanism: Block NCC cotransporter in DCT
Unique: Retain Ca²⁺ (useful in hypercalciuria/kidney stones)
✓ First-line for hypertension, CCF
✕ Hypokalaemia, hyperuricaemia (gout), hyperglycaemia
✕ Ineffective if GFR <30 mL/min (except metolazone)

🟢 K⁺-sparing — Spironolactone, Amiloride

Spironolactone: Aldosterone receptor antagonist → ↓ENaC expression
Amiloride: Directly blocks ENaC channel
✓ Heart failure (spiro proven to reduce mortality), hyperaldosteronism, oedema with hypokalaemia
✕ Hyperkalaemia — DANGEROUS with ACE inhibitors/ARBs/K⁺ supplements
⚠ Spironolactone: gynaecomastia (anti-androgen effect)

🔮 Electrolyte Changes Summary

Diuretic	K⁺	Na⁺	Ca²⁺
Loop	↓↓	↓	↓
Thiazide	↓	↓	↑ (retained)
K⁺-sparing	↑ (retained)	↓	—

Chapter 06

Clinical Scenarios

This is how the exam tests you. Read each case, choose your answer, then reveal the explanation.

Chapter 07

Flashcards Practice

Tap to flip. Master the most important facts for your exam.

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Question · tap to flip

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Answer

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Chapter 08

Quick Quiz

Test your knowledge. No hints — just like the real exam.

CardiovascularPharmacology

The Formula — Learn This First

What You'll Master

Vascular Tone Drugs

Antiarrhythmics

Inotropes

Coagulation Drugs

Diuretics

Clinical Scenarios

Drugs Influencing Vascular Tone

🧠 The Big Picture First

Drug Families

Mechanism

Key Drugs

Uses

Adverse Effects & Why NOT

🧠 Key Concept: ARBs vs ACE Inhibitors

Three Classes — VERY Different Effects!

⚙️ Mechanism

🚫 Key Contraindications

⚙️ How Nitrates Work

💊 Drugs & Uses

Catecholamine Receptor Actions

📊 Quick Reference: All Vascular Tone Drugs

Antiarrhythmic Drugs

🧠 Why do arrhythmias happen?

Vaughan-Williams Classification

Class 0 — HCN Channel Blockers

Class 1 — Na⁺ Channel Blockers

Class 2 — Autonomic Modulators

Class 3 — K⁺ Channel Blockers (Amiodarone — learn this well!)

Class 4 — Ca²⁺ Channel Blockers (cardiac)

🔬 Digoxin — The Classic Drug

Mechanism

Toxicity (very important!)

Inotropic Drugs

🧠 One Principle: Increase Intracellular Ca²⁺

💊 Dobutamine

💊 PDE Inhibitors (Milrinone, Enoximone)

💊 Levosimendan — The Modern Inotrope

Drugs Used in Coagulation

1. Anticoagulants

The Big 3: Heparin vs Warfarin vs DOACs

2. Antiplatelet Drugs

Aspirin

Clopidogrel (P2Y12 blocker)

GP IIb/IIIa Antagonists

3. Thrombolytics (Fibrinolytics)

Drugs

Uses & Contraindications

Diuretics & Fluid Replacement

🗺️ Where Each Drug Acts in the Nephron

🔵 Loop Diuretics — Furosemide

🟡 Thiazides — HCTZ, Indapamide

🟢 K⁺-sparing — Spironolactone, Amiloride

🔮 Electrolyte Changes Summary

Clinical Scenarios

Flashcards Practice

Quick Quiz

Cardiovascular
Pharmacology