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1. ACE Inhibitors

Mechanism of Action

• Cleaves angiotensin I → angiotensin II (potent vasoconstrictor)
• Degrades bradykinin (a vasodilator that stimulates NO and prostacyclin release)

• ↓ Angiotensin II → less vasoconstriction, ↓ aldosterone → ↓ Na⁺/water retention
• ↑ Bradykinin → enhanced vasodilation
• Dilation of both arterioles and veins → ↓ preload and afterload
• Renal: efferent arteriolar vasodilation → ↓ intraglomerular pressure

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Spectrum of Indications

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Pharmacokinetics

• All are orally bioavailable (as drug or prodrug)
• Most (except captopril and lisinopril) require hepatic conversion to active metabolite — these two are preferred in severe hepatic impairment
• Most are renally eliminated — except fosinopril (no dose adjustment in renal impairment)
• Enalaprilat is the only IV formulation

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Adverse Effects

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Contraindications

• Pregnancy (teratogenic — fetal renal dysplasia)
• Bilateral renal artery stenosis (can precipitate acute renal failure)
• History of ACE inhibitor-induced angioedema
• Hyperkalemia
• Concurrent use with ARB + ACE inhibitor (not recommended — similar mechanism, additive toxicity)
• Aliskiren + ACE inhibitor in diabetic patients (contraindicated)

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Drug Interactions

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2. Drugs for Bradyarrhythmia

Definition & Classification

• Supraventricular: sinus/junctional bradycardia, AV blocks (1°, 2° Mobitz I/II)
• Ventricular: 3° (complete) AV block with idioventricular escape

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Drugs Used (Step-wise Approach per 2020 AHA Guidelines)

1. Atropine (First-line)

• Acute symptomatic sinus bradycardia
• 1° AV block (vagally mediated)
• Mobitz type I (Wenckebach) 2° AV block

• Not effective in transplanted hearts (denervated — no vagal input)
• Not preferred for Mobitz type II or 3° AV block (block is infranodal, not vagally mediated) — may worsen outcome
• Narrow-angle glaucoma, BPH (relative)

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2. β-Adrenergic Agonists (Second-line if atropine fails)

Dopamine

Epinephrine

Isoproterenol

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3. Transcutaneous/Transvenous Pacing (Non-pharmacological)

• Used when pharmacotherapy fails or for Mobitz II / 3° AV block
• TCP is painful — sedation required in awake patients
• Definitive: transvenous pacing

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Summary Table

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1. ACE Inhibitors

Mechanism of Action

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Indications

• Hypertension (first-line)
• Heart failure (systolic dysfunction)
• Post-MI (ventricular remodeling)
• Diabetic nephropathy / CKD (renoprotective)
• LV hypertrophy

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Side Effects

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Contraindications

• Pregnancy
• Bilateral renal artery stenosis
• Prior ACE inhibitor-induced angioedema
• Severe hyperkalemia
• Combined ACE inhibitor + ARB (not recommended)

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Drug Interactions

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2. Drugs for Bradyarrhythmia

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Drug 1: Atropine (First-line)

• Mechanism: Blocks M2 muscarinic receptors → ↓ vagal tone → ↑ SA automaticity & AV conduction
• Dose: 1 mg IV q3–5 min (max 3 mg); avoid < 0.5 mg (paradoxical bradycardia)
• Indications: Sinus bradycardia, junctional bradycardia, Mobitz type I (Wenckebach)
• Side Effects: Dry mouth, urinary retention, blurred vision, confusion, tachycardia
• Contraindications/Limitations: Ineffective in heart transplant patients (denervated); ineffective & potentially harmful in Mobitz type II or 3° AV block
• Interactions: Additive anticholinergic effects with antihistamines, TCAs, antipsychotics; antagonized by cholinesterase inhibitors (neostigmine)

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Drug 2: Dopamine (Atropine fails)

• Mechanism: β1 > α1 agonist → ↑ HR, ↑ contractility; vasoconstriction at high doses (>10 mcg/kg/min)
• Indications: Atropine-refractory bradycardia, hemodynamically unstable
• Side Effects: Tachycardia, arrhythmias, hypertension, peripheral ischemia at high doses
• Interactions: MAO inhibitors → severe hypertensive crisis; β-blockers antagonize effects

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Drug 3: Epinephrine (Atropine fails)

• Mechanism: α1 + β1 + β2 agonist → ↑ HR, ↑ contractility, vasoconstriction
• Indications: Atropine-refractory bradycardia, cardiac arrest
• Side Effects: Arrhythmias, severe hypertension, myocardial ischemia
• Interactions: MAO inhibitors → potentiate effects; β-blockers antagonize

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Drug 4: Isoproterenol

• Mechanism: Pure β1 + β2 agonist → ↑ HR + vasodilation (no α effects)
• Dose: 2–10 mcg/min IV infusion
• Indications: β-blocker overdose, denervated heart (transplant), torsades de pointes
• Side Effects: Tachycardia, palpitations, hypotension (β2 vasodilation), arrhythmias
• Interactions: MAO inhibitors; antagonized by β-blockers

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Quick Reference Table

Non-pharmacological: If drugs fail → Transcutaneous pacing (temporary) → Transvenous pacing (definitive), especially for Mobitz II / 3° AV block.

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Case 17 — Answers

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Station 1

• Onset on day 7 of hospitalization
• Fever, mucopurulent cough, bilateral crackles, RR 26/min
• Leukocytosis 16.2×10⁹/L, neutrophilia (n.14)
• Bilateral lower lobe infiltrates on chest X-ray
• Sputum culture: P. aeruginosa

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Station 2

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• Piperacillin (ureidopenicillin): Binds penicillin-binding proteins (PBPs) → inhibits bacterial cell wall synthesis (cross-links peptidoglycan) → bactericidal
• Tazobactam: β-lactamase inhibitor → irreversibly inhibits β-lactamases produced by bacteria → protects piperacillin from enzymatic degradation
• Together: extends spectrum to cover P. aeruginosa, Enterobacterales, anaerobes

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Rp:
Sol. Piperacillini/Tazobactami 4.5 g
D.t.d. No. 28 (vials)
S: Dissolve in 50–100 mL NS; infuse IV over 30 min–4 hrs
   every 6–8 hours

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Station 3

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• Penicillin/β-lactam allergy (anaphylaxis history — absolute contraindication)
• Severe hepatic failure (use with caution)
• Dose adjustment required in renal impairment (GFR < 20 mL/min)
• Not recommended as monotherapy if confirmed MDR/XDR Pseudomonas — combine with aminoglycoside or fluoroquinolone

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Prescriptions in Kazakhstan Format

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📋 Prescription 1 — Piperacillin/Tazobactam

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📋 Prescription 2 — Atropine Sulfate

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📋 Prescription 3 — ACE Inhibitor (Enalapril)

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Note on Kazakhstan Format:

• Prescriptions are written in Latin for the drug name (Rp.), dosage, and form
• Instructions (Signa / S.) are in Kazakh and/or Russian
• All hospital prescriptions require doctor's signature + institutional stamp (М.П.)
• Narcotic/controlled drugs require a special pink-form бланк — these drugs do not