Cardiovascular Pharmacology Lecture Notes

ACE Inhibitors & ARBs

• Prototype agents discussed: captopril (ACE-I) and losartan (ARB).
• Core clinical roles
  • Potent antihypertensives.
  • Kidney protection in chronic renal disease and in conditions that threaten renal function (e.g., type 2 diabetes) — sometimes used even when baseline BP is normal.
  • Post-myocardial-infarction (post-MI) standard therapy (patients usually leave hospital on “5 new meds,” ACE-I/ARB is one of them).
• Common combinations: often paired with thiazide diuretics and/or beta blockers; generics cost 5\text{–}10\text{ USD}/month, so highly accessible.
• Key adverse effects & clinical pearls • Hyperkalaemia (\uparrow K^+) — applies to ACE-Is & ARBs. • Angio-edema (swelling lips/tongue ⇒ airway risk) → absolute contraindication to all agents acting on the renin–angiotensin system.
  • If angio-edema occurs on captopril, you may NOT “just switch” to losartan; the whole class is banned for that patient.
    • ACE-I–induced dry cough (benign but annoying).
  • If troublesome (e.g., librarian who must stay quiet), switch ACE-I → ARB; same BP/kidney benefits, cough disappears.

Beta Blockers (BBs)

• Selective (β1) examples: atenolol, metoprolol.
• Non-selective example mentioned for contrast: propranolol.
• Negative chronotrope & inotrope ⇒ \downarrow HR, \downarrow cardiac workload.
• Dual indications • Hypertension. • Rate/rhythm control in arrhythmias such as atrial fibrillation (A-fib).
  • For rhythm indications, cardio-selective BBs (atenolol, metoprolol) preferred over non-selective agents.

Calcium Channel Blockers (CCBs)

• Two structural subclasses

1. Non-dihydropyridines: verapamil, diltiazem
   • Act on peripheral vasculature & cardiac calcium channels ⇒ \downarrow BP, \downarrow HR, rhythm control.
2. Dihydropyridines: nifedipine, amlodipine
   • Peripheral vasodilation only ⇒ strong BP reduction, minimal direct chronotropy.

• Clinical overlap
  • Verapamil/diltiazem double as anti-arrhythmics (A-fib).
• Adverse effects
  • Bradycardia (mainly non-DHPs).
  • Constipation — often overlooked; investigate CCBs when unexplained.

Digoxin

• MOA: inhibits Na^+/K^+-ATPase ⇒ alters intracellular Ca^{2+} ⇒ positive inotropy & altered conduction.
• Indications
  • A-fib rate/rhythm control.
  • Heart failure (HF) — NOT first-line; improves quality of life (morbidity) but not survival (mortality).
• Toxicity concerns (narrow therapeutic index)
  • Precipitants: hypokalaemia (e.g., from loop diuretics such as furosemide/lasix).
  • Early S/Sx: anorexia, nausea/vomiting, confusion.
  • Pathognomonic S/Sx: visual disturbances — yellow-green halos around lights ("Van Gogh Starry Night" analogy; foxglove plant/digitalis link).
  • Late/fatal: palpitations, arrhythmias.

Nitrates

• Acute angina: sublingual nitroglycerin (NTG).
  • Placed under tongue to bypass first-pass metabolism; swallowed tablets are ineffective.
• Potent systemic vasodilator ⇒ quick \downarrow BP; risk of profound hypotension if misused.
• Chronic angina: NTG PO, isosorbide dinitrate, NTG patches.
  • MANDATE: \ge 12-hour “nitrate-free” interval (esp. patches) to avoid tolerance.

Second-Line / Rescue Agents

• Milrinone
  • IV in acute decompensated HF; inotropic/vasodilator (phosphodiesterase-3 inhibitor).
• Ranolazine
  • Second-line for chronic stable angina when nitrates/β-blockers inadequate.

Antiarrhythmics

• Classes already covered doubling as antiarrhythmics:
  • β-blockers
  • Non-DHP CCBs (verapamil, diltiazem)
  • Digoxin
• Dedicated agents • Amiodarone — powerful oral maintenance drug for A-fib.
  • Adverse effects: hypotension, vision changes, blue-gray skin discoloration ("Smurf" nickname); extensive drug-drug interactions; requires serum level monitoring.
    • Procainamide — used after failure of BB/CCB/digoxin/amiodarone.
    • Adenosine (IV) — emergent conversion to sinus rhythm; transiently stops heart then restarts it.
  • Warn awake patients of "impending sense of doom."

Organizing Drugs by Indication (Study Tip)

• Hypertension: ACE-I, ARB, β-blocker, CCB (both DHP & non-DHP), nitrates (by vasodilation).
• Heart Failure: ACE-I/ARB, β-blocker, loop diuretics (next week), digoxin (later), milrinone (acute).
• Atrial Fibrillation: β-blocker (cardio-selective), non-DHP CCB, digoxin, amiodarone, procainamide, adenosine (rescue).

Cholesterol Panel: Targets & Interpretation

• Components measured:
  • HDL ("good")
  • LDL ("bad")
  • Triglycerides (TG)
  • Total Cholesterol = HDL + LDL
• Goal values
  • Total < 200 mg/dL. • HDL > 60 mg/dL (≥40 often accepted).
  • LDL < 100 mg/dL (some cardiologists aim <70).
  • Triglycerides < 150 mg/dL; marked elevation often signals hyperglycaemia/diabetes or pancreatitis risk.
• Note: High total cholesterol may be acceptable if driven by high HDL.

Lipid-Lowering Drugs

• Statins (HMG-CoA reductase inhibitors) — "gold standard"; atorvastatin is flagship.
  • Target doses required for % LDL reduction (e.g., \ge 20–40 mg atorvastatin for full effect).
  • Adverse: myalgia, myopathy, rhabdomyolysis, hepatotoxicity; monitor LFTs.
• Ezetimibe
  • Blocks intestinal cholesterol absorption; modest LDL lowering.
  • Usually adjunct to statin; GI side-effects due to unabsorbed lipids.
• Cholestyramine
  • Bile-acid sequestrant; lowers LDL, relieves pruritus.
  • Impairs absorption of fat-soluble vitamins A, D, E, K — counsel spacing.
• Gemfibrozil (fibrate)
  • Good for TG lowering; risk of myopathy ↑ when combined with statin.
• Niacin (vitamin B3/nicotinic acid)
  • Best for severe hyper-TG when LDL OK.
  • Adverse flushing (histamine) — pre-dose aspirin (30 min prior) mitigates; many cardiac patients already on aspirin.

Ethical / Practical / Historical Notes

• Van Gogh/foxglove lore illustrates visual halo symptom of digoxin toxicity.
• "Smurf clinics" nickname for amiodarone follow-up reflects blue-skin side effect — terminology discouraged for sensitivity.
• Patients should not blame themselves if diet fails to normalize lipids; strong genetic component justifies pharmacotherapy.

Quick Numerical & Formula References

• Nitrate-free period ≥ 12 h per day.
• Cost of generic ACE-I/ARB therapy ≈ 5–10 USD/month.
• Digoxin toxicity probability ↑ when K^+ low; often due to loop diuretic–induced hypokalaemia.
• Adenosine: transient AV block; explains momentary asystole feeling.

Wrap-Up Study Strategy

1. Build three master tables: Hypertension, Heart Failure, A-fib. Place each drug accordingly (duplicates welcome).
2. For each agent, annotate: class, MOA, indications, target dose (if any), hallmark side effects, contraindications, rescue antidotes.
3. Use clinical “stories” (cough librarian, Van Gogh, Smurf) as memory anchors.