Cardiac Medications

• ACE inhibitors (ACEi) and angiotensin II receptor blockers (ARB)

  Drugs

  • ACEi include enalapril, ramipril, and lisinopril.
  • ARBs include losartan and candesartan.

  Mechanism

  • Reduce levels (ACEi) or effects (ARB) of angiotensin II.
  • Angiotensin II increases BP via systemic vasoconstriction, sodium retention, and aldosterone and ADH release.
  • Lower efficacy in black patients, so not 1st line in this group.

  Side effects

  ACEi-specific:

  • Dry cough (10%). Switch to ARB if occurs.
  • Angio-oedema: rare (0.1%) but 3x commoner in black patients.

  ACEi and ARB:

  • ↑K+ due to ↓aldosterone.
  • ↓↓BP when starting, so start low and titrate.

  Renal effects:

  • Can impair renal function: ↓GFR via efferent dilation, especially dangerous in bilateral renal artery stenosis.
  • However, it is often kidney protective via increased renal blood flow, so is used in chronic kidney disease and diabetes.
  • ↓GFR only occurs when efferent dilation outweighs the increased blood flow.

  Contraindications

  Absolute:

  • K+ >5.5.
  • Bilateral renal artery stenosis. However, used in unilateral disease.
  • Pregnancy: causes cleft palate.

  Cautions:

  • K+ >5.
  • Use ↓dose in kidney failure.

  Management

  Check K+ and creatinine at the following times:

  • Baseline: 1 wk pre + post starting.
  • After each dose increase.
  • During severe illness, especially if dehydration risk.
  • Routinely: annually, or more if ↓GFR.

  Actions:

  • If creatinine ↑20% from baseline or GFR ↓ 15%, recheck within 2 wks and if no better discuss with nephrologist.
  • If K+ >5.5, reduce dose, if K+ >6, stop.

• Beta blockers

  Mechanism

  • Cardiac β1 receptors increase HR at the sinus node and contractility in the myocytes; blockade therefore provides negative chronotropy and negative inotropy.
  • Selective for β1 receptors, B1 MAN: BIsoprolol, Metoprolol, Atenolol, Nebivolol.
  • Non-selective: carvedilol, labetalol, propranolol, timolol.
  • Metoprolol is the most short-acting, so often used IV acutely.

  Side effects

  • Fatigue. Consider dose reduction if occurs.
  • Cardiac: ↓HR, heart block.
  • Symptomatic hypotension. Consider stopping other agents (e.g. nitrates) first if β-blocker given for prognostic improvement e.g. in heart failure.
  • Wheeze
  • Erectile dysfunction.
  • May worsen diabetes control if combined with thiazide.
  • Cold peripheries from vasoconstriction, mainly with non-selective drugs. Switch to nebivolol if this occurs.
  • Sleep disturbance.

  Contraindications

  • Asthma
  • Non-selective agents should be avoided in COPD, but selective agents should be given when indicated.
  • Heart block.
  • ↓HR or ↓BP.
  • Pregnancy: restricts fetal growth.

  Cautions

  May not be appropriate for those who are physically active.

• Calcium channel blockers

  Mechanism

  Block L-type Ca2+ channels, reducing calcium inflow to cells:

  • Rate-limiting CCBs – verapamil and diltiazem – mainly affect myocardiocytes and nodal tissue, causing negative inotropy and chronotropy.
  • Non rate-limiting CCBs: amlodipine, nifedipine, lercanidipine. Known as dihydropyridines, the molecule from which they're derived. Mainly affect arterial smooth muscle, causing vasodilation and hence ↓BP.

  Side effects

  • Head and face: flushes, headache (especially non rate-limiting), gum hyperplasia.
  • Peripheral oedema. Less common with lercanidipine.
  • Constipation, especially verapamil.
  • Rate-limiting CCBs: heart failure.

  Contraindications and interactions

  • Heart block.
  • HF, especially rate-limiting CCBs.
  • β-blockers interact with rate-limiting CCBs.

• Diuretics

  Mechanisms

  • Loop diuretics (furosemide, bumetanide) block Na+-K+-2Cl- cotransporter in loop of Henle.
  • Thiazide (bendroflumethiazide) and thiazide-like diuretics (chlorthalidone, indapamide, metolazone) block Na+-Cl- cotransporter in distal convoluted tubule (DCT).
  • Potassium-sparing diuretics block ENaC in DCT (amiloride) or block aldosterone (spironolactone) which works via Na+-K+ ATPase and ENaC.

  Side effects

  All:

  • Urinary frequency.
  • Altered electrolytes.
  • Renal impairment, mainly due to volume depletion.

  Furosemide:

  • ↓K+
  • Muscle cramps.
  • Kidney stones, due to ↑Ca2+ excretion.
  • Gout

  Thiazides:

  • Electrolytes: ↓Na+, ↓K+ (↑Na+ is left in DCT then Na+-K+ ATPase removes some in exchange for K+), ↓Mg2+, ↑Ca2+.
  • Photosensitive rash.
  • ↑Glucose
  • Gout

  Spironolactone:

  • ↑K+
  • Tender gynecomastia.

  Contraindications

  • Gout
  • Renal failure
  • Pregnancy: thiazides, which cause oligohydramnios.

• Alpha blockers

  Drugs

  Tamsulosin, doxazosin, and prazosin.

  Mechanism

  • Systemic vasodilation by blocking α1 receptors.
  • Good for HTN in patients with prostatism, as they also help relieve urinary obstruction by relaxing smooth muscle in the prostate and bladder neck.

  Side effects

  • Peripheral oedema.
  • Worsen heart failure.
  • Postural ↓BP.

  Contraindications

  Urinary incontinence.