Antihypertensives

Antihypertensives consist of vasodilators and diuretics

Antihypertensives, their major side effects, and their indications

Diuretics

All increase urinary flow and are contraindicated in pregnant patients, gout, or lithium.

Thiazide Diuretics

Hydrochlorothiazide (HCTZ), Metozalone, Indapamide, Bendrofluazide, Chortalidone

First drug of choice in newly diagnosed essential hypertension and in patients with edema and congestive heart failure. Usually given a once-daily dose.

• Kinetics
  • Good oral absorption = Good bioavailability
  • Excreted through the renal system (impaired secretion in renal failure)
  • Quick onset of action (lasts 12 hours)
• Adverse effects
  • **Hypokalemia (**will get rid of more potassium as more sodium is presented to the Na+/ K+ ATPase in the collecting duct)
  • Low blood pressure (Hypotension)
  • Hyperuricemia (Gout)
  • Hypercalcemia
  • Hyperglycemia
  • Impotence, Thrombocytopenia, and skin rashes (idiosyncratic)

Loop Diuretics

Furosemide, Bumetanide. Useful for patients with edema. Can be used to treat Milk-alkali syndrome

• Adverse effects
  • Hypokalemia
  • Low blood pressure (Hypotension)
  • Gout

Potassium-sparing Diuretics

Triamterene, Amiloride, Spironolactone, Eplerenone. Useful for patients with significant edema where two diuretics are needed OR in patients who tend to develop hypokalemia with other diuretics. Can be used to treat Liddle’s syndrome (Congenital metabolic alkalosis)

• Adverse effects
  • Hyperkalemia
  • Metabolic acidosis

Carbonic Anhydrase Inhibitors

Acetazolamide. Rarely used for hypertension. Used more for intracranial hypertension.

• Adverse effects
  • Hyperkalemia (can precipitate metabolic acidosis)
  • Metabolic acidosis (can precipitate hyperkalemia)

RAAS Inhibitors

ACE inhibitors (ACEIs)

Lisinopril, Enalapril, Capropril.

Widely prescribed because they are renal-protective. Used in hypertensive patients w/evidence of renal disease (Diabetes mellitus, microalbuminuria). Can also be used as an adjunct to chronic kidney disease (glomerulonephritis)

• Adverse effects
  • ACEi Cough (15%, due to increased bradykinin)
  • Angioedema
  • 1st dose hypotension (start with a small dose and increase with tolerance)
  • Hyperkalemia
  • Skin rash and taste disturbance (Captopril)
• Contraindications
  • Bilateral renal artery stenosis or Thrombosis (Kidney’s rely on AAS to maintain perfusion in renal vascular disease)
  • Pregnancy and breasfeedin (affects kidney development of the fetus and infant)

Angiotensin Receptor Blockers (ARBs)

Losartan, Valsartan, Candesartan.

Particularly used in patients where ACEIs are contraindicated or of African descent. Hydrochlorothiazide **(**HCTZ) + Losartan is a common combination of antihypertensives. Absolutely contraindicated in pregnancy. Relatively contraindicated in Bilateral renal artery stenosis.

• Contraindications
  • Pregnancy and Breastfeeding
  • Renal vascular disease (stenosis or thrombosis)
• Adverse effect
  • Cough (non-significant, used as a substitute in patients who cannot tolerate ACEi cough0
  • 1st dose hypotension (orthostatic)
  • Hyperkalemia
  • Rash
  • Dizziness, headache, fatigue

Sympatholytics

Beta Blockers

Metoprolol, Atenolol, Propranolol, Labetalol (mixed a/b).

Used in pts with hypertension and a history of MI or CHF. Can also be used in arrhythmias (SVT), essential tremors, and performance anxiety. NEVER USED BETA BLOCKERS FIRST TO LOWER PRESSURE IN SUSPECTED PHEOCHROMOCYTOMA. (Can use labetalol however since it is mixed a/b)

• Kinetics
  • Lipid soluble and undergoes hepatic metabolism (Propranolol)
  • 1st pass metabolism = poor oral availability
  • Water soluble and excreted via kidneys (Atenolol)
• Adverse effects
  • Bronchospasms (avoided in asthmatic patients)
  • Bradycardia
  • Peripheral vasoconstriction (aggravates Raynaud’s phenomenon)
  • Hallucinations, Vivid dreams, and Nightmares (Propranolol crosses the BBB)
  • Fatigue
  • Lipid disturbance
  • Masks hypoglycemia
• Contraindications
  • Asthma
  • COPD

Alpha Blocker

Prazosin, Doxazosin, Terazosin, Phenoxybenzamine.

Useful in suspected pheochromocytoma (phenoxybenzamine) or BPH (terazosin). No significant contraindications. Considered in severe hypertension.

• Adverse effect
  • Syncope (first dose; make sure patient knows that this is a possibility when prescribing)

Calcium Channel Blockers

Verapamil, Dilitiazem

Nifedipine, Amlodipine (Dihyropiridines)

Often used to treat hypertension, specifically for pregnant women as they are not teratogenic. Can also be used in angina pectoris and esophageal spasms

• Kinetics
  • Undergo 1st pass metabolism (Poor oral bioavailability)
  • Hepatic enzyme inhibitors
• Adverse effect
  • Syncope, Headache, Facial flushing, and Ankle edema (d/t vasodilation)
  • Bradycardia, AV conduction delay (Verapamil and Diltiazem)
  • Constipation (Verapamil)
• Contraindications
  • Patients with Arrhythmia (use Beta-blockers instead)
  • Patients with CHF (use Beta-blockers instead)

Centrally Acting Agents

Clonidine, Methyldopa

Work by inhibiting the release of norepinephrine. Centrally acting agents are considered in severe hypotension. Methyldopa is a first-antihypertensive in pregnancy.

Hydralazine

Hydralazine is indicated in severe hypertension, hypertensive emergency, and severe hypertension in pregnancy (Pre-eclampsia, eclampsia). It is a direct vasodilator.

• Contraindications
  • Idiopathic SLE
  • Severe tachycardia
• Adverse effects
  • Rebound tachycardia
  • Fluid retention
  • SLE like Rask (part of SHIPPE)
  • Nausea and vomiting
  • Headache

Treating Hypertension in Pregnancy

Hypertension in pregnancy is treated with either hydralazine, a-methyldopa, and any CCB (verapamil, nifedipine, amlodipine, diltiazem). Stay away from everything else (Diuretics, ACEIs, ARBs – never ok to use in pregnancy). In hypertensive crisis/emergency use IV nitroprusside.

• Hypertension in pregnancy
  • Pre-eclampsia (hypertension, proteinuria, edema)
  • Severe Pre-eclampsia (Severe hypertension, proteinuria, edema, neurologic symptoms)
  • Eclampsia (Pre-eclampsia/Severe pre-eclampsia + seizure)
  • HELLP syndrome (Pre-eclampsia → evidence of hemolysis, elevated liver enzymes, Thrombocytopenia)