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Updated: Dec 28 2021

Antihypertensives

  • Snapshot
    • A 54-year-old man presents to his primary care physician for an annual examination. In his previous visit, he was diagnosed with hypertension. In today's visit, his blood pressure has not improved given his difficulty to adhere to a diet with more fruits and vegetables and exercise. His medical history is significant for type II diabetes mellitus and he is currently taking metformin. Physical examination is remarkable for a blood pressure of 152/99 mmHg and mildly decreased vibration and proprioception sense in his lower extremities. He is started on lisinopril.
  • Introduction
    • Antihypertensive medications are used to manage hypertension in patients where conservative measures are ineffective
      • there are four commonly used antihypertensive medications
        • diuretics
          • thiazides
          • potassium-sparing diuretics
        • sympatholytics
          • β-blockers
          • α-blockers
        • vasodilators
          • calcium channel blockers
          • hydralazine
          • minoxidil
        • renin-angiotensin-aldosterone inhibitors
          • angiotensin-converting enzyme (ACE) inhibitors
          • angiotensin receptor blockers (ARBs)
          • direct renin inhibitors
  • Diuretics
    • Medications
      • thiazides
        • mechanism of action
          • inhibits the NaCl transporter in the distal tubule
          • vasodilation (mechanism is unclear)
      • potassium-sparing diuretics
        • mechanism of action
          • promotes Na+ excretion in the distal nephron
    • Note that loop diuretic abuse can result in an increased sodium and potassium level in the urine
  • Sympatholytics
    • Medications
      • β-blockers
        • mechanism
          • decreases heart rate, which decreases cardiac output
          • decreases renin release, which decreases total peripheral resistance
        • notes
          • can result in bronchospasm, impotence, and hypoglycemia
          • can cause Raynaud phenomenon
            • treat with dihydropyridine calcium channel blocker
        • e.g., metoprolol
      • α-blockers
        • mechanism
          • central α2-agonists
            • decreases the sympathetic outflow to blood vessels, heart, and kidneys
              • e.g., methyldopa and clonidine
          • α1-blockers
            • blood vessel smooth muscle relaxation
              • e.g., prazosin and terazosin
  • Vasodilators
    • Medications
      • hydralazine
        • mechanism
          • increases cGMP to cause direct vascular smooth muscle relaxation
        • note
          • this causes a reflex tachycardia; therefore, β-blockers are often given together
      • minoxidil
        • mechanism
          • direct arteriolar smooth muscle relaxation
      • calcium channel blockers
        • mechanism
          • decreases cardiac and vascular calcium influx, resulting in a decreased cardiac output and total vascular resistance
        • can result in peripheral edema
          • treat with ACE inhibitors, changing the CCB, or changing the dose
  • Renin-Angiotensin-Aldosterone Inhibitors
    • Medications
      • angiotensin-converting enzyme (ACE) inhibitors
        • mechanism
          • inhibits ACE, which decreases circulating angiotensin II (ATII)
            • recall that ATII causes
              • vascular vasoconstriction
              • increased aldosterone secretion from the adrenal gland (zona glomerulosa)
        • notes
          • decreases mortality in patients with
            • acute myocardial infarction
            • heart failure with decreased ejection fraction
          • can result in a cough
          • beneficial for patients with diabetes
      • angiotensin receptor blockers (ARBs)
        • mechanism
          • directly blocks the AG-II receptor
        • notes
          • beneficial for patients with diabetes
  • Antihypertensives in Pregnancy
    • Medication options used to manage hypertension in pregnancy include
      • hydralazine
      • labetalol
      • methyldopa
      • nifedipine
  • Antihypertensives in Hypertensive Emergencies
    • Nitroprusside
      • mechanism
        • arteriolar and venous dilation via cGMP
      • notes
        • is metabolized into cyanide, which can potentially lead to cyanide poisoning
    • Fenoldopam
      • mechanism
        • a peripheral dopamine-1 receptor agonist
      • notes
        • maintains renal perfusion while the blood pressure is being decreased
          • therefore, it is beneficial in patients with renal impairment
    • Nicardipine and clevidipine
      • mechanism
        • decreases cardiac and vascular calcium influx
    • Labetalol
      • mechanism
        • α- and β-blocker
  • Antihypertensive Medications That Address Comorbid Conditions
    • Individualizing Antihypertensive Therapy
      ConditionAntihypertensive Medication
      Benign prostatic hyperplasia
      • α-blockers
      Essential tremor
      • β-blocker
      Hyperthyroidism
      • β-blocker
      Migraine
      • β-blocker
      • Calcium channel blocker
      Osteoporosis
      • Thiazide diuretics
      Raynaud phenomenon
      • Dihydropyridine calcium channel blocker
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