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Table of Contents

Nitroprusside sodium (Nipride), Diazoxide (Hyperstat)  

• Vasodilators used for acute management of hypertensive crisis or malignant hypertension include sodium nitroprusside and diazoxide.

• Nitroprusside sodium (Nipride) is the agent of choice.

  • Administered by a continuously variable rate i.v. infusion pump, precise blood pressure control can be obtained.

  • Nitroprusside sodium (Nipride), a nitrovasodilator, is metabolized by smooth muscle cells to nitric oxide which dilates both arterioles and venules.

•  Side effects are mainly due to excessive vasodilation.

  • Much less commonly, toxicity may result from conversion of nitroprusside to cyanide and thiocyanate.

  • Risk of toxicity due to thiocyanate increases after 24 to 48 hours.

  • Nitroprusside sodium (Nipride) can worsen arterial hypoxemia in patients with obstructive pulmonary airway disease since nitroprusside will interfere with hypoxic pulmonary vasoconstriction. A result is increasing ventilation-perfusion mismatching.

• Diazoxide (Hyperstat) is infrequently used unless accurate infusion pumps are unavailable.

  • The mechanism of action involves activation of ATP-sensitive potassium channels, hyperpolarization of arteriolar smooth muscle, relaxation and dilation.

  • Adverse effects include salt and water retention and hyperglycemia. Diazoxide inhibits insulin release.

Hydralazine (Apresoline) Minoxidil (Loniten) 

• Vasodilators used for chronic treatment include hydralazine (Apresoline) and minoxidil (Loniten).

  • These drugs are not typically administered as monotherapy due to significant reflex-mediated cardiac stimulation and water retention. Instead they may be combined with sympatholytic drugs.

• Adverse effects include those induced by vasodilation such as: hypotension, palpitation, tachycardia, fluid retention, headache, angina

• A drug-induced lupus syndrome is associated with hydralazine (Apresoline).

• A drug-induced hypertrichosis is associated with minoxidil (Loniten).

Amlodipine (Norvasc)   Felodipine (Plendil) 

• Calcium channel blockers are effective in treating hypertension because they reduce peripheral resistance.

• Amlodipine (Norvasc) and Felodipine (Plendil) have relatively little effects on reducing myocardial contractility compared to verapamil (Isoptin, Calan) or diltiazem (Cardiazem).

• Arteriolar vascular tone depends on free intracellular Ca²⁺ concentration.

  • Calcium channel blockers reduce transmembrane movement of Ca²⁺

  • A reduction in the amount of Ca²⁺ reaching intracellular sites results in a reduced vascular smooth muscle tone.

• All calcium channel blocks appear similarly effective for management of mild to moderate hypertension.

• For low-renin hypertensive patients (elderly and African-American groups), Ca²⁺ channel blockers appear good choices for monotherapy (single drug) control.

Adverse Effects

• SA nodal inhibition may lead to bradycardia or SA nodal arrest.

  • This effect is more prominent if beta adrenergic antagonists are concurrently administered.

• GI reflux.

• Negative inotropic are augmented if beta-adrenergic receptor antagonists are concurrently administered.

• Calcium channel blockers should not be administered if the patient has SA or AV nodal abnormalities or in patients with significant congestive heart failure.

Nimodipine (Nimotop)

• Overview

  • Highly lipid-soluble nefedipine analog

  • Ready access to the CNS -- reduces large cerebral arterial contraction

• Clinical Use:

  • Cerebral Vasospasm:

    • Useful in preventing/reducing cerebral vasospasm associated with subarachnoid hemorrhage

    • Vasospasm -- mediated by calcium ion influx

    • Nimodipine (Nimotop) administered over a three week course (oral administration) results and decreased frequency of neurologic defects secondary to cerebral vasospasm in subarachnoid hemorrhage patients.

      • For comatose patients: deliver through nasogastric tube

    •  Side effects/Concerns:

      • systemic hypotension (with excess nimodipine (Nimotop) effect)

      • possible increase in intracranial pressure -- especially in patients with decreased intracranial compliance

Stoelting, R.K., "Calcium Channel Blockers", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, p. 350.

Diltiazem (Calcium Channel Blocker) 

• Calcium channel blockers are effective in treating hypertension because they reduce peripheral resistance.

• Arteriolar vascular tone depends on free intracellular Ca²⁺ concentration.

  • Calcium channel blockers reduce transmembrane movement of Ca²⁺ , reduce the amount reaching intracellular sites and therefore reduce vascular smooth muscle tone.

• All calcium channel blocks appear similarly effective for management of mild to moderate hypotension.For low-renin hypertensive patients (elderly and African-American groups), Ca²⁺ channel blockers appear good choices for monotherapy (single drug) control.

• Diltiazem has a direct negative chronotropic effect on the heart sufficient to block reflex-mediated tachycardia secondary to the decrease in peripheral resistance.

• The reflex-mediated adrenergic stimulation tends to counteract negative inotropic properties of diltiazem.

 Adverse Effects

•  SA nodal inhibition may lead to bradycardia or SA nodal arrest.

  • This effect is more prominent if beta adrenergic antagonists are concurrently administered.

• GI reflux.

• Negative inotropic are augmented if beta-adrenergic receptor antagonists are concurrently administered.

• Calcium channel blockers should not be administered if the patient has SA or AV nodal abnormalities or in patients with significant congestive heart failure.

• Angiotensin II, a potent vasoconstrictor, is produced by the action of angiotensin converting enzyme (ACE) on the substrate angiotensin I. Angiotensin II activity produces

  • a rapid pressor response

  • a slow pressor response and

  • vascular and cardiac hypertrophy and remodeling.

• Antihypertensive effects of ACE inhibitors are due to the reduction in the amount of angiotensin II produced.

• ACE inhibitors are efficacious in management of hypertension and have a favorable side effect profile.

• ACE inhibitor are advantageous in management of diabetic patients by reducing the development of diabetic neuropathy and glomerulosclerosis.

• ACE inhibitor are probably the antihypertensive drug of choice in treatment of hypertensive patient who have hypertrophic left ventricles.

  • Hypertensive patients who have ischemic heart disease with impaired left ventricular function also benefit from ACE inhibitor treatment.

• ACE inhibitors reduce the normal aldosterone response to sodium loss (normally aldosterone opposes diuretic-induced sodium loss).

  • Therefore, the use of ACE inhibitors enhance the efficacy of diuretic treatment, allowing the use of lower diuretic dosages and improving control of hypertension.

•  If diuretics are administered at higher dosages in combination with ACE inhibitors significant and undesirable hypotensive reactions can occur with attendant excessive sodium loss.

•  Reduction in aldosterone production by ACE inhibitors also affects potassium levels.

  • The tendency is for potassium retention, which may be serious in patients with renal disease or if the patient is also taking potassium sparing diuretics, nonsteroidal anti-inflammatory agents or potassium supplements.

Captopril (Capoten)

• Overview

  • Orally effective, competitive inhibitor of angiotensin I-converting enzyme (peptidyl dipeptidase) [enzyme converts angiotensin I to angiotensin II (active)]

  • Decreases circulating angiotensin II & aldosterone {angiotensin II stimulates aldosterone secretion by the adrenal cortex}

    •  Compensatory response: increase in angiotensin I & increased renin levels {loss of negative feedback control}

  • Decrease in aldosterone cause slight increase in serum potassium

• Pharmacokinetics:captopril

  • well absorbed; 25%-30% protein bound

  • rapid converting enzyme inhibition (within 15 minutes following oral administration)

  • 50% drug excreted unchanged

  • elimination half-life: two hours -- oxidation, real excretion

• Cardiovascular Effects: captopril (Capoten)

  • Decrease systemic vascular resistance (secondary to a decrease in Na⁺ & water retention)

  • Prominent decrease in renal vascular resistance

  • Reduced systemic blood pressure: no change in heart rate & cardiac output

    • Absence of heart rate change despite reduced blood pressure may suggest alteration baroreceptor sensitivity

  • No orthostatic hypotension (captopril does not interfere with sympathetic nervous system function)

  • captopril may improve vasodilator drug treatment efficacy in management of CHF by blocking vasodilator-induced increases in renin secretion

Adverse Effects

• Angioedema, although rare, may be potentially fatal.

• ACE inhibitiors should not be used during pregnancy.

• Dry cough.

• In renovascular hypertension, glomerular filtration pressures are maintained by vasoconstriction of the post-glomerular arterioles, an effect mediated by angiotensin II. Used of ACE inhibitors in patients with renovascular hypertension due to bilateral renal artery stenosis can therefore precipitate a significant reduction in GFR and acute renal failure.

• Initial dose of an ACE inhibitor may precipitate an excessive hypotensive response.

Losartin (Cozaar);  Irbesartin

• Angiotensin II receptor antagonists: Losartin (Cozaar) and Irbesartin, AT1 angiotensin II receptor antagonists, act by blocking the interaction between angiotensin II and its receptor.

• The magnitude of the blood pressure decrease associated with losartin may be somewhat less than that seen with ACE inhibitors.