Conn Syndrome Medication

As mentioned previously, potassium-sparing agents, especially spironolactone, are useful for patients with primary hyperaldosteronism.

A sodium-restricted diet (< 80 mEq or < 2 g of sodium per day), maintenance of ideal body weight, and regular aerobic exercise contribute substantially to the success of pharmacologic treatment.

Frequently, hypertension and hypokalemia in primary hyperaldosteronism can be controlled with a potassium-sparing agent (first-step agent), such as spironolactone.^[9] These agents act as specific antagonists of aldosterone. Hypokalemia is promptly corrected, but hypertension may take as long as 4-8 weeks to correct. Potassium supplementation should not be routinely administered with spironolactone because of the potential for the development of hyperkalemia. If hypertension persists despite titration, a second-step agent is added to the treatment.

Second-step agents include thiazides diuretics, ACE inhibitors, calcium channel antagonists, and angiotensin II blockers.^[11]

GRA is treated with physiologic doses of glucocorticoid, which correct the hypertension and hypokalemia.

Class Summary

Thiazide diuretics inhibit the reabsorption of sodium in the distal tubules, increasing the excretion of sodium, water, and potassium and hydrogen ions. They have been effective in treating hypertension of various etiologies. Besides diminishing sodium reabsorption, they also appear to diminish the sensitivity of blood vessels to circulating vasopressor substances. In all patients treated with diuretics, electrolyte levels should be monitored. Examples of thiazide diuretics are hydrochlorothiazide and chlorthalidone.

Hydrochlorothiazide (Microzide)

Hydrochlorothiazide inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water as well as of potassium and hydrogen ions.

Chlorthalidone (Thalitone)

Chlorthalidone inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water as well as of potassium and hydrogen ions.

Class Summary

Calcium-channel blockers affect blood pressure by decreasing vascular peripheral resistance. With short-acting calcium-channel blockers, the cardiac response to this action is variable, resulting in tachycardia. Long-acting preparations may cause a decrease in the heart rate.

Calcium-channel blockers are classified by their structure, and they have different degrees of selectivity in their effects on vascular smooth muscle. The dihydropyridines do not exert electrophysiologic effects and are commonly used to manage hypertension. Facial flushing may occur. Examples of calcium-channel blockers are include amlodipine and isradipine.

Amlodipine (Norvasc)

Amlodipine is generally regarded as a dihydropyridine, although experimental evidence suggests that it also may bind to nondihydropyridine binding sites. It is appropriate for the prophylaxis of variant angina and has antianginal and antihypertensive effects. Amlodipine blocks the postexcitation release of calcium ions into cardiac and vascular smooth muscle, thereby inhibiting the action of adenosine triphosphatase (ATPase) on myofibril contraction.

The overall effect is reduced intracellular calcium levels in cardiac and smooth-muscle cells of the coronary and peripheral vasculature, resulting in dilatation of coronary and peripheral arteries. Amlodipine also increases myocardial oxygen delivery in patients with vasospastic angina, and it may potentiate ACE inhibitor effects.

During depolarization, amlodipine inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium. It benefits nonpregnant patients with systolic dysfunction, hypertension, or arrhythmias. It has a substantially longer half-life than nifedipine and diltiazem and is administered once daily.

Felodipine

Felodipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery. It benefits nonpregnant patients with systolic dysfunction, hypertension, or arrhythmias. It can be used during pregnancy if clinically indicated.

Calcium-channel blockers potentiate ACE inhibitor effects. Renal protection is not proven, but these agents reduce morbidity and mortality rates in congestive heart failure. Calcium-channel blockers are indicated in patients with diastolic dysfunction. They are effective as monotherapy in black patients and elderly patients.

Isradipine (DynaCirc)

Isradipine is a dihydropyridine calcium-channel blocker. It inhibits calcium from entering select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization. This causes relaxation of coronary vascular smooth muscle, which results in coronary vasodilation. Vasodilation reduces systemic resistance and blood pressure, with a small increase in resting heart rate. Isradipine also has negative inotropic effects.

Nifedipine, extended-release (Adalat CC, Nifedical XL, Procardia XL)

Extended-release nifedipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery. Sublingual administration is generally safe, despite theoretical concerns.

Class Summary

ACE inhibitors prevent conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, and lower aldosterone secretion. They are effective and well-tolerated drugs with no adverse effects on plasma lipid levels or glucose tolerance. They prevent the progression of diabetic nephropathy and other forms of glomerulopathies but appear to be less effective in black patients than in white patients.

Patients with high plasma renin activity may have an excessive hypotensive response to ACE inhibitors. Patients with bilateral renal vascular disease or with single kidneys, whose renal perfusion is maintained by high levels of angiotensin II, may develop irreversible acute renal failure when treated with ACE inhibitors.

ACE inhibitors are contraindicated in pregnancy. Cough and angioedema are less common with newer members of this class than with captopril. Serum potassium and serum creatinine concentrations should be monitored for the development of hyperkalemia and azotemia. Examples of agents from this class include captopril, lisinopril, and enalapril.

Captopril

Captopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion. It is rapidly absorbed, but bioavailability is significantly reduced with food intake. Captopril achieves a peak concentration in 1 hour and has a short half-life. It is cleared by the kidney; impaired renal function requires reduction of the dosage. The drug is absorbed well orally.

Give captopril at least 1 hour before meals. If it is added to water, use it within 15 minutes. The dose can be low initially, then titrated upward as needed and as tolerated by the patient.

Enalapril (Vasotec)

Enalapril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. It helps control blood pressure and proteinuria. It decreases the pulmonary-to-systemic flow ratio in the catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance.

Enalapril has a favorable clinical effect when administered over a long period. It helps prevent potassium loss in distal tubules. The body conserves potassium; thus, less oral potassium supplementation is needed.

Lisinopril (Prinivil, Zestril)

Lisinopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

Benazepril (Lotensin)

Benazepril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

When pediatric patients are unable to swallow tablets or the calculated dose does not correspond with tablet strength, an extemporaneous suspension can be compounded. Combine 300 mg (15 tablets of 20-mg strength) in 75 mL of Ora-Plus suspending vehicle and shake well for at least 2 minutes. Let the tablets sit and dissolve for at least 1 hour, then shake again for 1 minute. Add 75 mL of Ora-Sweet. The final concentration is 2 mg/mL, with a total volume of 150 mL. The expiration time is 30 days with refrigeration.

Fosinopril

Fosinopril is a competitive ACE inhibitor. It prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. It decreases intraglomerular pressure and glomerular protein filtration by decreasing efferent arteriolar constriction.

Quinapril (Accupril)

Quinapril is a competitive ACE inhibitor. It reduces angiotensin II levels, decreasing aldosterone secretion.

Class Summary

ARBs lower blood pressure by blocking the final receptor (ie, angiotensin II) in the renin-angiotensin axis. Like ACE inhibitors, they are contraindicated in pregnancy. Serum electrolyte and creatinine levels should be monitored. Examples of ARBs are irbesartan and losartan.

Irbesartan (Avapro)

Irbesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II at the tissue receptor site. It may induce a more complete inhibition of renin-angiotensin system than ACE inhibitors do, it does not affect the response to bradykinin, and it is less likely to be associated with cough and angioedema.

Losartan (Cozaar)

Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It may induce a more complete inhibition of renin-angiotensin system than ACE inhibitors do, it does not affect the response to bradykinin, and it is less likely to be associated with cough and angioedema. It is suitable for patients unable to tolerate ACE inhibitors.

Olmesartan (Benicar)

Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to angiotensin I receptors in vascular smooth muscle. Its action is independent of the pathways for angiotensin II synthesis.

Valsartan (Diovan)

Valsartan is a prodrug that produces direct antagonism of angiotensin II receptors. It displaces angiotensin II from angiotensin I receptors and may lower blood pressure by antagonizing angiotensin I-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses.

Valsartan may induce a more complete inhibition of renin-angiotensin system than ACE inhibitors do, it does not affect the response to bradykinin, and it is less likely to be associated with cough and angioedema. It is suitable for patients unable to tolerate ACE inhibitors.

Spironolactone (Aldactone)

Spironolactone competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions. It may block the effects of aldosterone on arteriolar smooth muscles.

Eplerenone (Inspra)

Eplerenone is indicated for hypertension. It selectively blocks aldosterone at mineralocorticoid receptors in epithelial (eg, kidney) and nonepithelial (eg, heart, blood vessels, brain) tissues. In this way, eplerenone decreases blood pressure and sodium reabsorption.