Pediatric Nephritis Medication
- Author: Sahar Fathallah-Shaykh, MD; Chief Editor: Craig B Langman, MD more...
Medications used to treat patients with glomerulonephritis (GN) generally fall into 3 categories: antihypertensives, diuretics, and anti-inflammatories or immunosuppressives.
Pharmacotherapy may include numerous drug classes that have antihypertensive effects and possess different pharmacologic actions. Thiazide diuretics and beta blockers have been the mainstay of drug therapy for hypertension. The availability of other drugs (eg, calcium channel blockers, ACE inhibitors, alpha blockers, angiotensin II receptor antagonists) now allows regimens to be customized to the population treated and permits enhanced compliance and an improved ability to tolerate treatment. (For more information, see Pediatric Hypertension and Neonatal Hypertension.)
As previously mentioned, some recommend a short course of steroids or cyclophosphamide for tubulointerstitial nephritis (TIN), but these drugs are usually not necessary. Most often, stopping the offending agent leads to recovery.
These agents are used to remove excess fluid in children with edema secondary to renal disease and as an adjunct to manage hypertension.
Furosemide is a loop diuretic. It is often effective in removing fluid even when the glomerular filtration rate is reduced secondary to nephritis. This agent increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and the distal renal tubule.
Hydrochlorothiazide (HCTZ) acts on the distal nephron to impair sodium reabsorption, enhancing sodium excretion. It has been in use for more than 40 years and is generally an important agent for the treatment of essential hypertension.
These agents reduce the systemic arterial blood pressure, reducing injury caused by elevated blood pressure. They may not only reduce cardiovascular risk but also slow progression of renal failure. ACE inhibitors may also slow progression of renal failure by lowering intraglomerular pressure or other intrarenal mechanisms.
A dry cough is a common adverse effect of ACE inhibitors. If the cough occurs with one ACE inhibitor, it is likely to occur with another. A reasonable substitute for an ACE inhibitor if a cough develops is an ARB, such as losartan, valsartan, or candesartan.
Captopril, a competitive ACE inhibitor, prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, increasing levels of plasma renin and reducing aldosterone secretion. It has been clinically used for more than 20 years and is effective in experimental radiation nephropathy. Captopril may slow the progression of renal failure by lowering intraglomerular pressure or other intrarenal mechanisms.
A competitive ACE inhibitor, enalapril reduces angiotensin II levels, decreasing aldosterone secretion. The drug lowers systemic arterial blood pressure, reducing injury caused by elevated blood pressure. It may slow the progression of renal failure by lowering intraglomerular pressure or other intrarenal mechanisms. Enalapril may be used every day or twice per day, which may improve compliance in comparison with a 3-time-per-day medication, such as captopril.
Angiotensin II Receptor Antagonists
ARBs antagonize the action of angiotensin II at the type 1 receptor, reducing systemic arterial blood pressure and blunting the intrarenal effect of angiotensin II. If ACE inhibitors cause cough, ARBs may be substituted.
Losartan is a prototype ARB. It is specific for the type 1, as opposed to type 2, angiotensin receptor. It may induce more complete inhibition of the renin-angiotensin system than do ACE inhibitors. Losartan does not appear to affect bradykinin and is less likely to be associated with cough and angioedema. Use it in patients who are unable to tolerate ACE inhibitors.
Valsartan is a prodrug that directly antagonizes angiotensin II receptors. It displaces angiotensin II from the AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses. Valsartan may induce more complete inhibition of the renin-angiotensin system than do ACE inhibitors. It does not affect bradykinin and is less likely to be associated with cough and angioedema. Valsartan is for use in patients who are unable to tolerate ACE inhibitors.
Calcium Channel Blockers
Antihypertensive agents other than or in addition to ACE inhibitors and ARBs may be needed for blood pressure control in many subjects with hypertension and chronic renal failure. The same is true for subjects with radiation nephritis. No evidence indicates that one type of calcium channel blocker is preferred over another for radiation nephritis. However, one should avoid verapamil, because the use of this drug in a subject with hyperkalemia may cause atrial arrest.
Like other calcium channel blockers, nifedipine causes peripheral arterial vasodilation by inhibiting calcium influx across vascular smooth-muscle cell membranes. Long-acting formulations are used for control of blood pressure.
Beta Adrenergic Blockers
These agents inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation
An ultra–short-acting beta-1-blocker, esmolol is particularly useful in patients with elevated arterial pressure, especially if surgery is planned. It may be useful as a means to test beta-blocker safety and tolerance in patients with history of obstructive pulmonary disease who are at uncertain risk for bronchospasm from beta-blockade. The elimination half-life of esmolol is 9 min.
Labetalol blocks alpha-1 beta 1-, and beta 2-adrenergic receptor sites, decreasing BP.
A class II antiarrhythmic nonselective beta-adrenergic receptor blocker, propranolol has membrane-stabilizing activity and decreases automaticity of contractions. Propranolol is not suitable for emergency treatment of hypertension. Do not administer IV in hypertensive emergencies.
Metoprolol is a selective beta 1–adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor BP, heart rate, and ECG. When considering conversion from IV to oral (PO) dosage forms, use the ratio of 2.5 mg PO to 1 mg IV metoprolol.
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