Diabetic Nephropathy Medication

Major therapeutic interventions include near-normal blood glucose control, antihypertensive treatment, and restriction of dietary proteins.^[8] Drug classes employed include hormones (ie, insulin), sulfonylureas, biguanides, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-adrenergic blocking agents, calcium channel blockers, and diuretics.

Class Summary

Hormones stimulate proper use of glucose by cells and reduce blood sugar levels. Based on their duration of action, several types of insulin are available.

Insulin regular human (Novolin, Humulin)

The structure of insulin was established in 1960, leading to complete synthesis by 1963. Human insulin was approved by the US Food and Drug Administration (FDA) in 1982. Bovine, porcine, and recombinant human insulin preparations are currently available for use in diabetes treatment worldwide; however, insulin derived from bovine tissue is no longer available in the US market as of 1999 because of FDA concerns over transmission of bovine spongiform encephalopathy. Regular insulin has a rapid onset of action of 0.5-1 hours and duration of action of 4-6 hours. The peak effects are seen within 2-4 hours.

Insulin aspart (NovoLog)

Insulin aspart has a short onset of action of 5-15 minutes and a short duration of action of 3-5 hours. The peak effect occurs within 30-90 minutes. Insulin aspart is FDA approved for use in insulin pumps.

Insulin glulisine (Apidra)

Insulin glulisine has a rapid onset of action of 5-15 minutes and a short duration of action of 3-5 hours. The peak effect occurs within 30-90 minutes. Insulin glulisine is FDA approved for use in insulin pumps.

Insulin lispro (Humalog)

Insulin lispro has a rapid onset of action of 5-15 minutes and a short duration of action of 4 hours.

Insulin Glargine (Lantus)

Insulin glargine is a long-acting insulin that has an onset of action of 4-8 hours and a duration of action of 24 hours. The peak effects occur within 16-18 hours.

Insulin NPH (Humulin N, Novolin N)

Insulin NPH is an intermediate-acting insulin that has an onset of action of 3-4 hours and a duration of action of 16-24 hours. The peak effect of insulin NPH occurs within 8-14 hours.

Class Summary

Sulfonylureas act primarily by stimulating release of insulin from beta cells. Extrapancreatic actions include increasing the number of insulin receptors and enhancing insulin-mediated glucose transport independent of increased insulin binding. The use of oral agents has decreased because more emphasis is placed on better control as a means of slowing the development of late complications.

Sulfonylureas are indicated for some patients with relatively mild disease. Commonly used sulfonylureas include chlorpropamide, tolazamide, tolbutamide, glyburide, and glipizide.

Chlorpropamide (Diabinese)

Chlorpropamide is a first-generation sulfonylurea that stimulates release of insulin from pancreatic beta cells.

Tolazamide (Tolinase)

Tolazamide is a first-generation sulfonylurea that stimulates release of insulin from pancreatic beta cells.

Tolbutamide (Orinase)

Tolbutamide is a first-generation sulfonylurea that stimulates release of insulin from pancreatic beta cells.

Glyburide (DiaBeta, Micronase)

Glyburide is a second-generation sulfonylurea that stimulates release of insulin from pancreatic beta cells.

Glipizide (Glucotrol)

Glipizide is a second-generation sulfonylurea that stimulates release of insulin from pancreatic beta cells.

Class Summary

Biguanides are useful in patients with type 2 diabetes mellitus (DM) who are not responsive to diet and exercise. They are usually added as an adjunctive agent in patients whose disease is not controlled by maximal doses of sulfonylureas. Occasionally, they may be prescribed as monotherapy in diabetic patients who are obese.

Metformin (Glucophage)

Metformin reduces hepatic glucose output, decreases intestinal absorption of glucose, and increases glucose uptake in peripheral tissues (muscle and adipocytes). It is a major drug used in obesity and type 2 DM. In contrast to sulfonylureas, metformin does not cause hypoglycemia.

Class Summary

Thiazolidinedione derivatives are active only in the presence of insulin. They are approved for use in patients who are obese, have type 2 DM, and whose diabetes is poorly controlled on insulin. Some physicians administer thiazolidinedione derivatives as add-on agents in patients with type 2 DM who are on maximal doses of other oral agents.

Pioglitazone (Actos)

Pioglitazone improves target cell response to insulin without increasing insulin secretion from the pancreas. It decreases hepatic glucose output and increases insulin-dependent glucose use in skeletal muscle and, possibly, liver and adipose tissue.

Rosiglitazone (Avandia)

Rosiglitazone is used to treat type 2 diabetes associated with insulin resistance and has an effect on the stimulation of glucose uptake in skeletal muscle and adipose tissue.

Class Summary

All of these agents except fosinopril are excreted primarily by the kidney. They have similar actions and adverse effects, including severe hypotension, acute renal failure (especially in bilateral renal artery stenosis), hyperkalemia, dry cough (sometimes accompanied by wheezing), and angioedema. Cough and angioedema are believed to be mediated by bradykinin.^[8]

Captopril (Capoten)

Captopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Enalapril (Vasotec)

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

Lisinopril (Zestril, Prinivil)

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

Class Summary

ARBs are specific and selective angiotensin II receptor antagonists.^[8] Compared with ACE inhibitors, ARBs are associated with a lower incidence of drug-induced cough, rash, and/or taste disturbances.

Losartan (Cozaar)

Losartan is a nonpeptide angiotensin II receptor antagonist that blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It may induce more complete inhibition of the 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.

Valsartan (Diovan)

Valsartan produces direct antagonism of angiotensin II receptors. It may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses.

Irbesartan (Avapro)

Irbesartan is used to treat diabetic nephropathy with an elevated serum creatinine and proteinuria (>300 mg/d) in patients with type 2 diabetes and hypertension. It reduces the rate nephropathy progression. It blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively binding to the AT1 angiotensin II receptor.

Class Summary

Beta-adrenergic blocking agents affect blood pressure via multiple mechanisms. Actions include a negative chronotropic effect that decreases heart rate at rest and after exercise, a negative inotropic effect that decreases cardiac output, reduction of sympathetic outflow from the central nervous system, and suppression of renin release from kidneys.

Metoprolol (Lopressor)

Metoprolol is used to treat hypertension. It is a beta-adrenergic blocking agent that affects blood pressure via multiple mechanisms. Actions include negative a chronotropic effect that decreases the heart rate at rest and after exercise, a negative inotropic effect that decreases cardiac output, reduction of sympathetic outflow from the CNS, and suppression of renin release from the kidneys. During intravenous administration, carefully monitor blood pressure, heart rate, and ECG.

Atenolol (Tenormin)

Atenolol is used to treat hypertension. It selectively blocks beta1-receptors, with little or no affect on beta 2 types. It is also used to improve and preserve hemodynamic status by acting on myocardial contractility, reducing congestion, and decreasing myocardial energy expenditure.

Labetalol (Trandate)

Labetalol is a beta-adrenergic blocking agent that reduces blood pressure via multiple mechanisms. Actions include a negative chronotropic effect that decreases the heart rate at rest and after exercise, a negative inotropic effect that decreases cardiac output, a reduction of sympathetic outflow from the CNS, and suppression of renin release from the kidneys.

Class Summary

Calcium channel blockers inhibit the influx of extracellular calcium across myocardial and vascular smooth muscle cell membranes. Serum calcium levels remain unchanged. The resultant decrease in intracellular calcium inhibits contractile processes of myocardial smooth muscle cells, resulting in dilation of coronary and systemic arteries and improved oxygen delivery to myocardial tissue. In addition, total peripheral resistance, systemic blood pressure, and afterload are decreased.

Calcium channel blockers provide control of hypertension associated with less impairment of function of the ischemic kidney. Calcium channel blockers may have beneficial long-term effects, but this remains uncertain. During depolarization, these agents inhibit calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium. Amlodipine is longer acting.

Diltiazem (Cardizem)

Diltiazem is a nondihydropyridine calcium channel blocker. It relaxes the vascular smooth muscle, causing a decrease in peripheral vascular resistance and leading to antihypertensive effects.

Verapamil (Calan, Covera-HS)

Verapamil is a nondihydropyridine calcium channel blocker. It inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes.

Nifedipine (Adalat)

Nifedipine is a dihydropyridine calcium channel blocker. It relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery. In addition, it decreases peripheral resistance, systemic blood pressure, and afterload.

Amlodipine (Norvasc)

Amlodipine is a dihydropyridine calcium channel blockers that has antianginal and antihypertensive effects. It inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle.

Class Summary

Furosemide and bumetanide are loop diuretics that appear primarily to inhibit reabsorption of sodium and chloride in the ascending limb of the loop of Henle. These effects increase urinary excretion of sodium, chloride, and water, resulting in profound diuresis. Following administration, renal vasodilation occurs, renal vascular resistance decreases, and renal blood flow is enhanced.

Hydrochlorothiazide is a thiazide diuretic that inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water and potassium and hydrogen ions.

Furosemide (Lasix)

Furosemide is a loop diuretic that increases the excretion of water by interfering with the chloride-binding co-transport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and the distal renal tubule. It increases renal blood flow without increasing the filtration rate. The onset of action generally is within 1 hour. It increases potassium, sodium, calcium, and magnesium excretion.

Hydrochlorothiazide (Esidrix, HydroDIURIL, Microzide)

This is a thiazide diuretic that inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water, as well as potassium and hydrogen ions. Diuretics are used only as an as an adjunct to other medications.

Bumetanide (Bumex)

Bumetanide increases the excretion of water by interfering with the chloride-binding co-transport system, which, in turn, inhibits sodium, potassium, and chloride reabsorption in the ascending loop of Henle. These effects increase urinary excretion of sodium, chloride, and water, resulting in profound diuresis. Renal vasodilation occurs following administration, renal vascular resistance decreases, and renal blood flow is enhanced.

Class Summary

This is the newest class of antihypertensive drugs. They act by disrupting the renin-angiotensin-aldosterone system feedback loop.

Aliskiren (Tekturna)

Aliskiren is a direct renin inhibitor that decreases plasma renin activity and inhibits the conversion of angiotensinogen to angiotensin I (as a result, also decreasing angiotensin II) and thereby disrupts the renin-angiotensin-aldosterone system feedback loop. It is indicated for hypertension as monotherapy or in combination with other antihypertensive drugs.