Drug Topics - January 14, 2008 - (Page 38) 38 DRUG TOPICS JANUARY 14, 2008 www.drugtopics.com CONTINUING EDUCATION In the CALM study, Type 2 diaCalcium channel blockers Table 4 betes patients with hypertension and Calcium channel blockers, comprised microalbuminuria were randomized of non-dihydropyridines and dihyPertinent nonpharmacologic to candesartan 16mg/day, lisinopril dropyridines, provide different effects counseling points 20mg/day, or both. Twelve weeks of on the kidney based on their mecha1. Quit smoking combination therapy were begun afnism of action. Non-dihydropyridine 2. Lose weight if overweight (body ter 12 weeks of monotherapy. There drugs consist of verapamil and diltimass index 25-29.9 kg/m2) or obese were 199 participants in the study. azem. Dihydropyridines consist of (BMI >30 kg/m2) Patients included in the study had a amlodipine, felodipine, and nifedip3. Restrict sodium intake to no more urinary albumin:creatinine ratio of than 2,400 mg of sodium or 6,000 mg ine. These classes differ in mecha2.5-25mg/mmol and DBP of 90nism. Drugs such as verapamil and of sodium chloride per day 110 mmHg. After 24 weeks of therdiltiazem work primarily in the heart, 4. Limit alcohol intake to no more than apy, mean reduction of DBP was sigslowing the influx of calcium, relaxone drink per day for women and nificantly greater in the combination ing the coronary smooth muscle, and two drinks per day for men group than either lisinopril or caninducing coronary vasodilation. 5. 30-45 minutes of aerobic activity on desartan alone. Combination theraThese agents, to a lesser extent, also most days of the week py was also significantly more effeccause vasodilation in the peripheral 6. Maintain adequate potassium tive for reducing urinary arterial system. Dihydropyridines’ and calcium intake albumin:creatinine ratio (50% with primary mechanism is vasodilation of 7 DASH diet . combination, 24% with candesarthe peripheral arterial system and to a tan, and 39% with lisinopril). All lesser extent smooth muscle relaxregimens were well tolerated. Respiratory infection, cough, and ation and vasodilation in the heart. headaches were the most common adverse effects, which ocNon-dihydropyridines provide a small beneficial effect on procurred in less than 10% of the patients. teinuria. They reduce proteinuria by reducing intraglomerular hypertension, thus decreasing albumin excretion. Dihydropyridines Diuretics do not provide benefit for reducing proteinuria or preserving reThiazide diuretics such as hydrochlorothiazide or chlorthalidone nal function. Their inability to provide benefit in the kidneys rehave not shown to decrease urinary albumin excretion as effec- lates to their effect on renal autoregulation and glomerular prestively as ACEIs or ARBs. These drugs work at the distal convo- sure transmission. Unlike non-dihydropyridines, these agents luted tubule inhibiting sodium reabsorption. As a result, sodium, increase intraglomerular pressure and permeability to albumin, water, potassium, and hydrogen ions are excreted from the body. thus promoting kidney dysfunction. In the IDNT trial (previousTheir effect on proteinuria is dependent solely on BP reduction ly discussed) amlodipine increased proteinuria by 6% versus baseunlike ACEIs or ARBs. These agents are not recommended as line and conferred a 23% higher incidence of doubling of serum monotherapy but will provide additive reductions on urinary al- creatinine, onset of ESRD, or death compared with irbesartan. bumin excretion to ACEIs and ARBs. Non-dihydropyridine calcium channel blockers are recomThese agents are recommended as second-line agents for mended as third-line antihypertensive agents after ACEIs or blood pressure in patients with diabetes or non-diabetic pa- ARBs and diuretics in the presence of hypertension and nontients with nephropathy. Thiazide diuretics optimize the effect diabetic kidney disease with proteinuria, or diabetic nephropaof ACEIs and ARBs. Low sodium intake activates the RAAS thy. In Type 2 diabetes with overt nephropathy, these agents in and enhances the efficacy of ACEIs and ARBs. Deterioration of combination with ACEIs provided greater reduction of prothe kidneys results in sodium and water retention. Sodium re- teinuria than did higher doses of either agent alone, while simtention will blunt the antiproteinuric effect of ACEIs and ilar levels of blood pressure control were maintained. ARBs, thus providing a need for diuretics. Thiazide diuretics are effective for GFR >40ml/min/1.73m2. Loop diuretics (i.e., Beta-blockers furosemide, torsemide, etc.) are usually necessary for a GFR The SNS can regulate renal function via activation of B1 (car<40ml/min/1.73m2. Unlike thiazide diuretics, these agents also diac output and renin release), α1 (renovascular and systemic work at the ascending loop of henle inhibiting sodium and constriction), and B2 (renovascular dilation) receptors. Sympachloride, thus causing increased excretion of water, sodium, thetic overactivity is often secondary to chronic kidney disease chloride, magnesium, and calcium. and may play a prevalent role in progression of further renal deData from a small pilot study showed that spironolactone, terioration. Evidence shows that heart disease is the major cause an aldosterone antagonist, can significantly reduce protein- of death for all people with chronic kidney disease. Cardioselecuria in patients with non-diabetic chronic kidney disease al- tive beta-blockers (i.e., atenolol, metoprolol) in particular have ready treated with an ACEI or ARB. Aldosterone, as previous- shown to decrease BP and reduce proteinuria in diabetic and ly mentioned, causes sodium and water retention, leading to non-diabetic patients. Beta-blockers may reduce proteinuria by high blood pressure. Combination therapy was associated blocking the B1 receptors in the kidney and decreasing renin with a significant increase in hyperkalemia. This indicates that secretion, thus improving BP, decreasing protein excretion, and proteinuria may be associated with high production of aldos- reducing the incidence of cardiovascular events. terone. Long-term randomized trials are still needed to conThe AASK trial (African American Study of Kidney Disease firm efficacy and safety. and Hypertension) looked at two levels of BP control on GFR http://www.drugtopics.com
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