METICRANE

CARDIOVASCULAR-DEURITCS BANNED MEDICATION

 Thiazide diuretics include hydrochlorothiazide,benzthiazide, trichlormethiazide, meticrane and cyclothiazide. A long-acting analogue ischlorthalidone. These drugs affect the intermediate segment of the distal tubules, where they inhibit a Na+/Cl cotransport. Thus, reabsorption of NaCl and water is inhibited. Renal excretion of Ca2+ decreases, that of Mg2+ increases. Indications are hypertension, cardiac failure, and mobilization of edema. Unwanted effects of sulfonamidetype diuretics: (a) hypokalemia is a consequence of excessive K+ loss in the terminal segments of the distal tubules where increased amounts of Na+ are available for exchange with K+; (b) hyperglycemia and glycosuria; (c) hyperuricemia increase in serum urate levels may precipitate gout in predisposed patients. Sulfonamide diuretics compete with urate for the tubular organic anion secretory system

MOA

 rapidly and almost completely absorbed from the gastrointestinal tract and at steady state has a half-life of 36 to 47.5 hours. About 60% of an oral or intravenous dose is excreted in the urine as unchanged drug and metabolites over 7 days reabsorption of NaCl and water is inhibited. Renal excretion of Ca2+ decreases, that of Mg2+ increases. Indications are hypertension, cardiac failure, and mobilization of edema

PHARMOCOKINETICS & PHARMCODYNAMICS

 The adverse effects of thiazideson glucose metabolism, such as insulin resistance, impaired glucose tolerance, precipitation of overt diabetes, and worsening of diabetic control, are well established but appear to be dose-related and may not be significant at lower doses (for example, meticrane 6.25 or 12.5 mg).1 A study2 in 16 non-diabetic hypertensive patients found that bendroflumethiazide, in a dose of 1.25 mg daily, had no effect on insulin sensitivity whereas a daily dose of 5 mg produced hepatic insulin resistance..

METABOLISM

CONTD
Similarly, the high doses, for example bendroflumethiazide 5 mg twice daily, used in the Medical Research Council Study on Mild to Moderate Hypertension3 resulted in an incidence of glucose intolerance that led to withdrawal from the study of 9.38 per 1000 patient-years in men and 6.01 per 1000 patient-years in women compared with 2.51 and 0.82 per 1000 patient-years respectively in patients taking placebo. A later prospective study4 in non-diabetic hypertensive patients found that those taking thiazides [doses not specified] were at no greater risk for developing diabetes than those not receiving antihypertensivetherapy

SIDE EFECTS
(a) hypokalemia is a consequence of excessive K+ loss in the terminal segments of the distal tubules where increased amounts of Na+ are available for exchange with K+; (b) hyperglycemia and glycosuria; (c) hyperuricemia increase in serum urate levels may precipitate gout in predisposed patients. Sulfonamide diuretics compete with urate for the tubular organic anion secretory system DOSAGE AND TOXICITY: NO INFO AVAIALBE(BANNED MEDICATION)