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METICRANE

CARDIOVASCULAR-DEURITCS

BANNED MEDICATION

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MOA• Thiazide diuretics include

hydrochlorothiazide,benzthiazide, trichlormethiazide,

meticrane and cyclothiazide. A long-acting analogueischlorthalidone. These drugs affect the intermediatesegment of the distal tubules, where they inhibit a Na+/Cl –  cotransport. Thus, reabsorption of NaCl and water isinhibited. 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 aconsequence of excessive K+ loss in the terminal segmentsof the distal tubules where increased amounts of Na+ are

available for exchange with K+; (b) hyperglycemia and glycosuria; (c) hyperuricemia —  increase in serum uratelevels may precipitate gout in predisposed patients.Sulfonamide diuretics compete with urate for the tubularorganic anion secretory system

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PHARMOCOKINETICS & PHARMCODYNAMICS

• rapidly and almost completely absorbed from the gastrointestinal tract and at steady state has ahalf-life of 36 to 47.5 hours. About 60% of an

oral or intravenous dose is excreted in the urineas 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, cardiacfailure, and mobilization of edema

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METABOLISM• The adverse effects of thiazideson glucose

metabolism, such as insulin resistance, impaired glucose tolerance, precipitation of overt diabetes,and worsening of diabetic control, are wellestablished but appear to be dose-related and

may not be significant at lower doses (forexample, meticrane 6.25 or 12.5 mg).1 A study2in 16 non-diabetic hypertensive patients found

that bendroflumethiazide, in a dose of 1.25 mgdaily, had no effect on insulin sensitivity whereasa daily dose of 5 mg produced hepatic insulinresistance..

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CONT’D 

• Similarly, the high doses, for examplebendroflumethiazide 5 mg twice daily, used in theMedical Research Council Study on Mild to ModerateHypertension3 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 per1000 patient-years in women compared with 2.51and 0.82 per 1000 patient-years respectively inpatients taking placebo. A later prospective study4 in

non-diabetic hypertensive patients found that thosetaking thiazides [doses not specified] were at no greater risk for developing diabetes than those notreceiving antihypertensivetherapy 

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SIDE EFECTS

• (a) hypokalemia is a consequence of excessive K+loss in the terminal segments of the distal tubuleswhere increased amounts of Na+ are availablefor exchange with K+; (b) hyperglycemia and

 glycosuria; (c) hyperuricemia —  increase inserum urate levels may precipitate gout inpredisposed patients. Sulfonamide diureticscompete with urate for the tubular organic anion

secretory system• DOSAGE AND TOXICITY: NO INFO

AVAIALBE(BANNED MEDICATION)