Thiazide Diuretics - Cardiovascular Poison

Thiazide Diuretics

·              These agents are inhibitors of sodium chloride symport, acting mainly in the distal convoluted tubule, with secondary action in the proximal tubule. Excretion of sodium and chloride is increased, but thiazides are only moderately effective in prac-tice, since 90% of the filtered load is reabsorbed before reaching the distal convoluted tubule.

·              Common thiazides and thiazide-like drugs include bendrofl-umethiazide, benzthiazide, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methyclothiazide, polythiazide, trichlo-rmethiazide, chlorthalidone, indapamide, metozalone, clopa-mide, clorexolone, cyclothiazide, cyclopenthiazide, fenquizone, mefruside, metolazone, xipamide and quinethazone.

Uses

Treatment of

■■  Oedema (cardiac, hepatic, or renal causes)

■■  Hypertension

■■ Nephrogenic diabetes insipidus

■■ Calcium nephrolithiasis

■■  Bromide poisoning.

Drug Interactions

·      Increased ototoxicity with aminoglycosides

·              While interactions with several drugs are common, thiazides can produce life-threatening ventricular tachy-cardia and fibrillation with quinidine. 

Adverse Effects and Toxic Features

·      Fluid and electrolyte disturbances: Extracellular volumedepletion, hypotension, hypokalaemia, hyponatraemia, hypochloraemia, metabolic alkalosis, hypomagnesaemia, hypercalcaemia, hyperuricaemia. Hypochloraemic meta-bolic alkalosis has occurred following chronic therapeutic use and abuse of thiazide diuretics.

·      GIT: Vomiting, diarrhoea/constipation, cramps. Rarely chol-ecystitis and pancreatitis. Hyperglycaemia has been reported with thiazide use.

·      CNS: Headache, vertigo, paraesthesias.

·      CVS: Atrioventricular block with premature atrialcomplexes has been reported following high-dose hydro-chlorothiazide therapy.

·      RS: Pulmonary oedema has been reported in several casesafter therapeutic ingestion of hydrochlorothiazide.

·      Blood: Dyscrasias.

·      Skin: Rashes.

·      Sexual: Impotence, decreased libido.

·      Other: Hyperuricaemia and hyperlipidaemia may occurfollowing chronic use of thiazides.

Treatment

·      Treatment comprises supportive and symptomatic meas-ures. Diuretic overdoses are generally benign, with the greatest risk being dehydration. Emesis or gastric lavage may potentiate fluid and electrolyte disturbances and are unnecessary.

·      If the ingestion is recent and substantial, administer acti-vated charcoal (in aqueous solution without cathartic).

·      Diuretic blood levels are not clinically useful.

·      Monitor fluid and electrolyte balance carefully and provide replacement therapy as needed.

·      Haemodialysis may be useful.