Trichlormethiazide Side Effects
Applies to trichlormethiazide: oral tablet
Hyperuricemia may be an important consideration in patients with a history of gout. Hypophosphatemia and low serum magnesium concentrations may occur, but are usually clinically insignificant except in malnourished patients.
Rare cases of hypercalcemia, milk-alkali syndrome (hypercalcemia, metabolic alkalosis, and renal insufficiency) have been associated with the use of a related drug, chlorothiazide.[Ref]
Metabolic changes associated with trichlormethiazide, as with other thiazide diuretics, are relatively common, especially when daily doses greater than 4 mg are used. Mild hypokalemia (decrease of 0.5 mEq/L) occurs in up to 50%, and may increase the risk of cardiac arrhythmias. Metabolic alkalosis, hyponatremia, hypomagnesemia, hypophosphatemia, hypercalcemia, hyperglycemia hypercholesterolemia, and hyperuricemia are also relatively common. The electrolyte and intravascular fluid shifts that may occur during trichlormethiazide diuresis can provoke hepatic encephalopathy in patients with hepatic cirrhosis.[Ref]
Cardiovascular complications of diuretic therapy include orthostatic hypotension secondary to intravascular volume depletion. This has resulted in syncope and, in some patients with glaucoma, temporary loss of vision. Rare cases of cerebrovascular accident have been associated with thiazide-induced diuresis.[Ref]
Hypersensitivity reactions usually involve the skin (cutaneous vasculitis, urticaria, rash, purpura), but may involve the gastrointestinal system (nausea, vomiting, or diarrhea), the genitourinary system (interstitial nephritis), and the respiratory system (acute noncardiogenic pulmonary edema, pneumonitis). Thiazide diuretics may induce phototoxic dermatitis.[Ref]
Dermatologic reactions may indicate hypersensitivity to the drug. Erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis (including toxic epidermal necrolysis), and alopecia have been reported in rare cases.[Ref]
A retrospective case-controlled drug surveillance study has revealed the relative risk of acute cholecystitis associated with the use of a thiazide diuretic is 2.0. The suspected explanation for this association is the potentially deleterious effect thiazides have on the serum lipid profile. Trichlormethiazide-induced hypercholesterolemia or hypertriglyceridemia may enhance the formation of some types of gallstones.[Ref]
Gastrointestinal side effects include diarrhea, vomiting, constipation or abdominal pain in approximately 5% of patients. Thiazide diuretics have been associated with acute cholecystitis and rare cases of pancreatitis.[Ref]
Renal side effects including new or worsened renal insufficiency associated with trichlormethiazide therapy is a probable sign of intravascular volume depletion, and serves as a signal to reduce or withhold therapy. Rare cases of allergic interstitial nephritis have been associated with the use of some thiazide diuretics.[Ref]
Endocrinologic changes associated with thiazide diuretics include decreased glucose tolerance and a potentially deleterious effect on the lipid profile. This may be important in some patients with or who are at risk for diabetes or coronary artery disease.[Ref]
Musculoskeletal cramping or spasms have occasionally been associated with trichlormethiazide diuresis.[Ref]
1. Coe FL, Kavalach AG "Hypercalciuria and hyperuricosuria in patients with calcium nephrolithiasis." N Engl J Med 291 (1974): 1344-50
2. Seltzer HS, Allen EW "Hyperglycemia and inhibition of insulin secretion during administration of diazoxide and trichlormethiazide in man." Diabetes 18 (1969): 19-28
3. Takeda R, Ueno T, Tsutchiya M, Kawasaki S, Masuya H "Sinus arrest following diuretic therapy in a patient with myxedema and hypertension." Cardiology 60 (1975): 185-91
4. "Product Information. Metahydrin (trichlormethiazide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
5. el-Meheiry MM, Nabih AE, Soliman MD "A clinical study of a new diuretic, Trichlormethiazide." J Trop Med Hyg 69 (1966): 209-14
6. Pickkers P, Schachter M, Hughes AD, Feher MD, Sever PS "Thiazide-induced hyperglycaemia: a role for calcium-activated potassium channels?" Diabetologia 39 (1996): 861-4
7. Kansal PC, Buse J, Buse MG "Thiazide diuretics and control of diabetes mellitus." South Med J 62 (1969): 1372-9
8. Stokkeland OM, Sangvik K, Ditlefsen EM "A comparative study of metoprolol and trichlormethiazide in hypertension." Curr Ther Res Clin Exp 18 (1975): 755-68
9. Jinnouchi T, Mimura G, Sadanaga T, Ono K, Sakamoto Y "Proceedings: Study on the effect of long-term administration (one year) of trichlormethiazide upon glucose metabolism of SHR." Jpn Heart J 17 (1976): 412-3
Some side effects of trichlormethiazide may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
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