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Pronunciation:

(meth i kloe THYE a zide)

U.S. Brand Names:

Enduron® [DSC]

Generic Available:

Yes

Canadian Brand Names:

Aquatensen®; Enduron®

Use:

Management of mild to moderate hypertension; treatment of edema in congestive heart failure and nephrotic syndrome

Pregnancy Risk Factor:

Lactation:

Excretion in breast milk unknown/use caution

Contraindications:

Hypersensitivity to methyclothiazide or any component, thiazides, or sulfonamide-derived drugs; anuria; renal decompensation

Warnings/Precautions:

Avoid in severe renal disease (ineffective). Electrolyte disturbances (hypokalemia, hypochloremic alkalosis, hyponatremia) can occur. Use with caution in severe hepatic dysfunction; hepatic encephalopathy can be caused by electrolyte disturbances. Gout can be precipitate in certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure. Cautious use in diabetics; may see a change in glucose control. Hypersensitivity reactions can occur. Can cause SLE exacerbation or activation. Use with caution in patients with moderate or high cholesterol concentrations. Photosensitization may occur. Correct hypokalemia before initiating therapy.

Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with thiazide or sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.

Adverse Reactions:

1% to 10%:

Cardiovascular: Orthostatic hypotension

Dermatologic: Photosensitivity

Endocrine & metabolic: Hypokalemia

Gastrointestinal: Anorexia, epigastric distress

<1% (Limited to important or life-threatening): Agranulocytosis, aplastic anemia, cutaneous vasculitis, erythema multiforme, hemolytic anemia, hepatic function impairment, hypercalcemia, leukopenia, necrotizing angiitis, pancreatitis, respiratory distress, Stevens-Johnson syndrome, thrombocytopenia, vasculitis

Overdosage/Toxicology:

Symptoms of overdose include hypermotility, diuresis, and lethargy. Treatment is supportive.

Drug Interactions:

ACE inhibitors: Increased hypotension if aggressively diuresed with a thiazide diuretic.

Beta-blockers increase hyperglycemic effects in type 2 diabetes mellitus (noninsulin dependent, NIDDM)

Cyclosporine and thiazides can increase the risk of gout or renal toxicity; avoid concurrent use.

Digoxin toxicity can be exacerbated if a thiazide induces hypokalemia or hypomagnesemia.

Lithium toxicity can occur by reducing renal excretion of lithium; monitor lithium concentration and adjust as needed.

Neuromuscular blocking agents can prolong blockade; monitor serum potassium and neuromuscular status.

NSAIDs can decrease the efficacy of thiazides reducing the diuretic and antihypertensive effects.

Ethanol/Nutrition/Herb Interactions:

Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid dong quai, St John's wort (may also cause photosensitization). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid garlic (may have increased antihypertensive effect).

Mechanism of Action:

Inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water, as well as, potassium and hydrogen ions

Pharmacodynamics/Kinetics:

Onset of action: Diuresis: 2 hours

Peak effect: 6 hours

Duration: ~1 day

Distribution: Crosses placenta; enters breast milk

Excretion: Urine (as unchanged drug)

Dosage:

Adults: Oral:

Edema: 2.5-10 mg/day

Hypertension: 2.5-5 mg/day; may add another antihypertensive if 5 mg is not adequate after a trial of 8-12 weeks of therapy

Monitoring Parameters:

Blood pressure, fluids, weight loss, serum potassium

Patient Education:

Take exactly as directed - with meals. May take early in day to avoid nocturia. Include bananas or orange juice in daily diet but do not take dietary supplements without advice or consultation of prescriber. Do not use OTC medication without consulting prescriber. Weigh weekly at the same time, in the same clothes. Report weight gain >5 lb/week. May cause dizziness or weakness; change position slowly when rising from sitting or lying position and avoid driving or tasks requiring alertness until response to drug is known. You may experience nausea or loss of appetite (small, frequent meals may help); impotence (reversible); constipation (increased exercise, fluids, fruit, or fiber may help); or photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). This medication does not replace other antihypertensive interventions; follow instructions for diet and lifestyle changes. Report flu-like symptoms, headache, joint soreness or weakness, respiratory difficulty, skin rash, or excessive fatigue, swelling of extremities, or respiratory difficulty. Breast-feeding precaution: Consult prescriber if breast-feeding.

Nursing Implications:

Assess weight, I & O reports daily to determine fluid loss; take blood pressure with patient lying down and standing

Cardiovascular Considerations:

Thiazide diuretics are effective first-line therapeutic agents in the management of hypertension and have proven to be of benefit in terms of cardiovascular outcome. They may act synergistically to lower blood pressure when combined with an ACE inhibitor or beta-blocker. The initial concern about thiazide diuretic-induced hypokalemia, glucose intolerance, and lipid profiles does not appear to be of substantial clinical consequence in the treatment of hypertension. The benefits of this class of agents in the treatment of hypertension is established and compares well with other first-line therapeutic agents.

Diuretics are standard therapy for the management of edema in patients with heart failure.

Dental Health: Effects on Dental Treatment:

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

No information available to require special precautions

Mental Health: Effects on Mental Status:

May cause drowsiness

Mental Health: Effects on Psychiatric Treatment:

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; may cause photosensitivity; use psychotropics with caution; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels

Dosage Forms:

Tablet: 5 mg

International Brand Names:

Aquatensen® (CA); Enduron® (CA, HK)

References

Chobanian AV, Bakris GL, Black HR, et al, "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,"JAMA, 2003, 289(19):2560-71.

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