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Hydrochlorothiazide

Pronouncation: (high-droe-klor-oh-THIGH-uh-zide)
Class: Thiazide diuretic

Trade Names:
Hydrochlorothiazide
- Tablets 12.5 mg
- Tablets 25 mg
- Tablets 50 mg

Trade Names:
Microzide
- Capsules 12.5 mg

Apo-Hydro (Canada)
PMS-Hydrochlorothiazide (Canada)

Pharmacology

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Enhances excretion of sodium, chloride, and water by interfering with transport of sodium ions across renal tubular epithelium.

Pharmacokinetics

Absorption

Bioavailability is 65% to 75%, C _max is 70 to 490 ng/mL (dose dependent), and T _max is 1 to 5 h. Food reduces the bioavailability 10% and the C _max 20%; increases the T _max from 1.6 to 2.9 h. Plasma concentrations are linearly related to administration doses.

Distribution

Protein binding is 40% to 68% and crosses the placenta, but not the blood brain barrier. It is also excreted in breast milk.

Metabolism

Hydrochlorothiazide is not metabolized.

Elimination

Hydrochlorothiazide is eliminated primarily by renal pathways (as unchanged by the kidneys; 55% to 77% or the administration dose appear in urine with more than 95% of the absorbed dose excreted in urine unchanged). Plasma t _½ is 5.6 to 14.8 h.

Peak

The time to peak effect is about 4 h.

Duration

Hydrochlorothiazide activity may persist for up to 24 h.

Special Populations

Renal Function Impairment

Hydrochlorothiazide plasma concentration is increased and the t _½ is prolonged.

Indications and Usage

Adjunctive therapy for edema associated with CHF, hepatic cirrhosis, renal function impairment, and corticosteroid and estrogen therapy; treatment of hypertension.

Unlabeled Uses

Prevention of formation and precurrence of calcium nephrolithiasis; therapy for nephrogenic diabetes insipidus.

Contraindications

Hypersensitivity to thiazides, related diuretics, or sulfonamide-derived drugs; anuria; renal decompensation.

Dosage and Administration

Edema
Adults

PO 25 to 100 mg/day. Rarely patients may require 200 mg/day.

Hypertension
Adults

PO 25 to 50 mg/day as single dose or 2 divided doses.

Children (2 to 12 yr of age)

PO 37.5 to 100 mg/day in 2 doses.

Infants (6 mo to 2 yr of age)

PO 12.5 to 37.5 mg/day in 2 doses.

Infants (younger than 6 mo)

PO Up to 3.3 mg/kg/day in 2 doses.

Storage/Stability

Store tablets in tightly closed container at room temperature.

Drug Interactions

Bile acid sequestrants

May reduce thiazide absorption; give thiazide at least 2 h before resin.

Diazoxide

May cause hyperglycemia.

Digitalis glycosides

Diuretic-induced hypokalemia and hypomagnesemia may precipitate digitalis-induced arrhythmias.

Lithium

May decrease renal excretion of lithium.

Loop diuretics

Synergistic effects may result in profound diuresis and serious electrolyte abnormalities.

Sulfonylureas, insulin

May decrease hypoglycemic effect of sulfonylureas. May need to increase dosage of sulfonylureas or insulin.

Laboratory Test Interactions

Drug may decrease serum protein-bound iodine levels without signs of thyroid disturbance. May cause diagnostic interference of serum electrolyte levels, blood and urine glucose levels, serum bilirubin levels, and serum uric acid levels. Drug may increase serum magnesium levels in uremic patients. Drug may cause increased concentrations of total serum cholesterol, total triglycerides, and LDL.

Adverse Reactions

Cardiovascular

Orthostatic hypotension.

CNS

Dizziness; lightheadedness; vertigo; headache; paresthesias; weakness; restlessness; insomnia.

Dermatologic

Purpura; photosensitivity; rash; urticaria; necrotizing angiitis, vasculitis, cutaneous vasculitis; alopecia; exfoliative dermatitis; toxic epidermal necrolysis; erythema multiforme; Stevens-Johnson syndrome.

EENT

Blurred vision; xanthopsia (yellow vision).

GI

Anorexia; gastric irritation; nausea; vomiting; abdominal pain or cramping; bloating; diarrhea; constipation; pancreatitis; sialadenitis.

Genitourinary

Impotence; reduced libido; interstitial nephritis.

Hematologic

Leukopenia; thrombocytopenia; agranulocytosis; aplastic or hypoplastic anemia; hemolytic anemia.

Hepatic

Jaundice.

Metabolic

Hyperglycemia; glycosuria; hyperuricemia; electrolyte imbalance.

Respiratory

Respiratory distress; pneumonitis; pulmonary edema.

Miscellaneous

Muscle cramp or spasm; fever; anaphylactic reactions.

Precautions

Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy have not been established in controlled clinical studies.

Hypersensitivity

May occur in patients with or without history of allergy or bronchial asthma; cross-sensitivity with sulfonamides may also occur.

Renal Function

Drug may precipitate azotemia; use drug with caution.

Hepatic Function

Minor alterations of fluid and electrolyte balance may precipitate hepatic coma; use drug with caution.

Lupus erythematosus

Exacerbation or activation may occur.

Postsympathectomy patients

Drug may enhance antihypertensive effects.

Overdosage

Symptoms

Orthostatic or general hypotension, tachycardia, shock, weakness, syncope, confusion, dizziness, electrolyte abnormalities, potassium deficiency, vomiting, nausea, lethargy, cramps of calf muscles, thirst, polyuria, anuria.

Patient Information

Tell patient to take medication early in day with food or milk.
Instruct patient to monitor weight daily.
Advise patient to avoid exposure to sunlight and to use sunblock or wear protective clothing to avoid photosensitivity reaction.
Instruct diabetic patients to report increased levels of blood glucose to health care provider.
Caution patient to avoid intake of alcoholic beverages.
Caution patient to rise slowly from lying or sitting position and to lie down if blurred vision or dizziness occurs.
Tell patient to report these symptoms to health care provider: GI disturbances, decrease in urinary output, jaundice, muscle cramps, weakness, nausea, blurred vision, dizziness.
Instruct patient to drink 2 to 3 L of fluids daily unless contraindicated by health care provider.
Advise patient that drug may cause dizziness and blurred vision and to use caution while driving or performing other tasks requiring mental alertness.
Tell patient that therapeutic effect may require 2 to 3 wk.