CHLOROTHIAZIDE

CHLOROTHIAZIDE (klor-oh-thye'a-zide) CHLOROTHIAZIDE SODIUM Diuril Classifications: electrolyte & water balance agent; thiazide diuretic; antihypertensive; Therapeutic: thiazide diuretic; antihypertensive Prototype: Hydrochlorothiazide Pregnancy Category: C

Availability

250 mg, 500 mg tablets; 500 mg injection

Action

Thiazide diuretic whose primary action is production of diuresis by direct action on the distal convoluted tubules. Inhibits reabsorption of sodium, potassium, and chloride ions. Promotes renal excretion of sodium (and water), bicarbonate, and potassium.

Therapeutic Effect

Antihypertensive mechanism is due to decreased peripheral resistance and reduced blood pressure.

Uses

Adjunctively to manage edema associated with CHF, hepatic cirrhosis, renal dysfunction, corticosteroid, or estrogen therapy. Used alone as step 1 agent in stepped-care approach, or in combination with other agents for treatment of hypertension.

Unlabeled Uses

To reduce polyuria of central and nephrogenic diabetes insipidus, to prevent calcium-containing renal stones, and to treat renal tubular acidosis.

Contraindications

Hypersensitivity to thiazide or sulfonamides; anuria; hypokalemia; renal failure; jaundiced neonates; SLE; pregnancy (category C).

Cautious Use

History of sulfa allergy; impaired renal or hepatic function or gout; hypercalcemia, diabetes mellitus, older adult or debilitated patients, pancreatitis, sympathectomy.

Route & Dosage

Hypertension, Edema Adult: PO 250 mg–1 g/d in 1–2 divided doses IV 500 mg–1 g/d in 1–2 divided doses Geriatric: PO 500 mg qd or 1 g 3 times/wk Edema Child: PO <6 mo, 20–40 mg/kg/d in 1–2 divided doses; >6 mo, 20 mg/kg/d in 2 divided doses

Administration

Oral

• Give with or after food to prevent gastric irritation. Extent of absorption appears to be increased by taking it with food.
• Schedule daily doses to avoid nocturia and interrupted sleep.

Intravenous Reserve for emergency or when patient unable to take oral medication. IV administration to infants and children: Verify correct IV concentration and rate of infusion with physician. PREPARE: Intermittent: Reconstitute the 500 mg vial with at least 18 mL sterile water for injection. May be further diluted with D5W or NS.   ADMINISTER: Intermittent: Give at a rate of 0.5 g over 5 min.   INCOMPATIBILITIES Solution/additive: Amikacin, chlorpromazine, codeine, fluorouracil, hydralazine, insulin, levorphanol, methadone, morphine, norepinephrine, pentobarbital, polymyxin B, procaine, prochlorperazine, promazine, promethazine, streptomycin, triflupromazine, vancomycin, vitamin B complex with C, warfarin. Thiazide preparations are extremely irritating to the tissues, and great care must be taken to avoid extravasation. If infiltration occurs, stop medication, remove needle, and apply ice if area is small.

• Store tablets, PO solutions, and parenteral dosage forms at 15°–30° C (59°–86° F) unless otherwise directed by manufacturer. Unused reconstituted IV solutions may be stored at room temperature up to 24 h. Use only clear solutions.

Adverse Effects (≥1%)

Body as a Whole: Fever, respiratory distress, anaphylactic reaction. CV: Irregular heart beat, weak pulse, orthostatic hypotension. GI: Vomiting, acute pancreatitis, diarrhea. Hematologic: Agranulocytosis (rare), aplastic anemia (rare), asymptomatic hyperuricemia, hyperglycemia, glycosuria, SIADH secretion. Metabolic: Hypokalemia, hypercalcemia, hyponatremia, hypochloremic alkalosis, elevated cholesterol and triglyceride levels. CNS: Unusual fatigue, dizziness, mental changes, vertigo, headache. Skin: Urticaria, photosensitivity, skin rash.

Diagnostic Test Interference

Chlorothiazide (thiazides) may cause: marked increases in serum amylase values, decrease in PBI determinations; increase in excretion of PSP; increase in BSP retention; false-negative phentolamine and tyramine tests; interference with urine steroid determinations, and possibly the histamine test for pheochromocytoma. Thiazides should be discontinued at least 3 d before bentiromide test (thiazides can invalidate test) and before parathyroid function tests because they tend to decrease calcium excretion.

Interactions

Drug: Amphotericin B, corticosteroids increase hypokalemic effects of chlorothiazide; the hypoglycemic effects of sulfonylureas and insulin may be antagonized; cholestyramine, colestipol decrease thiazide absorption; intensifies hypoglycemic and hypotensive effects of diazoxide; increased potassium and magnesium loss may cause digoxin toxicity; decreases lithium excretion, increasing its toxicity; increases risk of nsaid-induced renal failure and may attenuate diuresis.

Pharmacokinetics

Absorption: Incompletely absorbed PO. Onset: 2 h PO; 15 min IV. Peak: 3–6 h PO; 30 min IV. Duration: 6–12 h PO; 2 h IV. Distribution: Throughout extracellular tissue; concentrates in kidney; crosses placenta. Metabolism: Does not appear to be metabolized. Elimination: In urine and breast milk. Half-Life: 45–120 min.

Nursing Implications

Assessment & Drug Effects

• Monitor for therapeutic effect. Antihypertensive action of a thiazide diuretic requires several days before effects are observed; usually optimum therapeutic effect is not established for 3–4 wk.
• Lab tests: Baseline and periodic determinations are indicated for blood count, serum electrolytes, CO₂, BUN, creatinine, uric acid, and blood glucose.
• Monitor for hyperglycemia. Thiazide therapy can cause hyperglycemia (see Appendix F) and glycosuria in diabetic and diabetic-prone individuals. Dosage adjustment of hypoglycemic drugs may be required.
• Monitor patients with gout. Asymptomatic hyperuricemia can be produced because of interference with uric acid excretion.
• Establish baseline weight before initiation of therapy. Weigh patient at the same time each a.m. under standard conditions. A gain of more than 1 kg (2.2) within 2 or 3 d and a gradual weight gain over the week's period is reportable. Tell patient to report signs of edema (hands, ankles, pretibial areas).
• Monitor BP closely during early drug therapy.
• Inspect skin and mucous membranes daily for evidence of petechiae in patients receiving large doses and those on prolonged therapy.
• Monitor I&O rates and patterns: Excessive diuresis or oliguria may cause electrolyte imbalance and necessitate prompt dosage adjustment.
• Monitor patients on digitalis therapy for S&S of hypokalemia (see Appendix G). Even moderate reduction in serum potassium can precipitate digitalis intoxication in these patients.

Patient & Family Education

• Urination will occur in greater amounts and with more frequency than usual, and there will be an unusual sense of tiredness. With continued therapy, diuretic action decreases; hypotensive effects usually are maintained, and sense of tiredness diminishes.
• If orthostatic hypotension is a troublesome symptom (and it may be, especially in the older adult), consult physician for measures that will help tolerate the effect and to prevent falling.
• Report to physician any illness accompanied by prolonged vomiting or diarrhea.
• Avoid drinking large quantities of coffee or other caffeine drinks. Caffeine is a CNS stimulant with diuretic effects.
• Report S&S of hypokalemia, hypercalcemia, or hyperglycemia (see Appendix F).
• Hypokalemia may be prevented if the daily diet contains potassium-rich foods. Eat a banana and drink at least 6 oz orange juice every day. Collaborate with dietitian and physician.
• Report photosensitivity reaction to physician if it occurs. Thiazide-related photosensitivity is considered a photoallergy (radiation changes drug structure and makes it allergenic for some individuals). It occurs 1?–2 wk after initial sun exposure.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug