Hydrochlorothiazide
**Hydrochlorothiazide (HCTZ)** is a moderately efficacious **thiazide diuretic** that has largely been replaced by loop diuretics (like furosemide) for general edema management in veterinary medicine, but remains highly valuable for specific indications. Key clinical uses include: * **Calcium Oxalate Urolithiasis**: Used to prevent recurrence in dogs (and potentially cats) due to its unique ability to decrease urinary calcium excretion (hypocalciuric effect). * **Systemic Hypertension**: Often used as an adjunctive or second-line antihypertensive agent. * **Nephrogenic Diabetes Insipidus (DI)**: Paradoxically reduces urine output in DI patients and serves as the primary drug therapy for the nephrogenic form. * **Refractory Heart Failure**: Used sequentially with loop diuretics to overcome diuretic resistance (sequential nephron blockade). * **Hyperkalemic Periodic Paralysis (HyPP)**: Used in horses as an alternative to acetazolamide when dietary management is insufficient. > **Clinical Pearl**: While the monograph highlights "hypoglycemia" in the prescriber highlights, thiazides are actually known to *cause or exacerbate hyperglycemia* by decreasing insulin release and peripheral glucose utilization. They are occasionally used to manage hyperinsulinemic hypoglycemia (e.g., insulinoma), though diazoxide is more common.
Mechanism: Hydrochlorothiazide acts primarily on the **distal convoluted tubule (DCT)** (cortical diluting segment) of the nephron. * **Diuretic Effect**: It competitively antagonizes the **Naโบ/Clโป cotransporter (NCC)** โ inhibits sodium and chloride reabsorption โ enhances excretion of Naโบ, Clโป, and water. * **Electrolyte Alterations**: Increased distal delivery of Naโบ stimulates the renin-angiotensin-aldosterone system (RAAS) โ increased aldosterone โ enhanced secretion of **Kโบ and Hโบ** (leading to hypokalemia and metabolic alkalosis). It also increases excretion of magnesium, phosphate, iodide, and bromide. * **Calcium Sparing**: Unlike loop diuretics, thiazides *decrease* calcium excretion. By depleting intracellular Naโบ in the DCT, they enhance the activity of the basolateral **Naโบ/Caยฒโบ exchanger** โ increased calcium reabsorption into the blood. * **Paradoxical Effect in Diabetes Insipidus**: Mild volume depletion induced by the diuretic โ compensatory increase in proximal tubule reabsorption of Naโบ and water โ decreased delivery of water to the distal nephron โ overall reduction in polyuria.
Dosing by species
- Treatment of systemic hypertension ยท 1 mg/kg PO q12-24h ยท PO ยท q12-24h ยท As a second choice agent; may combine with spironolactone (1-2 mg/kg PO q12 hours) to reduce potassium loss
- Treatment of systemic hypertension ยท 2-4 mg/kg PO q12h ยท PO ยท q12h ยท Not effective as a single agent in cats, and may be contraindicated (e.g., chronic renal failure). Possibly helpful acutely with retinal detachment.
- Diuretic for heart failure ยท 1-2 mg/kg PO q12h ยท PO ยท q12h ยท In combination with furosemide in patients who have become refractory to furosemide alone
- Ascites in patients with liver disease ยท 0.5-1 mg/kg PO twice daily ยท PO ยท twice daily ยท Using the fixed-dose combination with spironolactone (Aldactazide); dosed empirically based on the spironolactone content
- To reduce calcium oxalate saturation in urine ยท 1 mg/kg PO q12h ยท PO ยท q12h ยท Study done in normal cats, unknown what effect HCTZ will have in cats with spontaneously occurring calcium oxalate urolithiasis
- Refractory congestive heart failure / Calcium oxalate urolithiasis prevention / Hypertension ยท 1-2 mg/kg ยท PO ยท q12-24h ยท Long-term ยท Start at low dose and titrate upwards cautiously. Monitor urea, creatinine, electrolytes and blood pressure.
- Adjunctive therapy of hyperkalemic periodic paralysis (HyPP) ยท 0.5-1 mg/kg PO q12h ยท PO ยท q12h ยท When diet adjustment does not control episodes. Note: ARCI UCGFS Class 4 Drug
Routes of administration
Contraindications
- Hypersensitivity to thiazides or sulfonamides
- Anuria
- Pregnancy (relative contraindication in otherwise healthy patients with mild edema)
- Dogs with absorptive (intestinal) hypercalciuria (may result in hypercalcemia)
- Renal impairment (due to reduction in GFR)
- Severe electrolyte imbalances (e.g., severe hypokalaemia or hyponatraemia)
Adverse effects
- Hypokalemia (most common)
- Hypochloremic alkalosis
- Dilutional hyponatremia
- Hypomagnesemia
- Hypercalcemia (hyperparathyroid-like effects)
- Hypophosphatemia
- Hyperuricemia
- Gastrointestinal reactions (vomiting, diarrhea)
- Polyuria
- Hyperglycemia
- Hyperlipidemias
- Orthostatic hypotension
- Hypersensitivity/dermatologic reactions
- Hypokalaemia
- Hyponatraemia
- Hypochloraemia
- Hyperglycaemia
Drug interactions
- Amphotericin B ยท Increased risk for severe hypokalemia
- Corticosteroids, Corticotropin ยท Increased risk for severe hypokalemia
- Diazoxide ยท Increased risk for hyperglycemia, hyperuricemia, and hypotension
- Digoxin ยท Thiazide-induced hypokalemia, hypomagnesemia, and/or hypercalcemia may increase the likelihood of digitalis toxicity ยท major
- Insulin ยท Thiazides may increase insulin requirements
- Lithium ยท Thiazides can increase serum lithium concentrations
- Methenamine ยท Thiazides can alkalinize urine and reduce methenamine effectiveness
- NSAIDs ยท Thiazides may increase risk for renal toxicity and NSAIDs may reduce diuretic actions of thiazides
- Neuromuscular Blocking Agents ยท Tubocurarine or other nondepolarizing neuromuscular blocking agents response or duration of effect may be increased
- Probenecid ยท Blocks thiazide-induced uric acid retention (used to therapeutic advantage)
- Quinidine ยท Half-life may be prolonged by thiazides (thiazides can alkalinize the urine)
- Vitamin D or Calcium Salts ยท Hypercalcemia may be exacerbated if thiazides are concurrently administered
Monitoring
- Serum electrolytes (especially potassium, sodium, chloride, calcium, magnesium)
- Renal function (BUN, Creatinine)
- Hydration status and body weight
- Blood pressure (if treating hypertension)
- Urine output and clinical signs of congestion (if treating heart failure)
- Blood Urea Nitrogen (BUN)
- Serum Creatinine
- Serum Electrolytes (Potassium, Sodium, Chloride, Calcium)
- Blood pressure
Overdose
Acute overdosage may cause: * **Electrolyte and water balance problems** (hypokalemia, hyponatremia, dehydration) * **CNS effects** (ranging from lethargy to coma and seizures) * **GI effects** (hypermotility, GI distress) * Transient increases in BUN **Treatment**: * Empty the gut after recent oral ingestion using standard protocols. * **Avoid concomitant cathartics** as they may exacerbate fluid and electrolyte imbalances. * Monitor and treat electrolyte and water balance abnormalities supportively. * Monitor respiratory, CNS, and cardiovascular status; treat supportively and symptomatically if required.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.