히드로클로로티아지드

티아지드계 이뇨제

**히드로클로로티아지드(HCTZ)**는 중간 정도의 효능을 가진 **티아지드계 이뇨제**입니다. 수의학에서 일반적인 부종 치료용으로는 루프 이뇨제(예: 푸로세미드)로 대체되었으나, 특정 적응증에는 여전히 매우 유용합니다. 주요 임상 용도: * **칼슘 옥살레이트 요석증**: 소변으로의 칼슘 배설을 감소시키는 독특한 능력(저칼슘뇨 효과)으로 인해 개(및 잠재적으로 고양이)의 재발 방지에 사용됩니다. * **전신성 고혈압**: 보조적 또는 2차 항고혈압제로 자주 사용됩니다. * **신성 요붕증(DI)**: 요붕증 환자에서 역설적으로 소변량을 감소시키며, 신성 요붕증의 일차적인 약물 치료제입니다. * **불응성 심부전**: 이뇨제 내성을 극복하기 위해 루프 이뇨제와 순차적으로 사용됩니다(순차적 네프론 차단). * **고칼륨혈성 주기성 마비(HyPP)**: 식이 관리만으로 조절되지 않는 말에서 아세타졸아마이드의 대안으로 사용됩니다. > **임상 팁**: 처방 요약에는 "저혈당증"이 언급되어 있으나, 티아지드계 약물은 인슐린 분비와 말초 포도당 이용을 감소시켜 실제로는 *고혈당증을 유발하거나 악화*시키는 것으로 알려져 있습니다. 인슐린종과 같은 고인슐린성 저혈당증 관리에 간혹 사용되지만, 디아족사이드(diazoxide)가 더 일반적입니다.

작용 기전: Hydrochlorothiazide acts primarily on the **distal convoluted tubule (DCT)** (cortical diluting segment) of the nephron. * **Diuretic Effect**: It competitively antagonizes the **Na⁺/Cl⁻ cotransporter (NCC)** → inhibits sodium and chloride reabsorption → enhances excretion of Na⁺, Cl⁻, and water. * **Electrolyte Alterations**: Increased distal delivery of Na⁺ stimulates the renin-angiotensin-aldosterone system (RAAS) → increased aldosterone → enhanced secretion of **K⁺ and H⁺** (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 Na⁺ in the DCT, they enhance the activity of the basolateral **Na⁺/Ca²⁺ exchanger** → increased calcium reabsorption into the blood. * **Paradoxical Effect in Diabetes Insipidus**: Mild volume depletion induced by the diuretic → compensatory increase in proximal tubule reabsorption of Na⁺ and water → decreased delivery of water to the distal nephron → overall reduction in polyuria.

동물 종별 용량

Cats

Treatment of systemic hypertension · 1 mg/kg PO q12-24h · PO · q12-24h · As a second choice agent; may combine with spironolactone (1-2 mg/kg PO q12 hours) to reduce potassium loss
Treatment of systemic hypertension · 2-4 mg/kg PO q12h · PO · q12h · 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 · 1-2 mg/kg PO q12h · PO · q12h · In combination with furosemide in patients who have become refractory to furosemide alone
Ascites in patients with liver disease · 0.5-1 mg/kg PO twice daily · PO · twice daily · Using the fixed-dose combination with spironolactone (Aldactazide); dosed empirically based on the spironolactone content
To reduce calcium oxalate saturation in urine · 1 mg/kg PO q12h · PO · q12h · 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 · 1-2 mg/kg · PO · q12-24h · Long-term · Start at low dose and titrate upwards cautiously. Monitor urea, creatinine, electrolytes and blood pressure.

Horses

Adjunctive therapy of hyperkalemic periodic paralysis (HyPP) · 0.5-1 mg/kg PO q12h · PO · q12h · When diet adjustment does not control episodes. Note: ARCI UCGFS Class 4 Drug

Dogs

투여 경로

금기

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)

이상반응

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

약물 상호작용

Amphotericin B · Increased risk for severe hypokalemia
Corticosteroids, Corticotropin · Increased risk for severe hypokalemia
Diazoxide · Increased risk for hyperglycemia, hyperuricemia, and hypotension
Digoxin · Thiazide-induced hypokalemia, hypomagnesemia, and/or hypercalcemia may increase the likelihood of digitalis toxicity · major
Insulin · Thiazides may increase insulin requirements
Lithium · Thiazides can increase serum lithium concentrations
Methenamine · Thiazides can alkalinize urine and reduce methenamine effectiveness
NSAIDs · Thiazides may increase risk for renal toxicity and NSAIDs may reduce diuretic actions of thiazides
Neuromuscular Blocking Agents · Tubocurarine or other nondepolarizing neuromuscular blocking agents response or duration of effect may be increased
Probenecid · Blocks thiazide-induced uric acid retention (used to therapeutic advantage)
Quinidine · Half-life may be prolonged by thiazides (thiazides can alkalinize the urine)
Vitamin D or Calcium Salts · Hypercalcemia may be exacerbated if thiazides are concurrently administered

모니터링

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

과용량

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.

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