ヒドロクロロチアジド
**ヒドロクロロチアジド (HCTZ)** は中等度の効力を持つ**チアジド系利尿薬**です。獣医学における一般的な浮腫治療ではループ利尿薬（フロセミドなど）に取って代わられつつありますが、特定の適応症においては依然として非常に有用です。 主な臨床用途： * **シュウ酸カルシウム尿石症**：尿中カルシウム排泄を減少させる独自の作用（低カルシウム尿効果）により、犬（および潜在的に猫）の再発予防に使用されます。 * **全身性高血圧**：補助的または二次選択の降圧薬として頻繁に使用されます。 * **腎性尿崩症 (DI)**：尿崩症患者において逆説的に尿量を減少させ、腎性尿崩症の主要な薬物療法となります。 * **難治性心不全**：利尿薬抵抗性を克服するため、ループ利尿薬と組み合わせて使用されます（逐次ネフロン遮断）。 * **高カリウム性周期性四肢麻痺 (HyPP)**：食事療法だけではコントロールできない馬において、アセタゾラミドの代替薬として使用されます。 > **臨床のポイント**：処方ハイライトには「低血糖」と記載されていますが、チアジド系薬剤はインスリン分泌と末梢でのグルコース利用を低下させるため、実際には*高血糖を引き起こす、または悪化させる*ことが知られています。高インスリン性低血糖（インスリノーマなど）の管理に時折使用されますが、ジアゾキシドの方が一般的です。
作用機序: 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.
動物種別の用量
- 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.
- 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
投与経路
禁忌
- 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)
有害事象
- 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
薬物相互作用
- 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
モニタリング
- 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
過量投与
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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