メタゾラミド
**メタゾラミド**は、獣医学において主に**開放隅角緑内障**の内科的治療に使用される経口**炭酸脱水酵素阻害薬（CAI）**です。 歴史的に眼圧（IOP）を下げるための主力薬でしたが、現在では全身性CAIは主に局所点眼薬（ドルゾラミド、ブリンゾラミドなど）に取って代わられています。局所薬は同等の眼圧下降効果を持ちながら、全身性の副作用の発生率が大幅に低いためです。 臨床上の重要なポイント： * **全身への影響：** 経口投与されるため、メタゾラミドは全身の炭酸脱水酵素を阻害し、代謝性アシドーシスや電解質異常（特に低カリウム血症）を引き起こす可能性があります。 * **臨床的有用性：** 通常、局所治療に抵抗性のある緑内障の症例や、局所投与が困難な場合に限定して使用されます。 * **動物種による感受性：** 猫は経口CAIの副作用に特に敏感であり、著しい嗜眠や食欲不振を示すことがあります。
作用機序: Methazolamide acts via noncompetitive, reversible inhibition of the enzyme **carbonic anhydrase (CA)**, specifically the **CA-II isoenzyme**. * **In the Eye (Ciliary Body):** Inhibition of CA → reduces the formation of hydrogen (H+) and bicarbonate (HCO3-) ions from carbon dioxide and water → decreases the availability of these ions for active transport into the posterior chamber → **decreased aqueous humor production** → **reduced intraocular pressure (IOP)**. * **In the Kidneys (Proximal Tubule):** Inhibition of CA → increased renal tubular secretion of sodium (Na+), potassium (K+), and bicarbonate (HCO3-) → **increased urine alkalinity and volume**, often resulting in a mild **hyperchloremic metabolic acidosis**. * **In the CNS:** Exhibits anticonvulsant activity independent of its diuretic effects, potentially due to localized CA inhibition in the brain or secondary to systemic metabolic acidosis.
動物種別の用量
- Medical treatment of glaucoma · 3-4 mg/kg PO twice a day. · PO · twice a day · Cats may not tolerate oral carbonic anhydrase inhibitors (CAIs) as well as dogs. Reported side effects include lethargy, inappetence, vomiting. Topical CAIs may be better tolerated.
- Medical treatment of glaucoma · 1-2 mg/kg PO q8-12h · PO · q8-12h
- Medical treatment of glaucoma · 2.5-5 mg/kg PO q8-12h · PO · q8-12h
- Medical treatment of glaucoma · 2-4 mg/kg PO two to three times a day · PO · two to three times a day
- Medical treatment of glaucoma · 3-5 mg/kg divided q12h PO · PO · q12h
- Medical treatment of glaucoma · 2-5 mg/kg PO two to three times a day · PO · two to three times a day
- Medical treatment of glaucoma · 2.2-4.4 mg/kg PO two to three times a day. · PO · two to three times a day
- Medical treatment of glaucoma · 2-10 mg/kg PO two to three times a day. · PO · two to three times a day
用量は獣医療従事者向けの臨床リファレンスです。必ず最新の添付文書と個々の患者で確認してください。
投与経路
禁忌
- Significant hepatic disease (may precipitate hepatic coma)
- Renal or adrenocortical insufficiency
- Hyponatremia or hypokalemia
- Hyperchloremic acidosis or severe electrolyte imbalance
- Severe pulmonary obstruction (inability to increase alveolar ventilation to compensate for metabolic acidosis)
- Hypersensitivity to carbonic anhydrase inhibitors or sulfonamides
- Chronic, noncongestive, angle-closure glaucoma (long-term use may mask the condition by lowering IOP while angle closure progresses)
有害事象
- GI disturbances (vomiting, diarrhea, inappetence)
- Metabolic acidosis (often manifesting as heavy panting in dogs)
- CNS effects (sedation, depression, disorientation, excitement)
- Hematologic effects (bone marrow depression, thrombocytopenia)
- Renal effects (crystalluria, dysuria, renal colic, polyuria, polydipsia)
- Hypokalemia
- Hyperglycemia
- Hyponatremia
- Hyperuricemia
- Hepatic insufficiency
- Dermatologic effects (rash)
- Hypersensitivity reactions
- Weakness or cardiac arrhythmias (secondary to electrolyte imbalances)
薬物相互作用
- Antidepressants, Tricyclic · Alkaline urine caused by methazolamide may decrease excretion of tricyclic antidepressants.
- Aspirin (or other salicylates) · Increased risk of methazolamide accumulation and toxicity; increased risk for metabolic acidosis; methazolamide increases salicylate excretion.
- Digoxin · Methazolamide may cause hypokalemia, leading to an increased risk for digoxin toxicity.
- Insulin · Rarely, carbonic anhydrase inhibitors may interfere with the hypoglycemic effects of insulin.
- Methenamine compounds · Methazolamide alkalinizes urine, which may negate the urinary antiseptic effects of methenamine.
- Potassium-depleting drugs (corticosteroids, amphotericin B, corticotropin, diuretics) · Concomitant use may exacerbate potassium depletion and hypokalemia.
- Phenobarbital · Increased urinary excretion due to alkaline urine, which may reduce phenobarbital serum levels.
- Primidone · May result in decreased primidone concentrations.
- Quinidine · Alkaline urine caused by methazolamide may decrease quinidine excretion.
モニタリング
- Intraocular pressure (IOP) / tonometry
- Serum electrolytes (especially potassium and sodium)
- Blood pH / acid-base status
- Baseline CBC with differential, and periodic retests if using chronically
- Clinical signs of adverse effects (lethargy, GI upset, heavy panting)
過量投与
Information regarding acute overdosage of methazolamide in veterinary species is limited. **Clinical Signs:** Expected signs of toxicity include severe electrolyte imbalances (hypokalemia, hyponatremia), profound metabolic acidosis, CNS depression or disorientation, and dehydration secondary to diuresis. **Management:** * Monitor serum electrolytes, blood gases (for acidosis), volume status, and CNS status. * Treat symptomatically and supportively. * Administer intravenous fluids to correct dehydration and electrolyte deficits (especially potassium supplementation if indicated). * Correct severe metabolic acidosis with sodium bicarbonate if necessary, based on blood gas analysis.
VetSheet の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。