格列吡嗪
**格列吡嗪 (Glipizide)** 是一種第二代口服磺醯脲類抗糖尿病藥物，主要用於人類的第二型糖尿病，但在獸醫學中也有特定應用，特別是針對貓病患。 * **貓的應用**：對於仍具有功能性胰臟β細胞的單純性糖尿病貓可能有效。大約 **20% 至 30%** 新診斷的糖尿病貓對格列吡嗪治療有反應。 * **臨床實用性**：通常保留用於飼主絕對拒絕注射胰島素（通常因為害怕針頭），或者貓在極低劑量胰島素下控制良好且飼主希望轉換為口服藥物的情況。 * **狗的限制**：格列吡嗪對狗通常**無效**。當狗出現臨床高血糖症狀時，牠們通常已處於絕對或相對的胰島素缺乏狀態（類似人類第一型糖尿病），缺乏格列吡嗪發揮作用所需的功能性β細胞。 * **臨床要點**：格列吡嗪試驗需要耐心；可能需要 **4 到 8 週** 才能觀察到完整的治療效果。此外，貓長期使用可能會促進胰島澱粉樣蛋白沉積增加，潛在加速剩餘β細胞的破壞。
作用機制: Glipizide lowers blood glucose concentrations by stimulating the release of endogenous insulin from the pancreas and enhancing peripheral insulin sensitivity. * **Pancreatic Mechanism**: Glipizide binds to the **sulfonylurea receptor 1 (SUR1)** on the membrane of pancreatic **β-cells** → This binding closes **ATP-sensitive potassium (K+) channels** → Decreased potassium efflux leads to **cellular depolarization** → Depolarization opens **voltage-dependent calcium (Ca2+) channels** → Calcium influx triggers the exocytosis of **insulin**-containing secretory granules. * **Extrapancreatic Effects**: Ongoing use enhances peripheral tissue sensitivity to circulating insulin and reduces the production of hepatic basal glucose, though the exact mechanisms for these secondary effects remain partially unexplained.
各物種劑量
- Diabetes mellitus (non-ketotic, relatively healthy) · 2.5 mg per cat (initially), may increase to 5 mg per cat · PO · q12h · Ongoing if stable · Give in conjunction with a meal. Perform spot BG checks every 3-4h for initial 12-18h. Increase dose to 5 mg BID after 2 weeks if hyperglycemia persists and no adverse reactions occur.
- Diabetes mellitus · 2.5-5 mg per cat · PO · q12h · 2-3 months trial · Combine with dietary fiber therapy. Evaluate every 1-2 weeks. If fasting BG remains >200 mg/dL after 2-3 months, discontinue and institute insulin.
- Diabetes mellitus (mild weight loss, non-ketoacidotic, no peripheral neuropathy) · 2.5 mg (total dose) · PO · q12h
- Diabetes mellitus · 5 mg per cat, may increase to 7.5 mg (maximum) · PO · q12h · 4-8 weeks trial · Decrease dose if hypoglycemia occurs. Response may be delayed; evaluate over 4-8 weeks before determining efficacy.
- Non-ketotic diabetes mellitus · 2.5-5 mg per cat · PO · q12h · Start at the lower end of the dose range, increasing the dose as required if no adverse effects are reported after 2 weeks.
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
給藥途徑
禁忌症
- Severe burns, trauma, or infection
- Diabetic coma or other hypoglycemic conditions
- Major surgery
- Ketosis, ketoacidosis, or other significant acidotic conditions
- Known hypersensitivity to sulfonylureas
- Diabetic ketosis / ketoacidosis
- Hepatic impairment
- Renal impairment
- Absolute insulin deficiency (Type I diabetes)
- Insulin resistance
不良反應
- Gastrointestinal upset (anorexia, vomiting in ~15% of cats)
- Hypoglycemia (severe cases are rare)
- Hepatotoxicity (cholestatic jaundice and elevated liver enzymes in ~8% of cats)
- Increased pancreatic amyloid deposit formation
- Allergic skin reactions (reported in humans)
- Bone marrow suppression (reported in humans)
- Vomiting
- Hypoglycemia
- Jaundice (hepatotoxicity)
- Skin rashes
- Fever
藥物相互作用
- Alcohol · May cause a disulfiram-like reaction (anorexia, nausea, vomiting)
- Azole Antifungals (ketoconazole, itraconazole, fluconazole) · May increase plasma levels of glipizide
- Beta-blockers · May potentiate hypoglycemic effect and mask signs of hypoglycemia
- Chloramphenicol · May displace glipizide from plasma proteins, increasing effect · moderate
- Cimetidine · May potentiate hypoglycemic effect
- Corticosteroids · May antagonize insulin effects and reduce glipizide efficacy
- Thiazide Diuretics · May reduce hypoglycemic efficacy
- Isoniazid · May reduce hypoglycemic efficacy
- MAO Inhibitors · May potentiate hypoglycemic effect
- Niacin · May reduce hypoglycemic efficacy
- Phenothiazines · May reduce hypoglycemic efficacy
- Phenytoin · May reduce hypoglycemic efficacy
- Probenecid · May potentiate hypoglycemic effect
- Sulfonamides · May displace glipizide from plasma proteins, increasing effect
監測
- Physical examination and body weight (weekly during first month)
- Urine glucose and ketones
- Serial blood glucose measurements or spot checks
- Liver enzymes (ALT, AST, ALP) and bilirubin (every 1-2 weeks initially)
- Complete Blood Count (CBC)
- Clinical signs of hypoglycemia or gastrointestinal distress
- Blood glucose curves
- Fructosamine levels
- Liver enzymes (ALT, AST, ALP, Bilirubin)
- Renal function (BUN, Creatinine)
- Clinical signs of diabetes (water intake, urination, weight)
過量
**Toxicity Profile**: Oral LD50 is greater than 4 g/kg in all tested animal species. The primary and most dangerous consequence of an overdose is **profound hypoglycemia**. **Management**: * **Decontamination**: Employ gut-emptying protocols (emesis, activated charcoal) if the ingestion is recent and the patient is asymptomatic. * **Treatment**: Monitor blood glucose closely. Administer parenteral glucose (e.g., IV dextrose bolus followed by a CRI) as needed. * **Monitoring**: Because of its relatively short half-life, prolonged hypoglycemia is less likely compared to older sulfonylureas (like chlorpropamide), but blood glucose monitoring and supportive care may still be required for several days. Massive overdoses may require monitoring of blood gases and serum electrolytes.
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