阿塞丙嗪
**阿塞丙嗪 (Acepromazine)** 是獸醫學中經典且廣泛使用的吩噻嗪類神經阻滯劑,主要用於其可靠的鎮靜與安神作用。 **關鍵臨床要點:** * **無鎮痛作用:** 阿塞丙嗪**完全沒有止痛效果**。對於疼痛性操作,必須結合適當的鎮痛藥(如鴉片類藥物)使用(神經安定鎮痛)。 * **心血管效應:** 由於具有 α-1 腎上腺素受體阻斷作用,它是一種強效的血管擴張劑,常引起**低血壓**。應避免用於低血容、休克或血流動力學不穩定的病患。 * **品種敏感性:** 巨型犬和視覺獵犬(如格雷伊獵犬)對此藥高度敏感。帶有 **MDR1 (ABCB1) 基因突變**的犬隻(如牧羊犬、澳洲牧羊犬)需要大幅降低劑量(25-50%)。 * **馬匹注意事項:** 可能導致公馬陰莖長時間突出或陰莖異常勃起,進而造成陰莖牽引肌永久性麻痺。 雖然過去常用於旅行焦慮或噪音恐懼症,但現代獸醫行為學家通常不建議將其作為這些情況的單一療法,因為它可能僅讓動物鎮靜而無法減輕潛在的恐懼或恐慌,甚至可能增加對噪音的敏感度。
作用機制: Acepromazine exerts its effects through multiple receptor antagonisms: * **Dopamine (D2) Receptor Antagonism:** Blocks postsynaptic D2 receptors in the CNS (specifically the basal ganglia and limbic system) → depresses the reticular activating system → produces **sedation and tranquilization**. * **Alpha-1 Adrenergic Antagonism:** Blocks peripheral alpha-1 receptors → causes peripheral vasodilation → leads to **hypotension** and secondary hypothermia. * **Additional Blockade:** Possesses varying degrees of **anticholinergic** (muscarinic), **antihistaminic** (H1), and **antispasmodic** effects. * **Antiemetic Effect:** Blocks dopamine receptors in the Chemoreceptor Trigger Zone (CRTZ) of the medulla. > **Clinical Pearl:** Because of its alpha-blocking properties, administering epinephrine to an acepromazine-induced hypotensive patient can cause **"epinephrine reversal"** (unopposed beta-2 vasodilation), worsening the hypotension. Alpha-agonists like phenylephrine are preferred for treating severe acepromazine-induced hypotension.
各物種劑量
- Sedation · 0.05-0.1 mg/kg IM · IM
- Sedation · 0.05-0.1 mg/kg IM · IM
- Labeled dose · 0.55-2.2 mg/kg PO or 0.55-1.1 mg/kg IV, IM or SC · PO, IV, IM, SC · Considered by many clinicians to be 10 times greater than necessary.
- Restraint/sedation · 0.025-0.2 mg/kg IV; maximum of 3 mg or 0.1-0.25 mg/kg IM · IV, IM
- Preanesthetic · 0.1-0.2 mg/kg IV or IM; maximum of 3 mg; 0.05-1 mg/kg IV, IM or SC · IV, IM, SC
- To reduce anxiety in the painful patient (not a substitute for analgesia) · 0.05 mg/kg IM, IV or SC; do not exceed 1 mg total dose · IM, IV, SC
- Premedication · 0.03-0.05 mg/kg IM or 1-3 mg/kg PO · IM, PO · Give at least one hour prior to surgery (PO not as reliable).
- As a premedicant with morphine · acepromazine 0.05 mg/kg IM; morphine 0.5 mg/kg IM · IM
- Sedation and premedication (Non-Boxers) · 0.01-0.02 mg/kg · IV · single dose · up to 6 hours · Administer slowly. Generally given as part of a combination with opioids.
- Sedation and premedication (Non-Boxers) · 0.01-0.05 mg/kg · IM/SC · single dose · up to 6 hours · Onset of sedation is 20-30 minutes after IM administration.
給藥途徑
禁忌症
- Significant cardiac disease
- Hypovolemia, hypotension, or shock
- Tetanus or strychnine intoxication
- Intra-arterial injection in horses (can cause severe CNS excitement, seizures, death)
- Use with extreme caution in very young, geriatric, or debilitated animals
- Avoid in racing animals within 4 days of a race
不良反應
- Hypotension and cardiovascular collapse
- Bradycardia (vagally mediated) or reflex tachycardia
- Hypothermia or hyperthermia
- Penile protrusion/prolapse in large animals (especially stallions)
- Prolapse of the membrana nictitans (third eyelid)
- Decreased tear production (especially in cats)
- Paradoxical excitement, restlessness, or aggression
- Transient pain at IM injection sites
- Decreased hematocrit (due to splenic sequestration of RBCs)
藥物相互作用
- Acetaminophen · Possible increased risk for hypothermia
- Antacids · May cause reduced GI absorption of oral phenothiazines
- Antidiarrheal mixtures (Kaolin/pectin, bismuth) · May cause reduced GI absorption of oral phenothiazines
- CNS Depressant Agents (barbiturates, narcotics, anesthetics) · May cause additive CNS depression if used with acepromazine
- Dopamine · Acepromazine may impair the vasopressive action of dopamine
- Emetics · Acepromazine may reduce the effectiveness of emetics
- Epinephrine, Ephedrine · Concomitant use can lead to unopposed beta-activity causing vasodilation and increased cardiac rate (epinephrine reversal)
- Metoclopramide · May increase risks for extrapyramidal adverse effects
- Opiates · May enhance hypotensive effects; dosages of acepromazine are generally reduced when used with an opiate
- Organophosphate Agents · Effects may be potentiated; do not give within one month of worming with these agents
- Phenytoin · Metabolism may be decreased if given concurrently
- Procaine · Activity may be enhanced by phenothiazines
監測
- Cardiac rate, rhythm, and blood pressure (especially in compromised patients)
- Degree of tranquilization and sedation
- Male horses: Monitor to ensure the penis retracts and is not injured
- Body temperature (especially if ambient temperature is very hot or cold)
過量
The LD50 in mice is 61 mg/kg IV and 257 mg/kg PO. Dogs have survived oral dosages up to 220 mg/kg, but overdoses can cause serious **hypotension, CNS depression, pulmonary edema, and hyperemia**. **Clinical Signs of Toxicity:** * **Dogs:** Ataxia, sedation, lethargy, depression, protrusion of the third eyelid, somnolence, bradycardia, and recumbency. * **Cats:** Sedation, ataxia, lethargy, protrusion of the third eyelid, and depression. **Treatment:** * Because of relatively low toxicity, most overdoses are handled by monitoring and symptomatic treatment. * Massive oral overdoses should be treated by emptying the gut if possible. * **Hypotension:** Should *not* be treated initially with fluids. If fluids fail to maintain BP, use alpha-adrenergic pressor agents (e.g., phenylephrine). *Note: Avoid epinephrine due to the risk of "epinephrine reversal" causing further vasodilation.* * **Seizures:** May be controlled with barbiturates or diazepam. * **CNS Depression:** Doxapram has been suggested as an antagonist to the CNS depressant effects.
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