嗎啡
嗎啡是獸醫學中用於治療中度至重度急性疼痛的典型**鴉片類鎮痛藥**。它是一種源自鴉片的天然純粹 mu-鴉片受體促效劑。 **臨床要點與物種差異:** * **狗與靈長類:** 嗎啡通常會引起可預期的中樞神經系統抑制、鎮靜和鎮痛。由於直接刺激化學受體觸發區 (CTZ),它對狗是一種強效催吐劑。狗在首次給藥後通常會立即排便,隨後腸胃蠕動減少。 * **貓、馬與反芻動物:** 這些物種可能會表現出矛盾的**中樞神經系統興奮**(煩躁、狂躁、踱步)而非抑制,特別是在沒有同時使用鎮靜劑或鎮定劑(如 acepromazine 或 alpha-2 促效劑)的情況下。貓需要比狗高得多的劑量才會引發嘔吐。 * **組織胺釋放:** 嗎啡會引起肥大細胞非免疫性組織胺釋放。靜脈注射必須緩慢進行,以避免嚴重的低血壓、血管擴張和支氣管收縮。 * **體溫調節:** 嗎啡會導致狗和兔子體溫過低,但會導致貓、馬、牛和羊體溫過高。
作用機制: Morphine acts primarily as a full agonist at the **mu (μ) opioid receptors** in the central nervous system, with some secondary activity at delta receptors. * **Mechanism:** Binding to the G-protein coupled mu-receptor → inhibits adenylate cyclase → decreases intracellular cAMP. * **Presynaptic effect:** Closes voltage-gated calcium channels → decreases the release of excitatory nociceptive neurotransmitters (e.g., **Substance P**, **glutamate**). * **Postsynaptic effect:** Opens inward-rectifying potassium channels → hyperpolarizes the neuron → inhibits ascending pain transmission pathways. * **Secondary effects:** Direct stimulation of the **chemoreceptor trigger zone (CTZ)** causes emesis. Central vagal stimulation leads to bradycardia. Increased anti-diuretic hormone (ADH) release can reduce urine production.
各物種劑量
- As an analgesic · Up to 10 mg total dose, IM · IM · once
- As an analgesic · Up to 10 mg total dose, IM · IM · once
- For post-op pain · 0.1-0.3 mg/kg IM, SC · IM, SC · Not specified
- For analgesia · 0.1-0.2 mg/kg IM, SC or IV (slowly because of histamine release). · IM, SC, IV · q6h or as required · Easily titrated to effect.
- For analgesia · 0.1-0.4 mg/kg IM, SC q3-6h · IM, SC · q3-6h · Concomitant tranquilization recommended.
- For analgesia · 0.02-0.1 mg/kg IV q1-4hrs; 0.2-0.5 mg/kg IM, SC q3-4h; 0.2-0.5 mg/kg PO q6-8h. · IV, IM, SC, PO · q1-4h (IV), q3-4h (IM/SC), q6-8h (PO)
- Epidural administration for pain control · Using preservative-free morphine: epidural at 0.1-0.2 mg/kg q8h; spinal at 0.05 mg/kg q8h. · Epidural, Spinal · q8h
- As a preanesthetic in critical patients · 0.5-2 mg/kg IM. · IM · once · Use with diazepam or midazolam. Caution with IV use due to histamine release.
- For adjunctive treatment of cardiogenic pulmonary edema · 0.02-0.1 mg/kg IV q1-4 hours, or 0.2-0.5 mg/kg IM or SC q3-4hr · IV, IM, SC · q1-4h (IV), q3-4h (IM/SC)
給藥途徑
禁忌症
- Hypersensitivity to narcotic analgesics
- Patients receiving monoamine oxidase inhibitors (MAOIs)
- Diarrhea caused by a toxic ingestion (until toxin is eliminated)
- Scorpion envenomation (Centruroides spp. - potentiates venom)
- Conditions where vomiting is contraindicated (e.g., raised intraocular pressure)
不良反應
- Histamine release (hypotension, vasodilation)
- Respiratory depression
- Bronchoconstriction
- CNS depression (dogs, primates) or excitation (cats, horses, ruminants)
- Physical dependence (with chronic use)
- Hyperthermia (cattle, goats, horses, cats)
- Hypothermia (dogs, rabbits)
- Nausea and vomiting
- Decreased intestinal peristalsis and constipation
- Initial defecation (dogs)
- Panting (dogs)
- Bradycardia or tachycardia
- Histamine release (if given rapidly IV)
- Vomiting (common in non-painful pre-operative patients)
- Transient excitation (IV administration)
藥物相互作用
- CNS Depressants (anesthetics, antihistamines, phenothiazines, barbiturates) · May cause increased CNS or respiratory depression when used with morphine.
- Diuretics · Opiates may decrease diuretic efficacy in congestive heart failure patients.
- Monoamine Oxidase Inhibitors (MAOIs, e.g., amitraz, selegiline) · Use with extreme caution; contraindicated in humans due to risk of severe opiate overdose signs.
- Skeletal Muscle Relaxants · Morphine may enhance neuromuscular blockade.
- Tricyclic Antidepressants (clomipramine, amitriptyline) · Morphine may exacerbate the effects of tricyclic antidepressants.
- Warfarin · Opiates may potentiate anticoagulant activity.
- CNS depressants (anaesthetics, antihistamines, barbiturates, phenothiazines, tranquillizers) · Increased CNS or respiratory depression · major
監測
- Respiratory rate and depth
- CNS level of depression or excitation
- Blood pressure (especially with IV use)
- Analgesic activity
- Respiratory rate and depth (especially under general anaesthesia)
- Pain scores (to assess individual efficacy)
- Signs of histamine release (hypotension, tachycardia) during IV administration
- Gastrointestinal motility
過量
**Signs of Toxicity:** Overdosage may produce profound respiratory and/or CNS depression in most species. Newborns are more susceptible. Parenteral doses >100 mg/kg are thought to be fatal in dogs. Other toxic effects include cardiovascular collapse, hypothermia, and skeletal muscle hypotonia. Horses, cats, swine, and cattle may demonstrate CNS excitability (hyperreflexia, tremors) and seizures at high doses or if given rapidly intravenously. **Treatment:** * **Naloxone** is the agent of choice for treating respiratory depression. Doses may need to be repeated as naloxone's effects might diminish before sub-toxic levels of morphine are attained. * Mechanical respiratory support should be considered in severe cases. * Pentobarbital has been suggested for CNS excitement and seizures in cats, but extreme caution is required as barbiturates and narcotics have additive respiratory depressant effects.
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