Morphine
Morphine is the prototypical **opiate analgesic** used in veterinary medicine for the treatment of moderate to severe acute pain. It is a naturally occurring pure mu-opioid receptor agonist derived from opium. **Clinical Pearls & Species Differences:** * **Dogs & Primates:** Morphine typically causes predictable CNS depression, sedation, and analgesia. It is a potent emetic in dogs due to direct stimulation of the chemoreceptor trigger zone (CTZ). Dogs often defecate immediately following an initial dose, followed by decreased GI motility. * **Cats, Horses, & Ruminants:** These species may exhibit paradoxical **CNS excitation** (dysphoria, mania, pacing) rather than depression, especially if administered without a concurrent sedative or tranquilizer (like acepromazine or an alpha-2 agonist). Cats require significantly higher doses than dogs to induce vomiting. * **Histamine Release:** Morphine causes non-immunologic histamine release from mast cells. Intravenous administration must be performed slowly to avoid severe hypotension, vasodilation, and bronchoconstriction. * **Thermoregulation:** Morphine can cause hypothermia in dogs and rabbits, but hyperthermia in cats, horses, cattle, and goats.
Mecanismo: 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.
Dosificación por especie
- 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)
Vías de administración
Contraindicaciones
- 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)
Efectos adversos
- 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)
Interacciones farmacológicas
- 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
Monitoreo
- 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
Sobredosis
**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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