Alfaxalone
**Alfaxalone** is a neuroactive steroid molecule that functions as a rapid-acting central nervous system depressant and general anesthetic. It is primarily used for the induction and maintenance of anesthesia in veterinary patients. **Clinical Pearls & Pharmacological Profile:** * **Formulation Evolution:** The modern formulation (Alfaxan®) uses 2-hydroxypropyl-beta-cyclodextrin (HPCD) as a solubilizing agent. This is a significant improvement over the historical product (Saffan®), which contained polyethoxylated castor oil (Cremophor EL) and caused severe histamine release and anaphylaxis, particularly in cats. * **Cardiorespiratory Effects:** While generally considered to have a wide safety margin, alfaxalone can cause dose-dependent respiratory depression and post-induction apnea, especially if administered rapidly IV. Cardiovascular parameters are typically well-maintained, though compensatory tachycardia may occur. * **Analgesia:** Alfaxalone provides **negligible analgesic effects**. It must be combined with appropriate pure analgesics (e.g., opioids) for painful procedures. * **Recovery:** Recovery is generally rapid and smooth due to its short half-life and lack of accumulation, but patients can experience psychomotor excitement (paddling, vocalization, twitching) if stimulated or if inadequate premedication/analgesia was provided.
Mecanismo: Alfaxalone exerts its anesthetic effects by interacting with **GABA_A (gamma-aminobutyric acid type A) receptors** in the central nervous system. * **Mechanism:** It binds to specific transmembrane domains on the GABA_A receptor complex. * **Pathway:** Binding → Enhances the binding of the inhibitory neurotransmitter GABA to the receptor → Increases the frequency and duration of **chloride (Cl⁻) ion channel** opening → Influx of chloride ions into the neuron → **Hyperpolarization** of the postsynaptic cell membrane → Inhibition of neural action potential transmission → Dose-dependent CNS depression (ranging from sedation to general anesthesia).
Dosificación por especie
- Anesthesia Induction (Premedicated) · 3 mg/kg · IV · once · Administer over first 60 seconds to effect. If intubation not possible, one further similar dose may be administered.
- Anesthesia Induction (Unpremedicated) · 2 mg/kg · IV · once · Administer over first 60 seconds to effect.
- Anesthesia Induction (Alternative) · 1-2 mg/kg · IV · once · Slowly over 20-30 seconds while assessing degree of anesthesia.
- Anesthesia Maintenance (CRI, Premedicated) · 0.1-0.12 mg/kg/minute · IV · CRI · Up to 1 hour · Equivalent to 6-7 mg/kg/hour.
- Anesthesia Maintenance (CRI, Unpremedicated) · 0.13-0.15 mg/kg/minute · IV · CRI · Up to 1 hour · Equivalent to 8-9 mg/kg/hour.
- Anesthesia Maintenance (Bolus, Premedicated) · 1-1.2 mg/kg · IV · q10m · Up to 1 hour · Administer every 10 minutes as needed.
- Anesthesia Maintenance (Bolus, Unpremedicated) · 1.3-1.5 mg/kg · IV · q10m · Up to 1 hour · Administer every 10 minutes as needed.
- Anesthesia Maintenance (Alternative Bolus) · 5-12 mg/kg total dose · IV · incremental · 5-7 mg/kg total for short procedures; 8-12 mg/kg total for longer procedures.
- Anesthesia Induction · 5 mg/kg · IV · once · Premedicated or unpremedicated. Administer over first 60 seconds to effect.
Vías de administración
Contraindicaciones
- Concurrent use with other injectable general anesthetic agents (e.g., propofol, thiopental)
- Situations where endotracheal intubation, positive pressure ventilation, and oxygen support are unavailable
- Animals less than 12 weeks of age (safety not established)
Efectos adversos
- Respiratory depression
- Post-induction apnea
- Hypotension (dose-dependent)
- Cardiac arrhythmias (primarily secondary to hypoxemia/hypercapnia)
- Psychomotor excitement during recovery (especially if unstimulated or lacking premedication)
Interacciones farmacológicas
- CNS Depressants (e.g., acepromazine, opioids, alpha-2 agonists, benzodiazepines) · Potentiates the CNS and respiratory depressant effects. Significantly reduces the required induction and maintenance doses of alfaxalone.
- Propofol · Should not be used concurrently according to the manufacturer label.
- Thiopental · Should not be used concurrently according to the manufacturer label.
- Other IV anaesthetic agents · Increased risk of severe CNS and respiratory depression · major
- Premedicants (e.g., sedatives, opioids) · Synergistic CNS depression; significantly reduces the required induction dose of alfaxalone · moderate
- Opioids (e.g., methadone, buprenorphine) · Synergistic CNS depression; reduces the required induction dose of alfaxalone. · moderate
- Alpha-2 agonists (e.g., dexmedetomidine) · Profound synergy; significantly reduces alfaxalone dose requirements and may exacerbate cardiovascular and respiratory depression. · major
- Phenothiazines (e.g., acepromazine) · Enhanced sedation and increased risk of hypotension. · moderate
- Opioids (e.g., butorphanol, methadone) · Synergistic CNS depression; significantly reduces the required induction dose of alfaxalone. · moderate
- Benzodiazepines (e.g., midazolam) · Synergistic CNS depression; reduces alfaxalone dose requirements. · moderate
Monitorización
- Level of anesthesia / CNS depression (jaw tone, palpebral reflex)
- Respiratory rate, rhythm, and depth (capnography and pulse oximetry highly recommended due to apnea risk)
- Cardiovascular status (heart rate, ECG rhythm, blood pressure)
- Body temperature (monitor for hypothermia during anesthesia)
Sobredosis
Overdoses up to 25 mg/kg primarily result in severe cardiorespiratory depression. **Clinical Signs of Toxicity:** * Severe hypoventilation and prolonged apnea * Hypotension * Cardiac arrhythmias **Treatment:** * Immediate endotracheal intubation and positive pressure ventilation with 100% oxygen. * Cardiovascular support (IV fluids, vasopressors/inotropes if hypotension is severe). * Continuous monitoring until the drug is metabolized and cleared.
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