美托咪啶
**美托咪啶 (Medetomidine)** 是一種強效的合成 **Alpha-2 腎上腺素受體激動劑**,在獸醫學中廣泛用於其深度的鎮靜、鎮痛和肌肉鬆弛特性。 主要臨床特徵包括: - **雙相心血管反應**:初期的周邊血管收縮導致短暫的高血壓,隨後引發反射性心搏過緩及隨後的血壓正常或輕微低血壓。 - **可逆性**:其作用可透過特定的 Alpha-2 拮抗劑(如 **阿替美唑 Atipamezole**)迅速且完全地逆轉。 - **立體化學**:美托咪啶是兩種立體異構物的消旋混合物。其活性對映異構體為 **右美托咪啶 (Dexmedetomidine)**,目前在許多現代獸醫市場中已大幅取代消旋美托咪啶。 - **協同作用**:與鴉片類藥物、氯胺酮 (Ketamine) 及其他麻醉劑具有高度協同作用,可顯著降低併用麻醉劑的劑量。 > **臨床要點**:雖然它能提供極佳的體表與內臟鎮痛效果,但鎮靜作用的時間通常長於鎮痛作用。如果受到巨大噪音或粗魯操作的刺激,即使病患看起來處於深度鎮靜狀態,也可能會突然驚醒。
作用機制: Medetomidine produces its effects by binding to and activating **pre- and postsynaptic alpha-2 adrenergic receptors** in the central and peripheral nervous systems. - **Central Nervous System**: Activation of alpha-2 receptors in the **locus coeruleus** → inhibition of adenylyl cyclase → decreased cAMP → efflux of potassium (hyperpolarization) → decreased release of **norepinephrine**. This suppression of sympathetic outflow results in profound sedation, anxiolysis, and analgesia. - **Cardiovascular System**: Activation of peripheral **alpha-1 and alpha-2b receptors** in vascular smooth muscle → profound vasoconstriction → increased systemic vascular resistance (hypertension) → baroreceptor-mediated increased vagal tone → **reflex bradycardia**. - **Endocrine/Metabolic**: Inhibits insulin release from pancreatic beta cells → transient **hyperglycemia**. Decreases antidiuretic hormone (ADH) release → increased diuresis. Medetomidine is highly selective, with an alpha-2:alpha-1 selectivity ratio of 1620:1 (approximately 10 times more specific than xylazine).
各物種劑量
- Sedation/analgesia · 40-80 micrograms/kg IM · IM · Single dose · Higher doses increase duration, not depth of sedation
- For use with an IM opioid · 5-10 micrograms/kg · IM · Single dose
- Sedation/analgesia · 0.001-0.01 mg/kg (1-10 micrograms/kg) IV, IM or SC · IV/IM/SC · Single dose
- Large, exotic cat (tigers, etc.) immobilization · Midazolam (0.1 mg/kg) plus medetomidine (0.05-0.07 mg/kg) IM followed by ketamine (4-10 mg/kg) IM, if needed. May antagonize with atipamezole (0.25-0.35 mg/kg) IV, SC. · IM · Single dose
- Premedication (in combination with an opioid) · 5-20 μg (micrograms)/kg · IV/IM/SC · single dose · Analgesia lasts approx 1 hour at 10 μg/kg · Use lower end of dose range for IV administration.
- Management of excitation in the recovery period · 1-2 μg/kg · IV · single dose · Animals must be monitored carefully following administration.
- Perioperative analgesia and rousable sedation · 2-4 μg/kg/h · IV · CRI · perioperative period · Particularly useful when administered as an adjunct to opioid-mediated analgesia.
- Sedative/analgesic · 15 minutes prior to medetomidine, give atropine (0.05 mg/kg) or glycopyrrolate (0.01 mg/kg) then give medetomidine at 60-80 micrograms/kg IM or SC. · IM/SC · Single dose · Sedation lasts for up to 3 hours · May be reversed with atipamezole (400 micro-grams/kg IM)
給藥途徑
禁忌症
- Cardiac disease
- Respiratory disorders
- Liver or kidney diseases
- Shock or severe debilitation
- Animals stressed due to heat, cold, or fatigue
- Pregnancy (insufficient safety data; use only if benefits clearly outweigh risks)
- Cardiovascular disease
- Systemic disease
- Geriatric patients
- Pregnant animals
- Conditions where vomiting is contraindicated (e.g., gastrointestinal foreign body, raised intraocular pressure)
- Diabetes mellitus
不良反應
- Bradycardia (often profound)
- Atrioventricular (AV) blocks
- Decreased respiratory rate and potential apnea
- Hypothermia
- Increased urination (diuresis)
- Vomiting (especially in cats)
- Hyperglycemia
- Pain on intramuscular injection
- Blanched or cyanotic mucous membranes (due to peripheral vasoconstriction)
- Rarely: prolonged sedation, paradoxical excitation, hypersensitivity, death from circulatory failure
- Bradycardia
- Decreased cardiac output
- Initial hypertension followed by normotension/hypotension
- Vomiting (especially common after IM administration)
- Diuresis (due to ADH suppression)
藥物相互作用
- Atropine / Glycopyrrolate · Controversial. Using anticholinergics to treat medetomidine-induced bradycardia can lead to severe hypertension, increased myocardial work, and arrhythmias. Concomitant use is generally discouraged, especially at higher medetomidine doses (>20 mcg/kg).
- Opiates (Fentanyl, Butorphanol, Meperidine) · Synergistic enhancement of sedation and analgesia. Adverse cardiovascular and respiratory effects may also be pronounced. Reduced dosages and careful monitoring are advised.
- Propofol · When used after medetomidine, severe hypoxemia may occur. Significant dosage reductions of propofol are required along with adequate respiratory monitoring.
- Yohimbine · May reverse the effects of medetomidine, but atipamezole is the preferred and more specific reversal agent.
- Other anesthetic agents (e.g., propofol, alfaxalone) · Significantly reduces the dose required for induction and maintenance of anesthesia. · major
- Volatile anesthetics (e.g., isoflurane, sevoflurane) · Reduces the dose required to maintain anesthesia by up to 70%. · major
- Sympathomimetic amines · Contraindicated; may cause severe cardiovascular complications. · major
- Opioids · Synergistic sedation and analgesia (beneficial interaction). · moderate
監測
- Level of sedation and analgesia
- Heart rate and rhythm (ECG recommended in high-risk patients)
- Body temperature (monitor for hypothermia)
- Blood pressure
- Respiratory rate and depth
- Pulse oximetry (SpO2)
- Heart rate and rhythm (bradycardia is expected, but monitor for severe arrhythmias)
- Blood pressure (initial hypertension followed by normotension/hypotension)
- Oxygen saturation (SpO2)
- Body temperature (risk of hypothermia due to reduced metabolic rate and peripheral vasoconstriction)
- Depth of sedation
過量
Single doses of up to **5X (IV)** and **10X (IM)** have been tolerated in dogs, though severe adverse effects (profound bradycardia, AV blocks, respiratory depression) can occur. Death has occurred rarely in dogs (1 in 40,000) receiving 2X doses. > **Important**: Treatment of medetomidine-induced bradycardia with anticholinergic agents (atropine or glycopyrrolate) is **not recommended** due to the risk of severe hypertension, increased myocardial oxygen demand, and arrhythmias. **Atipamezole** (an alpha-2 antagonist) is the safest and most effective choice to reverse medetomidine-induced cardiovascular and sedative effects.
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