๋ฉํ๋
๋ฉํ๋์ ํฉ์ฑ ๊ฐ๋ ฅ **๋ฎค-์คํผ์ค์ด๋ ์์ฉ์ฒด ์์ฉ์ (mu-opioid agonist)**๋ก, ์ฃผ๋ก ๊ฐ์ ๊ณ ์์ด์์ ๋ง์ทจ ์ ํฌ์ฝ ๋ฐ ์งํต์ ๋ก ์ฌ์ฉ๋ฉ๋๋ค. ๋ชจ๋ฅดํ๊ณผ ๋น๊ตํ์ฌ ์ ๋งฅ ์ฃผ์ฌ ์ ํ์คํ๋ฏผ ๋ฐฉ์ถ์ด ํ์ ํ ์ ๊ณ , ๊ตฌํ ๋ ๊ณผ๋ํ ์ง์ ์ ๋ ์ ๋ฐํฉ๋๋ค. **์์ ํต์ฌ ๋ฐ ์ฝ๋ฆฌ์ ์ฅ์ :** * **์ผ์ค ์์ฉ ๊ธฐ์ :** ๋๋ถ๋ถ์ ์ ํต์ ์ธ ์คํผ์ค์ด๋์ ๋ฌ๋ฆฌ ๋ฉํ๋์ ๋ฎค-์์ฉ์ ์ผ ๋ฟ๋ง ์๋๋ผ **๋น๊ฒฝ์์ NMDA ์์ฉ์ฒด ๊ธธํญ์ ** ๋ฐ **๋ชจ๋ ธ์๋ฏผ(์ธ๋กํ ๋ ๋ฐ ๋ ธ๋ฅด์ํผ๋คํ๋ฆฐ) ์ฌํก์ ์ต์ ์ **๋ก๋ ์์ฉํฉ๋๋ค. * **์ ๊ฒฝ๋ณ์ฆ์ฑ ํต์ฆ:** NMDA ๊ธธํญ ์์ฉ ๋๋ถ์ ๋์น์ฑ ํต์ฆ, ์ ๊ฒฝ๋ณ์ฆ์ฑ ํต์ฆ ์น๋ฃ ๋ฐ ์ค์ถ ๊ฐ์(์์ธ๋์ ํต์ฆ) ์๋ฐฉ์ ํนํ ์ ์ฉํฉ๋๋ค. * **์์ฒด์ด์ฉ๋ฅ :** ๊ฐ์์ ๊ฒฝ๊ตฌ ์์ฒด์ด์ฉ๋ฅ ์ด ๋งค์ฐ ๋ฎ์ ์์ํ์์๋ ๋น๊ฒฝ๊ตฌ ํฌ์ฌ(IV, IM, SC)๊ฐ ํ์ค ๊ฒฝ๋ก์ ๋๋ค. * **๊ท์ :** ์ธ์ฒด ๋จ์ฉ ๊ฐ๋ฅ์ฑ์ด ๋์ ์ค์ผ์ค II(C-II) ํต์ ์ฝ๋ฌผ๋ก ๋ถ๋ฅ๋ฉ๋๋ค.
์์ฉ ๊ธฐ์ : Methadone provides analgesia through a unique, multi-modal mechanism of action: * **Mu-Opioid Receptor (MOR) Agonism:** Binds to MORs in the central nervous system โ inhibits adenylyl cyclase โ decreases cAMP โ promotes opening of inward-rectifying potassium channels and closing of voltage-gated calcium channels โ hyperpolarization of neurons and decreased release of nociceptive neurotransmitters (e.g., Substance P, glutamate). * **NMDA Receptor Antagonism:** Acts as a non-competitive antagonist at the **N-methyl-D-aspartate (NMDA)** receptor โ blocks glutamate binding โ reduces central sensitization and hyperalgesia. * **Monoamine Reuptake Inhibition:** Inhibits the presynaptic reuptake of **serotonin (5-HT)** and **norepinephrine (NE)** โ increases monoamine concentrations in the synaptic cleft โ enhances descending inhibitory pain pathways in the spinal cord.
๋๋ฌผ ์ข ๋ณ ์ฉ๋
- For perioperative pain control ยท 0.05-0.5 mg/kg IV , IM or SC q4-6h ยท IV, IM, SC ยท q4-6h
- As a pre-anesthetic ยท 0.1-0.2 mg/kg SC, IM; or a combination of methadone 0.1-0.3 mg/kg with acepromazine 0.02-0.05 mg/kg SC, IM ยท SC, IM
- For moderate to severe pain ยท 0.1-0.2+ mg/kg IM or SQ ยท IM, SQ, IV ยท Duration of effect is 2-6 hours (IM/SQ) or 1-4 hours (IV) ยท For IV dosing use ยฝ the low end dose, titrate over 35 minutes
- For pain ยท 0.1-0.2 mg/kg SC, IV ยท SC, IV ยท Duration of effect 2-3 hours
- Analgesia ยท 0.1-0.5 mg/kg ยท IM ยท prn ยท Duration of action is typically 3-4 hours.
- Analgesia ยท 0.1-0.3 mg/kg ยท IV ยท prn ยท Monitor respiratory function if anaesthetized.
- Analgesia ยท 0.6 mg/kg ยท OTM ยท prn ยท Authorized preparation contains preservative and causes salivation when given by the OTM route.
- As an analgesic ยท 0.1-0.2 mg/kg PO ยท PO ยท Anecdotal; author has not prescribed this drug
- As a pre-anesthetic ยท 0.2-0.5 mg/kg SC, IM; or a combination of methadone 0.1-0.3 mg/kg with acepromazine 0.02-0.05 mg/kg SC, IM ยท SC, IM
ํฌ์ฌ ๊ฒฝ๋ก
๊ธ๊ธฐ
- Late-term pregnancy (due to risks of respiratory depression and stillbirths)
- Known hypersensitivity to methadone
- No specific contraindications available in the monograph, but use with caution in patients with severe respiratory compromise or hepatic impairment.
์ด์๋ฐ์
- Panting
- Whining or vocalization
- Sedation
- Defecation
- Constipation
- Bradycardia
- Respiratory depression
- Pronounced CNS excitement (in horses at IV doses โฅ 0.1 mg/kg)
- Respiratory depression (primarily under general anaesthesia)
- Transient excitation (when given IV)
- Salivation (when given via oral transmucosal route in cats due to preservatives)
- Constriction of gastrointestinal sphincters (e.g., pyloric sphincter)
- Reduction in gastrointestinal motility (with prolonged use)
- Neonatal sedation (crosses the placenta)
์ฝ๋ฌผ ์ํธ์์ฉ
- Class I & III Antiarrhythmics (e.g., lidocaine, procainamide, quinidine, amiodarone) ยท May increase risks for arrhythmias
- Alpha2-Agonists (e.g., medetomidine, xylazine) ยท Potentiates sedative and analgesic effects; combination with medetomidine may cause severe hypoxemia in dogs breathing room air
- Azole Antifungals (fluconazole, itraconazole, ketoconazole) ยท May increase methadone levels in humans (does not appear to be true for dogs)
- Calcium Channel Blockers ยท May increase risks for arrhythmias
- CNS Depressants (anesthetics, antihistamines, phenothiazines, barbiturates, tranquilizers) ยท May cause increased CNS or respiratory depression
- Corticosteroids (Mineralocorticoids) ยท May increase potential for electrolyte abnormalities
- Diuretics ยท Opiates may decrease diuretic efficacy in CHF patients
- Macrolide Antibiotics (erythromycin, clarithromycin) ยท May inhibit metabolism of methadone and increase levels in humans (does not appear to be true for dogs)
- Monoamine Oxidase Inhibitors (MAOIs) (e.g., amitraz, selegiline) ยท Potential for severe CNS/behavioral reactions; concomitant use should be avoided
- Skeletal Muscle Relaxants ยท Methadone may enhance neuromuscular blockade
- Phenobarbital, Phenytoin ยท May decrease methadone levels in humans (probably does not affect dogs)
๋ชจ๋ํฐ๋ง
- Analgesic or preanesthetic efficacy
- Respiratory rate and depth (monitor for respiratory depression, especially at higher doses)
- Heart rate (bradycardia)
- CNS depression or excitation
- Respiratory rate and depth (especially under general anaesthesia)
- Pain scores (due to individual variation in response)
- Level of sedation
- Gastrointestinal motility (with prolonged use)
๊ณผ์ฉ๋
Overdosage may produce profound **respiratory and/or CNS depression** in most species. Newborns are particularly susceptible. Other toxic effects include cardiovascular collapse, hypothermia, and skeletal muscle hypotonia. **Treatment:** * **Naloxone** is the reversal agent of choice for treating respiratory depression. In massive overdoses, naloxone doses may need to be repeated because naloxone's effects might diminish before sub-toxic levels of methadone are attained. * Mechanical respiratory support should be considered in severe cases. * Dialysis, charcoal hemoperfusion, or forced diuresis do not appear to be beneficial.
VetSheet ์ฝ๋ฌผ ๋ ํผ๋ฐ์ค๋ ๋ฉดํ ์์ ์ ๋ฌธ๊ฐ๋ฅผ ์ํ ์์ ์์ฌ๊ฒฐ์ ๋ณด์กฐ ๋๊ตฌ์ด๋ฉฐ, ์ ๋ฌธ์ ํ๋จ์ด๋ ์ ์กฐ์ฌ์ ์ต์ ๋ผ๋ฒจ์ ๋์ ํ์ง ์์ต๋๋ค.