MethadoneA synthetic opioid analgesic

Prepared and presented by: Kiran NiureRoll No. : 25BVSc & AH, AFU

Contents:

• Introduction• Pharmacological effects• Pharmacokinetics• Side effects/Adverse effects• Contraindications and precautions• Drug interactions• Clinical uses• Dose

Introduction• A synthetic diphenylpropylamine derivative

opioid (µ receptor) agonist• opioid used to treat pain and as maintenance

therapy or to help with detoxification in people with opioid dependence

• Molecular formula: C21H27NO• Brand name: dolophine, methadose

Mode of action

Binds to µ receptor

Inhibitory G-coupled receptor

Inhibit adenylate cyclase, inhibit cAMP

k+ channel activation (outflux) and inhibition of ca++ channel

Hyperpolarization, inhibit ca++ releaseInhibit neurotransmitter release and show analgesic effect

Pharmacological effect• analgesic potency almost equal to morphine

but less sedative

• Effects similar to morphine i.e.– CNS depression– suppression of cough centre– respiratory depression– decreased intestinal or stomach motility– Emesis

Pharmacokinetics• Readily absorbed following parenteral or

oral administration• High oral: parenteral activity ratio (i.e 2:1)• higher bioavailability, a much longer half-

life (15 to 60 hours with a mean of around 22) than morphine

• Bioavailability: 41–99% (oral)• Protein binding: 85–90%

• hepatically metabolized by cytochrome P450 enzymes

• Rate of metabolism and excretion resembles morphine

• Primarily excreted as metabolites in bile and urine along with small amounts (about10%) of unchanged drugs

• After repeated use, methadone gets accumulated and duration of action is increased due to gradual release of drug from these site

Side Effects/Adverse Effects

Similar to morphine• Hypotension, • sedation,• vomiting, • initial defecation followed by constipation,• urinary retension, • alteration of thermoregulation (panting in dogs,

sweating in horses), • respiratory depression• Confusion, hallucination

Contraindications and precautions

• Contraindicated in traumatic shock, biliary spasms, acute renal insufficiency

• Contraindicated in head injury and raised intraocular pressure

• Contraindicated in any situation where opioids are contraindicated, such as: patients with respiratory depression & with acute bronchialasthma or hypercarbia.

• contraindicated in any patient who has or is suspected of having a paralytic ileus.

• Careful use of methadone in cats due to increased sensitivity of this species to opioids

Drug interactions• No specific drugs interactions reported for

animals but In horses, methadone and acepromazine in combination for analgesia and chemical restraint

• Coadministration of these anti-retroviral agents resulted in increased clearance or decrease plasma levels of methadone. Eg. Abacavir, amprenavir, efavirenz, nelfinavir, nevirapine, ritonavir, lopinavir+ritonavir combination

• Shows additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.

Clinical Uses• Primary use for relief of pain and as pre-

anaesthetic• Ocassionally employed as antitussive• In horses, methadone and acepromazine

in combination for analgesia and chemical restraint

• In humans, employed in opioid abstinence syndrome and treatment of heroin users

Dose• For analgesia

Dogs: 0.5-2 mg/kg. IM or SC, repeated at 3-4 hours intervals: 0.1 mg/kg, IV

Cats: 0.1 -0.5 mg/kg , IM or SC, repeated at 3-4 hours intervals: 0.05 – 0.1 mg/kg, IV

Dogs and cats: 0.2 mg/kg, IM in combination with acepromazine 0.02 mg/kg

Horses: 0.1 mg/kg, IV: 0.1mg/kg methadone and 0.1 mg/kg acepromazine , IV for analgesia and chemical restraint

References

• Essentials of veterinary pharmacology and therapeutics, 2nd edition, Harpal Singh Sandhu

• http://www.rxlist.com/methadone-hydrochloride-drug

• Ferrari_Methadone-metabolism-pharmacokinetics-and-interactions_Pharmacol-Res-2004

• http://atforum.com/documents/com_ctrd_mmt

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