Introduction of methadone along with pharmacological effects, pharmacokinetics, adverse effects, contraindications, drug interactions, clinical uses and dose

1. A synthetic opioid analgesic
Prepared and presented by:
Kiran Niure
Roll No. : 25
BVSc & AH, AFU

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

3. 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

4. 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++ release
Inhibit neurotransmitter release and show
analgesic effect

5. 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

6. 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%

7. • 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

8. 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

9. 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

10. 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

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

12. 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

13. 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

14. 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