Opioid Use Disorder Medications - Pharmacokinetics

Buprenorphine ...

Opioid Use Disorder Medications - Pharmacokinetics

Buprenorphine is a partial mu-opioid receptor agonist with low intrinsic activity, high binding affinity, and a slow dissociation rate, leading to prolonged effects in suppressing opioid withdrawal and displacing full agonists such as morphine and methadone. As a partial agonist, buprenorphine produces a ceiling effect in which higher doses do not result in increased pharmacological effects. Buprenorphine thus effectively functions as a dual agonist and antagonist in modulating opioid withdrawal symptoms by blocking the effects of exogenous opioids. Buprenorphine is also a kappa-opioid receptor antagonist. This mechanism of action has been suggested as a strategy in modulating relapse, since the kappa-opioid receptor may be involved in anxiety and depression at certain stages of the addiction cycle.

Methadone is a long-acting full mu-opioid receptor agonist with a long half-life. Its pharmacological action prevents withdrawal symptoms, reduces cravings, and blocks mu-opioid-receptor-mediated euphoric effects from illicit opiates. However, full agonists have the highest abuse potential.

Naltrexone is a mu-opioid antagonist with a higher affinity for receptors than heroin, morphine, or methadone; it displaces opioid full and partial agonists to block their effects. Because of its antagonistic action, it can precipitate withdrawal symptoms in patients not abstinent from short-acting opioids for 7 days or long-acting opioids for 10 days, limiting to its use to highly motivated individuals. As an antagonist, naltrexone does not have abuse potential or withdrawal upon discontinuation of the medication. 

Safety concerns with opioid agonists are mostly due to mu-opioid-receptor activation, which may be responsible for adverse effects of buprenorphine and methadone such as respiratory depression and constipation. As a partial agonist, buprenorphine exhibits a ceiling effect when used alone and severe mu-opioid-medicated adverse effects such as respiratory depression are less likely to occur. However, caution is advised when combining with additional CNS depressants such as benzodiazepines, as its ceiling effect is lost in this combination. Methadone exhibits the narrowest margin of safety in pharmacology studies and has been associated with potentially fatal cardiac arrhythmia from QT interval prolongation. For buprenorphine, no effect of QT prolongation was reported in the sublingual tablet formulation.

Safety concerns with an opioid antagonist involve the loss of opioid tolerance, which increases the risk of death from opioid overdose if opioid use is resumed following naltrexone therapy.

#Opioid #UseDisorder #Medications #Pharmacokinetics #Comparison #Table #Pharmacology #Methadone #Naltrexone #Buprenorphine
Contributed by

Dr. Gerald Diaz
Board Certified Internal Medicine Hospitalist, GrepMed Editor in Chief πŸ‡΅πŸ‡­ πŸ‡ΊπŸ‡Έ - Sign up for an account to like, bookmark and upload images to contribute to our community platform. Follow us on IG:  https://www.instagram.com/grepmed/ | Twitter: https://twitter.com/grepmeded/
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