Opioid Agonists and Antagonists

Subclass, Drug Mechanism of Action Effects Clinical Applications P, T, I

Strong Agonists: Strong mu receptor agonist Analgesia Adjunct in anesthesia Respiratory depression,
Phenanthrenes: Variable affinity for delta and Relief of anxiety Severe pain severe constipation,
kappa receptors Sedation Pulmonary edema addiction liability,
Morphine Subarachnoid injection for Slowed GI transit convulsions
post-op analgesia
Like morphine in efficacy, Severe pain
Hydromorphone but higher potency
Like morphine in efficacy, Severe pain
Oxymorphone but higher potency
Phenylheptylamines: Strong mu receptor agonist Its racemic mixture of D- and Opioid abuse Respiratory depression,
Variable affinity for delta and L- methadone isomers can Severe pain sever constipation, addiction
kappa receptors do block both NMDA Detoxification and for liability, convulsions
Methadone A synthetic opiate receptors and maintenance of the chronic
monoaminergic reuptake relapsing heroin addict
transporters Maintenance in
Analgesia, relief of anxiety, rehabilitation programs
sedation, slowed GI transit
Phenylpiperidines: Strong mu receptor agonist Analgesia Severe pain Respiratory depression,
Variable affinity for delta and Relief of anxiety Adjunct in anesthesia severe constipation,
kappa receptors Sedation addiction liability,
Fentanyl Can be given by transdermal Slowed GI transit convulsions
patch
Strong agonist with Tachycardia, seizures
anticholinergic effects
Meperidine (anitmuscarinic effects)
(-) inotropic action on the
heart and potential for
producing seizures
Morphinans: Synthetic opioid analgesic
closely resembling morphine
that has mu, delta, kappa
Levorphanol agonist actions, serotonin-
norepinephrine reuptake

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 inhibition, and NMDA
receptor antagonist
properties
Mild to Moderate Less efficacious than Like strong agonists Mild to moderate pain
Agonists: morphine Weaker effects Cough
Phenanthrenes: Can antagonize strong
agonists
Codeine
Dihydrocodeine
Less efficacious than Like strong agonists Mild to moderate pain
morphine Weaker effects
Hydrocodone Can antagonize strong
agonists
More potent and is Dose-dependent analgesia
prescribed alone in higher
Oxycodone doses as immediate release
or controlled release for the
tx of moderate to severe
pain
Phenylheptylamines: Chemically related to
methadone but has
extremely low analgesic
activity
Its low efficacy makes it
Propoxyphene unsuitable, even in
combination with aspirin, for
severe pain
Phenylpiperidines: Together with its metabolite Given in combination with Likelihood for abuse is
(difenoxin), are not used for atropine to reduce likelihood remote
Diphenoxylate analgesia but for tx of of abuse The poor solubility of their
diarrhea use for parenteral injection
Phenylpiperidine derivative
Loperamide used to control diarrhea
Opioids with Mixed
Receptor Actions:
Phenanthrenes:

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 A potent and long-acting Like strong agonists but can Moderate pain May precipitate abstinence
phenanthrene derivative that antagonize their effects Some maintenance syndrome, psychotomimetic
is a partial mu receptor Reduces craving for alcohol rehabilitation programs effect
agonist and an antagonist at As effective as methadone in Opioid dependence
Buprenorphine the delta and kappa the detoxification and
receptors maintenance of heroin
Mixed agonist-antagonist abuses
A benzomorphan
Pentazocine Kappa agonist with weak mu
antagonism or partial
Strong kappa receptor Similar to buprenorphine Moderate pain Like buprenorphine
Nalbuphine agonist and a partial mu
receptor antagonist
Morphinans: Produces analgesia
equivalent to nalbuphine but
appears to produce more
Butorphanol sedation at equianalgesic
doses
Benzomorphans: Kappa agonist with weak mu Not recommended for
antagonist or partial agonist subcutaneous injection
Pentazocine properties because it is an irritant
Oldest mixed agent available
Miscellaneous: Centrally acting analgesic May serve as an adjunct with Moderate pain Seizures, serotonin
whose MOA is pure opioid agonist in the tx Adjunct to opioids in chronic syndrome, nausea, dizziness
predominantly bases on of chronic neuropathic pain pain sydromes
Tramadol blockade of serotonin Analgesia
reuptake
NET inhibitor
Weak mu agonist
Moderate SERT inhibitor
Moderate mu agonist Analgesia Moderate pain Headache, nausea and
Strong NET inhibitor As effective as oxycodone vomiting, possible
Tapentadol Analgesic with modest mu but with reduced GI dependence
opioid receptor affinity and complaints
significant norepinephrine
reuptake-inhibiting action
Antitussives:

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 Poorly understood but Reduces cough reflex Acute debilitating cough Minimal when taken as
strong and partial mu Dextromethorphan, directed
Dextromethorphan agonists are also effective levopropoxyphene not
antitussives analgesic
Has useful antitussive action
at lower than required for
Codeine analgesia
15 mg is usually sufficient to
relieve cough
Stereoisomer of the weak The used antitussive dose is
Levopropoxyphene opioid agonist 50 – 100 mg every 4 hours
dextropropoxyphene
Noscapine
Opioid Antagonists: Antagonists at mu, delta, Rapidly antagonizes all opiod Opioid overdose Precipitates abstinence
kappa receptors effects Major application: tx of syndrome in dependent
Naloxone Glucuronide conjugation acute opioid overdose users
Like naloxone but longer Morphine sulfate = used in Maintenance drug for
duration of action (10h) control of prolonged post-op addicts in the tx program
Alternative drug for pain Alcohol and nicotine
detoxification of heroin dependence
Naltrexone addiction When combined with
bupropion, may be effective
in weight-loss programs
Like naloxone but longer
duration of action (10h)
Nalmefene Derivative of naltrexone
available in IV administration
Potent mu antagonist with Tx of constipation in patients
poor entry into the CNS with late-stage advanced
Methylnaltrexone illness
Severe opioid-induced
Bromide constipation without
precipitating an abstinence
syndrome
Potent mu antagonist with Tx of postoperative ileus
Alvimopam poor entry into the CNS following bowel resection
surgery

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Severe opioid-induced
constipation without
precipitating an abstinence
syndrome