Opioid analgesics

Question 1

What are strong agonists?

Answer 1

Heroin, morphine, fentanyl, methadone.

Question 2

What are weak-mid agonists?

Answer 2

Codeine, hydrocodone, oxycodone, tramadol.

Question 3

All agonists agonize which receptor?

Answer 3

Mu opioid receptor. Inhibits ascending transmission of nociceptive information from spinal cord dorsal horn; activates pain control circuits that descend from midbrain to spinal cord dorsal horn.

Question 4

Agonists: Indication

Answer 4

Management of moderate-to-severe pain, cough suppression, antimotility agents for treatment of diarrhea.

Question 5

Agonists: Side effects

Answer 5

N/V, depressed respiration, constipation, exacerbation of gall bladder disease (except meperidine), euphoria/tranquility/other mood alterations (modulated by nucleus accumbens), pupillary constriction (parasym. excitation), depressed cough reflex (direct effect on cough center in medulla), urinary retention (inhibition of urinary voiding reflex and increased tone of external sphincter), pruritus, tolerance and physical dependence.

Question 6

Agonists: Metabolism

Answer 6

Hepatic

Effect of given dose is less with the oral route (compared to parenteral route) because of variable but significant first-pass metabolism in liver.

Question 7

Codeine: Indications

Answer 7

Used for analgesic, antitussive, antidiarrheal properties. Less potent than morphine.

Question 8

Hydrocodone

Answer 8

Most frequently prescribed opiate in US; usually prescribed with weaker analgesic such as acetaminophen, ibuprofen, or aspirin.

Question 9

Fentanyl

Answer 9

100x more potent than morphine.

Used in anesthesia because short time to peak analgesic effect, rapid termination of effect after small bolus doses, and cardiovascular stability.

Mostly given via IV.

Question 10

Methadone

Answer 10

Relieves chronic pain, treats opioid abstinence and heroin addiction.

Methadone=Racemic mix of NMDA receptor antagonist and mu agonist. NMDA-receptor-antagonism prevents opioid tolerance.

Methadone can also be used to treat neuropathic pain.

Question 11

Meperidine

Answer 11

Synthetic opioid no longer used for pain control because of concerns over metabolite toxicity resulting in seizures. Unique among other opioids in that it does not constrict sphincter of Oddi. Drug of choice for gallbladder pain.

Question 12

Tramadol

Answer 12

Codeine analog; well-absorbed orally. Traditionally considered lower risk compared to other opioids.

Two severe adverse reactions: Seizures and serotonin syndrome.

Question 13

Agonists: Drug interactions

Answer 13

Depressant effects of some opioids may be exaggerated and prolonged by phenothiazines, MOA inhibitors, and tricyclic antidepressants.

Respiratory depression can be additive with alcohol and benzodiazepines.

Question 14

Partial agonists?

Answer 14

Buprenorphine
High affinity but low efficacy at mu receptor=partial agonist effect.
Also acts as kappa receptor antagonist.

Useful for analgesia, opioid abuse deterrence, detox, maintenance therapy.

Question 15

Mixed agonist-antagonists?

Answer 15

Nalbuphine

Competitive mu receptor antagonist; exerts analgesic actions as kappa receptor agonist.

Question 16

Antagonists

Answer 16

Naloxone and naltrexone

Reverse effects of mu receptor agonists in patients with respiratory depression. Increase in respiratory rate seen in 1-2 minutes.

Question 17

Nalbuphine is used especially to treat…?

Answer 17

Opioid-induced pruritus.

Question 18

Naloxone is used to treat…?

Answer 18

Opioid intoxication/overdose.

Question 19

Naltrexone is used to treat…?

Answer 19

Alcoholism

Question 20

Which of the antagonists has the shorter half-life?

Answer 20

Naloxone=Short half-life. May need to be re-dosed to prevent recurrence of opioid toxicity and respiratory depression.

Subcutaneous doses of naloxone precipitate mod-to-severe withdrawal syndrome (similiar to that seen after abrupt withdrawal of opioids).