Specific Opioid Agents

Question 1

Moving on to the specific properties of each opioid. First up is morphine (strong agonist), What are some features?

Answer 1

High affinity = mu receptors

Low affinity = kappa and omega receptors

Question 2

2nd are hydromorphone and oxymorphone, what are some features?

Answer 2

Strong agonist

–used in treating severe pain

Question 3

3rd is Heroin (Strong agonist), what are some features?

Answer 3

Hydrolyzed to 6-monoacetylmorphine (6-MAM) which is hydrolyzed to morphine

• -both 6-MAM and heroin are more liposoluble therefore enter the brain more readily
• -excreted in urine

Question 4

4th is Meperidine (Strong agonist) ,what are some features?

Answer 4

Mu receptor agonist
No longer used in chronic pain due to metabolite toxicity
Pupillary constriction
Significant antimuscarinic effects, which may be contraindication if tachycardia would be a problem
Negative inotropic action on the heart

Question 5

What happens when large doses of Merperidine is given?

Answer 5

Tremors, Muscle twitches, dilated pupils and hyperactive reflexes and convulsions

• -due to accumulation of the metabolite normeperidine which has a half life of 15-20 hours compared with 3 hours for merperidine
• -eliminated by both kidney and liver therefore failure of either of these increases toxicity

Question 6

What are the drug interactions for merperidine?

Answer 6

Serotonin Syndrome: delirium, hyperthermia, headache, hyper or hypotension, rigidity, convulsions, coma and death
–ability of meperidine to block neuronal reuptake of serotonin therefore serotonergic overactivity
Avoid serotonergic agents such as MAOI

Question 7

5th drug is Fentanyl (Strong agonist), what are some features?

Answer 7

Mu agonist
Rapid onset and short duration of action
100x more potent than morphine
Used in chronic pain (through transdermal patches)
Oral transmucosal formulation is approved for pain in cancer patients taking strong opioids already
Buccal tablet is also available

Question 8

6th drug is Methadone (Strong agonist), what are some features?

Answer 8

Less euphoria and longer duration of action than morphine but just as potent
Mu receptor agonist, NMDA receptor antagonist and serotonin and NE reuptake inhibitor
Dose related QT interval prolongation, torsades de pointes and death have been found

Question 9

Explain methadone substitution

Answer 9

Managing opioid withdrawal for addicted patients
—due to its long half life and less sedation
Due to the long half life of methadone the abstinence syndrome is prolonged but less severe than that from a shorter acting opiate such as heroin.

Question 10

What is the primary use of methadone?

Answer 10

Relief of chronic pain, treatment of opioid abstinence syndromes and treatment of heroin users

Question 11

A related compound to methadone, Levomethadyl Acetate, has been found, what does this drug do?

Answer 11

Longer half life than methadone

–used for detox

Question 12

The 7th and final strong agonist is Levorphanol what are some features?

Answer 12

Closely parallel effects of morphine

Question 13

Next set of drugs are the mild to moderate agonist. First up are codeine, oxycodone and hydrocodone. what are some features?

Answer 13

Less efficacious than morphine
–rarely used along but in combo with aspirin or acetaminophen
Codeine has low affinity for opioid receptors
-the analgesic effect of codeine is due to its conversion to morphine by CYP26D
–antitussive effect may involve distinct receptors that bind to codeine

Question 14

The other mild to moderate agonist is tramadol, what are some features?

Answer 14

Weak mu agonist
NE and serotonin reuptake inhibitor
Neuropathic Pain
Increased risk of seizures in patients with a seizure disorder and those taking seizure medications
Use of tramadol with other serotonergic drugs should be avoided due to risk of serotonin syndrome

Question 15

Next set of drugs are the mixed agonist-antagonist. What are some general features?

Answer 15

Potent analgesics in opioid-naive patients but precipitate withdrawal in patients who are dependent
Tx: mild to moderate pain (poor choice in patients with severe pain due to ceiling effect)
Developed to reduce addiction potential of the opioids while retaining analgesic potency of drugs

Question 16

The mixed agonist-antagonist drugs are?

Answer 16

Pentazocine: kappa agonist and mu antagonist/partial agonist
Butorphanol: kappa agonist and mu antagonist/partial agonist
Nalbuphine: kappa agonist and mu antagonist
—use of all three is associated with psychotomimetic effects
Buprenorphine: partial mu agonist and kappa antagonist

Question 17

What is buprenorphine used for?

Answer 17

Management of opioid addiction

• -followed by maintenance therapy with a combo of buprenorphine and naloxone
• -psychotomimetic effects are uncommon

Question 18

Care should be taken not to administer any partial agonist or drug with mixed opioid receptor actions to patients receiving what drug?

Answer 18

pure agonist drugs
–because of the unpredictability of both drugs effects (reduction of analgesia or precipitation of an explosive abstinence syndrome)

Question 19

Finally are the opioid antagonist. Naloxone and Naltrexone, what are some features?

Answer 19

High affinity for mu receptors
Low affinity for omega and kappa receptors
–can reverse the action of agonist at omega and kappa receptors
Naloxone: tx of acute opioid overdose
Naltrexone: longer duration of action therefore used as maintenance drug for addicts. Also used to decrease craving for alcohol in chronic alcoholics

Question 20

Next set of drugs are the antitussives, dextrometorphan and codeine. What are some features?

Answer 20

Receptors for antitussive effects are different than opioid action receptors
Use in caution in patients taking MAOI
Codeine: needs to be used a lower dose
Dextrometorphan: no analgesic effects therefore free of addictive properties and is less constipation

Question 21

Lastly are drugs we have touched on before the antimotility agents, Diphenoxylate and Loperamide. What are some features?

Answer 21

Opioid agonist used in the treatment of diarrhea
Diphenoxylate: no analgesic properties at standard doses. Higher doses can see CNS effects
–commercial preparation contain atropine to discourage overdose
Loperamide: does not cross the BBB and no analgesic properties.