Opioids

Question 1

3 major opioid receptors
How do they work?
Which one is clinically useful. What are the effects?

Answer 1

Delta, kappa, mu (clinically useful)
All are G protein-coupled receptors
Mu –> analgesia, euphoria, respiratory depression, miosis, and constipation.

Question 2

Analgesic effects of opioids

Answer 2

No ceiling effect for full agonists. Do not alter pain threshold of nerves nor conductance, but rather changes the perception of pain and emotional response to pain.

Question 3

Adverse effects of opioids

Answer 3

Respiratory depression, sedation, constipation, nausea / vomiting, bradycardia (cholinergic effect), puririts / orthostatic hypotension (histamine effect), decreased renal blood flow, decreased libido / erection / amenorrhea / infertility (due to decreased LH / testosterone)

Question 4

Smooth muscle effects of opioids (4)

Answer 4

• Contraction of biliary tract smooth muscle
• Increased ureteral and bladder sphincter tone
• Decreased uterine tone
• Miosis is characteristic of all opioids except meperidine, which has muscarinic blocking action. Pinpoint pupils is a red flag for opioid overdose

Question 5

Withdrawal sxs of opioids
How long do they last?
How do you prevent withdrawal?
What treats the autonomic effects of withdrawal?

Answer 5

• Flu-like sxs: Nausea, diarrhea, coughing, lacrimation, yawning, sneezing, rhinorrhea, diaphoresis, twitching muscles, abdominal and muscle pain / cramps, hot and cold flashes, and piloerection
• Usually resolve after 5-14 days w/o treatment
• Taper dose by 10-20% every 1-2 days to avoid withdrawal sxs
• Clonidine (a2 agonist; decreases NE release) can be used to treat autonomic hyperactivity sxs

Question 6

Morphine
Use
Mechanism
Dosing
Adverse rxns

Answer 6

• Use – analgesic used for moderate / severe pain, preop sedation, and supplement to anesthesia. DOC for MI and cancer pain. Analgesic during labor. Some cough suppression. Reduces pulmonary edema in LVHF by decreasing preload (decreased venous tone) and afterload (decreased TPR)
• Mechanism – Full agonist at mu receptors. Weak agonist at delta and kappa receptors.
• Dosing – no predictable relationship b/w serum concentrations and analgesic response. Must ask px what their pain is like.
• Adverse rxns – see above

Question 7

Codeine
Use
Mechanism
Pharmacokinetics
Adverse rxns

Answer 7

• Use – Antitussive agent. May be used in combo w/ acetaminophen for mild / moderate pain.
• Mechanism – weak agonist at mu and delta receptors.
• Pharmacokinetics – O-demethylation of codeine into morphine by CYP2D6 is essential for analgesic activity to work. CYP2D6 has high genetic variability, so some pxs may need higher / lower doses
• Adverse rxns – Less analgesic, respiratory depressive, and other side effects compared to morphine.

Question 8

Buprenorphine
Brand name
Use
Mechanism
Adverse rxns

Answer 8

• Suboxone
• Use – IV form is 30x more potent than morphine for moderate / severe pain. Sublingual form is used for treatment of opioid dependence (combined w/ naloxone so IV route does not produce high)
• Mechanism – mixed. Partial agonist at mu, antagonist at kappa. Ceiling effect is present, reducing risk of overdose, abuse, and toxicity
• Adverse rxns
• Normal rxns seen above
• Antagonism of kappa receptor → anxiety, insomnia, confusion, disorientation, and depersonalization

Question 9

Naloxone
Brand name
Use
Mechanism
Pharmacokinetics

Answer 9

• Narcan
• Use – DOC for opioid overdose. Also treats opioid-induced constipation and respiratory depression.
• Mechanism – competitive antagonist at all opioid receptors. No effect in people who have not received opioids.
• Pharmacokinetics – IV form only. Short acting (45 min), so pxs may need multiple doses.

Question 10

Meperidine
Use
Mechanism

Answer 10

• Use – 2nd line for acute (not chronic) pain

* Mechanism – Mu and kappa agonist

Question 11

Tramadol
Use
Mechanism

Answer 11

• Analgesic effects

* Mechanism – Synthetic analog of codeine. Weak mu receptor agonist.

Question 12

Hydrocodone use

Answer 12

Antitussive and analgesic

Question 13

Mechanism of methadone

Answer 13

Full mu receptor agonist w/ long half-life

Question 14

Dextromethorphan use

Answer 14

Antitussive

Question 15

Loperamide
Brand name
Use

Answer 15

Imodium

Antidiarrheal effects

Question 16

Fentanyl use

Answer 16

Induction / maintenance of general anesthesia

Question 17

Drugs used for cough suppression

Answer 17

Codeine and dextromethorphan