Pharm (Comp 3)

Question 1

Endogenous opioids

Examples and MOA

Answer 1

Endorphins, Enkephalins, Dynorphins

mu, delta, and kappa reptor agonists

Question 2

Effects mediated by mu opioid receptor

Answer 2

• Analgesia
• euphoria
• physical dependence
• bradycardia
• GI transit slowing
• respiratory depression
• Modulator of hormone and NT release

Question 3

Effects mediated by kappa opioid receptor

Answer 3

• spinal analgesia
• miosis
• sedation, psychomimetic effects
• diuresis
• slowed GI

Question 4

Effects mediated by delta receptor

Answer 4

• Dysphoric effects
• Analgesia
• Modulator of hormone and NT release

Question 5

Strong agonist opioids

Answer 5

Morphine, methadone,

heroin, meperidine, fentanyl

Question 6

Partial/mixed opioid agonist

Answer 6

Pentazocine, buprenorphine

Question 7

Weak opioid agonists

Answer 7

codeine, hydrocodone

Question 8

Morphine, Hydromorphone, Oxymorphone

MOA and action/use

Answer 8

• Opioid receptor agonist (miu, kappa, and delta)

- Use: Alter mood/anxiolytic, sedation, depress pain reaction

Question 9

Morphine, Hydromorphone, Oxymorphone

Toxicity

Answer 9

• Respiratory depression, vasodilation
• Nausea/vomiting, constipation, Biliary colic
• Itching, hypotension, bronchoconstriction (H1)
• Miosis
• Increased prolactin release, inhibition of LH release
• Tolerance, withdrawal, physical dependence, addiction
• Increases intracranial pressure
• Not in pregnancy. Meperidine preferred in labor.

Question 10

Codeine, Hydrocodone

MOA and use

Answer 10

MOA: Weak opioid receptor
agonist; Metabolized to
morphine

Use: Moderate pain treatment, Anti-tussive

Question 11

Codeine, Hydrocodone

Toxicity

Answer 11

• Nausea, vomiting
• drowsiness, dizziness
• constipation
• Combined with NSAIDs or acetaminophen
• Codeine –> CYP2D6 metabolism. Genetic polymorphisms may increase toxic effects.

Question 12

Methadone

MOA and Use

Answer 12

• Opioid receptor agonist;
  antagonism on NMDA receptor
• Use: Avoidance of
  the withdrawal reaction in opioid dependence patients
• Long t1/2 allows a slow taper

Question 13

Methadone

toxicity

Answer 13

Accumulates with repeated doses, which can cause respiratory depression.

Question 14

Meperidine (Demerol)

MOA and use

Answer 14

Opioid receptor agonist; Antimuscarinic effects; Serotonin effects

Use: Like morphine, but less analgesia

• Good in obstetrics: less neonatal respiratory
  depression. Inc contractions

Question 15

Meperidine

Toxicity

Answer 15

• Normeperidine (metabolite) can induce CNS stimulation esp. renal dysfunction pts
• Serotonin syndrome with SSRIs
• Drug interactions with monamine oxidase inhibitors (MAOIs)
• Hyperrexia coma

Question 16

Fentanyl, Alfentanil, Sufentanil, Remifentanil

MOA and Use

Answer 16

• Opioid receptor agonist
• 100x more potent than morphine
• IV analgesic. Used for extra-anesthetic analgesia.

Question 17

Fentanyl, Alfentanil, Sufentanil, Remifentanil

Toxicity

Answer 17

Respiratory depression

Available as transdermal (patch) and transmucosal (lozenge) formulations.

Question 18

Heroin/Diacetylmorphine

MOA and Use

Answer 18

• Opioid receptor agonist
• Semisynthetic is
  metabolized to morphine for action.
• Lipid soluble and crosses blood brain barrier quickly

Question 19

Heroin/Diacetylmorphine

Toxicity

Answer 19

• Super CNS action
• analgesia
• Euphoria
• dependence and addiction
• Illicit use only

Question 20

Tramadol

MOA and Use

Answer 20

• Mu receptor agonist. NE and 5-HT reuptake inhibitor.
• Weak analgesic, neuropathy
  Little opioid toxicities.
• High bioavailability, active metabolite.

Question 21

Tramadol

Toxicity

Answer 21

• May cause hypertensive crisis with MAOI

- Often combined with acetaminophen (added liver toxicity)

Question 22

Diphenoxylate, Loperamide

MOA

Answer 22

• Weak mu or kappa agonists

- Antidiarrheal

Question 23

Diphenoxylate, Loperamide

Answer 23

• Diphenoxylate –> combined with atropine to reduce abuse potential
• Loperamide –> no CNS effects, does not cross BBB (Imodium, OTC use)

Question 24

Opioid drug interactions

Answer 24

CNS depression with:

• ethanol
• antipsychotics
• tricyclic antidepressants
• sedative-hypnotics (eg. benzos)
• antihistamines

Question 25

Opioid OD S&S, Treatment

Answer 25

- Pupillary constriction - Comatose state - Hypotension - Bradycardia - Respiratory depression Administer naloxone and ventilation.

Question 26

Serotonin Syndrome - Drugs involved - S&S - Treatment

Answer 26

- SSRIs, TCAs, meperidine, dextromethorphan, St. John’s Wort, linezolid, “triptans” (2 of these combined together) Symptoms: rigidity, hyperthermia, myclonus, delirium, hypertension, tachycardia, GI symptoms - within 24 hrs of taking the two drugs Treatment: Benzodiazepines, cyproheptadine, ventilation

Question 27

Naloxone | MOA and Use

Answer 27

- Antagonist at all opioid receptors. IV use. | - Rapidly antagonizes all opioid effects. Precipitates withdrawal in dependent users.

Question 28

Naloxone | Toxicity

Answer 28

- Fast onset and short duration of action | - Repeated administration needed until opioid is cleared from the body.

Question 29

Naltrexone | MOA and Use

Answer 29

- Like Naloxone but 5x more potent; up to 72 hr duration. - Binds all opioid receptors. Oral use. - Maintenance therapy; May reduce alcohol cravings in alcoholics

Question 30

Naltrexone | Toxicity

Answer 30

Caution in hepatic impaired pts.

Question 31

Methylnaltrexone | MOA and Use

Answer 31

- μ opioid receptor antagonist | - Treats opioid-induce constipation

Question 32

Methylnaltrexone | Toxicity

Answer 32

- Does not cross BBB (compound is methylated) | - Targets GI tract

Question 33

Butorphanol, Buprenorphine, Nalbuphine, Pentazocine | MOA of each

Answer 33

- Butorphanol (κ agonist) - Buprenorphine (partial μ agonist, κ antagonist). Slow dissociation from μ receptor. - Nalbuphine and Pentazocine (κ agonist, μ antagonist)

Question 34

Butorphanol, Buprenorphine, Nalbuphine, Pentazocine | Use

Answer 34

- Analgesia without euphoria, less chance for dependence. - Buprenorphine used in some rehabilitation programs. Slow dissociation from the mu receptor

Question 35

Butorphanol, Buprenorphine, Nalbuphine, Pentazocine | Toxicity

Answer 35

- Sim to morphine - Administering these drugs with a pure agonist (eg. morphine) can reduce efficacy of the agonist or precipitate withdrawal. - Pentazocine can increase psychomimetic effects (kappa mediated)

Question 36

Opioid withdrawal symptoms

Answer 36

- Yawning, hyperventilation - Lacrimation, piloerection, mydriasis - Fever, chills, hyperthermia - muscular aches, vomiting - anxiety and hostility