Opioids

Question 1

Morphine (prototype)

Answer 1

1. Strong Opioid agonist, given orally/paraenterally,intrathecally, epidurally, rectally.
2. Binds to and stimulates all opiate receptors, high first past effects. Metabolism in liver (conjugated w/glucuronic acid), 3-metabolite can cause hyperalgesia and seizures, 6-metabolite is also active and can accumulate. Excretion in urine.
3. Opioid SE
4. Opioid interactions
5. Schedule 2

Question 2

Hydromorphone (Dilaudid)

Answer 2

1. Strong opioid agonist: oral/subQ/IV/IM/rectal administration
2. Morphine derivative, very strong analgesic (more potent than morphine and as effective).
3. SE same as other opioids.
4. Drug interactions same as with all opioids.
5. Metabolites don’t accumulate like morphine, less histamine release (less itching), useful in renal dysfunction, duration of action shorter than morphine.

Question 3

Methadone (Dolophine)

Answer 3

1. Strong Opioid agonist, potent mu agonist that also blocks NMDA receptors and inhibits reuptake of monoamines.
2. Longer t1/2 than morphine, tolerance/dependence occur more slowly than morphine.
3. Opioid SE
4. Opiod interactions
5. Used in maintenance therapy of heroin addicts and to decrease withdrawal symptoms (methadone withdrawal may be milder although longer than other opioids).

Question 4

Meperidine (Demerol)

Answer 4

1. Strong Opiod agonist: oral and paraenteral
2. Use 48 hrs or less only in healthy pts (t1/2 too short, metabolites cause anxiety and seizures, large doses tremor/muscle twitches/convulsions). Second line agent for acute pain. Normeperidine may also accumulate and cause seizures in pts w/renal failure.
3. Tachycardia and pupil dilation due to antimuscarinic effects, does NOT suppress cough, euphoria (significant addiction potential).
4. Do not use w/MAOIs!!! including phenelzine, selegiline, or linezolid (antibiotic)- 5-HT syndrome. Probably avoid TCAs and SSRIs too.
5. Blocks neuronal reuptake of 5HT in addition to mu agonist.

Question 5

Fentanyl (Sublimaze)

Answer 5

1. Strong Opioid agonist, 100x more potent than morphine, t1/2 and duration of action shorter than morphine/meperidine.
2. Used for short surgeries, often w/Midazolam. Used for induction/maintenance of gneral anethesia and to supplement regional/spinal analgesia. Preffered for anethesia over morphine-attenuates hemodynamic responses and maintains cardiac stability.
3. May cause truncal rigidity if given rapidly IV
4. Metabolized by CYP3A4 dont use with inhibitors (ketoconazole, itraconazole, HIV protease inhibitors, erythro/clarithromycin, diltiazem, nicardipine, verapamil).
5. Transdermal used for chronic pain, comes in lozenges/lollipops, used for premedication or to induce conscious sedation prior to diagnostic/therapeutic procedures.

Question 6

Alfentanil, Sufentanil, Remifentanil

Answer 6

1. Strong opioid agonist. Synthetic Opiate agonists, used primarily in anesthesia. IV or epidural.
2. Faster onset and shorter durations than fentanyl.
4. Alfentanil undergoes liver biotransformation via CYP3A4, drug interacts w/drugs that inhibit this enzyme.

Question 7

Heroin

Answer 7

1. Schedule I, not available for medical use.

2. Easily crosses BBB and metabolized to morphine. 10x potency of morphine, high abuse potential.

Question 8

Hydrocodone

Answer 8

1. Moderate to strong agonist, semisynthetic codeine derivative, moderate to severe pain. Oral, well absorbed. Schedule 2
2. Frequently combined w/other agents such as acetaminophen. Complex hepatic metabolism, portion is converted to hydromorphone by CYP2D6 (this metabolite responsible for some analgesia)
3. Homatropine, anticholinergic, included in subtherapeutic amts in some hydrocodone antitussives to discourage deliberate OD.
4. CYP2D6 inhibitors (SSRIs, quinidine)
5. Often combined w/acetaminophen: watch dosing.

Question 9

Oxycodone

Answer 9

1. Moderate to strong agonist, similar to hydrocodone and morphine. Used widely to control sever pain, also used in non-pain such as restless legs, tourrettes. Oral (immediate or controlled release)
2. Distributed to skeletal muscle, liver, GI, lungs, spleen, CNS, has been found in breast milk.
4. Requires CYP2D6 for activity, avoid inhibitors such as SSRIs.
5. Metabolism in liver, excretion in urine. Often combined with acetaminophen: watch dosing.

Question 10

Oxymorphone

Answer 10

1. Moderate to strong agonist. Moderate to severe pain.
2. Active metabolite of oxycodone, very potent, good when pts are on CYP2D6 inhibitors.
3. Long-acting form suggested as an alternative to XR oxycodone, waxy formulation difficult to crush and inject.

Question 11

Codeine

Answer 11

1. Moderate agonist, widely used as antitussive, analgesic for mild-moderate pain, much less effective than morphine.
2. Analgesic and addictive doses are much higher than antitussive. Does not bind to mu receptor so will not compete w/strong agonists. Must be metabolized by CYP2D6 for analgesic effect.
3. Be careful in using in children under 2.
4. frequently combined w/aspirin and acetaminophen: be careful of dosing.

Question 12

Pentazocine

Answer 12

1. Mixed agonist/antagonist, agonist at K, partial at mu, useful for moderate pain, oral/paraenteral.
2. Less sedation, respiratory depression and GI effects than other opioids (these effects mediated by mu).
3. dysphoria, CNS stim, hallucinations may occur, can precipitate withdrawal in opioid addicts.
4. Dont combine w/strong agonists.
5. Schedule 4

Question 13

Buprenorphine

Answer 13

1. Mixed: partial agonist at mu and possibly k.
2. Analgesic effects slightly less than morphine, abuse potential way less. Will act as antagonist in presence of agonist. Reduces drug craving in heroin addicts. Usually given injection but also effective subling/intranasal. Tablets combined w/naloxone (not absorbed subling) to prevent dissolving and injecting

Question 14

Tramadol

Answer 14

1. Multiple actions, approved for mild/moderate pain, weak mu agonist
2. inhibits NE/5HT reuptake, not completely inhibited by naloxone, equivalent in analgesia to codeine
3. good analgesia w/mild SE (dizziness/sedation/nausea/constipation).
4. Dosage adjustment required in pts w/renal or hepatic dysfunction. Combination with antidepressents may result in seizures, dont combine with TCAs, SSRIs, MAOIs may cause 5HT syndrome.
5. Schedule 4

Question 15

Tapentadol

Answer 15

1. Multiple actions, mu agonist.
2. Inhibits NE reuptake and stim a2 receptors, approved for moderate-severe pain, also for chronic/neropathic pain due to NE effects. XR form can be dosed twice daily.
3. N/V sedation
4. Schedule 2

Question 16

Dextromethorphan

Answer 16

1. Antitussive, not as good as codeine but available OTC
2. Less constipation than codeine, blocks NMDA: may potentiate analgesic effect of morphine.
3. Significant abuse among teens, can cause death if ingested in powdered form in excessive dose as well as causing brain damage, seizures, loss of consciousness, irregular heart beat
4. Can block neuronal uptake of 5HT, dont combine with MAOIs.

Question 17

Naloxone

Answer 17

1. Pure opioid antagonist, DOC for opioid OD.
2. High First pass metabolism, poor oral absorption, use paraenterally. Can reverse respiratory depression of opioids. Short duration of action, repeated dosing may be required.
3. Can precipitate withdrawal in addicts.
5. Sometimes included in combinations w/oral naracotics to prevent abuse. Low doses titrated to prevent adverse effects of IV or epidural opioids (nausea/vomitting/itching) while allowing analgesic effect.

Question 18

Naltrexone

Answer 18

1. Pure Opioid antagonist, orally effective, long acting
2. Used to prevent recovering addicts from getting “high” if they relapse. Opioid addict must first detox before use or it will precipitate withdrawal in addicts. Pt compliance is problem. Decreases cravings in recovering alcoholics.
3. Risk of hepatotoxicity.

Question 19

Nalmefine

Answer 19

1. Pure Opioid antagonist: approved for tx of opioid OD.
2. Appears similar to naloxone but has longer duration of action. used in chronic tx of alcoholism, less hepatotoxicity than naltrexone.