B-16. Semisynthetic and synthetic opiates Flashcards
Semi-synthetic opiates
all are phenanthrenes
- Strong μ agonists:
a. Heroin - diacetylmorphine
b. Oxycodone - Weak-Intermediate μ agonists:
a. Dihydrocodeine - Mixed agonist / antagonists:
a. Nalbuphine
b. Buprenorphine - Antagonists:
a. Naloxone
b. Naltrexone
Synthetic opiates
- Strong μ agonists: all are phenylpiperidines (exc. methadone)
a. Meperidine
b. Fentanyl; Al- / Su- / Remifentanil … (Fentanyl family consists of “Al, Sue and Remy”).
c. Methadone - Weak-Intermediate μ agonists:
a. Dextromethorphan
b. Diphenoxylate
c. Loperamide
d. Tramadol
e. Tapentadol - Mixed agonist / antagonists:
a. Butorphanol
b. Pentazocine
Heroin
a phenanthrene. diacetylmorphine. metabolized to morphine via tissue esterases.
Highly lipophilic → enters brain suddenly in high concentration.
Strong euphoric effect.
long-lasting (2 hour DOA).
no medical use - a drug of abuse
Oxycodone
phenanthrene derivative; similar to morphine, better oral absorption.
Indications:
- cancer-related pain and cough.
- other moderate-severe pain.
Often combined with atg naloxone (oral → high first-pass effect; only works in GI to prevent constipation)
Dihydrocodeine
stronger than codeine, weaker than morphine.
Indications: used as analgesic, antitussive (esp. in pleuritis).
Buprenorphine (MOA, kinetics, indications)
MOA: acts as a partial μ agonist and κ antagonist … (all “bu” drugs are partial μ agonists)
Kinetics: long DOA
sublingual admin to avoid first-pass metab; transdermal patch for chronic tx
Indications:
- Breakthrough pain - sublingual
- Chronic pain - transdermal
- Opiate addiction - as “bridge” therapy; slow receptor dissociation → milder withdrawal symptoms
Nalbuphine (MOA, SE, indications)
MOA: acts as a κ agonist and partial μ agonist … (all “bu” drugs are partial μ agonists)
κ receptor not involved in respiratory depression → respiratory dep. effects max out before lethality
Less euphoria → less dependence
Side Effects:
- Dysphoria - κ agonist effect
- Sedation
- Sweating
Indications:
- Pain - moderate to severe
- Surgery - in combo with other anesthetics + for pre- and post-op pain
- Obstetric - analgesia during labor/delivery
Naltrexone
semisynthetic μ atg; given orally; 10 hr DOA; used for treating opiate addiction.
Naloxone
semisynthetic μ atg; 1-2 hour DOA; parenteral; used for opiate overdose (short DOA → repeat doses).
Methadone
a diphenylheptane.
Good oral availability; accumulates in tissues → slow elimination → easier to discontinue due to weaker withdrawal sx.
Used for tx of opiate addiction
Phenylpiperidines (list)
- Meperidine (Pethidine)
- Fentanyl
- Diphenoxylate
- Loperamide
Meperidine (Pethidine) - trade name Demerol (indications, SE)
similar to morphine but with less urinary retention, uterine relaxation, and sedation
no constipation or antitussive effect; no meiosis → OD harder to detect.
Indications:
- Obstetrics - previously the #1 opioid analgesic for L&D; less now due to toxic metabolite + sfx.
- Diverticulitis - preferred analgesic due to effect of ↓ GI luminal pressure.
Side Effects:
- Antimuscarinic effects - dry mouth, visual disturbances, tachycardia, no meiosis
- With MAOI → serotonin syndrome
- metabolite norpethidine can cause seizures
Fentanyl (kinetics, indications, analogs)
100x analgesic effect of morphine; strongest clinical opioid.
Severe respiratory depression effect!
Kinetics: DOA only 30-60 mins → IV, transdermal patch, sublingual pill.
Indications:
- Neuroleptanalgesia - given IV in combo with antipsychotic (droperidol)
- Surgical analgesia - IV
- Chronic Cancer Pain - transdermal patch
- “Breakthrough” pain - any acute increase in pain in cancer pts; as sublingual pill
Analogs -
Sufentanil + Alfentanil - shorter DOAs; Remifentanil - shortest DOA (1-10 mins)
* Remember Sue, Al and Remy as the members of the Fentanyl family; longest name = shortest DOA
Diphenoxylate
antidiarrheal; low BBB entry; combo w/ atropine (trade name Reasec) for watery diarrhea.
Loperamide
antidiarrheal; not absorbed from GI tract
Morphinans (list)
- Dextromethorphan
2. Butorphanol
Dextromethorphan (MOA, indications, SE)
MOA: SERT/NET inhibitor; sigma-1 agonist, μ agonist
* also NMDA-R non-competitive atg; nAChR negative allosteric modulator; 5-HT/H1/α-2/M ligand
Indications: cough suppression
Side Effects: many, but not listed in slides… see Wiki
Butorphanol (MOA, indications)
MOA: μ and κ partial agonist …
(all “bu” drugs are partial μ agonists).
Indications:
- migraine as an intranasal spray.
- moderate pain - parenteral admin
Benzomorphans: Pentazocine
MOA: κ agonist and μ antagonist.
indications: pain (but has a “ceiling effect” → above certain doses no additional effect is achieved).
Other opiates (list)
- Tramadol
2. Tapentadol
Tramadol (MOA, indications, SE)
MOA: weak μ agonist; weak NE reuptake inhibitor; enhances 5HT release
less respiratory depression; low abuse potential
Indications:
Mild-Moderate Pain - when NSAIDs not sufficient
SE:
nausea/vomiting, dizziness, sweating
Seizures - with high doses
Serotonin syndrome - w/ MAOI, TCA, SSRI co-admin
Tapentadol (MOA, indications)
MOA: acts as a μ agonist and NET inhibitor → similar effect to tramadol
Indications:
Diabetic Neuropathy - NET inhibition is helpful in neuropathic pain conditions
Other musculoskeletal pain
Opiate Addiction Treatment
- Methadone - good for oral admin; withdrawal is slower/less severe.
- Naltrexone - pt first goes through withdrawal, then takes naltrexone as an antagonist
- 2 theories:
a. give original drug of abuse with naltrexone → disconnect drug of abuse from desired effect
b. give naltrexone alone → if pt relapses, drug of abuse does not have effect
- 2 theories:
- Buprenorphine - bridge therapy; replace original drug with partial agonist to decrease craving, withdrawal without strong euphoria
* slow elimination → eventual withdrawal is easier; less euphoria / resp depression than methadone - UROD - ultra-rapid opioid detoxification → anesthetize patient + administer antagonist
- Other drugs:
a. Clonidine - sedative, antihypertensive- releases β endorphin → diminished withdrawal symptoms
b. β Blockers - less tremor, anxiety, htn
c. BZDs - to ↓ anxiety
- releases β endorphin → diminished withdrawal symptoms
