B-16. Semisynthetic and synthetic opiates Flashcards
Semi-synthetic opiates, strength of agonism
Semi-synthetic: all are phenanthrenes
Strong μ agonists:
Heroin - diacetylmorphine
Oxycodone
Weak-Intermediate μ agonists:
Dihydrocodeine
Mixed agonist / antagonists:
Nalbuphine
Buprenorphine
Antagonists:
Naloxone
Naltrexone
Synthetic opiates, strength antagonism
Synthetic:
Strong μ agonists: all are phenylpiperidines (exc. methadone)
Meperidine
Fentanyl; Al- / Su- / Remifentanil … (Fentanyl family consists of “Al, Sue and Remy”)
Methadone
Weak-Intermediate μ agonists: Dextromethorphan Diphenoxylate Loperamide Tramadol Tapentadol
Mixed agonist / antagonists:
Butorphanol
Pentazocine
Heroin Type of molecule? Metabolisation? Characteristics? Effects? DOA?
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 Type of molecule? Absorption? Indications? First pass effect?
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 -
Characteristics compared to morphine and codeine?
Indications?
Stronger than codeine, weaker than morphine
Indications: used as analgesic, antitussive (esp. in pleuritis)
Buprenorphine
MOA?
Kinetics (doa)
metabolism
MOA :
acts as a partial μ agonist and κ antagonist … (all “bu” drugs are partial μ agonists)
kinetics :
long DOA
Metabolism : sublingual admin to avoid first-pass transderm
Buprenorphine
Indications:
Breakthrough pain - sublingual
Chronic pain - transdermal
Opiate addiction - as “bridge” therapy; slow receptor dissociation → milder withdrawal symptoms
Nalbuphine
MOA
Side Effects
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
DOA
Indication
- semisynthetic μ atg; given orally;
DOA : 10 hr
Indication : used for treating opiate addiction
Naloxone
DOA;
indication
semisynthetic μ atg
DOA 1-2 hour ;
parenteral;
indication : used for opiate overdose (short DOA → repeat doses)
synthetic opioids groups.
diphenylheptan Phenylpiperidines Morphinans Benzomorphans Others
synthetic opioids
diphenylheptans
Methadone
synthetic opioids
Phenylpiperidines
Fentanyl
Meperidine (Pethidine)
Diphenoxylate
synthetic opioids
Morphinans:
Dextromethorphan
Butorphanol
synthetic opioids
Benzomorphans
Pentazocine
synthetic opioids
others
Tramadol
Tapentadol
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
Meperidine (Pethidine)
moa
indication
side effects
trade name Demerol
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:
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
Fentanyl
Analogs
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
Loperamide
Diphenoxylate
antidiarrheal; low BBB entry; combo w/ atropine (trade name Reasec) for watery diarrhea
Loperamide
antidiarrheal; not absorbed from GI tract
Dextromethorphan
MOA
side efffects
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
Indications:
Butorphanol
- a μ and κ partial agonist … (all “bu” drugs are partial μ agonists)
Indications:
migraine as an intranasal spray; moderate pain - parenteral admin
Benzomorphans:
indications :
Pentazocine - a κ agonist and μ antagonist
Indications: pain - but has a “ceiling effect” → above certain doses no additional effect is achieved
Tramadol
MOA:
SFX:
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
SFX:
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
Opiate Addiction Treatment
Naltrexone
pt first goes through withdrawal, then takes naltrexone as an antagonist
2 theories:
give original drug of abuse with naltrexone → disconnect drug of abuse from desired effect
give naltrexone alone → if pt relapses, drug of abuse does not have effect
Opiate Addiction Treatment
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
Opiate Addiction Treatment
UROD
ultra-rapid opioid detoxification → anesthetize patient + administer antagonist
Other drugs:
Clonidine
β Blockers
BZDs
Clonidine - sedative, antihypertensive
releases β endorphin → diminished withdrawal symptoms
β Blockers - less tremor, anxiety, htn
BZDs - to ↓ anxiety
