Test 2 Narcotic Analgesics Flashcards
Endogenous Opioid peptide families
- Prepro-opiomelanocortin
- Preproenkephalin
- Preprodynorphin
- Prepronociceptin
Endogenous Opioid peptides
- Leu-enkephalin
- Dynorpin A
- Met-enkephalin
- Beta-endorphin
- Nociceptin
Opioid Receptor Subtypes
- MOP (µ)
- KOP (κ)
- DOP (δ)
- NOP = Nociceptin/Orphanin FQ peptide receptor
What is the most dangerous effect of opiates?
respiratory depression
Opioid Overdose Triad
- coma
- respiratory depression
- miosis (dose dependent, no tolerance, marker of opioid use)
Common Opioid Adverse Effects
- N/V
- euphoria
- constipation
- sedation
- orthostatic hypotension
- bradycardia
- fainting
- sensitivity reactions
- biliary spasm
- urinary retention
- hyperalgesia
define endogenous opioids
molecules found in the brain that produce their actions through one of the four opioid receptor subtypes
What are the types of MOA of opioid analgesics?
- indirectly inhibiting tonic release of GABA
- directly inhibiting release of neurotransmitters
- bind to mu receptors
MOA: indirectly inhibiting tonic release of GABA
- inhibits descending analgesic pathway
- GABA is a brake that is always on the descending analgesic pathway
- removing the brake = mu opioids allow the descending analgesic pathway to work; also activates the release of NE and 5HT
MOA: directly inhibiting release of neurotransmitters
- ex. Substance P, glutamate, CGRP which activate ascending pain pathways at the level of the spinal cord
MOA: bind to mu receptors
- this alters the perception of pain
limitations to naloxone
- short acting
- less potent than fentanyl and carfentanil
Analgesic Tolerance
Decrease in amount of pain relief over time with a given dose
Physical Dependence
presence of withdrawal symptoms when drug is stopped or antagonist added
symptoms of withdrawals
- diarrhea
- dilated pupils
- anxiety
- hyperventilation
- N/V
- fevers / chills
- increased BP, HR
- muscle aches
- appetite loss
- watery eyes
- runny nose
- restlessness / hostility
Psychological Dependence / Addiction
Characterized by drug-seeking behavior in addition to withdrawal syndrome
Which drug(s) have these drug-specific adverse effects: ↓ seizure threshold
- meperidine metabolite: normeperidine
- morphine metabolite: M3G
Which drug(s) have these drug-specific adverse effects: precipitate opioid withdrawal in opioid-dependent patient
- buprenorphine
- pentazocine
- butorphanol
- nalbuphine
- naloxone
- naltrexone
Which drug(s) have these drug-specific adverse effects: prolonged Q-T intervals
methadone
Which drug(s) have these drug-specific adverse effects: tendency to produce dysphoria
- pentazocine
- butorphanol
- nalbuphine
Which drug(s) have these drug-specific adverse effects: diuresis
- butorphanol
- nalbuphine
How different metabolizer phenotypes alter efficacy and adverse effect potential of tramadol.
- poor / intermediate metabolizers: will not be converted to active compounds
How different metabolizer phenotypes alter efficacy and adverse effect potential of codeine.
- Pro-drug: 5-10% bio-transformed by CYP2D6 to morphine and M6G; 80% to C6G
- poor / intermediate metabolizers: will not be converted to active compounds
- ultra rapid metabolizers: pro-drug will be metabolized quickly to produce toxicity
genetic variability of metabolizers
- Poor metabolizers: limited or inactive enzyme
- Intermediate metabolizers: partially deficient
- Extensive metabolizers: considered normal
- Ultra rapid metabolizers: excess activity
morphine metabolism
- by UGT
- 90% to M3G (non-opioid)
- 10% to M6G (active opioid; more potent than morphine