Narcotic Analgesics Flashcards
Name the 3 main families of molecules derived from precursor opioid peptides.
- beta-endorphins from preproopiomelanocortin
- enkephalins from preproenkaphalin
- dynorphins from preprodinorphin
What do Opioid Analgesics do? Where and How do Opioid Analgesics work?
WHAT: inhibit propagation of pain signals, alter emotional perception of pain, elevate pain threshold
WHERE: peripheral nocieptive terminals, spine, brain
HOW: on μ, δ and κ GPCRs
What are the effects of μ GPCR activation?
• Supraspinal, spinal and peripheral analgesia
• Respiratory depression
• Miosis
• Reduced GI motility
• Euphoria
• Sedation
• Physical dependence
What are the effects of δ GPCR activation?
• Spinal analgesia
• Respiratory depression
• Reduced GI motility
• Euphoria
What are the effects of κ GPCR activation?
• Spinal and peripheral analgesia
• Miosis
• Reduced GI motility
• Dysphoria
• Sedation
• Physical dependence
What are the clinical uses of Opioid Analgesics?
• Analgesia (codeine, morphine, pethidine)
• Anaesthetic adjuvant (fentanyl)
• Cough suppressant (codeine)
• Anti-diarrhoeal (diphenoxylate)
What are the principles guiding Opioid Analgesic dosage?
• lower dose for elderly, nociceptive pain, continual maintenance of pain relief
• higher dose for neuropathic pain
• start at low doses and titrate to analgesia effect
• if there is no analgesia in a naive patient, pain syndrome may be unresponse to opioid therapy
• if there is no analgesia in a chronic pain patient, titrate further to reach threshold dose
Describe the distinguishing features of the strong opioid agonists.
•morphine: strong μ agonist, weaker δ and κ agonist
• methadone and fentanyl: strong μ agonist only, methadone is long acting and fentanyl is short acting
• pethidine: strong μ agonist, N-methylated to norpethidine in liver (hallucinogenic and convulsant effects at high dose), causes restlessness, antimuscarinic
all have high maximum analgesic activity and have high liability for addiction and abuse.
Describe the distinguishing features of the moderate opioid agonists.
• Codeine: weak μ and δ agonist, low max analgesia and moderate liability for addiction
• Dihydrocodeine: similar to codeine, 10% of population converts to morphine, 10% of population have reduced analgesic effects due to lacking demethylating enzyme
• Tramadol: weak μ agonist, weak inhibitor of 5-HT and noradrenaline reuptake, analgesic effects can be blocked by onddansetron
Describe and distinguish Naloxone, Naltrexone, and Nalmefene.
• all opioid antagonists (strongest μ antagonism, also have κ and δ antagonism)
• used to counteract opioid overdose
• use with caution in opioid dependency due to potentially fatal withdrawal syndrome
• Naloxone is short acting IV, Naltrexone is long acting oral, Nalmefene is long acting IV
Name the 10 adverse effects of opioid analgesics.
- Respiratory depression
- Nausea/vomiting
- Drowsiness
- Constipation
- Miosis
- Urinary retention
- Postural hypotension and bradycardia
- Immunosuppressant
- Histamine release
- Withdrawal
Explain how use of opioid analgesics may lead to respiratory depression.
Actions in the nucleus tractus solitarius and nucleus ambiguus reduce CO2 and H+ responses, suppressing voluntary breathing. This can be lethal in overdosed respiratory disease, hepatic dysfunction, CNS depressant combination, and young children.
Why may opioid analgesic use cause postural hypotension and bradycardia?
Due to actions in cardio regulatory nuclei in medulla.
Which opioid analgesic triggers histamine release?
Morphine
State the withdrawal effects of opioid analgesics.
addiction and tolerance can lead to physical dependence and overdose, including anxiety and irritability, nausea and vomiting, chills and hot flushes, abdominal cramps and diarrhoea, joint pain, lacrimation and rhinorrhea
