Narcotic Opioid Analgesics Flashcards
What chemical class is Morphine, Codeine (& Thebaine) classified under?
Phenanthrenes
What are the 3 major families derived from precursors?
1) Beta-endorphin
2) Enkephalins
3) Dynorphins
- Previously known collectively as endorphins, now generally known as opioid peptides
Psychophysiology of pain
Subjective!
- Brain has modulatory circuits to regulate perception of pain
Pain to brain: i) Pri afferent neurone ii) Spinothalamic tract
Brain to pain: Efferent pathway
Role of opioid analgesia on endogenous mechanisms
1) Inhibit propagation of pain signals
2) Alter emotional perception of pain
3) Elevate pain threshold
Sites where opioid analgesics regulate pain
- Peripheral nociceptive terminals (Peripheral analgesia)
- Spine (Spinal analgesia)
- Brain (Supraspinal analgesia)
3 major opioid receptors types
Mu, Delta, Kappa
GPCRs
What are the dose-dependent effects? (From low-high dose)
- Peripheral analgesia
- Spinal analgesia
- Cough suppression
- Supraspinal analgesia
- Sedation
- Reduced gut motility
- Euphoria
- Pupil constriction
- Constipation
- Dysphoria
- Severe sedation
- Respiratory depression
Dosing features of Opioid Analgesics
- Elderly require lower dose
- Neuropathic pain require higher dose > nociceptive pain
- Lower doses for continuous maintenance of pain relief (chronic pain relief)
- Started at low dose & carefully titrated
- Failure of at least partial analgesia with incremental dosing may indicate that pain syndrome is unresponsive
- For some pts with chronic pain, opioids do not exert an appreciable analgesic effect until a threshold dose has been achieved
Opioid agonists for analgesia
Codeine, morphine, pethidine
Opioid agonists for anaesthetic adjuvant
Fentanyl
Opioid agonists for cough suppressant/antitussive
Codeine
Opioid agonists for anti-diarrhoeal
Diphenoxylate
[Strong Opioid Agonist] Morphine
Use: High maximum analgesic efficacy
- Strong Mu agonist (weaker beta & kappa agonist)
- High liability for addiction/abuse
[Strong Opioid Agonist] Methadone & Fentanyl
Use: High maximum analgesic efficacy
- -> Fentanyl (Short-acting) : Anaesthetic adjuvant
- -> Methadone (Long-acting) : Plasma t1/2 > 24h
- Strong Mu agonist (no sig. beta & kappa activity)
- High liability for addiction/abuse
[Strong Opioid Agonist] Pethidine (Meperidine)
Use: In labour
- Shorter DOA especially in neonate
- Strong Mu agonist (prob weaker beta & kappa agonist)
Adverse Side Effects:
- Hallucinogenic & convulsant effects @ high dose
- Restlessness (rather than sedation)
- Antimuscarinic (parasympatholytic)
- -> Dry mouth, blurring of vision, but no miosis & less muscle spasm
[Moderate Opioid Agonist] Codeine/ Dihydrocodeine
- Weak Mu & Beta agonist
- Low max analgesic efficacy
- Moderate liability for addiction/abuse
[Moderate Opioid Agonist] Tramadol
- Weak Mu agonist
- Weak inhibitor of 5-HT & noradrenaline re-uptake
Food for thought:
- Tramadol possibly a 5-HT3 agonist???
- -> Decreases the effect of Ondansetron (Blocks analgesic effect, a 5-HT3 antagonist) when used together
Why can respiratory depression happen with Opioid Analgesics?
The actions in the nucleus tractus solitarus & nucleus ambiguus can…
- Reduce responses to CO2 (& H+)
- Suppress voluntary breathing
Under what situations can respiratory depression possibly occur with Opioid Analgesics?
Can be lethal in…
- Overdose
- Respiratory disease
- Hepatic dysfunction
- Combi with other CNS depressants
- Young children
Common adverse effects of Opioid Analgesics
- N/V (due to actions on chemoreceptor trigger zone)
- Drowsiness
- Constipation (due to reduced GI motility)
- Urinary retention (due to increased bladder sphincter tone)
- -> Especially in pts with prostatic hypertrophy
- Miosis aka pinpoint pupils (due to actions in oculomotor nucleus)
- -> Pinpoint pupil is a diagnostic feature of opioid overdose! (pupils that are abnormally small)
- -> H/w mydriasis (dilation of pupil) can also follow if hypoxia occurs
- Postural hypot/s & bradycardia (due to actions in cardioregulatory nuclei in medulla)
- Immunosupressant effect with long-term use
Note: Morphine can also trigger histamine release from mast cells
–> Urticaria, itching, bronchoconstriction, hypot/s, vasodilation
Who should Opioid Agonists be used with caution in?
NOT to be used:
- Infants
Caution:
- Asthmatics
- Elderly
Tolerance, Physical dependence & addiction with Opioid Agonists
Tolerance:
- B/c less effective after prolonged use
- > Dose escalation required
Addiction:
- Psychological craving
- Compulsive use
- Loss of control over use
Physical dependence:
- Physiological dependence
- -> Physical withdrawal symptoms
What can lead to risk of Opioid overdose?
Addiction & tolerance
How can Opioid withdrawal manifest as?
Anxiety, irritability, chills, hot flushes, joint pain, lacrimation (tears), rhinorrhea (runny nose), N/V, abdominal cramps, diarrhea
Opioid antagonist for overdose
i) Naloxone (Short-acting, IV) - For immediate crisis
ii) Naltrexone (Long-acting, PO) - Overdose & addiction
iii) Nalmefene (Long-acting, IV) - New combination
- To use with EXTREME CAUTION in pts with opiate dependency as it can ppt potentially fatal withdrawal symptoms
