Narcotic Analgesics (Opioid) Flashcards
What are the chemical classes?
- Phenanthrenes
- Benzylisoquinolines
- Tetrahydroisoquinolines
- Cryptopines
Examples of Phenanthrenes?
- Morphine (strong agonist)
- Codeine (weak agonist)
- Thebaine (precursor for synthesis of naloxone, buprenorphine and others)
What are the precursors of 3 major families of endogenous opioid peptides?
- B-endorphin from preproopiomelanocortin
- Enkephalins from preproenkaphalin
- Dynorphins from preprodynorphin
Endogenous mechanisms
- Inhibit propagation of pain signals
- Alter emotional perception of pain
- Elevate pain threshold?
What are the sites of opioid receptors regulating pain?
- Peripheral nociceptive terminals (peripheral analgesia)
- Spine (spinal analgesia)
- Brain (supraspinal analgesia)
What are the three major opioid receptor types?
- μ (mu)
- δ (delta)
- κ (kappa)
G-protein coupled receptors
What are the effects of opioids and where do they come from?
- Nociceptive terminals: peripheral analgesia (+++)
- Spine: spinal analgesia (+++)
- Brainstem: supraspinal analgesia (++), sedation (+) , severe sedation (—)
- Emotional brain: Euphoria (-), dysphoria (–)
- Oculomotor: Pupil constriction (–)
- GI tract: reduced gut motility (-), constipation (–)
- Respiratory nuclei: cough suppression (++), respiratory depression (—)
Difference between dosage of elderly and younger patients
Elderly patients usually require lower dose to achieve effective pain relief than younger patients
Difference between dosage of neuropathic and nociceptive pain
Neuropathic pain usually require higher opioid doses than nociceptive pain
How should opioid analgesics be given?
Start at a low dose and carefully titrated until an adequate level of analgesia is obtained or until persistent and unacceptable side effect warrant a re-evaluation of therapy
Examples of clinical analgesia opioid agonists
Codeine, morphine, pethidine
Examples of clinical anaesthetic adjuvant opioid agonists
Fentanyl
Examples of clinical cough suppressant/antitussive opioid agonists
Codeine
Examples of clinical anti-diarrhoeal opioid agonists
diphenoxylate
Describe morphine
Receptor agonism, analgesic efficacy, liability for addiction/abuse
- Strong μ agonist (weaker κ and δ agnoist)
- High maximum analgesic efficacy
- High liability for addiction/abuse
Describe methadone and fentanyl
Receptor agonism, analgesic efficacy, liability for addiction/abuse
- Strong μ agonist (no sigificant κ and δ affinity)
- High maximum analgesic efficacy
- High liability for addiction/abuse
- Methadone is long-acting (plasma half life >24h)
- Fentanyl is short-acting (anaesthetic adjuvant(
Describe pethidine
- Strong μ agonist (probably κ and δ agonist)
- Shorter duration of action than morphine (esp. in neonate so used in labour)
Effects of pethidine
- N-demethylated in liver to norpethidine (hallucinogenic and convulsant effects at high dose)
- Restlessness rather than sedation
- Antimuscarinic: dry mouth, blurring of vision but no miosis and less spasm of smooth muscle
Describe codeine/dihydrocodeine
Receptor agonism, analgesic efficacy, liability for addiction/abuse
- Weak μ and δ agonist (probably not a κ agonist)
- Low maximum analgesic efficacy
- Moderate liability for addiction/abuse
Describe tramadol
- Weak μ agonist
- Weak inhibitor of 5-HT and noradrenaline uptake
What is the most serious side effect?
Respiratory depression
Mechanism that leads to respiratory depression
Actions in nucleus tractus solitarius and nucleus ambiguus reduces responses to CO2 and suppress voluntary breathing
Respiratory depression can be lethal in…
Overdose, respiratory disease, hepatic dysfunction, combination with other CNS depressants, young children
What are the common adverse effects?
- Nausea/vomiting: chemoreceptor trigger zone in area postrema of medulla
- Constipation: reduced gastrointestinal motility
- Drowsiness
What are other adverse effects?
- Miosis: actions in oculomotor nucleus (pinpoint pupil is diagnostic feature of overdose but mydriasis can follow if hypoxia occurs)
- Urinary retention: increased bladder sphincter tone
- Postural hypotension and bradycardia: cardioregulatory nuclei in medulla
- Immunosuppressant: long-term use through CNS effects
- Histamine release from mast cell (morphine) -> urticaria and itching, bronchoconstriction, hypotension due to vasodilation
Manifestations of opioid withdrawals
Anxiety, irritability, chills, hot flushes, joint pain, lacrimation, rhinorrhea, nausea, vomiting, abdominal cramps, diarrhoea
Example of opioid antagonist
Naloxone (short-acting, IV)/Naltrexone (long-acting, oral)/Nalmefene (long-acting, IV)
- Strong μ antagonism (also κ and δ antaognism)
What is opioid antagonists used for?
Counteract opioid overdose
