Narcotic (Opioid) Analgesics Flashcards
Opioid analgesia plays on endogeneous mechanisms to:
- Inhibit the propagation of pain signals
- Alter the emotional perception of pain
- Elevate the pain threshold
Sites of opioid receptors regulating pain include:
- Peripheral nociceptive terminals (peripheral analgesia)
- The spine (spinal analgesia)
- The brain (supraspinal analgesia)
What are the three major opioid receptor types?
- μ (Mu)
- δ (Delta)
- κ (Kappa)
What can you say about the functional effects of the three receptors?
μ (Mu) receptor exerts most of the functional effects, with the exception of dysphoria, which is exerted by the κ (Kappa) receptor.
μ (Mu) receptor has the strongest effect on euphoria, κ (Kappa) receptor does not.
What are the dosing features of narcotic analgesics?
- Elderly patients usually require a lower dose to achieve effective pain relief than younger patients.
- Neuropathic pain usually requires higher opioid doses than nociceptive pain.
- Lower doses are usually required for continuous maintenance of pain relief than administration in response to recurrence of pain.
Dosing to effect of narcotic analgesics
- Opioid analgesics should be started at a low dose, and carefully titrated until an adequate level of analgesia is obtained, or until adverse effects occur.
- Failure of at least partial analgesia with incremental dosing may indicate unresponsiveness to therapy.
- Opioids do not exert an appreciable analgesic effect until MEC is reached for some patients with chronic pain.
What are the clinical uses of opioid agonists?
- Analgesia: codeine, morphine, pethidine
- Anaesthetic adjuvant: fentanyl
- Cough suppressant/antitussive: codeine
- Anti-diarrhoeal: diphenoxylate
Characteristics of morphine
- Strong μ agonist (weaker δ and κ agonist).
- High maximum analgesic efficacy.
- High liability for addiction/abuse.
Characteristics of methadone and fentanyl?
- Strong μ agonists (no significant δ and κ affinity).
- High maximum analgesic efficacy.
- High liability for addiction/abuse.
Amongst methadone, morphine and fentanyl, which are long-acting and which are short-acting drugs?
Methadone: long-acting
Fentanyl: short-acting
Pethidine characteristics
- Strong μ agonist (probably weaker δand κagonist).
- Shorter duration of action than morphine (especially in neonate therefore used in labour) –> used as an epidural in labor.
- N-demethylated in the liver to norpethidine (hallucinogenic and convulsant effects at high dose)–> hallucination and epilepsy can be potential side effects.
- Restlessness rather than sedation
- Antimuscarinic (i.e. parasympatholytic) therefore dry mouth, blurring of vision but no miosis and less spasm of smooth muscle.
Codeine / Dihydrocodeine characteristics
- Weak μ and δ agonist (probably not a κ agonist).
- Low maximum analgesic efficacy.
- Moderate liability for addiction/abuse.
- ~10 % converted to morphine / dihydromorphine.
- ~10 % of population show reduced analgesic effect due to lack of demethylating enzyme.
- codeine is demethylated to become morphine which has much higher efficacy.
Tramadol characteristics
- Weak μ agonist.
- Weak inhibitor of 5-HT and noradrenaline re-uptake.
What is the relationship between ondansetron and tramadol?
- Ondansetron has 5-HT3 antagonist activity, binds to the 5-HT3 receptors and blocks it.
- Ondansetron + tramadol –> effect of analgesic activity on tramadol is reduced. Therefore tramadol may be a 5-HT3 agonist.
respiratory depression: where does it occur, when is it lethal, which group of people should avoid taking opioids?
- Actions in the nucleus tractus solitarius and nucleus ambiguus.
» Reduce responses to CO2 and H+.
» Suppress voluntary breathing.
- Becomes lethal in: >> overdose >> respiratory disease >> hepatic dysfunction >> combination with other CNS depressants >> young children - Opioids should be avoided in infants.
