Analgelsics: Opioids Flashcards
What is the mechanism of action of opioids?
Mimics the action of the 3 endogenous opioids (enkephalins, endorphins, dynorphins) on opioid receptors
3 main types of opioid receptors: μ, δ, κ (mu, delta, kappa)
Activation of opioid receptors 🡪
- Decreased Ca2+ flux 🡪 decrease in presynaptic neurotransmitter release of acetylcholine (ACh), substance P (primary MOA is presynaptic)
- Enhance K+ efflux 🡪 hyperpolarisation of postsynaptic neurons (secondary MOA is postsynaptic)
What are the side effects of opioids?
Histamine release (esp for morphine, codeine, pethidine) 🡪 pruritus
N&V (2’ to stimulation of CTZ in floor of 4th ventricle)
Opioid-induced constipation (this is not overcome even in opioid tolerance)
Urinary retention
Dizziness
Miosis/pinpoint pupils due to excitatory actions of opioids on autonomic component of the Edinger-Westphal nucleus of CN3 (oculomotor nerve)
Sedation: Occurs before respiratory depression 🡪 patient on PCA will be too sedated to administer more morphine to tip into respiratory depression
Respiratory depression: Direct depressant effect on brainstem respiratory centres
Tolerance: Refers to the development of the need to increase the dose of opioids to achieve the same analgesic effect
Dependence refers to physical dependence for baseline function, characterised by tolerance and, if the drug with abruptly stopped, withdrawal
Withdrawal: Occurs when a patient who is opioid dependent abruptly ceases opioid intake (abrupt discontinuation) or use of antagonist (e.g. naloxone)
- GI: Abdominal pain, N/V/D
- Sympathetic activation: CNS arousal, tachycardia, hypertension, tachypnoea, mydriasis
- Restlessness, tremor, agitation, insomnia, anxiety, irritability
- Flu-like symptoms: lacrimation, diaphoresis, rhinorrhoea, shivering, piloerection
Addiction is characterised by behavioural change (caused by biochemical changes in the brain after continuous drug use). The main priority of the drug addict is to obtain the drug, regardless of the harm they may cause to themselves or others (i.e. addiction =/= dependence!)
How is morphine administered?
Available in PO, IV, IM, SC forms
- IM dose is 0.1-0.2 mg/kg, time to peak effect is 30-60 mins, duration of action is 3-4 hours
- IV administration: should be titrated to effect, usually given in 1-2 mg boluses, total dose to achieve adequate analgesia is similar to IM dose. Onset of action is more rapid following IV administration
- PO: poor oral bioavailability, high first pass metabolism (parenteral morphine is 3x the potency of PO morphine)
How is morphine metabolised?
Hepatic: morphine-3-glucoronide (M3G) and M6G, which are renally excreted
- M3G is pharmacologically inactive
- M6G works on mu opioid receptors, has longer half-life, is renally excreted 🡪 can accumulate in renal failure, leading to opioid toxicity, e.g. respiratory depression
How is fetanyl administered?
Available in IV, IM, SC, transdermal forms: Transdermal fentanyl is for chronic opioid use, in opioid-tolerant patients. Not for management of acute pain, or in opioid-naive patients
100x as potent as morphine, high lipophilicity (can accumulate in adipose tissue)
IV bolus: rapid onset (1-2 mins), short duration of action (30 mins), but duration of effect increases with larger doses and infusions
What are side effects of remifentanil?
In increasing doses, can cause hypotension and bradycardia
What is the use of remifentanil?
Sedation/analgesia in OT and ICU (e.g. at induction; intra-operatively, it can be titrated quickly in accordance to sympathetic stress response)
How is Remifentanil administered?
Only IV form available
What is the use of pethidine?
- Opioid activity
- Post-op shivering
What are the side effects of pethidine?
- Has anticholinergic properties; is the only opioid that can cause tachycardia
- If used with MAOIs and SSRIs 🡪 possible serotonin syndrome
- Euphoria 🡪 high abuse potential
What is the mechanism of action of methadone?
- Opioid receptors
- NMDA receptor antagonist 🡪 useful for neuropathic pain, minimise potential for developing tolerance
How is codeine metabolised?
- 10% of codeine is demethylated into morphine, which is likely the reason for its analgesic effect
- CYP2D6 ultrametabolisers: codeine is rapidly and extensively converted into morphine, leading to possibility of increased opioid toxicity (0.5-1% of Japanese and Chinese)
what are the uses of codeine?
- Analgesia
- Antitussive effect
What is the mechanism of action of tramadol?
Tramadol and its active metabolite (O-desmethyltramadol) bind to opioid receptors in the CNS, causing inhibition of ascending pain pathways
Unique to tramadol, it also prevents the reuptake of noradrenaline and serotonin thus increasing the effect of these 2 compounds which are involved in the descending inhibitory pain pathway, thus also providing pain relief
What are the side effects of tramadol?
As with opioids
- Dizziness, sedation
- Nausea, vomiting
- Constipation
Serotonin syndrome: When used in combination with TCAs, SSRIs, MAOIs
Seizures (seizure threshold is reduced by tramadol!)
- Risk increased when used in combination with TCA, SSRI, MAOI, opioids
- Risk increased in patients with history of seizures or with risk of seizures (e.g. head trauma)
