Can opioid be used for pt with biliary colic?
No. Not effective
Methodone + rifamycin, would lead to methodone withdrawal
Because RIF increased renal clearance of methodone, leads to shorten T1/2 of methadone, increased risk for methadone withdrawal
Pentazocine (partial opioid agonist), morphine is full opioid agonist, avoid use them together, why?
Reduce analgesic effect and induce withdrawal
As they work on the same receptor
Caution or C/I when using opioids:
- Avoid full opioid agonist and partial opioid agonist together
- Avoid in pregnancy
- Avoid for pt with HI
- Avoid in pt with impaired resp function
- Avoid or reduce dose in pt with hepatic and renal function
- Avoid use in pt with sedative hypnotic, antipsychotics and MAOI
MOA of opioids
3 families of endogenous receptors,
3 families of endogenous opioid peptides (endophins, enkephalins and dynorphins)
Central and peripheral location of receptors, with the effects of:
1. Modulation of pain
2. Inhibition of respiration
3. Slows GI transit
4. Modulation of neurotransmitter and hormonal release
5. Psychomimetic effects
Opioid analgesics include full agonist, partial agonist and antagonist at the opioid receptors, mainly the mu receptor
Opioid PK:
- A:
- good absorption from s/c, IM and oral admin.
- high inter patient variability in 1st pass effects
2.D
- rapidly distributed to highly perfused tissues, such as brain, lungs, liver and kidneys
- accumulates in fatty tissues - M:
- morphine is metabolised to active compounds (has longer effects) (M3G and M6G)
- M3G (neurotoxic)
- M6G(more potent analgesics) - E:
- in kidney
Renal failure, given morphine, what side effect may happen?
- Seizure ( M3G occumulation , leading to neuro toxicity)
Pharmacodynamic for opioids
- Opioids analgesics bind to GPCR
- close voltage gated Ca channels on presynaptic nerve terminal, reduce the release of neurotransmitter (glutamate, ACh, NE, 5HT, substance P)
- open K channels (hyperpolarized and inhibit post synaptic neurons)
- keep the nerve activites down - Opioids can act on multiple synapses, transmitters and receptors
- direct action in inflammed or damaged peripheral tissues
- spinal (dorsal horn)
- descending inhibitory neuron (periaquaductal grey, rostral ventral medulla)
- release of endogenous ligands
Clinical use of opioids
- Analgesics ( severe constant pain, cancer pain, obstetric pain)
- Anaesthesia ( pre-med before anaesthesia, intraoperative, regional analgesia into epidural or subarachnoid space to act on spinal cord dorsal horn superficial neurons)
What are the effects of opioid will develop tolerance?
- Analgesics
- Sedation
- Resp depressant effects
The tolerance to sedating or respiratory effects dissipates after a few days of discontinuation
What effects of opioids do not develop tolerance?
- Miotic
- Convulsant
- Constipation action
Which opioid is common with cross tolerance? How to manage tolerance?
- Mu agonist is common with cross tolerance
- Cross tolerance may be partial or incomplete
Thus opioid rotation can help to reduce tolerance, i.e. where
Tolerance to one opioid is managed by changing to another
E.g. morphine to hydromorphine to methadone
Tolerenace can be managed by use of adjuvant non-opioid analgesics. Allowing “recoupling” of opioid receptor. Such as use ketamine to reduce post op pain and reduce opioid requirement in opioid tolerance pt
How to minimize risk of tolerance and dependence?
- Establisb therapeutic goals before starting opioid therapy with pt and family
2 limit dosage at lowest effective level (no early refills, avoid prescribers) - Consider alternative analgesics
- Frequent re-eveluate need for opioids
