opioid side effects

Question 1

which medications might affect opioid metabolism?

Answer 1

Medications that work through CYP 450 - can either prolong or shorten the opioid metabolism.
Oral anti fungal (fluconazole) may inhibit the metabolism of methadone and increase its concentration.

Question 2

Tx for respiratory depression?

Answer 2

Naloxone
Full dose : 0.4 mg
Can first try smaller doses 0.02-0.04 mg
Can give 0.4 mg / hr continuous IV for OD or of methadone.
Wait for 2 hours before terminating TX due to short T1/2.

Question 3

Mechanism of opioid related constipation?

Answer 3

Peripheral (opioid receptors in the gut) and central via CNS

Question 4

Mechanism of opioid related Nausea?

Answer 4

1. Activation of chemoreceptor trigger zone in the brain stem (dopamine and serotonin receptors)
2. decrease GI motility
3. Activation of the vestibular apparatus (histamine -1 R), presents as motion-related nausea (uncommon).
4. Renal impairment causing opioid metabolisms accumulation.

Question 5

Tx for opioid related nausea?

Answer 5

• prevention by giving antiemetic with both dopamine antagonism with GI prokinetic activity i.e. metoclopramide (or domperidone) 10 mg QID or q4h + PRN.
• up to 2/3 patients starting an opioid regime / switching / dose increase - might experience nausea.
• usually lasts for 3-7 days

Question 6

Strategies to deal with opioid related somnolence

Answer 6

• if pain is well controlled, reduce the opioid
• if pain is not controlled: switch opioid or reduce + add non opioid adjuvant
• in a very small select group, consider adding a psychostimulant such as methylphenidate 2.5 - 5 mg at 8am and noon. might be helpful if pt is also depressed.

Question 7

Define opioid neurotoxicity:

Answer 7

the collection of opioid related central nervous adverse effects including: 
Sedation
Confusion/ cognitive impairment
Agitation
Myoclonus
Hallucinations (visual>tactile>auditory)
Hyperalgesia / allodynia

Question 8

risks factors for neurotoxixity:

Answer 8

renal impairment
 long term high dose opioid Tx 
increased age
dehydration
concurrent treatment with other drugs like TCA and BZP
Delirium

Question 9

Management of opioid toxicity:

Answer 9

• exclude other causes
• hydration
• if pain is well controlled, toxicity is not severe: reduce the opioid
• if toxicity severe/ pain not well controlled:
  1. opioid rotation (usually takes up to 3 days to take effect)
  2. reduce dose and add non opioid adjuvant
  3. change route of administration
  4. Tx Sx: control myoclonus with gabapentin, baclofen or BZP
  5. Do not use naloxone unless there is significant narcotization - it is not effective and will precipitate opioid withdrawal and pain with no benefit. (can precipitate seizures. )

Question 10

Signs of opiate overdosing (narcotization)

Answer 10

respiratory depression
pinpoint pupils
decreased LOC
no other cause found

Question 11

Opioid related withdrawal

Answer 11

Normal physical dependency develop with opioid consumption.
Anxiety, agitation, lacrimation, rhinorrhoea, fever, sweating, tremor, muscular & abdominal cramps, diarrhea.
Treat by administration 25-50% of daily dose, prior to cessation in divided q4-6hr doses.

Question 12

Addiction / psychosocial dependency

Answer 12

Compulsive behavior to take the drug and expirience its psychic effects, despite the potential harm.
Risk factors
Prior hx of drug abuse