HNNS L16 - Opioid Analgesics Flashcards
Examples of strong opioid analgesics
Morphine & related compounds, e.g. codeine, heroin
Phenylpeperidines, e.g. pethidine, fentanyl and derivatives
Methadone
*For intense pain
Examples of mild opioid analgesics
Propoxyphene, e.g. dextropropoxyphene, Doloxene, Dologesic (banned???)
Partial agonists, e.g. Pentazocine, Buprenorphine (Temgesic), Butorphanol, Tramadol[?]
*For mild pain
Fentanyl
Strong opioid
Sufentanil
Strong opioid (fentanyl family)
Alfentanil
Strong opioid (fentanyl family)
Remifentail
Strong opioid (fentanyl family)
- ultra-short-acting
- low lipid solubility
- -> does not show much increase in the time required for a certain % drop in effector site concentration in prolonged infusion
Codeine
Morphine related opioid analgesic
Strong opioid
Heroin
Morphine related opioid analgesic
Strong opioid
Methadone
(Physeptone) Strong opioid Longest acting Used for getting over opioid addiction 'Complex' analgesic (activity not solely based on opioid receptor)
Effect when you use strong and mild opioids together
Weaker than using strong opioid alone.
(Mild opioids displacing the strong opioids)
*NO synergistic effect!!!
Dextroprophoxyphene
Under prophoxyphene
Mild opioid
Doloxene
Under prophoxyphene
Mild opioid
Pentazocine
Partial opioid receptor agonist (mixed agonist / antagonist)
Mild opioid analgesic
Buprenorphine (Temgesic)
Partial opioid receptor agonist (mixed agonist / antagonist)
Mild opioid analgesic
Butorphanol
Partial opioid receptor agonist (mixed agonist / antagonist)
Mild opioid analgesic
Tramadol
Partial opioid receptor agonist (mixed agonist / antagonist)[?]
Mild opioid analgesic
No major side effects except
- nausea / vomiting
- miosis
- constipation
- drug interaction with anti-depressants
Not a controlled drug
Which opioid analgesic is NOT a controlled drug?
Tramadol
(No major side effects e.g. respiratory depression;
No euphoria –> not likely to abuse)
Drug interaction of tramadol
(Mild opioid analgesic)
Drug interaction with anti-depressants
- decrease serotonin, NA uptake in CNS
Side effects of Tramadol
(Mild opioid analgesic)
- nausea / vomiting
- miosis
- constipation
- drug interaction with anti-depressants
What features of opioid analgesics cause higher addictive potential?
Euphoria
Higher lipid solubility + higher non-ionized fraction –> favour crossing of BBB
What parameter to look at when you want an opioid analgesic with faster onset? Is it preferrable to have a faster onset?
Lipid solubility (favour crossing of BBB) Non-ionized fraction????
Faster onset –> easier to correct the dosage (prevent respiratory depression)
Opioid analgesic: peak effect site concentration determined by… (explain in terms of plasma concentration and effect site concentration)
Peak effect site level = isoconcentration level (level at which plasma concentration = effect site concentration)
Before:
- plasma concentration dropping
- effect site concentration increasing
After isoconcentration, both drop.
What to take note of if you want to repeat administration of opioid analgesics?
Reduce subsequent doses if repeated administration of opioid analgesics is required.
Longer infusion time of opioid –> longer time required to show a certain % decrease in effector site concentration
- Drugs would accumulate in peripheral tissues, e.g. muscles and fat
- Slowly diffuse out –> redistribute to CNS
*Over therapeutic window: respiratory depression
Metabolism of morphine
Formation of normorphine, morphine-3-glucuronide and morphine-6-glucuronide in liver
Morphine-6-glucuronide is an ACTIVE metabolite (30% morphine activity)
- Do NOT miss it when considering the dose.
Excretion by kidneys
- dysfunction –> accumulation of active metabolites
Giving morphine to patients with
- Liver failure
- Renal failure
- Liver responsible for metabolising morphine into normorphine, morphine-3-glucuronide and morphine-6-glucuronide (active metabolite)
- -> accumulation of morphine - Kidney for excretion of metabolites of morphine
- -> accumulation of ACTIVE metabolites
Giving pethidine to patients with renal failure?
Pethidine: renal excretion of metabolite *norpethidine (from minor pathway)
*major pathway: esterification, conjugation
- -> Norpethidine may accumulate in kidney dysfunction
- -> convulsion
Route of administration for opioid analgesics
- IV
- Indwelling subcutaneous patch
- Transmucosal (lollipop-like)
- Epidural / Subarachnoid
- Transdermal
*Patient-controlled Analgesia
Oral administration not preferred
- Many side effects (vomit the drugs out!)
- Decreased absorption with first pass effect
Advantage of epidural / subarachnoid administration of opioid analgesic
Bypass BBB –> more effective
Acute side effects of opioid analgesics
- Sedation
- Nausea / vomiting
- Respiratory depression
- Euphoria
- Miosis
Side effects of prolonged use of opioid analgesics
- Constipation
- Tolerance / dependence
- Acute side effects:
- Sedation
- Nausea / vomiting
- Respiratory depression
- Euphoria
- Miosis
For opioid analgesics, instead of reading ED50 and LD50 for the therapeutic window, what should we read?
ED95 and LD05
- LD05 already very dangerous!
Which of the following causes the most severe euphoria?
Morphine, Methadone, pethidine
Pethidine > morphine > methadone
What defines physical dependence of morphine?
It is the physiological adaptation of the body to the presence of an opioid, an is defined by the development of withdrawal symptoms when
- opioids are discontinued,
- dose is reduced abruptly, or
- an antagonist (e.g. naloxone) or a partial agonist (e.g. pentazocine) is administered
What to take note of when administering opioid analgesics?
According to the Dangerous Drugs Regulations, medical practitioners are required to maintain proper records of ALL dangerous drugs, whether supplied, dispensed or administered.
*Lock it up as well
Antagonist of opioid analgesic
Naloxone (Narcan)
- For PCA overdose for exmaple
- IV
- Half-life shorter than most opioid analgesics –> keep the patient for observation after one dose
Naloxone (Narcan)
Antagonist of opioid analgesics
- e.g. for PCA overdose
- IV
- Half-life shorter than most opioid analgesics –> keep the patient for observation after one dose
Which opioid analgesic would interact with anti-depressants?
Tramadol
- increase serotonin and NA uptake in CNS
Can you release a patient with opioid overdose after giving one dose of naloxone (opioid antagonist)?
No.
Half life of naloxone is shorter than most opioid analgesics.
Keep the patient under observation after one dose of naloxone.
What to take note of when choosing an opioid analgesic?
- Efficacy
- Side effects
- Onset and duration
- Route of administration and availability
- Safety
- Addictive potential
