Pharmacology - Analgesia Flashcards

1
Q

What is the mechanism of action of morphine

A

-mechanism of action: full agonist mostly active at the mu receptor, but also active at kappa and delta (g protein)
reduces pre-synaptic neurotransmission (especially glutamate), inhibits postsynaptic neurons

-effect at different opioid receptors:
mu receptor (μ) = analgesia, sedation, euphoria, miosis, respiratory depression, constipation
kappa receptor (Ƙ) = analgesia, sedation, dysphoria, miosis, diuresis, constipation
delta receptor (𝛅) = analgesia
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2
Q

What are the pharmacokinetics and adverse effects of morphine

A

-pharmacokinetics: high first pass metabolism, conjugated to M3G in liver (has neuroexcitatory properties)
small amount is metabolised to M6G (increased analgesic potency), renal excretion

-adverse effect: sedation, respiratory depression, nausea/vomiting, histamine release, dysphoria, seizure
nervous system: analgesia, euphoria, sedation, respiratory depression, cough suppression, miosis, nausea
peripheral: constipation, biliary smc contraction, bradycardia, stimulate release of ADH/prolactin/somatotrophin

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3
Q

Why do opiates cause respiratory depression

A

due to inhibition of brainstem respiratory controls, allowing less response to hypercapnea

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4
Q

What is the mechanism of action, pk and side effects of fentanyl

A

-moa: agonist at the mu receptor

-pharmacokinetics: highly lipid soluble, high first pass metabolism, duration of action 1-1.5 hours, t1/2 5 minutes
hepatic metabolism, no active metabolites, can be given iv, im, in, sc, sl, buccal, td, epidural
good in renal failure

-adverse effects: respiratory depression, nausea, vomiting, dysphoria, cough, sedation, itch, laryngeal rigidity

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5
Q
  • compare potency to morphine:fentanyl

- draw dose response curve comparing fentanyl and morphine

A

100 x more potent than morphine

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6
Q

Compare morphine and fentanyl - receptors

A

-receptors:
morphine = mu agonist but also works on kappa and delta receptors
fentanyl = only agonist on mu receptors, more potent than morphine (100x)

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7
Q

Compare morphine and fentanyl - absorption

A
morphine = well absorbed, high first pass metabolism, onset 30-60 minutes, doa 3-4 hours
fentanyl = absorbed orally, high first pass metabolism, onset 2-5 minutes, doa 1-1.5 hours
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8
Q

Compare morphine and fentanyl - metabolism

A
morphine = conjugated to M3G in liver (neuroexcitatory property) and small amount of M6G (analgesic)
fentanyl = metabolised by P450CY3A4, no active metabolites
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9
Q

Compare morphine and fentanyl - elimination

A
morphine = mainly in the urine, t1/2 1.7-4.5 hours, need to adjust does in renal failure
fentanyl = small amount of renal excretion, t1/2 2 hours
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10
Q

How does methadone differ from morphine and fentanyl

A
  • methadone also blocks nmda receptors and monoamine reuptake
  • methadone also has a high oral:parenteral potency ratio (morphine and fentanyl have low)
  • t1/2 of methadone is longer than morphine and fentanyl
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11
Q

Describe the mechanism of action and pharmacokinetics of oxycodone

A

-moa: mu, kappa and delta agonist
-pharmacokinetics: good oral absorption, high vod, low first pass metabolism, doa 3-4 hours
metabolised by P450CYP2D6 to oxymorphone (active metabolite)
excreted in kidneys
-adverse effect: sedation, respiratory depression, nausea, vomiting, hypotension, dysphoria, biliary colic, renal
-strategy to reduce dependence: establish goals, combine with non-opioid analgesics, small dose at long intervals

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12
Q

Name some drugs used to treat opiate addiction

A

-buprenorphine: partial mu agonist and partial delta and kappa antagonist
long duration of action due to slow dissociation from mu receptors
resistant to naloxone reversal
high dose results in mu antagonism
-naltrexone: long acting pure antagonist for mu receptor
-methadone: long acting mu receptor agonist and blocks nmda reuptake
tolerance and dependance develop more slowly than with morphine

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13
Q

What are the advantages of using buprenorphine in treating heroin addiction over methadone

A
  • buprenorphine has a lower risk over overdose fatalities because high dose has antagonism effect
  • buprenorphine also has a long duration of action due to slow dissociation from mu receptors
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