Opioid Analgesics Flashcards
what are the major classes of opioid receptors and where do most opioid analgesics work
- μ, δ and κ.
- most work at the μ receptor
what are opioids action on neurons
- close voltage gated Ca channels on presynaptic nerve terminals –> reduced neurotransmitter release
- open K channels –> hyperpolarizing and inhibiting postsynaptic neurons
opioids reduce the release of large numbers of neurotransmitters. what are the neurotransmitters?
NAGSS
- norepinephrine
- acetylcholine
- glutamate
- serotonin
- substance P
where does the analgesic effects of opioids come from (aka what is the mechanism that leads to analgesia)
- directly inhibits ascending transmission of nociceptive info from spinal cord dorsal horn
- indirectly activates pain inhibitory circuits
receptors that opioids work on in spinal analgesia and the mechanism
- μ, δ and κ.
- inhibits the release of excitatory neurotransmitters substance P and glutamate from these primary afferents
- also inhibits the dorsal horn pain transmission neuron directly
receptors that opioids work on in supraspinal analgesia and mechanism
- μ, δ and κ.
- activation of pain inhibitory descending neurons
mechanism of peripheral analgesia
-stimulation of peripheral μ receptors by opioids decrease sensory neuron activity and release
what are the mixed agonists-antagonists of opioids (what do they agonize and antagonize)
Pentazocine
Butorphanol
Nalbuphine
Buprenorphine - partial μ agonist and κ antagonist
partial agonist/antagonist of μ receptors and are agonists of κ receptors
what are the opioid antagonist and what receptors do they antagonize
antagonize all - μ, δ and κ
naloxone and naltrexone
what are the opioid agonist
Morphine Fentanyl Meperidine Methadone Codeine
might need this box later
thanks
what are the CNS effects of opioids
- analgesia
- euphoria
- sedation and drowsiness
- respiratory depression
- cough suppression
- miosis
- truncal rigidity
- nausea and vomiting
peripheral effects of opioids
- hypotension
- GI effects: constipation
- Biliary Colic
- Decreased renal flow
- Uterus: prolongs labor
- Release of ADH, PRL, Somatotropin and inhibit LH
- Pruritis
how are opioids excreted
turned to metabolites mostly glucuronides then excreted by the kidney
what types of patients should be monitored when given opioids like morphine
those with renal impairment since it is conjugated to a glucuronide then excreted by the kidney
how are opioids like heroin and remifentanil metabolized
they are hydrolyzed by tissue esterases
which opioids causes seizures if in high concentration and what type of patients experience these seizures
normeperidine
patients with decreased renal function since it cannot be excreted hence –> seizures
clinical uses of opioid analgesics
5 As
- Analgesia: pain
- Acute pulmonary edema: relieves dyspnea by reducing cardiac preload and afterload
- Antitussives: relieve cough
- Antidiarrheals
- Anesthesia: sedative, anxiolytic, and analgesic properties
adverse effects of opioids
MAIN ONES: nausea vomiting sedation itching constipation
IN ADDITION:
urinary retention
hypotension
respiratory depression
contraindications/cautions in opioid therapy
- using pure agonists with partial: diminishes effect
- head injury: CO2 retention caused by respiratory depression –> cerebral vasodilation
- pregnancy: fetus becomes dependent and experiences withdrawal postpartum
- impaired pulmonary function: opioids respiratory depressive properties –> acute respiratory failure
- decreased renal function: can’t excrete it so leads to problems associated with high conc
- endocrine disease: adrenal insufficiency or hypothyroidism can have prolong and exacerbated response
drug interactions of opioids
- with sedative hypnotics –> resp depression
- antipsychotics –> increases sedation
- MAOI: meperidine and tramadol –> excitement, muscle rigidity, hyperthermia, unconsciousness
strong opioid agonists
Morphine, Hydromorphine, Oxymorphine Heroin Meperidine Fentanyl Methadone Levorphanol
affinity of morphine towards opioid receptors
high affinity towards μ receptors
lower affinity towards δ and κ
how is heroin hydrolyzed and explain which is more liposoluble and its importance
heroin –> 6-monoacetylmorphine (6-MAM) –> morphine
heroin and 6-MAM are more liposoluble hence enter the brain more readily
what are primarily μ receptor agonists
Fentanyl, Meperidine, Methadone
who is meperidine contraindicated in and why
- people with tachycardia because it has antimuscarinic effets
- those on MAOI/serotonergic agents because it can cause serotonin syndrome due to it blocking neuronal reuptake of serotonin
what happens with large doses of meperidine given in short intervals
produce tremors, muscle twitches, DILATED PUPILS, hyperactive reflexes, convulsion
mechanism of methadone (and its difference from morphine)
μ receptor agonist
NMDA receptor antagonist
serotonin and norepinephrine reuptake inhibitor
drug used for opioid abstinence syndrome or treatment of heroin users in those with withdrawal symptoms and why?
methadone
- less euphoria
- longer half life and though it prolongs the abstinence syndrome, it is less severe than short acting opiates like heroin
what are the mild to moderate opioid agonist
Codeine, oxycodone, hydrocodone
Tramadol
mechanism of codeine’s analgesic effect
it is converted to morphine by CYP2D6
mechanism of tramadol and use
weak μ agonist
norepinephrine and serotonin reuptake inhibitor
used for neuropathic pain (pain from injury to nervous system)
contraindication of tramadol
taken it with serotonergic agents like MAOIs because of its inhibition of serotonin reuptake and hence can lead to serotonin syndrome
adverse effects of mixed agonist-antagonist opioid analgesics(name them)
pentazocine, butorphanol, and nalbuphine are associated with psychotomimetic effects (not as common in buprenorphine)
uses of opioid antagonists analgesics (name them)
naloxone and naltrexone
naloxone - acute opioid overdose
naltrexone - decrease craving for alcohol in chronic alcoholics (longer duration than naloxone)
what are the antitussives
dextromethorphan
codeine
contraindication of antitussives
adverse effects/differences in the antitussives
do not give to those on MAOIs
dextromethorphan has no analgesic effect so it is preferred and less likely to have constipation
opioid anti motility agents/ antidiarrheals and are they agonists or antagonists
they are opioid agonists
diphenoxylate and loperamide
what does commercial use of diphenoxylate contain that discourages overdosage
atropine (antimuscarinic - might contribute to antidiarrheal action)
adverse effects of diphenoxylate
higher doses can cause CNS effects
