Opiod Cases Flashcards
Types of pain management and their sites of action
1) NSAIDs
- work on the periphery and spinal level
- better for fissure injuries rather than nerve injuries and neuro pain
2) COX-2 inhbitors
- same as 1
3) opioids
- work on the superaspinal and spinal level
- better for nerve injuries and CNS pain
4) anticonvulsants and tricyclic antidepressants
- same as 3
How do opioids work?
Reduce transmission of the pain in the spinal cord to the brainstem and lowers perception of pain in cortex
They raise the threshold of pain and inhibit signals
U-opioid receptors (MOR)
Can work to increase K+ conductance, decreases ca 2+ activity or decrease activity of cAMP/PKA
All of these suppress depolarization of pain nerves
Also has the following effects
- inhibits respiration (bradycardia)
- slows GI trains
- modulates hormone and neurotransmitter release
D-opioid receptors (DOR)
Can work to increase K+ conductance, decreases ca 2+ activity or decrease activity of cAMP/PKA
All of these suppress depolarization of pain nerves
Also have the following effects:
-modulate hormone and neurotransmitter release
K-opioid receptor (KOR)
Works to decrease calcium channel activity or decreases generation of cAMP and PKA
All of these suppress depolarization for nerves of pain.
Also has the following effects:
- psychotomimetic effects
- slows GI transit
Mechanisms of action of u-opioid receptor agonists at the spinal cord levels
Activation of MORs on presynaptic fibers results in dampened great the glutamate signals
Reduces glutamate and substance P releases which lowers pain signaling
Mechanisms of action of u-opioid receptor agonists at the brainstem levels
Induces supraspinal analgesia by hyperactivity of inhibitory descending fibers
Causes inhibition of excitatory neurons
Mechanisms of action of u-opioid receptor agonists at the thalamus levels
Induces agonism of u-opioid receptors in thalamus which causes reduced glutamate release in the cortex
What parts of the telencephalon and diencephalon do opioids work on
Thalamus
Cerebral cortex
Amygdala
Hippocampus
overall reduces emotional reactivity and perceptions to pain
What natural produced pain tolerance peptides are produced by the body
Enkephalins
Endorphins
Dynorphins
- these are produced by pre-propeptides*
What are the affinities for the natural pain tolerance peptides for each opioid receptor?
MOR = endorphins > enkephalins > dynorphins
DOR = enkephalins > endorphins = dynorphins
KOR = dynorphins»_space; endorphins = enkephalins
What is the main derivative/ prototype of exogenous opioids?
Morphine
Why are MOIs (monoamine oxidase Inhibtors) contraindicated as a coconmittal use with opioids?
Causes hyperpyrexic comas and/or HTN as a result
What the metabolism of most opioids?
Glucuronidation in the liver followed by renal excretion
What opioids are activated by CYPs?
Codeine
Oxycodone
Hydrocodone
What are the general contraindications for opioids
Concomitant use of agonists with partial agonists
- causes diminished effects and can both induce withdrawal or increase ADRs
Patients with head trauma
- increases intracranial pressure to dangerous levels
Pregnant patients
- baby becomes dependent on the drug
Impaired pulmonary/hepatic/renal functions
- causes respiratory distress and possible OD respectively
Patients with endocrine diseases
- causes increased apparent doses and possible overdoses
Stage 1 of opioid withdrawal
Lasts up to 8 hrs
Includes
- anxiety
- drug cravings
Stage 2 of opioid withdrawal
Lasts up to 8-24 hrs
Includes:
- anxiety
- insomnia
- GI distress
- rinhorrhea
- mydriasis
- diaphoresis
Stage 3 of opioid withdrawal
Lasts up to 3 days
Includes
- tachycardia
- nausea/vomiting
- HTN
- diarrhea
- fever
- chills
- tremors
- seizures
- muscle cramps
Buprenorphine
Partial agonist of MOR
Partial antagonist of KOR
used for mild-moderate pain only
only partial agonist
Can precipitate withdrawal symptoms and is useful in concomitant useage with naloxone for detox
Methadone
Synthetic opioid which blocks NMDA receptors and monoamine reuptake transports
Used for detoxification to limit withdrawal symptom magnitude
Morphine
hydromorphone, oxycodone, hydrocodone
Potent agonist of MOR
Distributes well within the BBB
useful adjunct in pulmonary edema and general anesthesia
Fentanyl
80-100 times stronger than morphine but works the same way (agonist of MOR)
- very easy to OD
Administered orally
Metabolized by CYP3A4
very high risk of respiratory distress and CNS depression if overdosing
Codeine
Common antitussive agent that is often do formulated with NSAIDs
Mild MOR agonist, mainly used for antitussive effects
is metabolized by the CYP2D6 enzymes to become morphine (since it is a prodrug of morphine)
Morphine/codeine is eliminated via hepatic glucuronidation and renal excretion
Codeine effects w/ poor CYP2D6 and hyperactive CYP2D6 metabolizes
Poor = no analgesic effect
- not converted into morphine
Hyperactive = increased apparent dose of morphine
What other opioid pro drugs are common?
Oxycodone -> oxymorphone
- more potent morphine
Hydrocodone -> hydromorphone
- more potent morphine
Heroin -> morphine + 6-monoacetylmorphine
- very potent metabolite
What are the 2 metabolites from morphine metabolism?
M6G
- produces analgesic effect in accumulation
M3G
- produces seizures in accumulation
both are renally excreted, so must be careful with patients who have renal dysfunctions
Meperidine
A potent MOR agonist W/ rapid onset
CONTRAINDICATED in extended use overall, renally impaired patients and patients with tachycardia
- not a 1st line agent either
- leads to seizures and arrhythmias
How does loperamide work for diarrhea (it’s intended use)
Activation of MOR receptors on excitatory neurons and secretomotor neurons
- causes constipation and decreased secretions
What is the difference between methylnaltrexone and naltrexone
Methylnaltrexone’s methyl group makes it not able to cross the BBB
- only acts on the periphery
Both are MOR/DOR/KOR antagonists
