Flashcards in PHARM: Opiates and Pain Pharmacotherapy Deck (105):
Where do NSAIDs work in the pain pathway?
modulate the initial signal transduction
Where do Na+ channel blockers work in the pain pathway?
act as local anesthetics to block signal conduction (AP generation) in nociceptive fibers
Where do opiods work in the pain pathway?
spinal cord (block pre-synaptic Na+ channels and open post-synaptic K+ channels to decrease likelihood of action potential)
How do NE and GABA work in the pain pathway?
act just like opiates
What receptors play a prominent role in the sensitizaiton phenomenon?
NMDA glutamatergic receptor
How is short-term sensitization achieved?
post-translational modifications (phosphorylation)
How is long-term sensitization achieved?
altered gene expression (phosphorylation of GRPs)
What is it called when pain arises from transection or mechanical damage to the nerve axon?
What receptor is OP-1?
What receptor is OP-2?
What receptor is OP-3?
What are OP-1 receptors specific for?
What are OP-2 receptors specific for?
What are OP-3 receptors specific for?
What occurs with activation of OP-1 receptors?
modulation of hormone and neurotransmitter release
What occurs with activation of OP-2 receptors?
psychotomimetic effects (decreased GI transit)
What occurs with activation of OP-3 receptors?
sedation, decreased respiration, decreased GI transit, and modulation of hormone and neurotransmitter release
Which opiates can be given rectally?
What opiates can be given in a lozenge form?
What opiate can be given in patch form?
What opiate is contraindicated in renal failure and breastfeeding?
Which opiates can be used in renal failure?
Which opiate has a long half-life and can be used to treat withdrawal?
Which opiate has a DDI with MAOIs?
Which opiate can cause long QT and reduced libido?
Which opiate can cause peripheral and central anti-cholinergic effects?
Which opiate can only be given IV?
Which opiates are NOT solely OP-3 agonists?
Codeine (OP-3 partial agonist)
Morphine (OP-3 agonist AND OP-2 minor agonist)
Which opiate can be converted to morphine by CYP2D6?
Which opiate has the lowest potency?
What is interesting about meperidine metabolism?
it is either broken down into an inactive form or into a form that is 3X more potent
What opiate is a substrate for P-gp and CYP?
What is the most potent opiate?
Which opiate is the same potency as morphine?
Which PD drugs are contraindicated with meperidine?
List the opiod partial agonists
Which opiod partial agonists are only IV?
Which opiod partial agonist has a very high potency and a ceiling effect?
Which opiod partial agonists is not simply a partial mu agonist?
Buprenorphine (partial Mu agonist and partial delta and kappa antagonist)
Which opiod partial agonist is metabolized by CYP3A4 and CYP2D6?
Which opiod partial agonist is used for withdrawal due to its very tight binding (long acting)?
What drug is given with Buprenorphine for withdrawal?
True or false: opiates commonly relieve pain completely.
FALSE they make pain more tolerable
What is a strange toxicity of opiates?
pruritis around nose
What symptom of opiates is more common with parenteral or spinal administration?
Which opiate toxicities have minimal or no likelihood of tolerance developing (will never get better as long as you are using the drug)?
Which opiate toxicity has moderate likelihood of tolerance developing?
Why does constipation occur with opiate treatment?
binding to opiate receptors in enteric nervous system produces anticholinergic action (Ach usually stimulates peristalsis, so anticholinergic leads to stasis and hardening of stool)
How do you treat opiate-induced constipation?
-prophylaxis with stool softener or laxative
-careful titration with opiate antagonist
Why does N/V occur with some people who are treated with opiates?
they get rapid initiation at high doses (not as likely if slow titration!
What do you do to treat opiate-induced respiratory depression?
-If in hospital setting, do not give next dose
-If overdose, try naloxone
Why does pruritis occur with opiate treatment?
central action or direct stimulation of mast cells
What is opiod rotation?
use of a different opiate to control pain and reduce adverse effects if a patient is "poorly responsive" to a treatment (has bad side effects)
What is the triad of opiate overdose?
Why does coma occur with opiate overdose?
decreased cortical stimulation via thalamus and hypothalamus
Why does pinpoint pupils occur with opiate overdose?
Edinger-westphal complex sitmulated
What drugs increase sedation and respiratory depression of opiates?
What is the mechanism by which tolerance occurs with opiates?
recycling of GPCRs
What protein phosphorylates opiate receptors to lead to internalization?
GRK (increases receptor affinity for beta-arrestin which enhances interaction between 2 proteins and leads to internalization)
How does endogenous enkephaline and morphine differ in respect to tolerance?
endogenous enkephalins have a relative balance between sensitization and resensitization while morphine has a slow perisstent desensitization and little recycling
How has the view of receptor recycling and resensitization changed?
resensitizaiton is now thought to be able to occur without the need for internalization (receptor dephosphorylation can occur if GRK2 and beta-arrestin proteins are inhibited with pharmacologic agents)
List the 3 opiate antagonists.
Which opiate antagonist has a very short half-life (30-80 minutes)?
Which opiate antagonist has a long half-life and can be used to treat opiate addiction and decrease alcohol cravings?
What is the indication for naloxone?
Opiate toxicity (treat respiratory depression or progressive obtundation suggestive of imminent decline)
Which opiate antagonist can precipitate withdrawal in dependent patients?
Which opiate antagonist can cause abstinence, aspiration and severe pain?
What precipitates opiate withdrawal symptoms?
when the levels of opiate in the blood decline below a threshold level
What are the symptoms of opiate withdrawal?
-Drug seeking (craving)
-Crawling sensation of skin, diaphoresis, rhinorrhea
-Anxiety, fear, sleep disturbance
-Nausea and diarrhea
Which symptoms are NOT present in opiate withdrawal?
HTN, tachycardia, hallucinations, seizures, fever, delirium
What signs are present in opiate withdrawal?
What is the short-term treatment for opiate withdrawal?
What is the long-term treatment for opiate withdrawal?
clonidine for 21 days
What receptors does clonidine bind to?
alpha-2 receptors that are regulators at both pre-synaptic and post-synaptic sites
What symptoms of withdrawal does clonidine NOT help with?
What is the characteristic molecular occurence in addiction?
surge of dopamine signaling in the nucleus accumbens
What causes the surge of dopamine signaling in the nucleus accumbens during addiction?
-Activation of ionotropic receptors
-Modulation of biogenic amine transport
All addictive drugs increase dopamine concentration in what structure?
True or false: every patient with physical dependence to opiates will become addicted.
What is addiction?
compulsive, relapsing drug use despite negative consequences
What treatment for opiate addiction has a very poor adherence?
What treatment for opiate addiction is favored in pregnant women?
Methadone (may need to increase dose in 3rd trimester)
Which treatment for opiate addiction requires a special state and federal license?
What treatment for opiate addiction is given in combination with naloxone?
Why do you give naloxone with buprenorphine?
because naloxone only works parenterally, so if the patient tries to crush up the pill and inject it to get high, it will activate the naloxone (which antagonizes the effect of the buprenorphine)
How does naltrexone block alcohol dependence craving?
block elevation of dopamine levels arising from signals in the VA and arcuate nucleus
List the NMDA antagonists.
When do you use ketamine?
-Prevent surgery-induced sensitizaiton
-acute, severe pain
When do you use dextromethorphan?
-Post-operative or chronic pain
What are the toxicities of ketamine?
increased intracranial pressure
What are the toxicities of dextromethorphan?
List the TCAs used for pain disorders and depression associated with chronic pain?
How do TCAs work in treating pain?
NE and 5-HT reuptake properties in ascending corticospinal monoamine pathways
Which anticonvulsants are used for ancillary pain?
Which anticonvulsant can be used to treat trigeminal neuralgia and ancillary pain?
Which anticonvulsant can be used to treat neuropathy, phantom, stroke and MS?
What anti-convulsants work by blocking Na+ channels that get upregulated in neuropathic pain?
What anti-convulsants work by inhibition of voltage gated Ca2+ channels via the alpha-2-delta subunit (prevent trafficking to the cell surface)?
Which CYP interactions do TCAs have?
Which anticonvulsant has a BBW for Stevens Johnson Syndrome?
Which anticonvulsants are dose adjusted in hepatic failure?
Which anticonvulsants are dose adjusted in renal failure?
Which anticonvulsants have an increased risk for suicidal ideation?
Which anticonvulsant is associated with rare agranulocytosis?