21-22 Analgesia Flashcards
Where do NSAIDs modulate pain?
at the initial signal transduction, and spinal cord transmission
Where do Na channel blockers modulate pain?
they are local anisthetics that block signal conduction in nociceptive fibers
Where do opioids modulate pain?
spinal cord and central perception
How do NE, GABA, endogenous opiates, endorphin, and encephalin inhbit spinal cord transmission?
they decrease pre-synaptic Ca entry and activate post-synaptic K channels to hyperpolarize the cells.
What receptor is involved in pain sensitization? What drugs inhibit it to prevent it?
NMDA. inhibited by ketamine and dextromethorphan
MOA of ketamine
NMDA inhibitor. Prevents pain sensitization
??
ADE of ketamine
hallucinations, amnesia, HTN (intracranial too)
MOA of dextromethorphan
NMDA inhibitor. Prevents pain sensitization
antitussive that acts on CNS cough center.
ADE of dextromethorphan
dizzy, confusion, fatigue.
Hallucinations when abused.
What effect do substance P (SP) and CGRP have?
generate inflammatory response and alter pain perception
What is a treatable cause of neuropathic pain? What drug would you use?
Na channel expression changes.
Na 1.3 goes up and cells are more easily excited.
Carbamazepine is a Na channel blocker used to treat trigeminal neuralgia and such neuropathic pain
MOA of carbamazepine
Na channel blocker. Can prevent neuropathic pain
ADE of carbamazepine
??
Which opioid receptor suppresses respiration and GI motility heavily?
OP-3 (mu)
Which opioids have the highest oral:IV potency ratio and what does that mean?
methadone, and meperidine slightly less so.
means that oral dosage requirement is similar to the IV dose, whereas a low oral:IV potency ratio would mean you need to give a lot more orally to equal what IV can do.
Which opioid is IV only?
remifentanil
Which opioids are mu (OP-3) selective?
H-FORMMM
hydromorphone, fentanyl, oxymorphone, remifentanil, methadone, and morphine (morphine has slight k (OP-2) action)
What drug has analgesic effects due to its metabolism in the body?
codeine and oxycodone, metabolized in part to morphine. Only effective after oral administration.
Which opioids act mainly on k (OP-2) receptor?
butorphanol, nalbuphine and pentazocine
Which opioids are delivered transdermal via patches?
fentanyl
Can morphine be given orally?
could, but it suffers from high first pass, unlike codeine and oxycodone, so oral dose has to be huge and that’s not recommended
How does sensitization to opioids occur?
GRK increases receptor affinity for beta-arrestin that leads to receptor internalization.
Which side effects of opioids do patients never really develop tolerance too?
miosis, constipation and convulsions
squint, shit and shake
What is major stimulatory transmitter for GI peristalsis?
Ach. Opioids inhibit it.
What is a benefit of fentanyl
less constipation than oral sustained release morphine
What is classical triad of opiate overdose?
coma, pinpoint pupils and respiratory depression
What are the opiate antagonists?
the Nal’s. Naloxone, naltrexone, and nalmefene.
Which opiate antagonist is used to treat opiate intoxication and why?
Naloxone because it has short duration of action
Which opiate antagonist is used to treat addiction and why?
naltrexone becuase of longer duration.
Or buprenorphine mixed with naloxone
How is naltrexone useful for alcoholics?
decreases alcohol craving in alcoholics by decreasing baseline B-endorphin release
What is an absolute contraindication of opiates?
MOA inihibitors because it will cause hyperpyrexic coma.
Also be careful with antipsychotics and sedatives.
ADE of meperidine?
is converted to normeperidine witch isn’t as potent of an analgesic but 3x more toxic to CNS.
Inhibits 5-HT and NE reuptake.
Which opiate is used to withdrawal treatment?
methadone because of its long elimination half-life.
clonidine because it treats drug craving, sweating, piloerection, anxiety and agitation (patient will still have insomnia, cramps and GI symptoms)
Symptoms of opiate withdrawal?
agitation, diaphoresis, heavy lacrimation, piloerection and dilated pupils
What is mechanism of naloxone?
IV only opiate antagonist. Mixed with buprenorphine (to treat dependence) to prevent abuse and help cure addiction. When taken orally it has no effects.
What is drug of choice for opiate-dependent preggers?
methadone
ADE of methadone?
QTc prolongation and arrhythmia.
Reduced testosterone and libido, ED.
What is used to identify morphine, heroin, hydrocodone and codiene use?
EIAs(antibody enzymatic immunoassays). Downfall is it won’t pick up synthetics like fenatyl
MOA of gabapentin?
upregulate Ca channels via alpha-2delta subunit to prevent trafficking to cell surface. Inhibits neuron excitability.
MOA of lamotrigine?
Na channel blocker useful for Neuropathy and phantom limb
ADE of lamotrigine?
BBW for rash and steven-johnson syndrome.
Diplopia and rarely hematologic toxic.
MOA of loperamide?
nonprescription opioid agonist used to treat diarrhea. No BBB access so no analgesia
MOA of diphenoxylate? What is it mixed with to prevent abuse?
prescription opioid agonist used for diarrhea. High doses can have analgesic effect. Atropine to prevent abuse
