adme Flashcards
paracetamol MOA
central inhibition of cox2 and postagladin synthase
antipyresis via inhibition of PGE2
progress of paraetamol toxicity
hepatic toxicity progresses to hepatic failure , enepalopathy and death within days
what nabqi does on a cellular level
covalently bind cellular proteins altering cell function resulting in cell injury and death
why is it that in paracetamol overdose glutathione is unable to detoxify all nabqi
glutathione reserve falls below 30%
Na acteryl cysteine
restores glutathioneallowing napqi detoxification
direct antioxidant thereforeimoprove organ function and
opioids MOA
opioid actions are mediated through interacctions with mu delta and kappa receptor.
myu rceptor is the primary site of action of opioid analgesics
mu delta and kappa receptors
g protein coupled receptors that are located in the brain and the spinal cord
opipid reeptor agonist, side effects
respiratiory depression (anti-tussive)
deddation
euphoria
opioid toxicity through overdose
causes respiratory depression which can lead to apnea
cessation of breathing
naloxone
antidote for opioid overdose
mu rceptor antagonist -reverses all signs of opioid intoxication
pharmcoology of morphine metabolite. m6g
active metabolite
relative potency depnent on route of administraiton
70-360 x more poretnt folliow icv administation
pharmaoclogy of morpgine metabolite. m36
inactive metabolite
metabolites of morphine and renal impariement
metabolites accumulate in renal impairment
m6g as an analgesic
similar analgesic effect of morphine
fewer side effects.
-less respiratory depression
significant reductions in incidences of nausea and anti emetic
pharmacohenomics, safety and efficacy
genetric polymorphisms in the enzymes responsible for phase 1 and 2 metabolism alter the safety aand efficacy of drugs
phase 1 metabolism of codeine to morphine
cyp2d6
poor metabolizers
poor emtabolised habe a decreased activation of cyp2d6 dependent analgesics
poor metabolisers do not get any analgesic benfits from codeine
sme frequency of side effects as normal metabolisers
ultrarapid emtabolisers
potential for increased risk of production of morphne from codeine
increased risk of opioid related adr
lead to serious complicaiton of opiod toxicity which can be fatal
tramadol metabolism
11 metabolites identified
m1 has the analgesic activity
pharmacological effects tramadol and its metabolites
+- tramadol:weak opioid agonist and serotonin reupake inhibitor
–trmadol:noradrenaline reuptake inhibitor
+-m1:700x greater affinity for mor than parent compound
–m1: mop analgesic activity
opmr1 115 allele
polymorphisms of the mu opioid receptor gene (opmr1) varies opioid response
increase in medication
decrease in pain relief
how can rapid metbaolisers stl benefit from opioids
benefit from a lower dose of opioids
