Exam review Flashcards
MOR Specificity
endorphins>enkephalins>dynorphins
DOR specificity
enkephalins
KOR Specificity
dynorphins
key features: structure of opioid receptor
–extracellular and intracellular loops: ligand binding and signaling
-intracellular C terminus including phosphorylation sites
-extracellular N-terminus including glycosylation sites
Opioids ascending pathway
-block release of excitatory NTs by blocking Ca channels
-enhance K channels causing hyperpolarization
-as a result, opioid block the release glutamate and substance P
Opioids in descending pathway
-enhance pain relief by reducing the release of GABA
DOR Opioid receptor
-agonist can have analgesic effect
-serious side effects
KOR opioid receptos
-analgesia
psychotomimetic effects
Opioid Receptor Signaling
1)Agonist binds
2) G protein binds
3) Arrestin recruitment, signaling and internalization
4) recycling or degradation
oxycodone metabolism
-3A4 -noroxycodone
-2D6-oxymorphone
Methadone metabolism
-3A4, 2B6, 2D6
-excreted in urine and bile
Buprenorphine
-partial mu agonist, antagonist
Embeda
morphine + naltrexone
Talwin
Pentazocin+Naloxone
Targiniq
Oxycodone+Naloxone
Simple partial
preserved consciosness
complex partial
impaired consciusness
absence seizure
staring and cessation of ongoing activities
myoclonic seizure
breif shock like contraction
tonic clonic seizure
sustained contraction, relaxation
GABA-B
-metabotropic(G-protein coupled)
-produces slow and prolonged inhibitory signals
Na Channel AEDs
1) Phenytoin
2) Carbamazepine
3) Lamotrigrine
4) Lacosamide
5) Zonisamide
Na fast inactivation
phenytoin and carbamzepine
Na slow inactivation
lacosamide, lamotrigine, valproate, zonisamide
Benzodiazepines
-increase frequency cof channel opening
Barbituates
increase duration of opening chloride channels
-directly activate chloride channels at high concentrations
Zolpidem
-decrease REM sleep but not slow wave sleep
-provides sustained sleep
Zalplon
-decrease latency of sleep onset
-used for patients who wake early in sleep cycle
Eszopiclone
-increase total sleep time
-increase 2 NREM sleep
-decrease REM at high dose
Rebound insomnia
only occurs with zolpidem and zaleplon at high doses
anestesia
diazepam, lorazepam, midazolam
muscle relaxation
-certain benzodiazepines and meprobamate
Buspirone
-anxiety reducing
-substrate of Cyp3A4
Ramelteon and Tasimelteon
-melatonin agonists
-no rebound insomnia or withdrawl effects
Orexin receptor antagonists
-Suvorexant+ first approved for insomnia
-2 others approved recently
Triazolam absorption
absorbed extremly rapidly
Sedative hypnotics PK
-hepatic metabolism
-microsomal oxidation and conjugated to be excreted in urine
Zolpidem PK
-peak levels 1-3 hours
Zaleplon PK
-metabolized by hepatic aldehyde oxidase and CYP3A4
-dose adjustment in elderly or liver issues
Tolerance
Decreased drug responsivness with repeates exposure, often requiring higher doses
Dependenance
-psycological dependance starts as simple behavioral patters
-physiological dependence is when drug is need to avoid withdrawal
Benzodiazepine for withdrawals
diazepam and chlordiazepoxide
treatment for delirium tremens
lorazepam
Toxic effects of sedative hypnotics
-CNS depression
-amnesia
-hangover
-elderly
Alcohol metabolism
-alcohol dehydrogenase
-MEOS
-acetyaldehyde dehydrogenase
What genetic variation is associated with being protective againist alcohol dependence
deficiency of ALDH2
-ADH1*2
Pharmacodynamics of acute alcohol consumption
-sedation, releif of anxiety
-decrease in myocardial contractility
-vasodilator and hypothermia
Short acting benzodiazepines
lorazepam and oxazepam
Naltrexone
-long acting opioid antagonist
-must be opioid free otherwise otherwise precipitates withdrawal
Acamprosate
-weak NMDA receptor antagonist and GABA-A activator
-may reduce relapse rates
Disulfiram
Inhibits aldehyde dehydrogenase
-extreme discomfort after drinking
-adhearence is low
Methanol poisoning
-absorbed through skin or respiratory tract
-slow conversation to toxic metabolites
-treat with fomepizole or IV ethanol
Ethylene glycol poisoning
-sweet taste
-treat with fomepizole or hemodialysis
