CNS Drugs: Interactions & Withdrawal Flashcards
This alcohol tolerance occurs with CYP2E1 induction… it leads to increased EtOH metabolism
pharmacokinetic
The downregulation of GABA receptors and upregulation of NMDA receptors results in what two things?
pharmacodynamic tolerance and withdrawal sxs
Anterograde amnesia occurs with blockade of…
NMDA receptors
What 2 drugs can be administered if seizures due to acute alcohol toxicity?
lorazepam, phenytoin
Chornic alcohol abuse can lead to Wernicke-Koraskoff Syndrome, which is due to a deficiency of…
Thiamine
Which pharmacologic tx for EtOH abuse can be used with liver disease?
acamprosate
What two BZs can be used to prevent seizures in EtOH withdrawal?
diazepam, chlordiazepoxide
what type of tolerance?
increased metabolism
pharmacokinetic
what type of tolerance?
receptor downregulation
pharmacodynamic
the opposite of tolerance is _______, it is increased responsiveness after repeated use. The dose/response curve is shifted ______
sensitization
left shift
does physiologic dependence mean addiction?
no
typically, abused drugs activate the ______
mesolimbic DA pathway (reward pathway)
VTA to NAc to PFC
the below Class I drugs act on what target?
opioids
THC
GHB
GCPRs in VTA
The below Class II drugs act on what target?
BZs
Nicotine
EtOH
Ion Channels in VTA
the below Class III drugs work on what target?
cocaine
amphetamine
ecstasy
transporters in VTA, NAc
Amphetamines can cause increased release of…
DA
this drug reverses DA transport through the DAT
amphetamines
Meth causes a decrease in ____
DA transporters
This drug inhibits DA reuptake leading to postsynaptic receptor downregulation and severe cravings, physical and psych dependence…
cocaine
what differentiates crack cocaine from powder cocaine?
rapid onset
This drug reduces overall brain activity, can cause formications, severe withdrawal and has an intense physiologic dependence
cocaine
Three overdose/toxic effects of chronic cocaine use
arrhythmia
stroke/hemorrhage
seizures
which drug can decrease craving for cocaine?
bromocriptine
This drug blocks reuptake of 5HT and increases expression of 5HT receptors
MDMA
What three complications lead to MDMA fatality?
hyperthermia
dehydration
kidney failure
the intense, depression-like hangover from MDMA is due to…
decreased 5HT
LSD, Mescaline, and psilocybin act on what receptors in the brain?
5HT
Do LSD, Mescaline, and psilocybin cause dependence? why?
no, don’t stimulate DA
NMDA receptor antagonists…
PCP/ketamine
weak GABA receptor agonist…
GHB
PCP psychosis can be treated with…
haloperidol
chronic nitrous oxide use can cause…
peripheral neuropathy
inhalants general have what mechanism?
smooth muscle relaxant
Phenytoin, carbamazepine and phenobarbital induce…
CYP450s
_______ is an anticonvulsant metabolized by, induces and inhibits CYP450s
phenytoin
______ increases the metabolism of anticonvulsants, haloperidol, and OCPs
carbamazepine (CYP450 inducer)
Carbamazepine, phenytoin, phenobarbital metabolism is inhibited by…
valproic acid
carbamazepine metabolism is increased by…
phenobarbital, phenytoin
What increases the metabolism of lamotrigine?
CYP450 inducers (carbamazepine, phenytoin, phenobarbital)
which drug doubles the half life of lamotrigine?
valproic acid (enzyme inhibitor)
Ethosuximide metabolism is inhibited by…
valproic acid (CYP450 inhibitor)
at low doses, valproic acid (induces/inhibits) its own metabolism
inhibits
Withdrawal from anticonvulsants results in…
rebound seizures
OD of anticonvulsant results in
non-fatal CNS depression
The withdrawal from ____ can be severe… it includes the below sxs…
orthostatic hypotension hyperactive reflexes seizures restlessness anxiety weakness
barbiturates
BZs should be prescribed with caution in what population?
elderly
which three BZs can be helpful to provide a tapered withdrawal from alcohol and barbiturates?
chlordiazepoxide, diazepam, lorazepam
abrupt discontinuation of BZs and Z drugs can result in ______, therefore they should be tapered slowly
rebound insomnia, anxiety
Ramelteon when combined with _____ has an additive effect
etoh, sedatives
which spasmolytic is similar to barbiturates and therefore should be used with caution in addicts?
carisoprodol (soma)
TCA metabolism by _____ makes drug interactions common
CYP2D6
tolerance to what three TCA effects can occur
sedation
hypotension
anticholinergic effects
Major issue with TCA toxicity
Torsades/cardiotoxic
TCAs + _____ can cause serotonin syndrome
MAOIs
severe CNS toxicity presented as hyperpyrexia, convulsions, coma
serotonin syndrome
TCAs compete with _____ which can lead to toxicity
SSRIs
TCAs can cause HTN when combined with…
amphetamine
TCAs potentiate the effects of.. (2)
depressants, anticholinergics
SSRIs (induce/inhibit) CYP450 meaning they have many drug interactions
inhibit
SSRIs + MAOIs can cause…
serotonin syndrome
CYP450 inhibition means increased toxicity of what three drugs?
TCAs, phenytoin, carbamazepine
fluoxetine inhibits conversion of this prodrug to active form…
codeine
SSRIs + Meperidine =
serotonin syndrome
SSRIs + tramadol =
seizure risk
MAOIs +
TCAs
Meperidine
DXM
SSRIs
serotonin syndrome (hyperpyrexia)
MAOIs + sympathomimetics (ephedrine, amphetamines)
HTN
MAOIs inhibit ______ which effects SSRI, CCB metabolism
CYP2D6
St. John’s wort + antidepressants =
serotonin syndrome
What drug class should be avoided with…
anticholinergics
sedative hypnotics (supraadditive)
TCAs (seizures, cardiotoxic)
CYP450 inducers (tobb, carbamazepine)
antihypertensives
antipsychotics
Can lithium/antipsychotics be taken with BZs?
yes
lithium + NSAIDs =
increased toxicity
tolerance is not developed for what three effects of opioids
miosis, constipation, seizures
opioid withdrawal can be reduced by use of… (2)
clonidine or methadone
morphine, hydrocodone (prodrug), oxycodone, codeine (prodrug) are metabolized by…
CYP2D6
fentanyl is metabolized by ____ making drug interactions likely
CYP3A4
Tramadol + MAOIs, TCAs, SSRIs =
serotonin syndrome, seizures
L-dopa + MAOI-As =
HTN
L-Dopa + pyridoxine =
increased peripheral metabolism
Apomorphine + odansetron =
HTN
AChE Inhibitors are metabolized by…
CYP450
Memantine cannot be taken with what two drugs?
meperidine, DXM
