PHARM - Sleep & MS drugs Flashcards
what is the role of the ventrolateral preoptic nucleus (VLPO) in sleep induction?
sleep promotion
- throughout the day, ATP is broken down to adenosine
- accumulating adenosine binds to A1 & A1 receptor on VLPO, a thalamic nucleus
- in resopnse, the VLPO releases GABA & galanin (inhibitory NTs)
- GABA opens Cl- channels, hyperpolarizing the membrane
- APs are mitigated -> sleep induction
what is the role of the lateral nucleus in sleep?
alertness
- lateral nucleus of hypothalamus releases orexin
- orexin projects to arousal regions of the brain:
- locus coerelulus
- tuberomamillary nucleus
what is the role of histaminergic neurons in sleep?
promote alertness
project to tuberomamillary nucleus, an arousal center
list the roles of GABA, melatonin, orexin, histamine in modulating sleep
- GABA - promote sleep
- melatonin - promote sleep
- orexin - promote arousal
- histamine - promote arousal
what are the four classes of hyponotic drugs?
- benzodiazepine-like drugs (GABA enhancers) - induce sleep
- melatonin agonists - induce sleep
- orexin antagonists - block arousal
- histamine 1 receptor antagonists - blcck arousal
what are the two classes of benzodiazepines?
list the drug names, clinical use, and MOA of the drugs belonging to each class.
both classes work by enhancing the affects of GABA.
- benzodiazepine like drugs (BLZs)
- include: zolpidem, zaleplon, eszopiclone
- clinical use: for hypnosis
- MOA: bind selectively alpha-1 subunit containing GABAA receptors
- benzodiazepines
- include: triazolam, - pams
- clinical use: for anxiolysis > hyponosis, anesthesia, muscle relaxation
- MOA: bind less selectively to alpha-1,2,3,5 containing GABAA receptors
describe the structure of GABAA receptors.
why is this clinically relevant?
- all made of 5 subunits: 2 alpha, 2 beta, 1 gamma
- the specific structure of the a-subunit can vary: a1, a2, a,3, a5
- BLZs (hypnotics):
- specifically bind a1 containg receptors
- benzodiazepines (anxiolytics):
- less specifically bind a1-a5 containing receptors
- BLZs (hypnotics):
- the specific structure of the a-subunit can vary: a1, a2, a,3, a5
benzodiazepine like drugs
- includes what drugs?
- clinical use
- MOA
- AE / CI / drug-drug interactions
- drugs: zolpidem, zaleplon, eszolpiclone
- clinical use: for hypnosis
- MOA: bind to alpha-1 containing GABAA receptors & enhance their affinity for GABA
- PK: metabolized by CYP-3A4
- AE / CI / drug-drug interactions:
- AE: drowsiness / insomnolence
- CI: in pt on CNS depressants - opiods, barbituates, ethanol
- drug-drug interactions:
- CYP-3A4 inhibitors: cimetidine, corbistat, ritonavir
- CYP-3A4 inducers: rifampin
- Flumenzenil
BZ-like drugs should be used with caution with patients taking what other drugs?
zolpedem, azleplon, escopiclone
- CYP-3A4 inhibitors (increase half life)
- cimetidine
- cobiscistat
- ritonavir
- CYP-3A4 inducers (decrease half life): rifampin
- competitive antagonists: flumazenil
administration of BZ-like drugs with which other drugs will limit their ability to induce sleep?
why?
zolpidem, zaleplon, eszopiclone
- rifapmin: induces CYP-450, which metabolizes BZ-like drugs
- flumazenil: a competitive antagonist at the BZ-like drug binding site
BZ-like drugs are absolutely contraindicated in patients taking what other drugs?
zolpidem, zaleplon, escopiclone
- CNS depressants:
- opiates
- ethanol
- barbiturates
what is flumazenil?
a competitive antagonist for BZ-like drugs
zolpidem is what kind of drug?
BZ-like drug
zaleplon is what kind of drug?
BZ like drug
eszopiclone is what kind of drug?
BZ-like drug
which BZ-like drug is most likely to cause rebound insonmia?
how does this rebound insomnia present?
zolpidem
insomnia the 1st night after discontinuation after chronic usage