Benzodiazepines and Sedative/Hypnotic Drugs Flashcards
BDZs
Z-hypnotics
barbiturates
Miscellaneous
Prev 1st line for anxiety and sleep…used for acute/short term anxiety tx
DOC for sleep
Primary prior to BDZs…now used as antiepileptics
OTC meds contain antihistmaines
Sdative hyponitcs
Dose-dependent CNS depressant effects
Sedatives- decrease aniety excitement, and produce calming
Hypnotics - dowsiness and for sleep
Dose-dependency of BDZs and barbs
At higher doses, barbs depresss breathing
Low dose - anxiety, anticonvulsant, muscle relaxer
Mod - sleep
High - anestheti
BDZ safety
Not general CNS depressatns like Barbs (no resp effect)
Severe overdose can occur if dosing with other things
MOA of BDZs
GABAA receptor chloride ion channels in the CNS
GABA binds to receptors and opens Cl channel, CL hyperpolarizes cell
BDZs are allosteric modulators because bind to other site than GABA
Additive effects can occur wit halcohol
Cross tolerance can occur (alcholoic may be tolerant)
BDZs and Barbs MOA and idfference
Both in GABA cl chennls in CNS
BDZs increase opening frequency
barbs increase opening time
at high doses barbs also bind directly to GABA site
Uses of BDZs
Anxiety insomnia Muscle spasm/spasiticty Epilepsy Sedation Alohol w/d
BDZs for GAD, Panic, social, secondary anxiety
GAD - persistent…alprazolam/lorazepam
Panic - sudden onset…alprazolam/clonazepam
Not good for social
To avoid issues with dependence and w/d
Favor short term with BZDs and use antidepressants for long term
BDZs vs. antidepressants
Benzos can be taken o nas needed basis
Effective immediately
Z-hypotics and definition of insomina
Used for sleep
Over 30 minutes to fall asleep…frequent awakenings…early-morning awakennings, less than 6 horus of sleep
Z-hypnotics things to know
Bind to BDZ receptors on GABAa receptor channel complex
Selective hypnotic effect but NO anxiety effect (or others)
SE - daytime sleepiness, dizziness, headache, confusion
Worry about using with sleep apena
BDZs vs. z-hypnotcis
Resotriave sleep Sleep arch alcohol intx Anterograde amenia Dose in eldery Dep Prescrip duration
Yes - both
Z changes little while trazolam decreaes 3,4, rem
Yes - both
Very little with Z
Reduced
Lower risk in Z
3-6 months for Z, less than a month for BDZ
Diazepam
Used for muscle injuries and muscle spastiicty in degenerative diseases
Increase presynaptic inhibition in the spinal cord
Clonazepam
Reduces spastiity at non-hypnotics doses
More potent and shorter 1/2 life than diazepam
Chronic and acute seizrue tx
Chronic - clonazepman but will get tolerance
Acute - diazepam, lorazepma in the ER…midazolam on the way
midazolam
Used for conscious sedation, muscle relaxation, amneisa, no analgesia
Worry about admin with opiodi bc of hypoxia
Contraindication in patients with narcotics or COPD
Conscois sedation
Minimkkally depressed consciousnness
Ability to maintain airway
Response to commands
Amenisa
Tx of acute alcohol withdrawl
12-48 hours after last drin (tonic clonic seizures)
Typical - prefer diazepam bc longer active metabolites
With cirrhosis - lorazepam bc no heptaic metabolism
Lots of cross tolerance s oup the dose
High potency BZs for anx
Pros - more selective at lower doses and fwerr side effects
Drug dependcy and withdrawl
Alpra
Lora
Clona
High potency BDZ for sleep
Traizolam
Same withdralw issues as above and some amnesia
BDZ and elderly
Reduce dose
Decreased hepatic metabolism in elderly and most metabolized by liver
Long acting
IM acting
Short acting
Very short
Diazepam, clonazepam (1-3 days)
Alprazolam, lorazapeam (10-20 hours)
Traizolam (3-8 hours)
Midazolam (1-6 hours)
BDZ absorption and distributuon
Lipophilic so quikc absoprtion
Raid uptake to brain and other highly perfused
BDZs are redistributied…faster for more lipid soluble (diazapm most*)…more pronounced in acute admin (seizures)
Cross placenta and secreted into breast milk so contraindicated
BDZs lipophilicity
Diazepam is most
Rate of onset of action determined by this
Diazepam better at stopping seiures but could also have them reappear because exits brain faster
Metab of BDZs
Diazepam to active metabolite
Half life of active is greater than parent
Lorazepam and alprazolam are shorter 1/2 and are quickly eliminated
Diazepam metab
Oxidation to active metabolite
Hydroxylation to another active
Conjugated to glucuornic yileds inactive that is excreted
BDZ interactions and other metab
Lorazepam bypassees phase 1 and has shorter t1/2…all others use phase 1
Phase 1 reduced in elderly and liver d (so use lorzaepaM)
Unlike Barbs, BDZs do NOT induce the heaptic microsomal enzymes
Cimetidine, contraeptivve, fluoxetine, GF juice
Ideal insomnia drug
Rapid onset, approrpaite DOA, and no reidual action
Traizolam is most potent BDZ…tolerance developed in days…use it on as needed basis
Adverse effects of BDZs and Z-hypnotics
Drowsiness and confusion
Motor
Cog impairment
Anterograde amnesia (more if IV, more with BDZs and alcohol)
Minimizing abuse and dep
W/d will occur on abrupt discontinuation
Gradual drug tapering needed
BDZ w/d
Severity depends on poetncy, dose, duration and t1/2
With long half life, have slef-tapering effect
Rbound insomnia and anxiety more iwth more potenty or shrt acting
Elderly Liver dz COPD Obsturctive sleep apnea Alcohol Pregnancy
Use lower doses, shorter 1/2 and no active mtabolites…hip fracutres
Use no active metabolites
Midazolam is porblem
Use caution
Additive effect and can leadto resp depression
Cross placenta nd enter breast milk
Buspirone
Acts at 5-HT1a receptors
Partial agonist (reduces activity)
Selective anxiolytic effect with minimkal CNS depression
No dependcence or w/d
No cross tolerance wit hBDZs
No alcohol intx
Very slow onset so good for elderly of sub abuse probs
Sme nervousness and tachy
Used for anxiety
Flumazenil
Reverses BDZ induced conscious sedation or BDZ overdose
Alpra Clona Dia Lora Tria Mida Zolp Fluma BUsp
Anx Anx, seiz Anx, seiz, muscle spaz, alc w/d Anx Insom Conscious sedation and anxiety Insom Reersal of BDZs Axiety
