Sedatives/Hypnotics Flashcards
Benzo Receptor Agonists
Z-Hypnotics
BDZ Ant
SRPA
Alprazolam/Clonazepam/Diazepam/Lorazepam?triazolam/midazolam
Zolpidem
Flumazenil
Buspirone
BDZs def
Sedative-hypnotics that produce dose-dependent CNS depressing effects
Sedative (anxiolytic)
Hypnotic
Dec activity, excitement, calming
Drowsiness, onset/maintenance of sleep
BDZs use
Z-hyp
Barb
Misc
Acute/short term anx
Antidep favored long term
DOC for sleep
Antiepileptics for HA
OTC sleep meds contain antihistamines (diphen)
Dose-dependent effects
BDZ
Barbs
Low - anx relief, anticonvulsant, muscle relax
Mod= sleep effects
High- anesthetic effects
Same with BDZs, very high doses can dep breathing/lead to coma
Safety
BDZs safe- not general CNS dep (unlike Barb), dont affect CNS resp centers
Safe when alone
Severe overdose can occur if used with S/H/alcohol/CNS depressant drugs
Mech of action of BDZ/Barb
GABA Cl ion channels in CNS (inhib)
GABA- binds neuronal rec, open Cl channel (hyperpolarizes, dec act) Allosteric modulators (bind distinct sites)
Special considerations for BDZ/Barbs
Additive effects- complex has binding sites for other CNS dep (alchol)/ think OD
Cross tolerance- multiple CNS dep sites on single complex (alcholics may be tolerant to BDZ)
BDZ/ Barb action @ Cl channel
BDZ- inc channel opening freq
Barb- inc channel open time
High doses, can bind GABA & potentiate inhibition
Therapeutic use of BDZs
Anx DO Insomnia Muscle spasms/spasticity Epilepsy/seizures Sedation for procedures AW
BDZ and anx
Chronic primary/secondary, anx w/ other psych illness/ acute anx
Primary anx
Secondary anx
GAD= alprazolam/lorazepam
Panic- Alprazolam/Clonazepam
Social Anx- BDZ not first line
Due to illness/condition/medication
BDZ popularity
Effective immediately (AD longer) As needed basis AD have neg SE= weight gain/sex dysfunction
Chronic insomnia
Risk factors
immune dysreg, altered stress response, dec 5HT, WG, DM
HBP, Breathing DO, GI DO, Cancer, Chronic Pain
Insomnia
> 30 min to fall asleep
Frequent awakenings
Early morning awakenings
<6hrs of sleep
Z hyp (Zolpidem)
Bind BDZ receptors on GABAa complex
Selective hypnotic effect
Minimal anxiolytic/anticonvulsant/muscle relaxant
SE- daytime sleepiness, dizziness, HA, confusion
Caution w/ Sleep Apnea
Z hypnotics vs BDZ
Restorative sleep
Sleep Arch
Interaction w Alcohol
AA
Zolpidem- Yes, little change, Yes, Little
Triazolam- Yes, dec stages 3/4/REM, Yes, Yes
Z Hyp vs BDZ
Dose in elderly
Phys dependence
Duration of Px
Zolpidem- Dec, Low risk, 3-6m
Triazolam- Dec, High risk, 1-4 w
BDZ in muscle spasm
Inc presynaptic inhib in SC
Diazepam- muscle injuries, spasticity in deg DO
Clonazepam- red spasticity @ non-hypnotic doses, more potent than diazepam, shorter 1/2 than D
BDZ epilepsy/seizure
Chronic Seizure Tx- Clonazepam (absence)
Acute Seizure Tx- Diazepam (IV), Lorazepam (IV), Midazolam IM
Midazolam
DOC for sedation in procedures
Conscious sedation, muscle relax, amnesia, NO analgesia
Conscious sedation
Min depressed consciousness
Maintain airway
Response to stimulation/verbal commands
Accompanied with amnesia
Midazolam Contraindicated in COPD
Death w/ RA when pt uses narcotics or COPD
BDZ AW
Alcoholism- inc risk of tonic-clonic seizure (12-48 hrs later)
Typ Tx- LA BDZ w active metabolites (ie Diazepam)
Tx with adv cirrhosis- BDZ w/out hepatic met (lorazepam)
Due to cross tolerance, max doses needed
BDZ Potency
Comp to Diazepam L= 5x A= 10x C= 20x T= 40x
High Potency BDZ & Anx
High Potency BDZ & sleep
A/L/C= more selective at lower dose, less SE, inc risk of drug dependency, drug withdrawal issues
T= drug withdrawal issues, amnestic effect
Reduce BDZ dose in elderly
Dec by 1/2 to 1/3
Hep met dec in elderly
BDZ= lot of Hep met
Blood levels elevated if reduced metabolism not accounted for
Considerations with BDZ
Age Liver dz Competing drugs Hx of SUD Duration of action of BDZ
Pharmacokinetics of BDZ
LA- D/C
Intermediate- A/L
SA- T
Very short acting- M
Absorption/Distrib of BDZ
Absorbed quick (Lipophilic) Rapid uptake to brain/HPO Redist to LPT Fastest w/ highest lipid solubility (D) Redis dec CNS effects for acute admin Contraindicated in preg (cross placenta/BM)
BDZ vary in lipophilicity
Rate of OoA determining
D= more lipo than L, stops seizures faster
But shorter 1/2, so seizures reappear
BDZ metabolism
Hep met to water soluble compounds for elim Usually active (greater 1/2 than parent) Mult doses of BDZ w long 1/2 can have lots of SE Shorter 1/2 life= not active, quickly eliminated (L/A)
Diazepam LA
Phase 1A- oxidation yields AM
Phase 1B- hydrox yields AM
Phase 2- conjug to IM, excreted in urine
BDZ Met Cont
BDZ that bypass phase 1= shorter 1/2 (L)
Phase 1 less in elderly/liver dz (use those that bypass phase 1 ie L)
Do not induce hep microsomal enzymes
BDZ/Hypnotic Pathway of Met
Phase 1= A/C/D/Zolpidem
Phase 2= L
Drug inhibition of phase 1
Fluoxetine
Oral contraceptives
Cimetidine
Grapefruit Juice
Insomnia drugs
RO- Triaz/ Zolp
SA- least with Z/T (short 1/2)
Before ZHyp, T used
But very potent, tolerant w/in days (use as needed)
Adverse effects of BDZ and Hyp
Drowsiness/confusion Motor incoordination (high dose) Cog impairment Anterograde amnesia (more potent BDZ & alcohol, as anesthetic, IV) Angioedema Sleep talking/driving/eating
Dissipate in wks
Use caution
Avoid/Minimize probs with Abuse/Dep
Identify suscept pt explain dependence with long term use Taper gradual (withdrawal can occur)
BDZ withdrawal
Symp similar to before using BDZ (insomnia/anx)
Depends on drug potency, dose, duration of use, 1/2
More potent, shorter 1/2= more severe, prevalent
Long 1/2= self tapering effect
withdraw graudally
Contraindications
Elderly= low dose, shorter 1/2, no AM, inc risk of hip fx
LD- dec hep met, no AM
COPD- m exaggerates asthma/bronchitis/COPD
OSA- aggravate sleep breathing DO, use caution with snoring
Alcohol/ others= BDZ effect is additive, lead to OD (resp dep)
Preg/Nursing= BDZ cross BM/placenta
Buspirone
5HT1A receptors
Partial Agonist, red 5HT act
Selective anxiolytic effect, min CNS dep
No phys dependence/wdr/cross tolerance w BDZ/interaction w alcohol
Buspar
Very slow OoA (2-4 wks)
Good for elderly, SUD
Some nervousness, tachycardia
