Sedatives/Hypnotics Flashcards by Nathan Hansen

Benzo Receptor Agonists

Z-Hypnotics

BDZ Ant

SRPA

Alprazolam/Clonazepam/Diazepam/Lorazepam?triazolam/midazolam

Zolpidem

Flumazenil

Buspirone

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BDZs def

Sedative-hypnotics that produce dose-dependent CNS depressing effects

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Sedative (anxiolytic)

Hypnotic

Dec activity, excitement, calming

Drowsiness, onset/maintenance of sleep

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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)

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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

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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

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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)

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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)

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BDZ/ Barb action @ Cl channel

BDZ- inc channel opening freq

Barb- inc channel open time
High doses, can bind GABA & potentiate inhibition

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Therapeutic use of BDZs

Anx DO
Insomnia
Muscle spasms/spasticity
Epilepsy/seizures
Sedation for procedures
AW

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BDZ and anx

Chronic primary/secondary, anx w/ other psych illness/ acute anx

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Primary anx

Secondary anx

GAD= alprazolam/lorazepam
Panic- Alprazolam/Clonazepam
Social Anx- BDZ not first line

Due to illness/condition/medication

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BDZ popularity

Effective immediately (AD longer)
As needed basis
AD have neg SE= weight gain/sex dysfunction

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Chronic insomnia

Risk factors

immune dysreg, altered stress response, dec 5HT, WG, DM

HBP, Breathing DO, GI DO, Cancer, Chronic Pain

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Insomnia

> 30 min to fall asleep
Frequent awakenings
Early morning awakenings
<6hrs of sleep

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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

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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

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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