Benzodiazepines and Sedative/Hypnotic Drugs

Question 1

BDZs
Z-hypnotics
barbiturates
Miscellaneous

Answer 1

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

Question 2

Sdative hyponitcs

Answer 2

Dose-dependent CNS depressant effects

Sedatives- decrease aniety excitement, and produce calming

Hypnotics - dowsiness and for sleep

Question 3

Dose-dependency of BDZs and barbs

Answer 3

At higher doses, barbs depresss breathing

Low dose - anxiety, anticonvulsant, muscle relaxer

Mod - sleep

High - anestheti

Question 4

BDZ safety

Answer 4

Not general CNS depressatns like Barbs (no resp effect)

Severe overdose can occur if dosing with other things

Question 5

MOA of BDZs

Answer 5

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)

Question 6

BDZs and Barbs MOA and idfference

Answer 6

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

Question 7

Uses of BDZs

Answer 7

Anxiety
insomnia 
Muscle spasm/spasiticty
Epilepsy 
Sedation
Alohol w/d

Question 8

BDZs for GAD, Panic, social, secondary anxiety

Answer 8

GAD - persistent…alprazolam/lorazepam

Panic - sudden onset…alprazolam/clonazepam

Not good for social

Question 9

To avoid issues with dependence and w/d

Answer 9

Favor short term with BZDs and use antidepressants for long term

Question 10

BDZs vs. antidepressants

Answer 10

Benzos can be taken o nas needed basis

Effective immediately

Question 11

Z-hypotics and definition of insomina

Answer 11

Used for sleep

Over 30 minutes to fall asleep…frequent awakenings…early-morning awakennings, less than 6 horus of sleep

Question 12

Z-hypnotics things to know

Answer 12

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

Question 13

BDZs vs. z-hypnotcis

Resotriave sleep
Sleep arch
alcohol intx
Anterograde amenia 
Dose in eldery
Dep
Prescrip duration

Answer 13

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

Question 14

Diazepam

Answer 14

Used for muscle injuries and muscle spastiicty in degenerative diseases

Increase presynaptic inhibition in the spinal cord

Question 15

Clonazepam

Answer 15

Reduces spastiity at non-hypnotics doses

More potent and shorter 1/2 life than diazepam

Question 16

Chronic and acute seizrue tx

Answer 16

Chronic - clonazepman but will get tolerance

Acute - diazepam, lorazepma in the ER…midazolam on the way

Question 17

midazolam

Answer 17

Used for conscious sedation, muscle relaxation, amneisa, no analgesia

Worry about admin with opiodi bc of hypoxia

Contraindication in patients with narcotics or COPD

Question 18

Conscois sedation

Answer 18

Minimkkally depressed consciousnness

Ability to maintain airway
Response to commands

Amenisa

Question 19

Tx of acute alcohol withdrawl

Answer 19

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

Question 20

High potency BZs for anx

Answer 20

Pros - more selective at lower doses and fwerr side effects

Drug dependcy and withdrawl

Alpra
Lora
Clona

Question 21

High potency BDZ for sleep

Answer 21

Traizolam

Same withdralw issues as above and some amnesia

Question 22

BDZ and elderly

Answer 22

Reduce dose

Decreased hepatic metabolism in elderly and most metabolized by liver

Question 23

Long acting
IM acting
Short acting
Very short

Answer 23

Diazepam, clonazepam (1-3 days)
Alprazolam, lorazapeam (10-20 hours)
Traizolam (3-8 hours)
Midazolam (1-6 hours)

Question 24

BDZ absorption and distributuon

Answer 24

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

Question 25

BDZs lipophilicity

Answer 25

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

Question 26

Metab of BDZs

Answer 26

Diazepam to active metabolite Half life of active is greater than parent Lorazepam and alprazolam are shorter 1/2 and are quickly eliminated

Question 27

Diazepam metab

Answer 27

Oxidation to active metabolite Hydroxylation to another active Conjugated to glucuornic yileds inactive that is excreted

Question 28

BDZ interactions and other metab

Answer 28

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

Question 29

Ideal insomnia drug

Answer 29

Rapid onset, approrpaite DOA, and no reidual action Traizolam is most potent BDZ...tolerance developed in days...use it on as needed basis

Question 30

Adverse effects of BDZs and Z-hypnotics

Answer 30

Drowsiness and confusion Motor Cog impairment Anterograde amnesia (more if IV, more with BDZs and alcohol)

Question 31

Minimizing abuse and dep

Answer 31

W/d will occur on abrupt discontinuation Gradual drug tapering needed

Question 32

BDZ w/d

Answer 32

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

Question 33

``` Elderly Liver dz COPD Obsturctive sleep apnea Alcohol Pregnancy ```

Answer 33

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

Question 34

Buspirone

Answer 34

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

Question 35

Flumazenil

Answer 35

Reverses BDZ induced conscious sedation or BDZ overdose

Question 36

``` Alpra Clona Dia Lora Tria Mida Zolp Fluma BUsp ```

Answer 36

``` Anx Anx, seiz Anx, seiz, muscle spaz, alc w/d Anx Insom Conscious sedation and anxiety Insom Reersal of BDZs Axiety ```