Anxiolytics&Sedative

Question 1

Benzodiazepines can be used for

Answer 1

• generalized anxiety disorders
• panic disorders
• social anxiety disorders
• performance anxiety

Question 2

Buspirone can be used for

Answer 2

• generalized anxiety disorders

- social anxiety disorders

Question 3

Tricyclic can be used for

Answer 3

panic disorders

Question 4

SNRIs can be used for

Answer 4

• generalized anxiety disorders

- social anxiety disorders

Question 5

selective 5-HT uptake inhibitors can be used for

Answer 5

• generalized anxiety disorders
• panic disorder
• OCD
• social anxiety disorders
• performance anxiety

Question 6

what can MAO inhibitors be used for

Answer 6

-performance anxiety

Question 7

Gabapentin pregabalin can be used for

Answer 7

-social anxiety disorders

Question 8

what is the main drug used for the short-term treatment of generalized anxiety disorder and sleep disorders

Answer 8

benzodiazepines

Question 9

what is the MOA of benzodiazepines

Answer 9

• release of GABA in GABA containing neurons
• release of GABA opens Cl- channels on the postsynaptic site
• Cl hyperpolarizes cell, making it more difficult to depolarize, therefore reducing neuronal excitability
• binding of GABA is enhanced by benzodiazepine resulting in greater chloride entry
• benzodiazepines facilitate GABA-ergic neurotransmission and potentiate postsynaptic inhibition by binding to sites on the receptor complex and allosterically increasing the affinity of GABA receptors for GABA and increasing the amount of chloride current generated by GABA receptor activation

Question 10

what drugs affect GABA/BZD receptors

Answer 10

• BZD receptor agonist (Zolpidem)
• Omega site (Zaleplon)
• Zolpiclone (GABA/BZD site)
• BZD antagoinst (Flumazenil)
• inverse agonist (experimental)

Question 11

pharmacological action of Benzodiazepines

Answer 11

• sedation/sleep induction
• anti-anxiety
• skeletal muscle relaxation
• anticonvulsant
• anterograde amnesia

Question 12

how do Benzodiazepines induce sedation/sleep induction

Answer 12

• low doses decrease activity and reduce conscious excitability; larger dose promote sleep
• excessive doses cause stupor/light coma w/o respiratory failure
• rapid tolerance develops to sedation

Question 13

how do Benzodiazepines induce anti-anxiety

Answer 13

• reduce the negative effects of punishment and produce disinhibition
• tolerance does not develop readily to these actions

Question 14

how do Benzodiazepines produce skeletal muscle relaxation

Answer 14

-exert depressive effects on multi synaptic pathway used in flex reflexes; they also decrease spasticity

Question 15

how do Benzodiazepines produce anticonvulsant effects

Answer 15

• effective, rapid acting anticonvulsants

- tolerance may develop quickly

Question 16

what effects do Benzodiazepines have on respiration

Answer 16

• sedative hypnotic doses of BZDs do not exert significant effects on respiration in normal subjects
• may worsen sleep apnea

Question 17

what effects do Benzodiazepines have on the CV sytem

Answer 17

• CV effects are minor

- some coronary vasodilation may occur after i.v. admin

Question 18

what effects do large IV doses of BZDs for preanesthetic medication have

Answer 18

depress alveolar ventilation and BP

Question 19

pharmacokinetics of BZDs

Answer 19

• single doses [absorption; lipid solubility (Kp)]

- chronic doses (active metabolites)

Question 20

metabolism of BZDs

Answer 20

-some converted to an active metabolite

Question 21

metabolism of Oxasepam and Lorazepam

Answer 21

no active metabolites

Question 22

Metabolism of Alprazolam

Answer 22

short-lived active metabolite

Question 23

AE of BZDs

Answer 23

• varying degree of CNS impairment
• dose-related dizziness, lightheadedness, motor dysfunction
• anterograde amnesia/memory impairment

Question 24

tolerance of BZDs

Answer 24

-develop to the sedative and ataxic effects of the benzodiazepines w/ continued administration of the same dosage

Question 25

tolerance of the anti anxiety effect of BZDs

Answer 25

-tolerance develops slowly and has relatively minor consequences

Question 26

tolerance to the hypnotic effect of BZDs

Answer 26

- rapidly develop (tachphylaxis) | - respiratory and CV depressant effects w/ overdosage

Question 27

depending on the dose and pd of use, discontinuation of BZDs may result in the appearance of symptoms that can be classified as

Answer 27

rebound recurrence withdrawal

Question 28

drug interactions w/ BZDs

Answer 28

CNS depression | hepatic metabolism

Question 29

what are other uses of BZDs

Answer 29

alcohol withdrawal seizure disorders spasticity localized skeletal muscle spasm preanesthetic medication induction of sedation or amnesia prior to certain procedures reduction of periodic movements in sleep

Question 30

use of Buspirone

Answer 30

antianxiety

Question 31

MOA of Buspirone

Answer 31

partial agonist at 5-HT 1A receptors; also has moderate to weak affinity for DA2, 5-HT2, and alpha2 adrenoceptors

Question 32

how does Buspirone different from BZDs

Answer 32

- lacks sedative-hypnotic, anticonvulsant, or muscle relaxant properties - does not cause memory impairment or psychomotor deficits - dependence liability appears to be negligible - one to 2 weeks are required for onset of anti anxiety effects - has also been used in treatment of depression or to augment the actions of actions of antidepressants in depression, OCD, and smoking cessation

Question 33

MOA of barbiturates

Answer 33

- reversibly depress activity of excitable tissues; CNS most sensitive - potentiation of GABA at lower doses - decrease in Ca currents and glutamate depolarization - direct impairment of Na+ and K+ channels at higher [ ]

Question 34

name a long acting barbiturate

Answer 34

phenobarbital

Question 35

medium-short acting barbiturates are

Answer 35

secobarbital, pentobarbital, amobarbital

Question 36

short acting barbiturates are

Answer 36

thiopental; thioamyl; methohexital

Question 37

MOA of low dose barbiturates

Answer 37

potentiate GABA action

Question 38

MOA of large dose barbiturates

Answer 38

- directly impair Na+ and K+ channel operation | - direct depression of neuronal activity

Question 39

pharmacodynamics of barbiturates

Answer 39

- depression of the CNS sedation --> [paradoxical agitation] --> hypnosis --> anesthesia --> coma --> death - respiratory depression - CYP enzyme induction

Question 40

pharmacokinetics of barbiturates

Answer 40

- weak acids that are well absorbed orally | - distribution, in turn is related to lipid solubility and plasma and protein binding

Question 41

how are barbiturates metabolized

Answer 41

- redistribution from brain to less well vascularized tissues - hepatic metabolism - alkaline urine enhances excretion, particularly of phenobarbital

Question 42

AE of barbiturates

Answer 42

-CNS related; drug hanover; rarely, connective tissue disorders

Question 43

precaution of barbiturates

Answer 43

- acute intermittent porphyria - addiction - drug interactions - P450 enzyme induction - additive effects w/ other CNS depressants

Question 44

therapeutic uses of barbiturates

Answer 44

Epilepsy (phenobarbital; primidone) Intravenous anesthesia Kernicterus of the newborn (historical) Sleep induction; daytime sedative or “anxiolytic” (replaced by BZDs)

Question 45

Miscellaneous agents

Answer 45

``` Paraldehyde Chloral hydrate Meprobamate Trazodone OTC sleep aids (antihistamines) ```