Sedative, Hypnotics, Anxiolytics And Narcolepsy

Question 1

Barbiturates - MOA and Uses

Answer 1

Bind Cl- channel and increase duration of channel opening which facilitates GABA’s action

Can directly open channel without requiring GABA - no ceiling effect

Uses - anxiety and insomnia, seizures (phenobarbital) and induction of anesthesia (thiopental)

Pentobarbital, secobarbital, phenobarbital, amebarbital, thiopental

Question 2

Barbituates - effects and toxicities

Answer 2

Respiratory arrest - needs supportive care and alkalinization of urine

Induce CYP450

Thiopental - lipid soluble and redistributes from CNS

Increased half-life in elderly and liver disease pt’s

Highly sedative - hangover effect

Tolerance and withdrawal

Question 3

Benzodiazepines - MOA and Uses

Answer 3

Potentiates GABA by increasing frequency of Cl- channel opening. Requires GABA to open the channel - meaning there is a ceiling effect (safer)

Use - anxiety , sedative/hyptonic, insomnia, muscle relaxant, anticonvulsant

Question 4

Chlordiazepoxide and Diazepam

Answer 4

Benzodiazepines - Long acting

used for alcohol detoxiification

Question 5

Alprazolam

Answer 5

Benzodiazepines - short acting

Panic disorder

Question 6

Lorazepam, Clonazepam, Diazepam

Answer 6

Benzodiazepines

Seizure disorder —- status epilepticus

Question 7

Midazolam

Answer 7

Benzodiazapine

anesthesia

Question 8

Estazolam and Flurazepam

Answer 8

Benzodiazepines

Insomnia

Question 9

Which benzo’s. Have metabolites which extend their length of acction?

Answer 9

Chlordiazepoxide

Diazepam

Flurazepam

Question 10

Which benzodiazepines are safe for elderly patients?

Answer 10

Oxazepam, temezepam and lorazepam

These bypass phase I metabolism and are metabolized by conjugation

Question 11

What is the antidote for benzodiapzepine toxicity?

Answer 11

Flumazenil

Antagonist the the binding site of benzo’s

Toxicities - agitation, confusion and the withdrawal symptoms from Benzos

Question 12

Toxicity of benzo’s

Answer 12

Drowsiness and hangover

Mild euphoria

Anterograde amnesia

Physical dependence and tolerance

Withdrawal - rebound anziety, insomnia and seizures

Fetal malformations

Question 13

Non- benzodiazepines (zdrugs)

Answer 13

Zolpidem, zaleplon and eszopiclone

Minor effect on REM sleep

Shorter duration of action

Less hangover effect

Targets GABAa subunit

Potentiated by ethanol

Question 14

Ramelteon/Tasimelteon

Answer 14

MT-1 and MT-2 melatonin agonist

Has no effect on GABAergic neurotransmission

Substrate for CYP 1A2

Melatonin - released from pineal gland, produces drowsiness, ussed for jet lag

Question 15

Other sedative drugs

Answer 15

Suvorexant - orexin antagonist

H1 receptor antagonists

TCA - doxepin

Ethanol

Question 16

Ethanol

Answer 16

Release NE - explains the cardio effects

Thiamine deficiency (wernickes) - give long-acting Benzo and thiamine

Fetal alcohol syndrome

Zero order kinetics

Induces CYP 2E1 - acetaminophen toxicitity

Increased inflammation - neoplasia

Loss of liver function

Question 17

Alcohol withdrawal

Answer 17

Seizures, alcohlic hallucinosis, delirium tremens

Question 18

Zolpidem Eszopiclone Zaleplon

Toxicities

Answer 18

Anterograde amnesia

Hallucinations

Delusions

Impaired Judgement

Sleepwalking

Question 19

Amphetamine///Dextroamphetamine

Answer 19

CNS stimulation - inhibits reuptake of NE and DA and increases their release from nerve terminals

Used for narcolepsy

Sympathomimetic effects - cardiostimulation, insomnia and weight loss

Question 20

Methylphenidate- modafanil

Answer 20

Inhibit DA reuptake

Used for narcolepsy

Produces less anxiety and anorexia than amphetamines

Question 21

Propranolol

Answer 21

Beta1 and beta 2 antagonist

Blanks SANS contribution to anxiety - used for situational anxiety

Toxicities - CNS depression, fatigue, bradycardia, asthma, hypoglycemia

Question 22

Buspirone

Answer 22

5-HT agonist

Used for generalized anxiety without sedation or addiction

Toxicities headache dizzy, nervous