Sedative Hypnotics

Question 1

classification of sedative-hypnotic Drugs

Answer 1

MN BOOBS

Melatonin Receptor agonists
Non Benzo Benzo-Receptor Agonists (NBBRAs)

Benzodiazepines
Older Sedative Hypnotics
Others: beta blockers, alpha 2 agonists, antihistaminics
Barbiturates
Serotonin 5-HT1A partial agonists

Question 2

what are the benzodiazepines

Answer 2

DMC FLOATT

Diazepam
Midazolam
Clonazepam

Flurazepam
Lorazepam
Oxazepam
Temazepam
Triazolam

Question 3

mechanism of action of benzodiazepines (name them)

Answer 3

diazepam, midazolam, clonazepam, flurazepam, lorazepam, oxazepam, temazepam, triazolam

bind to GABA-A receptors at an allosteric site as a positive allosteric modulator –> activates GABA’s inhibitory actions –> opens Cl channels –> influx of Cl –> hyperpolarization –> inhibits triggering of action potential

Question 4

what are the agonists of benzodiazepine receptors and what effects do they lead to

Answer 4

All the benzos plus the Non-benzo benzo receptor agonist (NBBRAs)

anxiolytic and anticonvulsant effects

Question 5

name the benzodiazepine receptor antagonist and its effects

Answer 5

Flumazenil

blocks action of benzos and NBBRAs

Question 6

what are inverse agonist and its effect

Answer 6

act as negative allosteric modulators of GABA receptor function –> anxiety and seizures

Question 7

action of benzos

Answer 7

Sedation
Anti convulsants
Anesthesia
Muscle relaxation

Question 8

classify the benzos in terms of length of action

Answer 8

Long acting (1-3 days): Diazepam and Flurazepam
Intermediate acting (10-20 hrs): Lorazepam, Alprazolam, Temazepam
Short acting (3 - 8 hrs): Oxazepam and Triazolam

Question 9

what do benzos undergo when being metabolized

Answer 9

Phase I: done by CYP3A4

Phase 2: conjugation to glucuronides to be excreted in urine

Question 10

which benzos don’t undergo the phase I of metabolism and its importance

Answer 10

LOT
Lorazepam, Oxazepam, Temazepam

their metabolism is not affected by liver disease since they skip phase I with CYP3A4 and go right into conjugation to glucuronides

Question 11

benzo used in muscular disorder and why

Answer 11

benzo is a muscle relaxant

Diazepam is used in skeletal muscle spasms and spasticity from degenerative disorders such as MS and Cerebral Palsy

Question 12

benzos used in seizures

Answer 12

Clonazepam: some types of epileptic seizures
Lorazepam: status epilepticus

Question 13

benzos used in management of alcohol withdrawal

Answer 13

DOCC for Ethanol

Diazepam
Oxazepam
Chlordiazepoxide
Clorazepate

Question 14

benzos prescribed for sleep disorders

Answer 14

Flurazepam
Temazepam
Triazolam

Question 15

AE of benzos

Answer 15

Drowsiness and confusion
Ataxia
Cognitive impairment
Psychological effects

Question 16

what is the benzo antagonist and what is it used for

Answer 16

Flumazenil

reverse CNS effects caused by benzo overdose

Question 17

barbituates used as sedative-hypnotics

Answer 17

Phenobarbital
Pentobarbital
Thiopental

Question 18

mechanism of barbiturates used as sedatives (name them)

Answer 18

phenobarbital, pentobarbital, thiopental

• potentiates effects of GABA by increase duration of GABA gated chloride channel opening
• block glutamate receptors
• block high frequency Na channels

Question 19

action of barbiturates in sedative hypnotics

Answer 19

CNS depression
Respiratory depression
Enzyme induction

Question 20

therapeutic uses of barbiturates (aka name what each drug is used for)

Answer 20

• Thiopental - Anesthesia
• Phenobarbital - anticonvulsant; treat hyperbilirubinemia and kernicterus by increasing glucuronyl transferase and bilirubin binding Y protein activity

Question 21

AE of barbiturates (name them)

Answer 21

phenobarbital, thiopental, pentobarbital

CCP3 RAPs in HHD

CNS effects (drowsiness, sluggishness etc)
CYP450 induction
Paradoxical excitement (opp of expected)
Pulmonary insufficiency –> resp depression
Porphyrin Synthesis

Respiratory Depression
Addiction
Poisoning (lead to death)

Heart collapse
Hypersensitivity (allergic rxn)
Drug hangover (effects seen after sleeping)

Question 22

contraindication of barbiturates (name them)

Answer 22

thiopental, pentobarbital, phenobarbital

• Pulmonary insufficiency –> resp depression
• Due to porphyrin synthesis, acute intermittent porphyria, variegate porphyria, hereditary copropporphyria, or symptomatic porphyria

Question 23

what are the non-benzodiazepine benzodiazepine receptor agonists (NBBRAs)

Answer 23

Zolpiden
Zaleplon
Eszopiclone

Question 24

mechanism of non-benzo benzo receptor agonists (NBBRAs) (name them)

Answer 24

zolpiden, zaleplon, eszopiclone

act on BZ1 subtype of benzodiazepine receptors which contain alpha 1 subunit

Question 25

what antagonizes zolpiden

Answer 25

flumazenil - benzo receptor antagonist

Question 26

clinical use of Zolpiden

Answer 26

short term treatment of insomnia characterized by difficulty initiating sleep

Question 27

what metabolizes Zaleplon

Answer 27

aldehyde oxidase and CYP3A4

Question 28

clinical use of Eszopiclone

Answer 28

insomnia –> decreases sleep latency and improves sleep maintenance

Question 29

what is the serotonin 5-HT1A partial agonist

Answer 29

Buspirone

Question 30

action of 5-HT1A partial agonist and what it is used to treat

Answer 30

anxiolytic

anxiety disorders or short term relief of anxiety

Question 31

what is the melatonin receptor agonist and its mechanism

Answer 31

Ramelteon - MT1 and MT2 melatonin receptor agonist

Question 32

what is melatonin receptor agonist used for

Answer 32

Ramelteon

insomnia characterized by difficulty with sleep onset

Question 33

AE of Ramelteon

Answer 33

decrease in testosterone

increase in prolactin

Question 34

what are the older drugs that were used as sedatives

Answer 34

Chloral Hydrate
Meprobamate
Paraldehyde

Question 35

what are the other classes of sedatives

Answer 35

alpha 2 agonist: Clonidine
beta blocker: Propanolol (specific situational phobias and performance anxiety)
histamine receptor blockers: Diphenhydramine, Doxylamine, Hydroxyzine