Sedative Hypnotics

Front 1

What is a sedative/anxiolytic agent

Back 1

An effective sedative/anxiolytic agent should decrease anxiety and, exert a calm effect

Front 2

What is a hypnotic effect

Back 2

A hypnotic drug should produce drowsiness and encourage the onset and maintenance of a state ofsleep though easily aroused from.

Front 3

Difference between hypnotics and sedatives

Back 3

Hypnotic effect involves a more pronounce depression of theCNS than sedation, and this can be achieved by increasing the dose

Front 4

Classes of sedative hypnotics

Back 4

1) Benzodiazepines

2) barbiturates

3) z-compounds

4) miscellaneous

Front 5

Classification of the Benzodiazepines

Back 5

A) Ultra short acting (>lhr) eg RemimazolamB) Short acting (3-5hrs) eg Triazolam, eszopiclone, Midazolam (TRIA and MIDA ZOLAM and ESZOPICLONE) C) Intermediate acting (6-24hrs) eg Estazolam, Temazepam, lorazepam, oxazepam, Nitrazepam, Clobazam, bromazepam, alprazolam.D) Long acting (24-72hrs or more) eg Diazepam, Flurazepam, Quazepam, Clorazepate, Chlordiazepoxide.( Dia, Flura, Qua ZEPAM and Clorazepate)

Front 6

Classification of the barbiturates

Back 6

A) Ultra-short acting; duration of action is > 0.5 hrs. They include the following: Thiopental, Methohexital and Thiamylal.B) Short acting; Duration of action is 3-4 hrs eg Pentobarbital

C) Intermediate acting:Duration of action is 4-6 hrs. They include the following: Amobarbital, Aprobarbital, Butabarbital and bultalbitalD) Long acting: duration of action is 6-12 hrs eg Mephobarbital, Phenobarbital

Front 7

Z compounds are also called

Back 7

The newer Hypnotics or non Benzodiazepines

Front 8

Examples of the z-compounds

Back 8

zolpidem, zaleplon, eszopiclone, zopiclone

Front 9

Examples of miscellaneous sedative Hypnotics

Back 9

1) alcohols(chloral hydrate, meprobamate)

2) ramelteon and glutethimide

3) tasimelteon

4) suvorexant and almorexant

Front 10

MOA of ramelteon

Back 10

Ramelteon is a melatonin I and 2 receptor agonist (MT1 and MT2)

Front 11

Use of tasimelteon

Back 11

Insomnia

Front 12

MOA of suvorexant and almorexant

Back 12

They are the orexins receptor antagonists; they improve sleep duration

Front 13

Which sedative Hypnotics have extremely high rate of absorption

Back 13

Alprazolam and Triazolam

Front 14

Duration of action of Triazolam and thiopental

Back 14

Rapid onset and short duration of action due to increase lipid solubility

Front 15

Why should sedative-hypnotics be avoided in pregnant and breast feeding mothers

Back 15

They cross the placenta also enter breast milk

Front 16

Metabolites of the sedative Hypnotics

Back 16

Desmethyldiazepam is the metabolite of clorazepate(a prodrug), diazepam, priazepam, and Chlordiazepoxide

Front 17

Why is Triazolam used as a hypnotic instead of a sedative

Back 17

Decreases elimination half-life of about 2-3hours

Front 18

Which sedative-hypnotic metabolites are excreted via the kidney

Back 18

water soluble metabolites of most sedative-hypnotics are excreted mainly via kidney a.g lorazepam and oxazepam

Front 19

Which metabolites are excreted via the liver

Back 19

diazepam and chlordiazepoxide accumulatein the liver).

Front 20

Which BZDP causes decrease in respiratory rate

Back 20

Midazolam

Front 21

MOA of Benzodiazepines

Back 21

Benzodiazepines bind to allosteric site (at BZ site) of GABA-A receptor-chloride ion channel to cause increase in frequency of channel opening events to enhance GABA-ergic transmission

Front 22

MOA of barbiturates

Back 22

Barbiturates bind directly to the receptor-channel complex which increases the durationof the channel opening events. Barbiturates (at high doses) also cause direct activation ofchloride channel. They also bind to AMPA to depress excitatory transmission of glutamicacid. These multiple actions of barbiturates result in their more pronounced dangerousCNS depressant effects.

Front 23

MOA of Z-compounds

Back 23

Z-compounds which are the newer agents are Nonbenzodiazepines which are selective agonist at BZ site of GABAA thus potentiate GABA-ergic transmission.

Front 24

Examples of sedatives and anxiolytics

Back 24

Alprazolam, Buspirone, Clorazepate, Chlordiazepoxide, Diazepam, Halazepam, Lorazepam, Oxazepam

Phenobarbital

Front 25

Examples of hypnotics

Back 25

Flurazepam, Estazolam, Triazolam, Quazepam, Temazepam, Flurazepam, Chloralhydrate, Amorbarbital, Butabarbital, Pentobarbital, Secobarbital, Eszopiclone, Zaleplon, zolpidem

Front 26

Drug interactions of sedative hypnotics

Back 26

The most common drug interactions involving sedative-hypnotics are nteractions with otherCNS depressant drugs, leading to additive effects.(increased CNS depression)

Front 27

Examples of drugs that increase the CNS depression when taken with sedative hypnotics

Back 27

alcoholic beverages, opioid analgesics, anticonvulsants, and phenothiazines. Less obviousbut just as important is enhanced CNS depression with a variety of antihistamines,antihypertensive agents, and antidepressant drugs of the tricyclic class.

Front 28

Uses of sedative hypnotics

Back 28

a) Relief of Anxiety

b) Relief of Insomnia

c) For sedation and amnesia in pre/post medical surgery procedures

d) For treatment of epilepsy and seizures

e) As a component of balanced anesthesia

f) For control of ethanol/other sedative-hypnotic withdrawal states

g) For muscle relaxation in specitic neuromuscular disorder

h) As diagnostic aid

I) For treatment in psychiatry

Front 29

Pharmacological effects of sedative hypnotics

Back 29

1) sedation2) hypnosis3) anesthesia4) anticonvulsants5) muscle relaxants6) effect on respiration and cardiovascular function

Front 30

How hypnotics affect sleep

Back 30

A) decrease time to fall asleep B) decrease REM(Rapid eye movement) duration C)decrease stage 4 NREM duration D) increase stage 2 NREM

Front 31

How sedative hypnotics cause anaesthesia

Back 31

Barbiturates (such as thiopental and methohexital) and Benzo diazepines(like Diazepam, Lorazepam and Midazolam) depress the CNS to the point known asstage 3 of general anesthesia upon IV administration.

Front 32

Which sedative Hypnotics cause muscle relaxation

Back 32

Meprobamate(anxiolytic drug) and Benzodiazepines

Front 33

Which sedative have cannot cause muscle relaxation

Back 33

Nonbenzodiazepines

Front 34

Disadvantages of Benzodiazepines

Back 34

1) tolerance

2) dependence

Front 35

Which drug is used to manage benzodiazepine poisoning

Back 35

1) flumazenil- it is a BDZP receptor antagonist

Front 36

MOA of flumazenil

Back 36

Have short half-life of about lhr thusmaybe given repeatedly. It blocks action of benzodiazepines and non- benzodiazepines as well asinverse agonists.

Front 37

Side effects of flumazenil

Back 37

Adverse effects of flumazenil include agitation, confusion, dizziness, andnausea. In patients who have ingested benzodiazepines with tricyclic antidepressants, seizuresand cardiac arrhythmias may follow

Front 38

MOA of inverse agonists of GABA-A

Back 38

inverse agonists act as negative allosteric modulators of GABA receptors. They produce effectsopposite to benzodiazepines in the absence of benzodiazepine-like agonist (they can blockbinding of and effects of benzodiazepines eg beta-carbo lines).

Front 39

Other agents that possess sedative-hypnotic properties

Back 39

A) Alcohols and aldehydes eg para lde hyde and chloral hydrate.

B) Acetylene derivatives like methy lpentynolC) Acyclic Nitrogen-containing hypnotics e.g Meprobromate and oxanamide.D) Piperidinediones and Quinazolineones eg Methylprylon and ThalidomideE) Inorganic substances e.g Sodium and potassium bromide but they cause brominism, GITand mental disorders, dermatitis etcF) Anti-histamines eg hydroxyzine and diphenhydramineG) Phenothiazines eg promethazineSH) Butyrophenones eg Droperidol