Sedatives and Hypnotics

Question 1

alpha beta receptor

Answer 1

endogenous agonist: GABA
exogenous agonist: Muscimol
competitive antagonist: Bicucilline

Question 2

Alpha Gamma receptor

Answer 2

agonist: benzodiapene
competitive antagonist: Flumazenil
Inverse agonist: beta carboline

Question 3

blocks cloride pore

Answer 3

picrotoxin

Question 4

ultrashort acting barbiturates

Answer 4

highly lipid soluble - redistribution into fats

1. Thiopentone/Na pentothal - general anaesthetic - inducing agent, narcoanalysis, reduces oxygen demand and is cerbro/cardio protective
   Thiopentone mixed in sodium bicarbonate
   never give intraarterial
2. Methohexitone/Methohexital
   reduces seizure threshold - DOC for ECT in psychiatric disorders, major depression, catatonia

Question 5

ECT

Answer 5

DOC: Methexitone
other barbiturates like Thiopentane
Propofol (most common)
Ketamine: preferred in depression

Question 6

Short acting barbiturates

Answer 6

Butabarbitone, Amobarbitone, Pentobarbitone, Secobarbitone

iv drug to produce sedation or anesthesia

Question 7

Long acting barbiturates

Answer 7

1. Primidone - oral - essential tremors (propranolol and primidone), epilepsy
   primidone (active drug) converted into phenobarbitone (active drugs)
2. Phenobarbitone -
   oral and iv
   metabolised by CYP3A4 + glucuronide conjugation (75%) + rest 25% unchanged, excreted
   DOC for neonatal seizure and neonatal jaundice
   Criggler Najar type 2, Gilbert syndrome
   SE: paradoxical excitation in children (idiosyncratic - suppression of inhibitory neurons) : increased seizures, hyperkinesia, increased pain

Question 8

essential tremors

Answer 8

Propranolol and Primidone

Question 9

clinical features of porphyria

Answer 9

pallor
photosensitivity
craving for blood
abdominal pain, vomiting

Question 10

drugs contraindicated in porphyria

Answer 10

Sulfonamides
Estrogens
Valproate
Ergotamine
Rifampicin
Erythromycin
Phenytoin
OCP
Barbiturates
Alcohol

Question 11

barbiturate poisoning clinical features

Answer 11

unconscious/ comatose and flabby
hypotension and cardiovascular collapse
renal shut down
pulmonary complications
bulbous eruption on skin
respiratory depression

Question 12

treatment of barbiturate poisoning

Answer 12

urea + malonioc acid = barbiturates

1. gastric lavage using activated charcoal
2. supportive measures such as maintenance of blood volume by fluid infusion and use of vasopressors- dopamine may be preferred
3. forced alkaline diuresis using NaHCO3
   4.. hemodialysis and hemoperfusion
4. analeptics - Doxapram and Bemegride
5. picrotoxin is effective

Question 13

Analeptics for barbiturates poisoning

Answer 13

Doxapram, Bemegride

Question 14

BZDs in antiseizures

Answer 14

Diazepam
Lorazepam
Clonazepam
Clobazam
Midazolam

iv Diazepam/Lorazepam - used to control life threatening seizures in status epilepticus (DOC - iv Lorazepam), tetanus, drug induced convulsions, febrile convulsions (Doc - rectal Diazepam; intranasal Midazolam also used)

Clonazepam - absence seizures

Question 15

BZDs in antianxiety

Answer 15

Diazepam
Clonazepam
Oxazepam
Lorazepam
Alprazolam
Chlordiazepoxide

Question 16

Anxiety

Answer 16

performance anxiety - Propranolol
anxiety disorder / neurosis - SSRi
acute anxiety attack - BZD

Question 17

BZDs as preanesthetic

Answer 17

Diazepam
Lorazepam
Midazolam
Remimazolam

sedation, anxiolytic, anterograde amnesia

Question 18

BZDs in insomnia (insomnia and daylight anxiety)

Answer 18

Flurazepam
Triazolam
Estazolam
Quazepam
Temazepam

Hypnosis-
Diazepam
Flurazepam
Nitrazepam
Alprazolam
Lorazepam
Triazolam

Question 19

BZDs as muscle relaxants and miscellaneous

Answer 19

muscle relaxants - all ( Diazepam is a GABA-A agonist and Baclofen (non sedative, non addictive muscle relaxant)is GABA-B agonist)

Delirium tremens - iv Diazepam
Anticipatory vomiting - Lorazepam

Question 20

Date rape drugs

Answer 20

Alcohol (most commonly misused)
Flunitrazepam (Rohypnol) - colourless and tasteless BZD, now banned
Ketamine
Barbiturates and BZDs
Gamma hydroxy butyrate

Question 21

Class B metabolism of BZDs

Answer 21

no CYP3A4 metabolism, inly glucuronide conjugation

Triazolam
Oxazepam
Temazepam
Estazolam
Lorazepam

Question 22

Longest acting BZD

Answer 22

Flurazepam

Question 23

Shortest acting BZD

Answer 23

Remimazolam
Midazolam

Question 24

Max plasma protein bound BZD

Answer 24

Diazepam

Question 25

Least plasma protein bound BZD

Answer 25

Flurazepam

Question 26

BZD with side effect of psychosis

Answer 26

Triazolam

Question 27

BZD with side effect of nightmares

Answer 27

Flurazepam

Question 28

BZD with mood elevating action
BZD with cardio protective action
BZD through many routes

Answer 28

Alprazolam
Diazepam
Midazolam

Question 29

Atypical BZD or Z drug

Answer 29

DOC: Insomnia (Sleep onset insomnia, transient insomnia)

Zolpiclone (longest)
Zolpidem
Zaleplon (shortest)

Eszopiclone
Etizolam

Question 30

Melatonin agonists

Answer 30

Ramelteon - MT1/MT2 agonist
DOC for night workers, jet lag, insomnia in old age

Agomelatine- MT1/MT2 agonist+ 5HT2C antagonist
insomnia and depression

Tasimelteon - maintanence of circadian rhythm in blind

Question 31

New drugs of insomnia

Answer 31

Suvorexant, Lemborexant - orexin antagonist (DORA - dual orexin receptor antagonist)

Promethazine - 1st gen antihistaminic-sedative

Mirtazapine, Mianserin - antidepressants with sedative action in insomnia in atypical depression

Question 32

stages of CNS depression

Answer 32

sedation
↓
hypnotics
↓
muscle relaxation
↓
anesthesia
↓
respiratory depression
↓
coma and death

Question 33

GABA receptor

Answer 33

GABA A (ionotropic)
GABA B (Gi GPCR)
GABA C (ionotropic)