tryptopatz (3FPH)

Sedative: Drugs that calm the patient and reduce anxiety without inducing normal sleep.
Hypnotic: Drugs that initiate and maintain the normal sleep.

tryptopatz (3FPH)

tryptopatz (3FPH)

Highly effective anxiolytic & hypnotic agents Long acting

Binding to benzodiazepine-binding sites on gamma amino butyric acid (GABAA) receptor results to: opening frequency of receptor influx of chloride ions, promoting membrane hyperpolarization = potentiate neurotransmission = increase activity
tryptopatz (3FPH)

Side chains Optimal for tolerated activity Aromatic ring (benzo> heteroaromatic ring INCREASES electronegativity INCREASES the activity
tryptopatz (3FPH)

Diazepine ring OH Non-polar Much more polar INCREASES activity

INCREASES activity
DECREASES activity GREATLY

CHLORDIAZEPOXIDE HCl
7-chloro-2-(methylamino)-5-phenyl-3H-1,4-benzodiazepine-4-oxide monohydrochloride

HCL

tryptopatz (3FPH)

CHLORDIAZEPOXIDE HCl
Uses Treats anxiety Used to relieve fear before surgery

tryptopatz (3FPH)

DIAZEPAM
7-chloro-1,3-dihydro-1-methyl-5-phenyl-1,4-benzodiazepine-2-one

Marks optimal activity

Increases electronegativity & activity

tryptopatz (3FPH)

DIAZEPAM
Uses Anti- convulsant Reduces anxiety, promotes sleep Pre-anesthetic Other info Rapidly and completely absorbed after oral administration
tryptopatz (3FPH)

CLORAZEPATE DIPOTASSIUM
7-chloro-2,3-dihydro-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3carboxylic acid dipotassium salt monohydrate

CO2K or COOH DECREASES activity = POLAR

Increases electronegativity & activity

tryptopatz (3FPH)

CLORAZEPATE DIPOTASSIUM
Uses Anti-anxiety for children Also used for those with psychic troubles and reactional depressions Other info Prodrug Similar clinical properties as Diazepam & Chlordiazepoxide
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FLURAZEPAM
7-Chloro-1-(2-diethylaminoethyl)-5-(2-fluorophenyl)-1,3-dihydro-1,4benzodiazepin-2-one

SAR Metabolism of the dialkylaminoalkyl side chain is extensive.

2-Fluorophenyl INCREASES activity

tryptopatz (3FPH)

FLURAZEPAM
Uses Mainly treats insomnia Anxiolytic and anticonvulsant Other info Long term use = rebound insomnia, drug dependence Recommended dose is 15 30 mg
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tryptopatz (3FPH)

ALPRAZOLAM
8-chloro-1-methyl-6-phenyl-4H-triazolo[4,3-a][1,4]benzodiazepine

tryptopatz (3FPH)

ALPRAZOLAM
Uses Intermediate sedative For panic attacks and major anxiety disorders

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TRIAZOLAM
8-chloro-6-(2-chlorophenyl)-1-methyl-4H-triazolo[4,3-a][1,4] benzodiazepine

Presence of thiazolo ring makes it a short-acting drug

2-chloro INCREASES activity Only difference with Alprazolam

tryptopatz (3FPH)

TRIAZOLAM
Uses Rapid onset = Shortacting hypnotic Used for jet lag and acute insomnia Other info Popular sleep inducer especially in elderly patients = less daytime sedation Drinking with grapefruit juice increases its peak plasma concentration by 30% = increased drowsiness
tryptopatz (3FPH)

MIDAZOLAM
8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo (1,5-a) (1,4)benzodiazepine

Presence of imidazole ring makes it a short-acting drug & INCREASES activity

2-fluoro INCREASES activity

tryptopatz (3FPH)

MIDAZOLAM
Uses Anti-anxiety & promotes sedation (IV/ IM) Pre-anesthetic for: Dentistry Cardiac surgery Endoscopic procedures Other info Its short duration and cardio respiratory stability makes it useful in poor-risk, elderly, and cardiac patients
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1 2

Must be replaced

tryptopatz (3FPH)

Branched chain substituted 7 to 9 carbons substitution gives greater hypnotic here increases lipophilicity activity blood-brain barrier = cross than straight chain. Alkyl substitution confers/ gives activity.

ALKYL = Increases lipophilicity = quicker onset & short duration of action

Methyl substitution decreases duration of action. Sulfuration here increases lipid solubility & hypnotic potency
tryptopatz (3FPH)

Replaced hydrogen to avoid Substitution here a highly tautomerization to = rapid metabolism acidic trihydroxypyrimidine Responsible for the sedative-hypnotic activity

PHENOBARBITAL
5-ethyl-5-phenyl-barbituric acid

Uses
Long-acting sedative and hypnotic (> 6 hours) Anti-convulsant, controls seizures Treatment of tremors, insomnia and for narcotic withdrawal.

tryptopatz (3FPH)

AMOBARBITAL
5-ethyl-5-isopentylbarbituric acid

Info
Intermediate-acting 3-6 hours 20-40 mg sedative dose, 100 mg hypnotic dose. Overuse lead to loss of reflexes and speech problems

tryptopatz (3FPH)

SECOBARBITAL
5-allyl-5-(1-methylbutyl) barbituric acid

Info
Short-acting (less than 3 hours Hypoventilation is the primary side effect if overused

ALLYL CH2 = CH CH2

tryptopatz (3FPH)

THIOPENTAL
5-ethyl-5-(2-methylpentyl)-4,6-dioxo-1,4,5,6-tetrahydropyrimidine2-thiolate

Info
Helps a patient relax before being given with general anesthesia tryptopatz (3FPH) Rapid-acting barbiturate

tryptopatz (3FPH)

similar structural and chemical properties: a nonpolar portion and a semipolar portion that can participate in H-bonding in some cases, activity is undetermined activity mostly similar to barbiturates and alcohol

Piperidinedione: Glutethimide Aldehydes: Chloral Hydrate Ethchlorvynol Disulfiram Soidum Bromide Hydroxyzine

GLUTHETIMIDE
2-ethyl-2-phenyl-glutarimide

One of the most active nonbarbiturate hypnotic Structure similar to barbiturates, especially phenobarbital Low aqueous solubility High lipophilicity Enzyme inducer Adverse effects infrequent at therapeutic dose; toxic effects in overdose as severe as barbiturates (or more)

tryptopatz (3FPH)

CHLORAL HYDRATE
Tricholoroacetaldehyde monohydrate, CCl3CH(OH)2
Barbiturate-like binding to GABA receptors Relatively stable Unstable in alkaline solutions In hydroalcoholic solutions, forms hemiacetal with ethanol A weak acid 10% aqueous solution has pH 3.5 to 4.4
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CHLORAL HYDRATE
Rxn and Metabolism

H2O

Reduction Chloral trichloroethanol Oxidation trichloroethanol chloral

Very quickly converted to trichloroeathanol

Conjugated & excreted

CHLORAL HYDRATE
Tricholoroacetaldehyde monohydrate, CCl3CH(OH)2

Synergism between 2 different CNS depressants The Mickey Finn Available: capsule, syrup, suppository Sedate in non-operating procedure for pediatric patients

ALCOHOLS
e.g., Ethanol: anesthetic; self-medication as sedative-hypnotic; seldom preferred medically CNS depressant potency increases to 8 carbon atoms, with activity decreasing thereafter Branching of alkyl chain increases depressant activity

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ALCOHOLS
In isometric series, potency is tertiary > secondary > primary Replacement of hydrogen atom in the alkyl group by a halogen increases the alkyl portion, and accordingly, for the lower molecular weight compounds, increases potency

tryptopatz (3FPH)

ETHCHLORVYNOL
1-chloro-3-ethylpent-1-en-4-yn-3-ol

Mild sedative-hypnotic Quick onset, short duration of action Highly lipophilic Induces microsomal hepatic enzymes Acute overdose similar to barbiturate overdose

3 2

tryptopatz (3FPH)

DISULFIRAM
Diethylcarbamothioylsulfanyl-N,N-diethylcarbamodithioate

Treatment for chronic alcoholism/alcohol dependency by producing an acute sensitivity to alcohol Exerts its effect by inhibiting the enzyme aldehyde dehydrogenase (ALDH)
tryptopatz (3FPH)

HYDROXYZINE
2-(2-{4-[(4-chlorophenyl)-phenylmethyl)piperazin-1-yl]ethoxy]ethanol

4
3

2
1 2 1

tryptopatz (3FPH)

HYDROXYZINE
antihistamine with anticholinergic and sedative properties may also be antiemetic, anxiolytic, antipruritic Active form: cetirizine synergism: adds to (exaggerates) the sedating effects of alcohol and other drugs that can cause sedation; also adds to anticholinergic properties of other medications
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SODIUM BROMIDE
NaBr; white, crystalline solid that resembles NaCl Bromide frequently as sedatives in the 19th and early 20th century chronic toxicity antiepileptic, particularly in veterinary medicine. potassium bromide is equally effective (bromide salts)

tryptopatz (3FPH)

THANK YOU!

tryptopatz (3FPH)