Barbiturates Flashcards
How are barbiturates formed?
condensation reaction between substituted malonic acid and urea.
How is the bioavailability and transport altered?
By altering the organic R groups
Barbiturates are weak acids or bases?
Acids
For a given pKa, increasing the pH increases the…
Phenobarbitone is largely — at acidic pH, so it’s readily —
Treatment for barbiturate overdose is an —/—.
This works by raising — and —/—
Ionised [A-]
unionised, absorbed
alkaline diuretic
[A-] and water solubility
Phenobarbitone:
This is the most widely used…
Has a long half-life of…
Barbiturates and diazopines cross the —/—/— at a rate dependent on the — values.
In general, increasing number of — atoms raises the —
and increasing numbers of — and — lower the —
Anticonvulsant 80-100 hours blood brain barrier log-P carbon log-P HBA and HBD log-P
Metabolism of Phenobarbital:
— group added to benzene ring, byproducts are – and –
then further groups are added by removing the – from that group.
Phenol, NADP+ and H20
H
Rate of transport across the —/—/— and the resultant —
is closely related to — and —/—.
The log-P predicts how —/— assist transport across BBB
BBB, anaesthesia
Log-p, drug structure
chlorine atoms
Mechanism of reaction of Barbiturates and Benzodiazepines:
GABAA receptor on neuron 2 is a —/— channel for — released from neuron 1.
The receptor has — subunits. Some drugs which are —/— can bind across…
A — change aids the binding, this increases influx of — ions. this decreases — of neuron 2
Gated ion, chloride 5, non-selective more than one subunit conformational chloride excitability
The lead was —
Tests revealed which 3 effects?
Barbiturates have been largely replaced by what?
chlordiazepoxide
hypnotic, anxolytic, muscle relaxant
Benzodiazepines
Conventional bench synthesis of Diazepines uses which 2 reaction mechanisms?
Electrophilic aromatic substitution
Nucleophilic substitution
Combinatorial synthesis of Benzodiazepines:
Uses successive — to build up the product —, then it is — from the support.
reactions
support
cleaved
Advantages of combinatorial synthesis:
Specific — are bound to specific —, then…
The products formed for each — are distinctive and — distinctive.
How is the reaction driven to completion?
What 2 things are easily removed?
—/— are attached to beads, and dont need to be… (2)
Individual — can be separated to isolate individual —
The beads can be regeenerated and reused.
reactants, beads. beads + reactants mixed in same vessel
be0ad, physically
With excess reagents
excess reagents and by-products
reaction intermediates, isolated and purified
beads, products
Diazepam: Hydrophilic or phobic? wide or narrow distribution? ease of crossing BBB + placenta? long/short rate of clearance? where does it collect? A higher dosage undergoes which sort of circulation?
Hydrophobic wide easy long fatty tissues post-hepatic recirculation
Where are the H-bonding sites on Benzodiazepines?
Oxygen + Nitrogen
Chlorazepate:
When -COOH is added to diazepine ring, the structure is more — with a slower —. This makes it a long lasting — which acts as a —.
It is — in the stomach to make active — and —
Polar onset anaesthetic prodrug decarboxylated oxazepam, nordiazepam
