Barbiturates and Benzodiazepines Flashcards
Which compounds fuse to form barbituric acid?
Malonic acid and urea
What are all barbiturates derived from?
Barbituric acid
What are the three main classes of barbiturates?
Long-acting, short-acting and very-short-acting
Which receptor do barbiturates act on?
GABAa
What are the effects of barbiturates?
Antioxylitic, sedative, relaxant, analgesics and anticonulsant
What are some issues with barbiturates?
Pharmacological tolerance and behavioural dependence
Name very-short-acting barbiturates
Thiopentone and Sodium Pentothal
Name short-acting barbiturates
Pentobarbitone
Name long-acting barbiturates
Barbitone and Phenobarbitone
What are the two classes of benzodiazepines
Short and long-acting
What makes a short-acting BZ?
The metabolite of the drug is inactive
What makes a long-acting BZ?
Only the metabolite is active
What are some effects of BZs?
Antioxylitic, sedative, relaxant and anticonvulsant
Which is used clinically more commonly out of barbiturates and BZs?
BZs have a (relative to barbiturates) high therapeutic index
What are some key issues with BZs?
Tolerance and behavioural and physiological dependence
5HTa agonists are useful in treating what?
anxiety
What are some benefits of using 5HTa agonists as anxiolytics over BZs?
They are less effective but result in fewer side effects (little drowsiness, nausea, headache, restlessness)
Name a 5HTa agonist
Azapirone
Name a 5HTa partial agonist
Buspirone
What do barbiturates and BZs bind to?
An allosteric site on GABAa and GABAb
What do the drugs do when they bind to GABAa allosteric site?
They increase the frequency of the GABA Cl-channel opening
What do drugs do when they bind to GABAb?
Via GPCR Gi, they inhibit AC and facilitate GABA channels opening
Where is the BZ binding site on GABA channels?
Between the alpha-1 and gamma-2 subunits
Where is the barbiturate binding site on GABA channels?
On the top and between alpha-1 and beta-2/3 subunits
Where is the GABA binding site?
Between the alpha-1 and beta-2/3 subunits, but closer to the membrane
Do drugs show GABA subunit selectivity?
Yes. This makes them desirable drug targets
Drugs targeting alpha-1 subunit usually result in which effects?
Sedative effects
Drugs targeting alpha-2 subunit usually result in which effects?
Anxiolytic effects
How do BZs most commonly affect the GABA channels?
Increase frequency of opening
How do barbiturates most commonly affect the GABA channels?
Increase the open time of the channel
How does propofol affect GABAergic transmission?
It enhances by acting on allosteric sites and acting directly on the main binding site
Name a BZ agonist drug
Diazepam
Name a BZ partial agonist drug
Ro 15-1788
Name a BZ competitive antagonist
Flumazenil
Name a BZ partial inverse agonist
FG 7142
Name a BZ inverse agonist
Beta-carbolines
How does a BZ agonist induce an effect in the precoupled ON state?
Increases GABA receptors affinity which increases the open time of the Cl- channel, which increases the intrinsic agonist
How does a BZ inverse agonist induce an effect in the unprecoupled state?
Keeps a receptor in the ‘off’ state which reduces the intrinsic efficacy
