Flashcards in Barbiturates Deck (21):
What are the CNS effects of Barbiturates? What are they actually used for?
Anxiolytic, anticonvulsants, sedation/hypnosis
Too much sedation to use for the first two
VERY LOW therapeutic index and rapid tolerance to sedation, so rarely used for that too
How to treat barbiturate toxicity?
Supportive treatment only
How do barbiturates effects on sleep compare to BDZ's?
Decrease sleep latency, increase sleep time
Increase stage 2
Decrease stages 1, 3, and 4 and REM sleep
How are barbiturates as anesthetics?
They are very short acting
How do barbiturates work?
They increase affinity of both BDZ and GABA binding site
Prolong channel open time
Can also directly open GABA channels themselves at high doses!
Also decrease glutamate AMPA receptor binding, inhibit voltage-gated calcium channels (dangerous), and fluidize membranes (dangerous)
What subunits are required for barbiturates to work?
Alpha and beta of any type
At what doses does bicuculline work? Why?
Bicuculline can only work at low barbiturate doses because at high enough doses barbiturates can open the channel themselves
At what doses can picrotoxin work? Why?
Picrotoxin can work at high barbiturate doses because it blocks the ion channel, so no matter if GABA or barb opens the channel, nothing can go through.
Why is therapeutic use of barbs limited?
They can cause decreased respiration
and an allergic reaction in asthmatic
Describe the pharmacokinetics of barbiturates
High lipophilicity, short duration of actions but they stick around. They can build up over time if given daily, and many have a half life over 24 hours.
Most orally absorbed.
Hepatically metabolized/conjugation followed by renal excretion
How do barbiturates affect liver metabolism?
Initially: Inhibit CYP2 and CYP3 activity to increase drug concentrations
Chronic: Induce CYP2 and CYP3 to decrease drug concentrations
Drugs included: Sedative/hypnotics, anesthetics, opiates, steroids, digitoxin, oral anticoags, B-antagonists, quinidine, phenytoin, ethanol, haloperidol, vitamins D and K, bile salts, and cholesterol
Which barbiturate is used as an anticonvulsant? How does it work?
Partial GABA agonist, less calcium inhibition
Less sedative side effects (rapid tolerance to it anyway)
Which barbiturates are used as anesthetics?
Which barbiturates are rarely used?
Pharmacokinetic tolerance to barbiturates is due to what
Induction of CYP3A4, reaches peak after 3 days
Pharmacodynamic tolerance peak occurs when?
No time limit
Tolerance to barbiturate effects mostly occurs to....
Less to ancitonvulsant
How does physical dependence with barbiturates compare to BDZ?
Occurs much more rapidly and severely
Physical dependence on barbiturates occurs due to...
Decreased GABA receptor function
Increased membrane rigidity
Increased glutamate receptors
What are side effects of chronic use of barbiturates?
Induces metabolism of many drugs
Increases fat and protein accumulation in the liver