Barbituates/Ethanol

Question 1

Barbituates

Answer 1

Prototype for NON-selective CNS depressants
Ethanol is similar but not a barbituate
Use= anesthetics, pre-anasethetic(not commonly used anymore)
Mechanism = binds Non-selectively to GABAa, making it more active

Question 2

Thiopental

Answer 2

VERY FAT SOLUBLE barbituate.
Causes loss of consciousness in SECONDS and has VERY SHORT duration.
Metabolized by the liver over 12 hours but consciousness is lost for only 10-15 minutes
Anesthetic action is terminated by redistribution

Acts on GABAa receptors

Question 3

Pentobarbital

Answer 3

Barbituate (Non-selective CNS Depressant)

Acts on GABAa receptors

Question 4

Phenobarbital

Answer 4

Barbituate (Non-slective CNS Depressant)

Acts on GABAa receptors

Question 5

Propofol

Answer 5

Similar function to Barbituates
Acts on GABAa receptors
Rapid onset of action (like thiopental), breif duration due to distribution. -rapid metabolism

*Greater decrease in BP and negative inotropic effect on myocardium

Is an oil at room temp so formulated as a 1% emulsion. Prolonged use of emulsion has negative effects called PRIs (Propofol Infusion Syndrome)

Fospropofol is a prodrug that is water soluble

Question 6

Ketamine

Answer 6

• An antagonist at NMDA-type glutamate receptors.
• Very different from barbituates and Non-selective CNS depressants
• Rapid onset/redistribution and metabolism
• Psychic effect
• Produces dissociative anesthesia-analgesia, amnesia, unresponsiveness, spontaneous breathing, limb movement
• ***Ketamine increases sympathetic activity, cerebral blood flow, brain oxygen consumption. Can be dangerous if CSF pressure is elevated.

Question 7

Ethanol

Answer 7

Nonselective CNS Depressant:

• **Acts on many neurotransmitter systems especially GABAa receptors
• ***Acts particularly on one-type of GABAa receptor in the CEREBELLUM
• *Metabolism/Excretion:
• Metabolized by: Alcohol dehydrogenase, CYP2E1

Ethanol + NAD (with Alcohol dehydrogenase) gives Acetaldehyde + NADH

(Fomepizol is the drug that inhibits Alcohol dehydrogenase for ethylene glycol/car antifreeze poisoning or methanol poisoning, and ethanol is also given to outcompete it while blood is filtered)

Then Acetaldehyde + NAD (and Aldehyde dehydrogenase) gives Acetate and NADH

(Disulfiram/antabuse is given to make alcoholics sick when they have alcohol; nasea/vomitting/headache is from buildup of acetaldehyde)…also east asian (chinese, etc) and natative american can have less amount of this enzyme so less able to handle alcohol.

Then acetate can go and become Acetyl-CoA

Question 8

Disulfiram

Answer 8

Antabuse is the common/prescription name

-It blocks Aldehyde dehydrogenase to cause a build-up of Acetaldehyde when ethanol is consumed. This causes flushing, headache, nausea, vomitting, dysapnea, hypotension, palpitation

(to treat alcohlics by making them sick when they drink alcohol)

Question 9

Fomepizole

Answer 9

Treatment for ethylene glycol or methanol poisoning

-Inhibits ADH so that toxic metabolites are not made from either