CNS drugs

Question 1

What are 3 main classes of sedative drugs?

Answer 1

Ethanol, benzodiazepines, barbiturates

Question 2

What is different about the dose-dependent sedation caused by benzodiazepines vs. ethanol and barbiturates?

Answer 2

Benzodiazepines - reaches a plateau vs. ethanol and barbiturates - keeps going to coma

Question 3

What happens as you increase the dose of a sedative drug?

Answer 3

1. Sedation
2. Anxiolytic
3. Possible anticonvulsant and muscle-relaxing activity

Question 4

Where does GABA bind on the GABA-A receptor?

Answer 4

Alpha subunit

Question 5

Where does benzodiazepine bind on the GABA-A receptor?

Answer 5

Gamma subunit

Question 6

Where does barbiturate bind on the GABA-A receptor?

Answer 6

Beta subunit

Question 7

What does stimulation of GABA-A affect?

Answer 7

Increased Cl influx - result in membrane hyperpolarization (inhibitory)

Question 8

How do benzodiazepines work?

Answer 8

Increase frequency of Cl channel opening

Question 9

Does benzodiazepine have a side effect of anterograde or retrograde amnesia?

Answer 9

Anterograde

Question 10

What does flumazenil do?

Answer 10

Inhibits BZ1 and BZ2 receptors - reverse the effect of benzodiazepines

Question 11

Can benzo’s or barbiturates open the GABA channel on their own?

Answer 11

Benzo’s - no, barbiturates - yes

Question 12

How do barbiturates work?

Answer 12

Prolong duration of Cl channel opening

Question 13

What does the liver do to benzodiazepines?

Answer 13

Metabolizes them to active forms

Question 14

What are 3 benzodiazepines that are not metabolized to active forms?

Answer 14

Oxazepam, temazepam, lorazepam

Question 15

Why do we like to use temazepam and oxazepam for sleep disorders?

Answer 15

Short half life

Question 16

What do we like to use benzo’s with long half life (e.g. alprazolam, diazepam, lorazepam) for?

Answer 16

Anxiety

Question 17

What is the ultra short acting benzo?

Answer 17

Midazolam - used for preop sedation

Question 18

What do we use phenobarbital for?

Answer 18

Seizures (especially good for pregnant women)

Question 19

What do we use thiopental for?

Answer 19

Induction of anesthesia

Question 20

Are barbiturates P450 inducers or inhibitors?

Answer 20

Inducers

Question 21

Why are barbiturates contraindicated in porphyrias?

Answer 21

All cytochrome p450 inducers are contraindicated in porphyrias because they induce activity of ALAS - they would lead to further build up of porphyrins

Question 22

Which has the least potential for abuse - benzos, barbs, or ETOH?

Answer 22

Benzos < Barbs, EtOH (remember the plateau effect of sedation caused by benzodiazepines)

Question 23

What drug-drug interaction do we worry about with our sedative drugs?

Answer 23

Other CNS depressants - anesthetics, antihistamines, opiates, beta blockers

Question 24

What are zolpidem and zalepon?

Answer 24

Nonbenzo’s that act on benzo receptors (BZ1) - used in sleep disorders, less effect on cognitive function

Question 25

What acid-base disturbance are alcohols associated with?

Answer 25

Metabolic acidosis

Question 26

Why does ethylene glycol cause nephrotoxicity?

Answer 26

Eventually metabolized to oxalic acid which makes crystals that damage renal tubules

Question 27

What is the general metabolism of an alcohol?

Answer 27

Alcohol --> aldehyde --> acid (all via action of dehydrogenases)

Question 28

What is fomepizole?

Answer 28

Long acting inhibitor of alcohol dehydrogenase that is used to treat alcohol overdose

Question 29

Why do alcoholics get thiamine deficiency?

Answer 29

The first metabolic product of alcohol is acetaldehyde which combines with both folate and thiamine

Question 30

How does chronic alcoholism affect glucose states?

Answer 30

Hypoglycemia from decreased gluconeogenesis (acetic acid - the eventual metabolic product of alcohol makes lots of acetyl coA which can be used for energy)

Question 31

Why do we get lactic acidosis with alcohol?

Answer 31

When we make pyruvate from lactate we need to also turn NAD into NADH. With lots of alcohol however, the body also makes lots of NADH to carry that energy. This reverses the reaction so instead we make lactate from pyruvate.

Question 32

Why do chronic alcoholics get gout?

Answer 32

Lactate competes with urate for excretion

Question 33

What does disulfiram inhibit?

Answer 33

Acetaldehyde dehydrogenase

Question 34

What drugs cause disulfiram like effects?

Answer 34

Any drugs with "zole" at the end (e.g. metronidazole, azoles), some cephalosporins, chlorpropamide, griseofulvin