3. Pharm: Sedatives and Hypnotics

Question 1

Benzo MOA

Answer 1

Benzodiazepines bind to an allosteric site on the GABA-A receptor and increase the frequency, not duration, of Cl- channel opening => Cl- influx => hyperpolarization => CNS depression by POTENTIATING GABA-A transmission.

Question 2

Barbituates MOA

Answer 2

Barbiturates bind to another allosteric site on the GABA-A receptor and increase the duration of Cl- channel opening => increase Cl- influx => hyperpolarization => CNS depression

Question 3

Metabolism of Benzos

Answer 3

Benzodiazepines are metabolized by the liver.

• Long-acting agents like chlordiazepoxide and diazepam are broken down into active metabolites, which have longer 1/2 lives.
• Short-acting drugs such as triazolam are processed into inactive molecules.
• Elderly population and patients with decreased liver function may metabolize the drug more slowly causing serum half-life to be extended.

Question 4

Benzodiazepines (e.g. lorazepam), barbiturates and alcohol all bind to _______ allosteric sites on the GABA-A receptor. All of these allosteric AGO _________ by opening the chloride ion channel.

Answer 4

Benzodiazepines (e.g. lorazepam), barbiturates and alcohol all bind to different allosteric sites on the GABA-A receptor. All of these allosteric agonists potentiate GABA-A transmission by opening the chloride ion channel.

Question 5

What occurs with chronic benzo use?

Answer 5

Chronic benzo use => downregulation of GABA-A receptor and upregulation of excitatory NMDA/AMPA receptors => tolerance and dependence: withdrawal causes anxiety, irritability, WL, tremor and poor sleep due to the increased levels of NMDA and AMPA receptors.

Question 6

By which MOA does flumazenil reverse benzodiazepine toxicity?

Answer 6

• Flumazenil is a competitive ANT at the GABA-A receptor benzodiazepine binding site => reverse the sedative effects.
• However, flumazenil may also precipitate withdrawal seizures especially in patients addicted to benzos.

Question 7

1st line of tx for patient with status epilepticus (convulsions that do not stop)

Answer 7

IV Short-acting Benzo (Lorazepam)

Question 8

___________ are contraindicated in patients with impaired liver function due to increased risk of toxicity.

Answer 8

Long-acting benzodiazepines (chlordiazepoxide)

Question 9

Short-acting Benzos

Answer 9

1. Lorazepam
2. (-zolams)
   
   1. Alprazolam
   2. Midazolam
   3. Triazolam

Question 10

_______ benzodiazepines have greater potential for addiction and abuse due to what?

Answer 10

Short- acting: rapid-onset of action and short 1/2 life

Question 11

1st line of treat for pt with alcohol withdrawal sx

Answer 11

Long-acting benzodiazepines

Question 12

Non-benzos (Zolpidem, zaleplon, eszopiclone) MOA

Answer 12

• Bind to SAME allosteric site on the GABA-A receptor as benzos, however, are MORE SELECTIVE FOR BZ1 sites (=> less anti-convulsant and anxiolytic effects), and increase the frequency, not duration, of Cl- channel opening => Cl- influx => hyperpolarization => CNS depression by POTENTIATING GABA-A transmission.

Question 13

Elderly patienst should avoid:

Answer 13

1. Benzos
2. Non-benzos (zaleplon, zolpidem, and eszoplicone) bc can increase risk of falling, delium, MVA, hospitilization)

Question 14

Ramelteon MOA

Answer 14

M1/M2 melatonin receptor AGO, G-proteins found in suprachiasmastic nucleus of hypothalamus => help maintain circadian rhythm in sleep-wake cycle;

Question 15

Advanced age is a relative contraindication for all the following sedative-hypnotic agents EXCEPT:

Answer 15

Ramelteon, a synthetic melatonin receptor AGO.

Question 16

What drug can be used to decrease jet lag by regulating circadium rhythm?

Answer 16

Ramelteon, esp helpful in elderly pts