L7- Sedatives, Hypnotics (others)

Question 1

barbiturates MOA

Answer 1

Main:

• bind GABA-(a) receptors
• inc the duration Cl- channel remains open

Alternative:
-blocks Glu receptors and Na channels (=> more pronounced CNS depression than benzos)

Question 2

explain why benzodiazepines replaced barbiturates

Answer 2

barbiturates induce:

• tolerance
• drug-metabolizing enzymes
• physical dependence (seen with benzos)
• severe withdrawal (possibly fatal, unlke with benzos)
• anesthesic / causes coma at high doses

Question 3

what are the 2 dangerous actions of barbiturates

Answer 3

1) respiratory depression: due to suppression of hypoxic and chemoreceptor response to CO2 –> can cause death
2) induction of CYP450 enzymes => drug interactions / inc drug metabolism

Question 4

______ barbiturate may be used to induce anesthesia

Answer 4

Thiopental, ultra-short acting via IV

Question 5

______ barbiturate may be used for seizure control (list specific disorders)

Answer 5

Phenobarbital: long-term management of tonic-clonic seizures, status epilepticus, eclampsia

Question 6

list the common AEs of barbiturates (hint- 4/5)

Answer 6

• drowsiness, impaired concentration
• paradoxical excitement
• hypersensitivity (with angioedema)
• hangover

Question 7

list the more severe AEs of barbiturates (hint- 4)

Answer 7

1a) respiratory depression in pulmonary impaired Pts
1b) poisoning / OD –> severe respiratory depression / death

2) dependence –> severe withdrawal Sxs (possibly fatal, unlike with benzos)
3) worsen perception of pain

Question 8

list the non-benzodiazepine benzodiazepine receptor agonists

Answer 8

(3 Zs)
zolpidem (Ambien)
zaleplon
eszopiclone

Question 9

non-benzodiazepine benzodiazepine receptor agonists:

• (1) MOA
• (2) main uses
• (3) advantages

Answer 9

1- agonists to BZ1 receptors (with α1)

2- hypnotic + minimal muscle relaxing / anticonvulsant effects

3- little/no tolerance, low incidence of AEs (overall safe drugs)

Question 10

zolpidem:

• (1) pharmacokinetics
• (2) uses

Answer 10

(non-benzodiazepine benzodiazepine receptor agonist)
1- short 1/2 life- 1.5-3.5h –> short duration of action

2- short-term Tx for insomnia, difficulties with sleep initiation

Question 11

zaleplon:

• (1) pharmacokinetics
• (2) uses

Answer 11

(non-benzodiazepine benzodiazepine receptor agonist)
1- short 1/2 half- 1h –> rapid onset & very short duration of action

2- short-term Tx for insomnia (for falling asleep??)

Question 12

eszopiclone:

• (1) pharmacokinetics
• (2) uses

Answer 12

(non-benzodiazepine benzodiazepine receptor agonist)
1- longest 1/2 life- 6h –> longer duration off action // (S) entantiomer of zopliclone

2- insomnia- dec sleep latency and improves sleep maintenance

Question 13

(1) is the 5-HT1A partial agonist, with only (2) as its main clinical effect.

Answer 13

1- buspirone

2- anxiolytic- for anxiety disorders, although SSRIs are drug of choice (no hypnotic, anticonvulsant, or muscle relaxant properties)

Question 14

Buspirone:

• (1) MOA
• (2) time for effects to occur

Answer 14

1- 5-HT1A partial agonist – analogous to mechanism of most antidepressants

2- 2-3 wks

Question 15

list Buspirone advantages as an anxiolytic to benzodiazepines

Answer 15

(note- SSRIs are still drug of choice for anxiety disorders)

• less psychomotor impairment
• no EtOH interactions
• no drug interactions
• no dependence
• no rebound anxiety or withdrawal with abrupt discontinuation

Question 16

(1) is a melatonin receptor agonist, acting on (2) receptors specifically, and is used to treat (3); it also has a (4) advantage over melatonin.

Answer 16

1- ramelteon
2- MT1, MT2
3- insomnia- difficulty of sleep onset
4- inc bioavailability

Question 17

(1) is an antihistamine with additional (2) activity. It can be used in adjunct to provide some relief for (3).

Answer 17

1- hydroxyzine- H1 receptor antagonist
2- anti-emetic (motion sickness)
3- anxiety disorders

Question 18

(1) is commonly used to control performance anxiety with (2) mechanism.
(3) works similarly to modify autonomic expression of anxiety through (4) mechanism.

Answer 18

1- propanolol
2- β blocker

3- clonidine
4- α2 agonist (ANS depression)

Question 19

(1) are an antihistamines used to treat milder forms of (2)

Answer 19

1- diphenhydramine, doxylamine: H1 receptor blocker (no anti-emetic effects)
2- mild insomnia