Anxiolytics & Sedatives

Question 1

pharmalogic targets of anxiolytics and sedatives

Answer 1

adrenergic modification
serotonin
GABA
orexin

Question 2

beta-1 receptors

Answer 2

cardiac m.

• inc HR/contractility
• lipolysis and renin secretion

Question 3

beta-2 receptors

Answer 3

smooth m.

• smooth m. relaxation
• skeletal m. stim, glycogenolysis, gluconeogenesis)

Question 4

Propanolol

Answer 4

non-selective beta blocker

Question 5

atenolol

Answer 5

beta-1 selective blocker

Question 6

metoprolol

Answer 6

beta-1 selective blocker

Question 7

Buspirone
MOA
side effects
advantages/disadvantages

Answer 7

increases 5HT

side effects: dizziness, nausea, HA

advantages: low cost, easy admin, low abuse
disadvantages: short acting, but takes 1-4 weeks to produce anxiolytic effects

Question 8

Selective Serotonin Re-uptake Inhibitors (SSRIs)

Answer 8

fluoxetine
paroxetine
sertraline
citalopram
escitalopram

Question 9

serotonin and NE re-uptake inhibitors (SNRIs)

Answer 9

venlafaxine

duloxetine

Question 10

GABA-A receptor stimulation

Answer 10

Cl- enters channel
Hyperpolarizes cell
CNS depression

Question 11

GABA-A-α1: Agonism causes

Answer 11

sedation

Question 12

GABA-A-α2,3: Agonism causes

Answer 12

anxiolysis

Question 13

GABA-A-α5: Agonism causes

Answer 13

ataxia

Question 14

Benzodiazepines

MOA

Answer 14

GABA facilitators (they themselves cannot open channel)

Bind to specific site to inc frequency of Cl- channel opening –> HYPERPOLARIZATION –> generalized CNS depression

(sedation, anti-convulsant, anxiolytic, muscle relaxation)

Question 15

Benzodiazepines

effect on cognition

Answer 15

Produces ataxia and short-term memory/cognitive deficits (anterograde amnesia).

• can be used advantageously during surgery
• disadvantage for elderly

Question 16

Why are benzodiazepines controlled substances?

Answer 16

Can develop tolerance and dependence, –> w/d sx [tonic-clonic seizure, anxiety] if halted abruptly (risk for abuse; schedule IV).

w/d med slowly!!

If combined with other CNS depressants (+opioid, alcohol, etc.) –> higher risk of death

Question 17

Benzodiazepines are often rx’d for ______ w/d

Answer 17

Benzodiazepines are often rx’d for ALCOHOL w/d, because alcohol binds to GABA-A receptors and produces similar CNS depressant effects

Question 18

How do benzos affect sleep architecture?

Answer 18

sedating.

• reduce awakenings
• inc sleep time
• improve sleep quality

Question 19

Examples of benzos

Answer 19

end w/ -epam

diazepam
lorazepam

Question 20

conditions where benzodiazepines are indicated

Answer 20

insomnia, anxiety, seizures

Question 21

What drug can reverse the benzodiazepine overdose?

What are the concerns with use of this reversing agent?

Answer 21

flumazenil (Romazicon)
- essentially a benzodiazepine receptor antagonist

• competitive neutral ligand for GABA receptor causing no effect; reduces binding of benzos

CONCERNS OF USE: fear of inducing withdrawal (quickly displaces benzo from receptor)

Question 22

Benzodiazepine-like drugs

Answer 22

• bind preferentially to GABA-A-α1 (sedation)
• relatively quick onset, short duration
• hepatic clearance (less efficient in elderly, adult females (any age))

exp.
zolpidem (ambien)
zalepon (sonata)
eszopiclone (lunesta)

Question 23

Zolpidem (ambien)

Answer 23

benzo-like drug

preferentially binds to GABA-A-α1

Question 24

Barbiturates
MOA
side effects

Answer 24

Enhance GABA activity and more widespread CNS depression
- POTENT, binds mult GABA sites –> inc duration of channel opening

HIGH TOXICITY at high doses (coma, death)

CYP450 inducer –> lots of drug-drug interactions

exp. phenobarbital (for seizures, severe alc w/d)

Question 25

orexin

Answer 25

orexin neurons bind to receptors that PROMOTE AROUSAL

Question 26

orexin-receptor antagonists

Answer 26

INDUCE SLEEP

• dose w/i 30 min of sleep, 7hr before wake time
• concerns: daytime drowsiness, cataplexy, suicidal thoughts
• schedule IV
  exp. suvorexant (belsomra)

Question 27

melatonin

Answer 27

serotonin analogue

useful for sleep disturbances due to circadian rhythm differences

Question 28

ramelteon (rozerem)

Answer 28

melatonin-like

way more expensive bc rx version so controlled, know what you’re getting

Question 29

suvorexant

Answer 29

orexin-receptor antagonist

induces sleep

Question 30

melatonin and ramelteon

Answer 30

to induce sleep

short-acting

especially useful for circadian rhythm disorder

Question 31

Why are barbiturates more toxic than benzos?

Answer 31

Rather than increasing the frequency of Cl- channel openings, barbiturates prolong the duration of Cl- channel openings.

Also barbiturates tend to induce CYP450.