CNS Depressants and Psychostimulants

Question 1

What is the MOA for benzodiazepines and barbiturates?

Answer 1

• Bind to allosteric site on GABA-A receptors
• Increase affinity of GABA-A receptor for GABA
• Potentiation of GABAergic inhibition of neuronal activity

Question 2

What are general therapeutic uses for benzodiazepines?

Answer 2

Insomnia, anesthesia, anxiety, seizures, essential tremor, and spasticity

Question 3

What are general adverse effects of benzodiazepines?

Answer 3

Drowsiness, confusion (esp in older patients), anterograde amnesia, psychomotor impairment, substance use disorder (tolerance and withdrawal)

Question 4

T/F: Patients that are elderly with liver disease should take lorazepam due to it being safer

Answer 4

True; This is also relevant if they asked about oxazepam or temazepam (also good for cyp inhibitors)

Question 5

T/F: If BDZ has been used for <3 days taper dose gradually to avoid rebound insomnia or anxiety

Answer 5

False, this is if the BDZ is taken for at least greater than a month

Question 6

What drug is a benzodiazepine antagonist?

Answer 6

Flumazenil

Question 7

What is the MOA of flumazenil?

Answer 7

Competitive antagonist at BDZ binding site

Question 8

What are the clinical uses for flumazenil?

Answer 8

Treats BDZ overdose and used in anesthesiology to reverse effects of BDZs

Question 9

What are novel BDZ receptor agonists?

Answer 9

Zolpidem, zaleplon, and eszopiclone

Question 10

What is the MOA of zolpidem, zaleplon, and eszopiclone?

Answer 10

• Bind to allosteric site on GABA-A receptors
• Increase affinity of GABA-A receptor for GABA
• Potentiation of GABAergic inhibition of neuronal activity

Question 11

What are the clinical uses for novel BDZ receptor agonists (zolpidem, zaleplon, and eszopiclone)?

Answer 11

Sleep onset and sleep maintenance insomnia–> approved for long-term use

Question 12

T/F: Z-compounds have fewer adverse effects than BDZs

Answer 12

True

Question 13

What drug is a melatonin receptor agonist?

Answer 13

Ramelteon

Question 14

What is the MOA of ramelteon?

Answer 14

Agonist at MT1 (regulates sleep) and MT2 (regulates circadian rhythm) melatonin receptors

Question 15

What are the clinical uses for ramelteon?

Answer 15

Sleep onset insomnia

Question 16

T/F: Ramelteon is more efficacious than BDZs and Z compounds

Answer 16

False; It is less effective but is the only approved sedative-hypnotic drug that is not controlled

Question 17

What drug is a orexin receptor antagonist?

Answer 17

Suvorexant

Question 18

What is the MOA of suvorexant?

Answer 18

Antagonist at OX1 and OX2 orexin receptors

Question 19

What are the clinical uses for suvorexant?

Answer 19

Sleep-onset and sleep-maintenance insomnia

Question 20

What are adverse effects of orexin receptor antagonists?

Answer 20

Daytime sedation, impaired driving, substance use disorder

Question 21

What are the therapeutic uses for the barbiturate pentobarbital?

Answer 21

Insomnia and seizures

Question 22

What are adverse effects of pentobarbital?

Answer 22

Tolerance, physical dependence, high addition potential, low therapeutic index, induces CYP enzymes, long half life

Question 23

What is the therapeutic indication and adverse effects seen with H1 antihistamines (diphenhydramine, doxylamine)

Answer 23

• Used for insomnia
• Adverse effects: significant daytime sedation (has a long half life) and anticholinergic effects (off target effects)

Question 24

What are clinical uses of psychostimulants?

Answer 24

1. Treatment of excessive sleepiness and fatigue (narcolepsy)
2. Improvement of attention (ADHD)

Question 25

What is the MOA of indirect acting sympathomimetic drugs?

Answer 25

Increase synaptic concentration of endogenous catecholamines--> increased NE, DA, and 5-ht

Question 26

What drug is part of the "releasing agents" class?

Answer 26

Amphetamine

Question 27

What drugs are part of the "reuptake inhibitors" class?

Answer 27

Cocaine, methylphenidate, and modafinil/armodafinil

Question 28

What are predictable effects of psychostimulants?

Answer 28

NE: Increased arousal and less need for sleep DA: euphoria, reward, potential for abuse, abnormal movements, psychosis 5-HT: hallucinations and decreased appetite

Question 29

What is the MOA of amphetamine?

Answer 29

Displaces stored catecholamines: uptake via NET and VMAT-2 and replaces DA in vesicles which leads to DA release via DA

Question 30

What are the clinical uses for amphetamine?

Answer 30

ADHD and narcolepsy

Question 31

What adverse effects are seen with amphetamine?

Answer 31

From increased NE: higher bp, cardiac arrhythmias, insomnia From increased DA: growth inhibition From increased 5-HT: anorexia

Question 32

What adverse effects are seen with amphetamine?

Answer 32

From increased NE: higher bp, cardiac arrhythmias, insomnia From increased DA: growth inhibition From increased 5-HT: anorexia

Question 33

What is the MOA for methylphenidate?

Answer 33

Blocks NET and DAT which leads to higher levels of dopamine and norepinephrine

Question 34

What are the clinical uses for methylphenidate?

Answer 34

ADHD and narcolepsy

Question 35

T/F: Adverse effects of methylphenidate are similar to amphetamine

Answer 35

True

Question 36

What is the MOA of modafinil?

Answer 36

May block NET and DAT which leads to higher levels of dopamine and norepinephrine

Question 37

What are the clinical uses for modafinil?

Answer 37

Narcolepsy or other disorders that cause excessive sleepiness

Question 38

What are the adverse effects of modafinil?

Answer 38

Less adverse effects than amphetamine or methylphenidate (d/t less sympathomimetic effects)

Question 39

T/F: Bupropion and atomoxetine can be used to treat ADHD and is first line

Answer 39

False; Bupropion and atomoxetine are indeed used to treat ADHD but are not first line

Question 40

T/F: All reuptake inhibitors are stimulants

Answer 40

False; TCAs, SSRIs, and SNRIs have different indications like depression and are not used for ADHD