Sedative/ Hypnotics, Anti Anxiety Agents

Question 1

What are of the brain regulates the heartbeat and other visceral functions and processes the emotion fear?

Answer 1

Amygdala

Question 2

What are of the brain is needed for establishment of long-term memory in regions of the cerebral cortex?

Answer 2

Hippocampus

Question 3

Drugs that reduce anxiety, exert calm are _, while drugs that produce drowsiness, encourage sleep are _

Answer 3

Sedatives

Hypnotics

Question 4

How can benzodiezapines be used to avoid producing sedation?

Answer 4

Low doses can relieve anxiety without sedation

Question 5

What are the 2 examples of non-benzodiezapines that interact with benzodiezapine receptors?

Answer 5

Zolpidem

Zaleplon

Question 6

What are the 4 examples of barbiturates provided?

Answer 6

Pentobarbital
Phenobarbital
Amobarbital
Thiopental

Question 7

What class of drug is the preferred agent for use as a sedative hypnotic, anxiolytic, muscle relaxant and or anticonvulsant?

Answer 7

Benzodiezapines

Question 8

True or false: Benzodiezapines can be used an anesthetics and analgesics at higher doses.

Answer 8

False. These drugs are neither anesthetics or analgesics

Question 9

What is the receptor target of benzodiezapines? Where are these receptors targets located? What is the effect of receptor activation?

Answer 9

GABA-A receptors
Limbic system
GABA mimetic, enhance neuronal inhibition

Question 10

When barbiturates and benzodiezapines bind GABA-A, what effect does that have on GABA activity?

Answer 10

Enhances GABA activity

Question 11

When GABA binds the GABA-A receptor, what is the effect?

Answer 11

Increased chloride conduction, hyperpolarization of neuron

Question 12

There were 2 examples of GABA antagonists provided. What were they? Which is competitive/non-competitive? What is the effect of their activity on the entire organism?

Answer 12

• Bicuculine - competitive
• Picrotoxin - Non-competitive
• Convulsions

Question 13

There was a single example of an inverse agonist at the GABA-A receptor provided.

• What is it?
• Why is it relevant?
• What is its mechanism?
• Any therapeutic use?

Answer 13

• Beta-carbolines
• Endogenous beta carbolines cause pathological anxiety
• Reduces chloride conductance
• No therapeutic use

Question 14

What is the example of an antagonist that can block agonists at both the benzodiezapine activity at GABA-A receptors?

Answer 14

Flumenazil

Question 15

How, mechanistically, do benzodiezapine enhance GABA conductance at the GABA-A receptor? What is their effect in the absence of GABA?

Answer 15

• Increase the FREQUENCY of channel opening in response to agonist
• No effect in the absence of agonist

Question 16

What are the 2 main CYP enzymes responsible for the metabolism of benzodiezapines?

Answer 16

CYP3A4

CYP2C19

Question 17

What is the active metabolite of diazepam? Alprazolam? Midazolam?

Answer 17

Diazepam - Desmethydiazepam

Alprazolam and Midazolam - alpha hydroxy metabolites

Question 18

Rank the following benzodiezapines in order of increasing half-life.
Alprazolam, Diazepam, Lorazepam and Midazolam.

Answer 18

Midazolam
Alprazolam
Lorazepam
Diazepam

Question 19

Of the following benzodiezapines, which is used as a preanesthetic medication? Anxiety? Insomnia? Muscle relaxant? Withdrawal?
[Alprazolam, Diazepam, Lorazepam and Midazolam]

Answer 19

Preanesthetic - Midazolam
Insomnia - Alprazolam, Lorazepam
Anxiety - Lorazepam, Diazepam
Muscle relaxant - Diazepam, Lorazepam
Withdrawal - Diazepam

Question 20

True or false, benzodiezapines have a high therapeutic index and overdose is not usually life threatening?

Answer 20

True, their major advantage over barbiturates

Question 21

In addition to supporting BP and respiration, gastric lavage, how can you quickly reverse respiratory depression brought about by benzodiezapine overdose? How many treatments and why?

Answer 21

Flumenzil IV

Multiple doses because flumenazil is short acting

Question 22

True or false, while abuse potential for benzodiezapines is low, physical and psychological dependence may still occur

Answer 22

True

Question 23

What are 2 ways by which withdrawal symptoms from benzodiezapines can be precipitated?

Answer 23

Stopping benzodiezapine use

Use of antagonists

Question 24

True or false: benzodiezapines induce a lot of CYP enzymes therefore can produce several drug interactions

Answer 24

False. They don’t induce a lot of CYP enzymes

Question 25

What is the cause of a lot of the deaths associated with benzodiezapines use?

Answer 25

Mixing / co-ingesting with other CNS depressants (e.g alcohol)

Question 26

Zolpidem and zaleplon act at what receptor? What is their effect at this receptor? What is the enzyme responsible for their metabolism? What is their main use?

Answer 26

- GABA-A receptor - Increase frequency of channel opening (more chloride) - CYP3A4 - Induce sleep

Question 27

Usually, zolpidem and zaleplon do not cause respiratory depression or cardiovascular depression. In what scenario is this not the case? (2)

Answer 27

IV administration | Heart failure patients (pt. with impaired cardiovascular function)

Question 28

What are 3 major disadvantages of barbiturates over benzodiezapines?

Answer 28

- Respiratory depression - cardiovascular depression - Induction of CYP450 enzymes in liver (drug interactions)

Question 29

What are the 3 main brain areas targeted by barbiturates? What receptor do they bind?

Answer 29

Pons, medulla and cortex GABA-A complex (Pons + medulla = reticular formation)

Question 30

What is the mechanism by which barbiturates enhance chloride conductance by GABA-A receptor? What is their action in the absence of GABA?

Answer 30

Increase the open time (vs. frequency) of channel | At high doses, can open channel in absence of GABA

Question 31

Arrange the following barbiturates in order of increasing halflife. Pentobarbital, thiopental, phenobarbital and amobarbital. What are they used for?

Answer 31

Thiopental - Anesthesia induction Amobarbital - Preoperative sedation Pento - Preoperative sedation Pheno - Anticonvulsant

Question 32

Drowsiness, confusion, diminished motor skills and impaired judgment. These are all side effects of _

Answer 32

Barbiturates

Question 33

What are the 2 major contraindications of barbiturates?

Answer 33

Pain | Pulmonary insufficiency

Question 34

Barbiturates enhance the CNS depressive effects of 3 types of drugs. They are _

Answer 34

Antipsychotics Antihistamines Ethanol

Question 35

True or false, barbiturates have a high therapeutic index and overdose is not usually life threatening?

Answer 35

False. Only 10X hypnotic does is enough to cause life threatening respiratory depression, circulatory collapse, renal failure and pulmonary complications

Question 36

How can you treat barbiturate poisoning? (2)

Answer 36

``` Support respiration and BP Gastric lavage (activated charcoal, sorbitol) ```

Question 37

What are 2 types of tolerance that occur with barbiturate use? How long does it take to occur?

Answer 37

- Metabolic (increased CYP metabolizing enzymes) | - Pharmacodynamic (decreased CNS response)

Question 38

True or false: Physical dependence and cross tolerance develops with continued use of barbiturates

Answer 38

True

Question 39

What are 2 other non-benzodiazapine, non-barbiturate antianxiety drugs discussed? What are their target receptors and actions at these receptors?

Answer 39

Propranolol - Beta-adrenoreceptor blocker | Buspirone - Partial 5HT-1A agonist

Question 40

What enzyme metabolizes buspirone? How does it interact with alcohol? How long does it take to cause its effects? What is the risk of dependence developing?

Answer 40

CYP3A4 No additive effects with ethanol 1-3 weeks before effects are observed No physical dependence develops

Question 41

Sedation and amnesia for surgery, epilepsy and seizure, control of alcohol withdrawal, muscle relaxation, insomnia. These can all be treated by _ class of drugs.

Answer 41

Sedative hypnotics

Question 42

Regardining benzodiazepines, what is the pharmacodynamic mechanism by which tolerance occurs? Does tolerance to benzos result in tolerance to other CNS depressants?

Answer 42

- Tolerance occurs by down regulation of CNS response | - Cross tolerance occurs to other benzos and CNS depressants

Question 43

True or false. anxiety, insomnia, irritability, bad dreams, tremors and anorexia are severe symptoms associated with benzodiazepine withdrawal.

Answer 43

False. These are considered mild symptoms

Question 44

True or false. agitation, depression, panic, paranoia, muscle twitches and convulsions are considered mild symptoms of benzodiezapine withdrawal

Answer 44

False, these are considered severe symptoms

Question 45

Why are barbiturates notorious for causing drug-drug interactions?

Answer 45

Barbiturates induce the activity and/or expression of | many CYPs.

Question 46

How are barbiturates metabolized (2 actions)? How are they excreted?

Answer 46

Dealkylated and glucuronidation | Renal excretion

Question 47

How are the following drugs related to barbiturates? Beta-blockers, Ca2+ channel blockers, corticosteroids, estrogens, phenothiazines, valproic acid and theophylline

Answer 47

Their metabolisms are all enhanced by barbiturates

Question 48

Severe respiratory depression, coma, severe hypotension and hypothermia. These are all signs of _

Answer 48

Acute barbiturate toxicity

Question 49

True or false: Anxiety, insomnia, dizziness and nausea are considered mild symptoms of barbiturate withdrawal?

Answer 49

True

Question 50

True or False: vomiting, hyperthermia, tremors, | delirium, convulsions and death are considered serious symptoms of barbiturate withdrawal

Answer 50

True

Question 51

Does buspirone produce CNS depression? Does it produce rebound anxiety or withdrawal signs? What is it used to treat?

Answer 51

No No Anxiety