Sedatives/Hypnotics

Question 1

MOA of Benzos and Baribiturates

Answer 1

Benzos–> increase the frequency of Cl- ion channels (by acting on GABAa receptors)

Barbi–> they increase the duration of Cl- ion channel opening (by acting on GABAa receptors)

*barbis block glutamic acid (excitatory transmitter) and at increasing concentrations, chloride channels

Question 2

How are Benzos metabolized?

Answer 2

mostly in the liver–> converted to active metabolites with long half-lives–> excessive sedation

however, some benzos like Lorazepam and Oxazepam are meatbolaized outside of the liver (Extraheaptic congucation–> no active metabolite)

Question 3

Adverse effects of Benzos

Answer 3

1) Respiratory depression
2) Cardiovascular and CNS depression

less sever side effects:
1) Nausea
2) Vomiting
3) cognitive impairement
4) Increased reaction time
5) Lightheadedness

Question 4

Patients taking Benzos may develop Tolerance to the drug, what measurements are taken to reverse this effect?

Answer 4

withdrawal is done slowly by switching the patient to a Benzo with a long Half-life

Question 5

What pharmacological Agent can be used to treat an overdose of Benzos? what is its MOA?

Answer 5

Flumazenil (BZP Antagonist)
MOA: reverses CNS depressant effect of benzo overdose

• it has no effect on Barbi’s

Question 6

What are the withdrawal symptoms of moderate Drug use of Benzos?

Answer 6

1) increased sensitivity to light and sound
2) Muscle cramps
3) Dizsiness
4) Anxiety & agitation
5) Myoclonic jerking
6) Sleep disturbance
7) Paresthesias

Question 7

What are the withdrawal symptoms of high-dose or long-term use of Benzos?

Answer 7

1) Seizures
2) Delirium

Question 8

Name a few Benzo drugs

Answer 8

1) Lorazepam (sedation)
2) Diazapam (anesthesia)
3) Estazolam (1st choice for insomnia)
4) Midazolam (Anasthesia)
5) Triazolam (insomnia)
6) Oxazepam (sleep disorders)
7) Temazepam (sleep disorders/Anxiety)

Question 9

Benzos used for Insomnia?

Answer 9

1) Estazolam–> primary insomnia
2) Triazolam
3) Oxazepam
4) Temazepam

• Estazolam and Triazolam cannot be given to patients with liver dysfunction
• Oxazepam and Temazepam are safe to give patients wiht liver problems as they undergo extrahepatic conjugation

Question 10

New drugs used for insomnia?

Answer 10

Zolpidem
–> Non-BZP agonist at the GABA receptors

Question 11

What are the adverse effects of Zolpidem?

Answer 11

1) confusion
2) Dizziness
3) Psychomotor depression with less amnestic effects

Question 12

Indication of Lorazepam?

Answer 12

1) Anesthesia
2) Anxiety
3) Epilepticus

safe to use on patients with liver dysfunction as it undergoes Extrahepatic conjugation

Question 13

Indication of Diazepam and Midazolam?

Answer 13

Diazepam:
1) Anesthesia
2) Epilepticus
3) muscle relaxant
4) Anxiety

Midazolam:
1) Anesthesia
2) Adjuvant (increase half-life)

*not safe for patients with liver dysfunction as they are metabolized in the liver

Question 14

Barbi’s block the excitatory transmitter ——— and at increasing concentrations , ————

Answer 14

Glutamic acid , sodium channel

Question 15

Adverse effects of Barbiturates?

Answer 15

1) Respiratory depression
2) Diarrhea
3) Vomiting
4) Nausea
5) Vertigo

Question 16

Overdose of Barbi’s result in induction of ——— metabolic enzymes of the liver microsomal enzyme –> ———— can occure

Answer 16

CYP450, Drug interaction

Question 17

How are Barbi’s metabolized?

Answer 17

Barbiturates are extensively metabolized (exception of phenobarbital)

Question 18

Barbi used for Anesthesia puroses?

Answer 18

Thiopental
(has short-action)

Question 19

Name a few Barbiturate drugs

Answer 19

1) Phenobarbital
2) Secobarbital

Question 20

Indication of Phenobarbital

Answer 20

1) Tonic-clonic seizures in children
2) Epilepticus
3) Sedation

Question 21

Indication of Secobarbital

Answer 21

1) Acute seizuers
2) Sedation
3) Insomnia

Question 22

Indication of Buspirone

Answer 22

1) Generalized anxiety disorders
2) Panic disorders (less effective in panic disorders)

Question 23

MoA of Buspiron

Answer 23

Selective anxiolytic, with minimal CNS
depressant effects.

Question 24

PK/PD of Buspiron

Answer 24

–> No anti-convulsant or muscle relaxant properties.
–> Interacts with the 5-HT1A receptor as a partial agonist (unknown precise MoA as
anxiolytic).
–> Less effective in panic disorders

Question 25

Adverse effects of Buspiron

Answer 25

1. Tachycardia.
2. Paresthesias.
3. Pupillary constriction.
4. GI distress.

Question 26

Category of Busprion

Answer 26

Atypical Sedative-Hypnotic, Non-BZP agonist at the GABA receptor

Question 27

What are the acute pharmacological effects of Ethanol?

Answer 27

1) CNS depression
2) Slurred speech
3) impaired motor function
4) depressed and impaired mental function
5) Respiratory depression
6) cutaneous vasodilation
7) Diuresis
8) GI side effects
9) impaired myocardial contractility

Question 28

What are the chronic pharmacological effects of Ethanol?

Answer 28

1) Alcoholic fatty liver
2) Alcoholic hepatitis
3) Cirrhosis
4) Peripheral neuropathy
5) alcohol amnesic syndrome
6) Gastritis
7) Pancreatitis
8) cerebellar degeneration

Question 29

How is alcohol metabolized?

Answer 29

1) Ethanol –> Acetaldehyde by alcohol dehydrogenase and at higher doses of ethanol by microsomal ethanol- oxidizing system (MEOS).
2) Acetaldehyde –> acetate by aldehyde dehydrogenase

Question 30

What is the pharmacologic basis for using Benzodiazepines to manage alcohol withdrawal?

Answer 30

Both alcohol and Benzos enhance the effect of GABA on GABAa neuroceptors, resulting in decreased overall brain excitibility.

–> this explains why A long-acting benzo (e.g. chlordiazepoxide, diazepam) is given – reduce the dose regimen until no withdrawal symptoms are seen.

Question 31

withdrawal symptoms of alcohol

Answer 31

1) Insomnia
2) Tremor
3) Anxiety
4) in sever cases , life-threatning seizures and delirium tremens

Question 32

Drugs used in acute ethanol withdrawal and protect against Wernicke-Korsakoff Syndrome?

Answer 32

Diazepam with Thiamine (IV)

Thiamine–> corrects electrolyte embalance (IV)