Exam 7: anxiolytic-sedative-hypnotic pharmacology

Question 1

What class is phenobarbital?

Answer 1

barbiturates

Question 2

What class is lorazepam and diazepam?

Answer 2

Benzodiazepines

Question 3

What drugs are classified as benzodiazepines?

Answer 3

lorazepam, diazepam

Question 4

What are examples of barbiturates?

Answer 4

Phenobarbital, pentobarbital, thiopental

Question 5

What do barbiturates bind to? To do what?

Answer 5

multiple isoforms of the GABAa receptor (in the intramembranous space) to keep it open longer after activation to allow chloride ions to enter the neuron

Question 6

Do barbiturates increase the duration of GABA-gated chloride channels, or activate the GABA channels?

Answer 6

Cause allosteric change to open up the chloride channel AND KEEP IT OPEN LONGER

Question 7

What other effects to barbiturates have on the body?

Answer 7

depress excitatory actions of glutamate by binding to AMPA receptors, nonsynaptic membrane effects

Question 8

Can barbiturates be given orally or IV? what are the effects of either?

Answer 8

oral for anxiolytic effects, IV for anesthetic induction

Question 9

How quickly do barbiturates effect for sleeping

Answer 9

Thiopentil: 30 seconds, phenobarbital: 20 mins

Question 10

Where are barbiturates metabolized? How long is their half-life?

Answer 10

Oxidized by hepatic enzymes. 4-5 days

Question 11

How can you increase excretion or stop an overdose of phenobarbital?

Answer 11

increase urinary pH by administering sodium bicarbonate IV

Question 12

What are the mechanisms of tolerance to barbiturates?

Answer 12

increase in rate of drug metabolism, changes in responsiveness of the CNS

Question 13

What are the effects of barbiturates?

Answer 13

Sedation at low doses, hypnosis at higher doses, anesthesia at highest doses

Question 14

What are the hypnotic effects of barbiturates?

Answer 14

decrease sleep onset, increased stage 2 sleep, decreased REM sleep, stage 4 sleep decreased

Question 15

What drugs can be used to prevent tonic-clonic seizures?

Answer 15

Phenobarbital and metharbital

Question 16

At hypnotic doses, what are the effects of barbiturates on respiration and CV system?

Answer 16

No significant changes

Question 17

Can patients become dependent on barbiturates?

Answer 17

Yes, continuous drug administration required to prevent an abstinence or withdrawal syndrome

Question 18

What are clinical uses of barbiturates?

Answer 18

Hypnosis, seizure control, anesthesia induction, can be combined to manage GI disorders and others for analgesia

Question 19

What are examples of benzodiazepines?

Answer 19

Diazepam, lorazepam

Question 20

What drug class are diazepam and lorazepam in?

Answer 20

Benzodiazepines

Question 21

Where do benzodiazepines bind?

Answer 21

Extracellular portion of GABAa Chloride channels

Question 22

What do benzodiazepines do to chloride channel opening events?

Answer 22

Increase the FREQUENCY of the events

Question 23

What to barbiturates do to chloride channel opening events?

Answer 23

Increase the DURATION of the events

Question 24

Where are all benzodiazepines metabolized?

Answer 24

In the liver

Question 25

Are benzodiazepines absorbed rapidly upon oral administration?

Answer 25

Fairly lipophilic, so yes

Question 26

What is the difference between barbiturates and benzodiazepines in terms of biodisposition?

Answer 26

Benzos have little impact on hepatic drug-metabolizing enzyme activity with continuous use, leading to less drug-drug interaction

Question 27

What is tolerance of benzodiazepines caused by?

Answer 27

down-regulation of brain GABAa receptors

Question 28

What are clinical uses of benzodiazepines?

Answer 28

Anxiety, insomnia, seizures, muscle relaxation, preanesthetic medication

Question 29

What is a worry about the sedating effects of benzodiazepines?

Answer 29

can exert dose-dependent anterograde amnesic effects

Question 30

What is the effect of benzodiazepines on hypnosis/sleep?

Answer 30

decreased time to fall asleep, increased stage 2 of sleep, decreased, decreased REM, decreased stage 4

Question 31

What can be used to reverse to depressant actions of benzodiazepines?

Answer 31

Flumazenil

Question 32

What can be caused by large doses of lorazepam and diazepam when used in combination with other drugs to induce anesthesia?

Answer 32

can cause postanesthetic respiratory depression

Question 33

What are examples of non-benzo benzo-receptor agonists?

Answer 33

The Z’s: zolpidem, zaleplon, eszoplicone

Question 34

What is the MOA of zolpidem, zaleplon, eszoplicone?

Answer 34

Bind to benzo’s spot on GABAa receptors more selectively

Question 35

What is the advantage of using zolpidem, zaleplon, eszoplicone over benzos?

Answer 35

rapid onset, short duration of action (with no residual effects upon waking), slow tolerance effect?

Question 36

What is buspirone used for?

Answer 36

selective anxiolytic effects, relieves anxiety without significant sedative or hypnotic effects

Question 37

How long does it take for Buspirone to work (decrease anxiety)?

Answer 37

more than a week

Question 38

Is buspirone good for acute anxiety attacks?

Answer 38

No, it takes more than 1 week to work

Question 39

Where is buspirone metabolized? What should it not be taken with?

Answer 39

CYP3A4; erythromycin, ketoconazole, grapefruit juice

Question 40

What is Ramelteon used for?

Answer 40

useful for patients who have difficulty in falling asleep

Question 41

Where does remelteon act?

Answer 41

Agonist at melatonin receptors (MT1 MT2) located in suprachiasmatic nuclei (“master clock” of brain)