Cns Pharmacology: Sedatives/hypnotics

Front 1

Describe the dose dependent progression of depressant effects seen with barbiturates.

Back 1

From low dose to high dose:

1) anti-anxiety
2) sedation
3) hypnosis/sleep
4) coma
5) anesthesia
6) death

Front 2

What is the major advantage of benzodiazepines over the older sedative/hypnotic drugs?

Back 2

Benzodiazepines do not depress respiration (unless other CNS depressants are taken concomitantly...then all bets are off).

Front 3

Describe barbiturate mechanism of action at low/therapeutic doses.

Back 3

-bind to GABA-A receptor in allosteric location
-potentiate action of GABA by prolonging chloride channel opening

Front 4

Describe barbiturate mechanism of action at high/toxic doses.

Back 4

-barbiturates directly stimulate the GABA-A receptor at high doses

Front 5

Describe the classification of barbiturates.

Back 5

(1) ultra short acting: half life 15-20min; example: thiopental

(2) short-intermediate acting: half life 3-6h; examples: pentobarbital, secobarbital, amobarbital

(3) long-acting: half life >6h; example: phenobarbital

Front 6

Describe barbiturate effects on CNS.

Back 6

-can induce all levels of depression
-low therapeutic index
-can increase reaction to pain
-tolerance to mood/hypnotic effects occurs more quickly than to lethal effects

-barbiturates are used to induce anesthesia and to manage seizure disorders

Front 7

Describe barbiturate effects on PNS.

Back 7

-depress autonomic ganglia (may be responsible for the initial hypotension that occurs after barbiturate administration)

-depress cholinergic transmission at NMJ (paralytic effects of curare are enhanced during barbiturate anesthesia)

Front 8

Describe barbiturate effects on respiration at:

(1) hypnotic dose
(2) 3X dose
(3) 10X dose

Back 8

(1) hypnotic dose: neurogenic drive is reduced

(2) 3X dose: neurogenic drive is gone; hypoxic and chemoreceptor drives are reduced

(3) 10X: all drives fail

Front 9

Describe barbiturate effects on cardiovascular system.

Back 9

-at anesthetic doses, may cause hypotension in patients with CHF

-at suicidal/toxic doses, causes depression of cardiac conduction

Front 10

Describe barbiturate effects on liver.

Back 10

-induce P450 enzymes
-contraindicated in porphyria

Front 11

Describe paradoxical excitement with the use of barbiturates.

Back 11

Paradoxical excitement is a toxicity effect. The patient, often an elderly person or a debilitated person, will show signs of inebriation.

Front 12

Phenobarbital can cause this rare hypersensitivity reaction.

Back 12

fatal toxic epidermolysis bullosum

Front 13

Barbiturates enhance the metabolism of many drugs, such as....

Back 13

(1) vitamin D and K
(2) anticoagulants
(3) steroids (ex: birth control pills)
(4) methylphenidate
(5) antihistamines

Front 14

Describe the CNS therapeutic uses of barbiturates.

Back 14

-induce anesthesia (thiopental)

-management of acute seizure disorders (phenobarbital)

-treatment of sustained seizures due to tetanus, eclampsia or convulsant poisoning

-therapeutic coma during neurosurgery or after a head injury

Front 15

What class of CNS depressants would be used to induce metabolism of hyperbilirubinemia in neonates?

Back 15

barbiturates

Front 16

What non-barbiturate drug could you administer to a child prior to taking him to get an MRI?

Back 16

chloral hydrate -- used to induce sedation in children

Front 17

You discover that your patient has gastric bezoars. You should probably ask him if he has a history of taking this non-barbiturate drug.

Back 17

meprobamate

Front 18

Describe benzodiazepine mechanism of action.

Back 18

-binds to GABA-A receptor
-enhances GABA mediated chloride influx by increasing the frequency of gating events

-benzodiazepines do NOT directly activate the GABA receptor...ever...not even at high doses

Front 19

TRUE OR FALSE

Barbiturates can activate the GABA receptor while benzodiazepines cannot.

Back 19

TRUE

Barbiturates activate the GABA receptor at high/toxic doses.

Front 20

Describe the classification of benzodiazepines.

Back 20

(1) short acting: half life <6h; examples: triazolam, midazolam

(2) intermediate acting: half life between 6 & 24h; example: temazepam

(3) long acting: half life >24h; examples: diazepam, flurazepam, chlordiazepoxide

Front 21

Describe benzodiazepine effects on the CNS.

Back 21

-CNS depression up to coma but do not induce respiratory depression
-preanesthetics

Front 22

Describe benzodiazepine effects on respiration.

Back 22

-no effect on respiration at hypnotic doses

-can suppress hypoxic drive at anesthetic doses which can lead to respiratory acidosis in COPD patients

Front 23

While benzodiazepines are relatively safe drugs, describe some of their toxic effects.

Back 23

-ataxia
-confusion, amnesia
-dependence & abuse
-overdose with benzodiazepine alone is rarely fatal

Front 24

Name the novel benzodiazepine receptor agonists.

Back 24

1. zaleplon
2. zolpidem
3. eszopiclone

These are hypnotic agents with low tolerance and dependence.

Front 25

Name the benzodiazepine receptor antagonist.

Back 25

flumazenil

-has rapid onset & short duration of action
-reverses sedative effects of benzodiazepines in anesthesia or overdose situations

Front 26

Describe the use of benzodiazepines in the treatment of acute anxiety (namely diazepam).

Back 26

Benzodiazepines are useful as premedication for anxious or apprehensive patient.

Diazepam is very useful because of its rapid onset & muscle relaxant effects.

Front 27

Describe the use of benzodiazepines in the treatment of chronic anxiety.

Back 27

Benzodiazepines are used in conjunction with psychotherapy for limited periods of time

Front 28

This adrenergic antagonist could be beneficial to a patient with stage fright.

Back 28

propranolol

Front 29

This antihistamine could be beneficial to a patient with anxiety.

Back 29

hydroxyzine (causes sedation)

Front 30

Why are benzodiazepines better than barbiturates in the treatment of insomnia?

Furthermore, why do benzodiazepine receptor agonists have an advantage over benzodiazepines?

Back 30

Barbiturates induce sleep, which resembles physiological sleep but they can disrupt normal sleep cycles. They reduce the amount of time spent in REM sleep.

Benzodiazepines are less likely to alter the sleep pattern compared to barbiturates.

Zolpidem & zaleplon -- non-barbiturate hypnotic agents -- have less residual mental impairment and less abuse potential compared to benzodiazepines.

Front 31

This class of barbiturates has been used to produce daytime sedation in severe anxiety attacks.

Back 31

long-acting barbiturates (phenobarbital)

Front 32

This class of barbiturates has been used as adjuncts in HTN treatment.

Back 32

short-intermediate barbiturates (pento-, seco-, amo- barbital)

Front 33

Which short acting benzodiazepine has replaced diazepam for use as a preanesthetic?

Back 33

Midazolam has replaced diazepam because it has better amnesia effects.

Front 34

Which barbiturate and which benzodiazepine are used to treat epilepsy?

Back 34

phenobarbital (long acting barb)
diazepam (long acting benzo)

Front 35

Which barbiturate and which benzodiazepene were listed as agents that induce anesthesia (pg. 286).

Back 35

1) thiopental (ultrashort barb)

2) midazolam (short benzo)

Front 36

Because barbiturates induce hepatic P450 enzymes, barbiturates are contraindicated in patients with...

Back 36

porphyria

Front 37

TRUE or FALSE

Barbiturates have a low therapeutic index while benzodiazepines have a high therapeutic index.

Back 37

TRUE