L2-3 Hypnotics/Anxiolytics

Question 1

“If rhymes were valiums, I’d be…

Answer 1

Comfortably numb.” -Sublime

Question 2

What is the effect of GABA binding to the GABAa receptor?

Answer 2

Opening of Cl- channel and Cl- uptake, leading to cell hyperpolarization and depressed synaptic transmission.

Question 3

How do most sedative-hypnotics and anxiolytics work?

Answer 3

Binding to a modulatory site on the GABAa receptor to intensify or prolong the effects of GABA.

Question 4

What is the major difference between benzos and barbituates?

Answer 4

Benzos only function in the presence of GABA, prolonging the effect of GABA. It would take “a bucket” of valium to OD. In high doses barbituates can activate GABA receptors in the absence of GABA, leading to massive CNS depression and respiratory arrest.

Question 5

What are the relative durations and uses of Thiopental (Pentothal), and phenobarbital (Luminal)?

Answer 5

Thiopental (Pentothal) is ultra short acting and used to induce anesthesia. Phenobarbital and other long acting barbituates are used as anticonvulsants (rarely). Some are used to decrease GI spasms and motility.

Question 6

What are the side effects of barbituates?

Answer 6

CNS depression: drowsiness, distortion of mood, impaired judgment and motor skills, REM sleep is impaired. Vertigo, nausea, vomiting, diarrhea, paradoxical excitement, and allergic reactions may occur

Question 7

What is the relative margin of safety for barbituates? What region of the brain is affected?

Answer 7

The dose to induce sleep is less than 10x the dose that will cause respiratory depression. They depress the vasomotor and respiratory centers in the medulla (somewhere between the cortex and cauda equina)

Question 8

What are the signs of a barbituate OD, treatment?

Answer 8

coma, respiratory depression, and decreased blood pressure Optimal treatment is supportive, stimulants should not be used. Barbituates are acids and can be cleared by forced diuresis and alkalinization of the urine (sodium bicarbonate or acetazolamide)

Question 9

What are the four anxiety disorders in which benzos are not used?

Answer 9

OCD Agoraphobia and panic disorders PTSD Anxiety in children and adolescents

Question 10

What are the three benzos that can be used for insomnia?

Answer 10

Glurazepam Temazepam Triazolam Cause less depression of REM sleep than barbituates

Question 11

What benzo if used for insomnia may cause the person to feel sluggish the next day due to is long duration of action?

Answer 11

Flurazepam

Question 12

What benzos are used in epilepsy and seizures?

Answer 12

Clonazepam: prevention of absence seizures Diazepam and Lorazepam: IV for status epilepticus Midazolam: used for seizures refractory to other meds

Question 13

What benzo is used for muscle relaxation?

Answer 13

Diazepam: acute muscle spasm and pain as a result of injury

Question 14

What benzos are used to provide a tapered withdrawl from alcohol or barbituates?

Answer 14

Chlordiazepoxide, Diazepam, and Lorazepam: tapered withdrawl over the first 3-4 days Long duration of action Prevent seizures and DTs

Question 15

Why aren’t benzos generally used in children?

Answer 15

They impair memory and learning

Question 16

What are the three contraindications to benzos?

Answer 16

Pregnancy Category D Children Sleep apnea: may decrease tone of upper airway and worsen apnea

Question 17

Flumazenil

Answer 17

Benzo antagonist: blocks GABAa receptor Administer IV very slowly to reduce risk of seizures Can be used to reverse CNS depressant effects of benzos with overdose or after surgergy Do not use if any signs of seizure disorder!!

Question 18

Zolpidem (Ambien) and Zaleplon (Sonata)

Answer 18

Bind the BZ1 subtype of benzo receptor (alpha subunit) Very strong and rapid sedative activity Preserve deep sleep with little effect on REM Approved for short-term use but are frequently used chronically Very short half-lives

Question 19

Eszopiclone (Lunesta)

Answer 19

Longer acting at BZ1 subtype of benzo receptor Less selective, actions more similar to the benzos Can cause morning drowsiness Approved for long-term tx of insomnia

Question 20

What are the side effects of the Z drugs?

Answer 20

GI, CNS Sleep-walking, driving, night eating Amnesia, confusion, falls, memory loss Very high margin of safety Less likely than benzos to cause tolerance and dependence Rebound insomnia and withdrawl symptoms

Question 21

Ramelteon

Answer 21

Agonist at melatonin MT1 and MT2 receptors Regulate sleepiness and maintain circadian rhythms Shortens delay to sleep onset Metabolized by liver enzymes-possibility of drug interactions Caution in mild liver disease, but no do not use in severe liver disease

Question 22

What are the significant drug interactions with Ramelteon?

Answer 22

Additive sedation with alcohol and other sedative hypnotics Rifampin: increases metabolism of ramelteon Metabolism inhibited by ketoconazole and fluconazole, HIV protease inhibitors

Question 23

What are the significant side effects of Ramelteon?

Answer 23

Drowsiness, dizziness, and nausea most common Increase in serum prolactin and decrease in testosterone May cause adrenocortical insufficiency No rebound insomnia or effect on REM sleep

Question 24

What are some antihistamines that have sedative properties?

Answer 24

Diphenhydramine, Doxylamine, Promethazine (nausea), Hydroxyzine (vertigo)

Question 25

Chloral hydrate

Answer 25

Acts similarly to barbituates on GABAa Low margin of safety, causes tolerance and dependence Gastric irritation, allergic responses, cardiac arrythmias Used in sx for sedation and to relieve anxiety Still used in nursing homes as sedative-hypnotic: not a good idea

Question 26

Buspirone (Buspar)

Answer 26

First drug in class that relieves anxiety without causing sedation Partial 5-HT1a agonist, esp in hippocampus Decreases release of serotonin from dorsal raphe neurons Increases activity of NE and DA neurons No effect on GABA receptors Full anxiolytic effects takes 2 weeks to develop Low addiction potential: excellent choice for anxiety in recovering alcoholics or addicts Does not potentiate CNS depression

Question 27

What are the uses for Buspirone?

Answer 27

Moderate generalized anxiety and anxiety with depression Can combine with antidepressents Good in Prementrual syndrome, Children, Austism with anxiety Not good for severe anxiety or panic disorder

Question 28

What are the drug interactions of Buspirone?

Answer 28

Metabolized by CYP3A4: levels may be increased by inhibitors (ketoconazole, erythromycin, etc), levels decreased by rifampin MAOIs: increased BP, serotonin syndrome Use caution in combo with other drugs that increase serotonin

Question 29

How are beta blockers used as an anxiolytic?

Answer 29

propranolol is effective against physical symptoms of performance anxiety and acute stress disorder decrease tremor, sweating, tachycardia, palpitations no effect on emotional experience of anxiety