Pharm Anxiety Sedative Hypnotics

Flumazenil is a competitive antagonist at benzodiazepine receptors.

Answer: F
All benzodiazepines have anticonvulsant and muscle relaxant activity. The latter is at least partly
related to the enhancement of GABA-induced inhibition of synaptic transmission in the spinal
cord, because they are effective in patients with cord transection. Since the condition of the
patient is a chronic one, a long-acting benzodiazepine is most appropriate.
A, B, C, D, E) All these drugs are devoid of muscle relaxant properties.

Buspirone is a partial agonist at 5-HT1A receptors.

Answer: B
Benzodiazepines bind to receptors located at the interface between alpha and gamma subunits
of the GABA-A receptor-chloride ion channel macromolecular complex. The binding increases
the affinity of the GABA-A receptor for GABA, which in turn causes an increased frequency of
chloride channel opening. Since extracellular chloride concentration is about 120 mM and
intracellular chloride concentration is about 20 mM, chloride channel opening will increase
inward Cl- current.
This in turn will increase the negative charges inside the cell so causing hyperpolarization of cell
membrane.
B, C, D, E) Benzodiazepines do not affect these currents. Moreover all these actions would
cause depolarization, not hyperpolarization of cell membrane.

Answer: D
Psychotic disorders (which include schizophrenic disorders, manic disorders, acute idiopathic
psychotic illnesses , etc.) are characterized by major disturbances in reasoning, often with
marked agitation, delusions and hallucinations. Virtually all drugs effective in psychotic disorders
block dopamine receptors and reduce dopaminergic neurotransmission in the forebrain.
Benzodiazepines do not block dopamine receptors and are ineffective as antipsychotics.
A, B, C, E) All benzodiazepines have sedative, hypnotic, muscle relaxant and anticonvulsant
properties.

Answer: B
Poisoning by benzodiazepines is not usually life threatening but can be very serious when these
drug are combined with alcohol because the additive depressant effects on CNS.
A, C, D, E, F) These drugs either do not cause additive effects when given concomitantly with
alcohol.

Answer: A
Sleep apnea is a breathing disorder characterized by frequent and prolonged (>15 seconds)
pauses in breathing that occur during sleep. Typical symptoms of sleep apnea include alteration
in sleep pattern with loud snoring, excessive daytime sleepiness and severe shortness of breath
on exertion. In sleep apnea the sensitivity of the respiratory center to carbon dioxide is
decreased. Sedative-hypnotics drugs are generally contraindicated in this disorder since they
further decrease the sensitivity of respiratory center to hypercapnia.
B, C, D, E) All these drugs have been used in sleep apnea with modest results.

Answer: D
In addition to the anxiolytic effect, benzodiazepines, given at high doses, can cause anterograde
amnesia, that is impairment of memory for events occurring after the administration of the drug.
This action is particularly useful when the patient has to undergo a disturbing diagnostic
procedure, like in the present case. Since the intervention is brief, a short acting benzodiazepine
like triazolam is most appropriate.
A) Buspirone is an anxiolytic drug, but the effect develops slowly (in 1-2 weeks) and anterograde
amnesia does not occur.
B, C, E) These drugs cause negligible anxiolytic effects and negligible anterograde amnesia.

Answer: C
A classical effect of benzodiazepines (mainly when high doses are give) is the anterograde
amnesia, i.e. loss of memory for events occurring during the drug’s duration of action. The effect
is exploited therapeutically, since the patient cannot remember the unpleasant sensations felt
during endoscopic or surgical procedures.
A) Actually benzodiazepines have some, thought very mild, antiemetic properties
B, D) Benzodiazepines tend to cause effects opposite to those listed.
E) Delusion and hallucinations are exceedingly rare effects of benzodiazepines.

Answer: B
The patient’s symptoms indicate that he is suffering from insomnia characterized by difficulty in
maintaining sleep during the night because of nightmares. A benzodiazepine hypnotic is
preferable in this patient because of the need for anxiolytic properties in addition to hypnotic
efficacy. Moreover benzodiazepines tend to decreased the slow waves sleep were nightmares
are more frequent. Therefore a medium-acting benzodiazepine like temazepam, which can
maintain sleep throughout the night, should be appropriate for this patient.
A, C, D, E) These drugs are devoid of hypnotic properties

Answer: A
It has been shown that a constituent of grapefruit juice can inhibit the P450 3A, one of the
enzymes of the P450 system involved in the metabolism of several drugs including
benzodiazepines. The interaction is clinically important, and at least one case of death due to
drug-grapefruit juice interaction is reported in the literature.
B) The transient ischemic attack was too remote to suggest a relationship between brain
ischemia and increased sensitivity to benzodiazepines.
D) Old age can increase brain sensitivity to CNS depressants, but the well know action of
grapefruit juice on drug metabolism makes the interaction more likely.
C, E) Grapefruit juice does not have these effect.

Thiopental is the most frequently used drug to induce general anesthesia.

Answer: C Non-benzodiazepines acting on GABA receptors (the so called Z-hypnotics) are today preferred in case of insomnia since they do not alter the sleep architecture and stages, do not have significant anxiolytic, and anticonvulsant properties and have a lower risk of dependence compared with the short acting benzodiazepines. Different hypnotic drugs should be used according to the type of insomnia presented by the patient. When there is difficulty in falling asleep a short-acting drug is appropriate, when there is difficulty in maintaining sleep during the night a medium acting drug like eszopiclone (t½ of 4-7 hours) is appropriate, like in the present case. A) Flunitrazepam is a long-acting benzodiazepine and is therefore not appropriate as an hypnotic because of the risk of daytime sedation and drowsiness. B, D, E, F) These drugs have negligible hypnotic activity.

Midazolam is a benzodiazepine with a very short half-life of 0.2 hours. It is commonly used as a sedative and hypnotic medication due to its fast onset of action and short duration of effects.

Buspirone is an anxiolytic drug that is often prescribed for the treatment of anxiety disorders. It is known to have negligible abuse liability, meaning that it is less likely to be misused or cause addiction compared to other sedative hypnotic drugs. This makes it a safer option for long-term use in patients who require ongoing anxiety management.

Answer: C
Redistribution of a drug from its site of action into other tissues or sites. is a main factor in
terminating drug effect primarily when a highly lipid-soluble drug that acts on the brain is
administered rapidly by intravenous injection. A good example of this is the use of IV injection of
diazepam (a highly lipid-soluble drug) to induce loss of consciousness. Because blood flow to
the brain is so high, the drug reaches its maximal concentration in brain within a minute of its
intravenous injection. After injection is concluded, the plasma concentration falls as diazepam l diffuses into other tissues, such as muscle.
A, D) Diazepam is extensively metabolized in the liver (not in the brain) to desmethyldiazepam
and oxazepam. Both metabolites are active, therefore the biotransformation cannot explain the
short action of the drug.
B) The renal excretion of diazepam is about 1%.
E) Tolerance can develop to the action of benzodiazepines, but only after a chronic treatment of
several days.

Zolpidem is a sedative hypnotic drug that has negligible effects on sleep architecture and stages.

Answer: D
The symptoms of the patient indicate that she was most likely suffering of a panic attack.
Benzodiazepines are the most effective, safe and commonly prescribed drugs for the rapid relief
of the acute anxiety symptoms. Since a panic attack usually last no more than 30 minutes, a
short acting benzodiazepine, like midazolam is appropriate.
A) Selective serotonin-norepinephrine reuptake inhibitors are today drugs of first choice for
anxiety disorders, but they cannot be used when an acute relief is needed since their onset of
action is delayed.
B, C, E) These drug are not effective in case of panic attack.

Answer: B
A neurocircuit arising from the output pathways of the central nucleus of amygdala is believed to
mediate fear and anxiety responses. Therefore amygdala seems the central processing unit for
fear and anxiety. Buspirone was shown to exert anxiolytic actions, even if it is a second choice
drug for anxiety since its efficacy is modest and its onset of effect is delayed (2 weeks or longer).
The molecular mechanism of action of the drug is still uncertain (likely it acts at a partial agonist
at 5-HT 1A receptors), but amygdala is most likely involved in buspirone action , given the
central role of amygdala in anxiety disorders.
A, C, D, E) (see explanation above)

Answer: D
By increasing GABA activity all benzodiazepines enhanced the inhibitory action of GABAergic
neurons, which are mainly short interneurons in several brain areas. When used as hypnotics
drugs with short or intermediate action are preferred.
A) Diazepam is not used as hypnotic since it has a long half life and therefore is more prone to
cause day time drowsiness.
B, C, E, F) These drugs are not used as hypnotics.