antixiolytic and hypnotic drugs Flashcards
what is anxiety?
• Anxiety is an unpleasant state of tension, apprehension, discomfort,
&/or fear that seems to result from an unknown source.
• Physical symptoms of severe anxiety are similar to those of fear and
involve sympathetic activation tachycardia, palpitation, sweating,
trembling.
• Anxiety is the most common mental disturbance.
• Episodes of mild anxiety are common life experiences and do not
warrant treatment.
• Drugs used to treat anxiety are called anxiolytics or minor
tranquilizers.
• Most of these drugs have a calming effect & ↓ excitement
(therefore called sedatives) or even induce sleep (called hypnotics).
• Psychotherapy can also be used to treat anxiety
what is anxiety?
• Anxiety is an unpleasant state of tension, apprehension, discomfort,
&/or fear that seems to result from an unknown source.
• Physical symptoms of severe anxiety are similar to those of fear and
involve sympathetic activation tachycardia, palpitation, sweating,
trembling.
• Anxiety is the most common mental disturbance.
• Episodes of mild anxiety are common life experiences and do not
warrant treatment.
• Drugs used to treat anxiety are called anxiolytics or minor
tranquilizers.
• Most of these drugs have a calming effect & ↓ excitement
(therefore called sedatives) or even induce sleep (called hypnotics).
• Psychotherapy can also be used to treat anxiety
what are the benzodiazepines MOA
The GABAA receptors are composed of a
combination of five α, β, and γ subunits. BDZs bind to a
selective site in the neuronal cell adjacent to GABA
binding site on the receptor.
• This binding ↑ affinity of GABA receptor for GABA
more opening of Cl-
-channels influx of more Cl-
hyperpolarization of the neuron and decreases
neurotransmission inhibition of neuronal firing (the
formation of action potentials).
what are the benzodiazepines actions
Benzodiazepines do not have any antipsychotic or analgesic action.
- Reduction of anxiety: at low dosesby selectively enhancing GABAergic
transmission in neurons having the α2 subunit in their GABAA
receptors,
thereby inhibiting neuronal circuits in the limbic system of the brain. - Sedative & hypnotic actions: All benzodiazepines have sedative and
calming properties, and some can produce hypnosis at higher doses. The
hypnotic effects are mediated by the α1-GABAA
receptors. - Anticonvulsant: some benzodiazepines.
- Muscle relaxant: At high doses,↓ spasm in skeletal muscles by an
inhibitory effect at the level of the spinal cord. - Anterograde amnesia: Temporary impairment of memory is mediated by
the α1-GABAA receptors.
the ability to learn and form new memories is also impaire
what are the therapeutic uses for benzodiazepines
1) Anxiety disorder:
Benzodiazepines are effective for the treatment of the anxiety symptoms
secondary to
panic disorder,
generalized anxiety disorder (GAD),
social anxiety disorder,
performance anxiety,
posttraumatic stress disorder,
obsessive–compulsive disorder,
and extreme anxiety associated with phobias, such as fear of flying.
Also useful in treating anxiety related to depression & schizophrenia
2) Sleep disorders:
In the treatment of insomnia, it is important to balance
the sedative effect needed at bedtime with the residual
sedation (“hangover”) upon awakening.
Hypnotics should be given for only a short period of time
3) Amnesia: the shorter-acting agents are often employed
as premedication for anxiety-provoking and unpleasant
procedures, such as endoscopy, dental procedures, and
angioplasty.
They cause a form of conscious sedation, allowing the
person to be receptive to instructions during these
procedures
Midazolam is a benzodiazepine used to facilitate amnesia
4) Muscular disorders: diazepam in diseases like
multiple sclerosis or cerebral palsy.
while causing sedation prior to anesthesia.
5) Seizures: clonazepam is occasionally used as
adjunctive for certain types of seizures.
Diazepam or lorazepam are used to terminate
status epilepticus and in alcohol withdrawal.
how can we treat anxiety with benzodiazepines
• These drugs should be reserved for severe anxiety only
and not used to manage the stress of everyday life.
• For short term to avoid addiction.
• Clonazepam, lorazepam, and diazepam, are often
preferred in those patients with anxiety that may require
prolonged treatment.
• The antianxiety effects of the benzodiazepines are less
subject to tolerance than the sedative and hypnotic
effects.
• SSRIs are preferred for long-term treatment of anxiety.
• Tolerance is associated with a decrease in GABA receptor
density.
what benzodiazepines do we use for sleeping disorders
a. Flurazepam: (long-acting) to ↓ sleep induction time,
↓ awakening during sleep, & ↑ duration of sleep.
Tolerance develops after ~ 4 weeks. Rebound insomnia is
infrequent.
Rarely used, due to excessive daytime sedation.
b. Temazepam: (intermediate-acting) to prevent frequent
wakening (for insomnia caused by the inability to stay asleep).
However, because the peak sedative effect occurs 1 to 3 hours
after an oral dose, it should be given 1 to 2 hours before
bedtime.
• c. Triazolam: (short-acting) to induce sleep in patients who have
difficulty in going to sleep.
• Tolerance frequently develops within a few days, & withdrawal
of the drug often results in rebound insomnia. Therefore, this
drug is not a preferred agent, and it is best used intermittently.
• d. Bromazepam is intermediate-long aciting.
• In general, hypnotics should be given for only a limited time,
usually less than 2 to 4 weeks.
what are the Pharmacokinetics of BDZs
The duration of action of BDZs may determine the therapeutic
usefulness.
• The BDZs can be roughly divided into short-, intermediate-, and
long-acting groups.
• For some BDZs, the clinical duration of action does not correlate
with the actual half-life. This may be due to:
1. Conversion to active metabolites with long half-lives.
2. Receptor dissociation rates in the CNS and
3. subsequent redistribution to fatty tissues and other areas.
• The BDZs are excreted in the urine as glucuronides or oxidized
metabolites.
BDZs are FDA pregnancy category D women on a BDZ should use
effective birth control and tell their doctor if they become pregnant
during treatment.
• All benzodiazepines cross the placenta and may depress the CNS of
the newborn if given before birth.
• BDZs may cause low blood pressure, breathing problems, or
addiction and withdrawal symptoms in a newborn if the mother
takes the medication during pregnancy.
• The benzodiazepines are not recommended for use during
pregnancy.
• Nursing mother on a BDZ should not breast-feed.
what are the Pharmacokinetics of BDZs
The duration of action of BDZs may determine the therapeutic
usefulness.
• The BDZs can be roughly divided into short-, intermediate-, and
long-acting groups.
• For some BDZs, the clinical duration of action does not correlate
with the actual half-life. This may be due to:
1. Conversion to active metabolites with long half-lives.
2. Receptor dissociation rates in the CNS and
3. subsequent redistribution to fatty tissues and other areas.
• The BDZs are excreted in the urine as glucuronides or oxidized
metabolites.
BDZs are FDA pregnancy category D women on a BDZ should use
effective birth control and tell their doctor if they become pregnant
during treatment.
• All benzodiazepines cross the placenta and may depress the CNS of
the newborn if given before birth.
• BDZs may cause low blood pressure, breathing problems, or
addiction and withdrawal symptoms in a newborn if the mother
takes the medication during pregnancy.
• The benzodiazepines are not recommended for use during
pregnancy.
• Nursing mother on a BDZ should not breast-feed.
what is causes dependence in BDZs
• Psychological and physical dependence on
benzodiazepines can develop if high doses of
the drugs are given for a prolonged period.
• A patient is considered benzodiazepine-
dependent if abrupt discontinuation of
benzodiazepine causes withdrawal symptoms,
including confusion, anxiety, agitation,
restlessness, insomnia, and tension.
• Withdrawal symptoms
may not occur until
several days after
stopping a long-acting
benzodiazepines.
• Stopping a short-acting
benzodiazepine causes
more abrupt & severe
withdrawal symptom
what are the side effects of BDZs
- Drowsiness & confusion: common.
- Cognitive impairment: ↓ long-term
recall,↓ learning of new knowledge. - Ataxia occurs at high doses and precludes
activities that require fine motor
coordination, such as driving an
automobile. - Triazolam often shows a rapid development
of tolerance, early morning insomnia &
daytime anxiety.
BDZs should be used
cautiously in patients with liver disease.
Coadministration with another depressant,
like alcohol enhance the sedative–hypnotic
effects
what is Flumazenil
is a GABA receptor antagonist that
can rapidly reverse the effects of
benzodiazepines.
The drug is available for intravenous (IV)
administration only. Onset is rapid, but the
duration is short Frequent administration may
be necessary to maintain reversal of a long-
acting benzodiazepine
what is zolpidem
A hypnotic that is an agonist at benzodiazepine receptor (although it is not a
benzodiazepine).
Little or no tolerance on prolonged use.
has no muscle-relaxing properties.
It shows few withdrawal effects, exhibits minimal rebound insomnia, and little
tolerance occurs with prolonged use.
It provides a hypnotic effect for approximately 5 hours
• undergoes hepatic oxidation by the CYP450 system to inactive products.
• Thus, drugs such as rifampin, which induce this enzyme system, shorten
the half-life of zolpidem, and drugs that inhibit the CYP3A4 isoenzyme may
increase the half-life.
• It can cause daytime drowsiness.
what is Eszopiclone
(Hypnotic) Has been shown to be effective for insomnia for up
to 6 months.
Can cause somnolense.
Unlike the benzodiazepines, at usual hypnotic doses, the
nonbenzodiazepine drugs, zolpidem, zaleplon, & eszopiclone,
do not significantly alter the various sleep stages and, hence,
are often the preferred hypnotics. This may be due to their
relative selectivity for the BZ1 receptor.
All three agents are controlled substances.
what is the use of antidepressant in anxiaty
• Many antidepressants are effective in the treatment of chronic
anxiety disorders and should be considered as first-line agents,
especially in patients with concerns for addiction or dependence.
• SSRIs and SNRIs have a lower potential for physical dependence
than the benzodiazepines and have become first-line treatment for
GAD.
• Doxepin is a TCA that was recently approved at low doses for the
management of insomnia.
• Other antidepressants, such as trazodon, mirtazapine, and some
TCAs with strong antihistamine properties are used off-label for the
treatment of insomnia
