anxiolytics slides

1. M W E B A Z A
VICTOR™
(MBchB 5th yr)
Ugandan
Kamapala International
University-western campus
Jinja Regional Referral
hospital (JRRHosp)
Psychiatric department
ANXIOLYTICS

2. Examples
of great
people
who we
diagnosed
of Anxiety
disorders

5. The first benzodiazepine to be introduced was
chlordiazepoxide (Librium) in1959. In 1963,
diazepam (Valium) became available.
The benzodiazepines derive their name from
their molecular structure They share a common
effect on receptors that have been termed
benzodiazepine receptors, which in turn
modulate GABA activity.

6. The GABA receptor is an ionotropic receptor and
ligand-gated ion channel. Its endogenous ligand
is γ-aminobutyric acid (GABA), the major
inhibitory neurotransmitter in the central nervous
system. Upon activation, the GABAA receptor
selectively conducts Cl− through its pore,
resulting in hyperpolarization of the neuron. This
causes an inhibitory effect on neurotransmission
by diminishing the chance of a successful action
potential occurring.

9. Mode of action
Benzodiazepines enhance the effect of the
neurotransmitter gamma-aminobutyric acid
(GABA) at the GABAA receptor, resulting in
sedative, hypnotic (sleep-inducing), anxiolytic
(anti-anxiety), anticonvulsant, and muscle
relaxant properties.
High doses of many shorter-acting
benzodiazepines may also cause anterograde
amnesia and dissociation. These properties
make benzodiazepines useful in treating anxiety,
insomnia, agitation, seizures, muscle spasms,
alcohol withdrawal and as a premedication for
medical or dental procedures.

10. All benzodiazepines except clorazepate (Tranxene)
are completely absorbed after oral administration
and reach peak serum levels within 30 minutes to 2
hours
Therapeutic Indications

14. Flumazenil for Benzodiazepine Overdosage.
Flumazenil is used to reverse the adverse
psychomotor, amnestic, and sedative effects of
benzodiazepine receptor agonists. Flumazenil is
administered IV and has a half-life of 7 to 15 minutes.
The most common adverse effects of flumazenilare
nausea, vomiting, dizziness, agitation, emotional
lability, cutaneous vasodilation, injection-site pain,
fatigue, impaired vision, and headache.

15. The most common serious adverse effect associated
with the use of flumazenil isthe precipitation of
seizures, which is most likely to occur in persons
withseizure disorders, those who are physically
dependent on benzodiazepines, and those who have
ingested large quantities of benzodiazepines.
Flumazenil alone may impair memory retrieval

17. Precautions and Adverse
Reactions
The most common adverse effect of
benzodiazepines is drowsiness, which occurs in
about 10 percent of all persons. Because of this
adverse effect, persons should be advised to be
careful while driving or using dangerous
machinery when taking drugs.
The most severe adverse effects of the
benzodiazepines occur when other sedative
substances, such as alcohol, are taken
concurrently. These combinations can result in
markeddrowsiness, disinhibition, or even
respiratory depression

18. High-potency benzodiazepines, especially triazolam,
can cause anterograde amnesia.
Allergic reactions to the drugs are rare , but a few
studies report maculopapular rashes and
generalized itching.
The symptoms of benzodiazepine intoxication
include
confusion, slurred speech, ataxia,
drowsiness, dyspnea, and hyporeflexia.
Persons with hepatic disease and elderly persons
are particularly likely to have adverse effects and
toxicity from the benzodiazepines, including hepatic
coma, especially when the drugs are administered
repeatedly or in high dosages.

19. Benzodiazepines can produce clinically significant
impairment of respiration in persons with chronic
obstructive pulmonary disease and sleep apnea.
Some data indicate that benzodiazepines are
teratogenic; therefore, their use during pregnancy is
not advised. Moreover, the use of benzodiazepines in
the third trimester can precipitate a withdrawal
syndrome in newborns. The drugs are secreted in the
breast milk in sufficient concentrations to affect
newborns. Benzodiazepines may cause dyspnea,
bradycardia, and drowsiness in nursing babies.

20. Tolerance, Dependence, and
Withdrawal.
When benzodiazepines are used for short
periods (1 to 2 weeks) in moderate dosages,
they usually cause no significant tolerance,
dependence, or withdrawal effects.
benzodiazepines (e.g., triazolam) may be an
exception to this rule because some persons
have reported increased anxiety the day after
taking a single dose of the drug and then
stopping its use

21. Abrupt discontinuation of benzodiazepines,
particularly those with short half-lives, is associated
with severe withdrawalsymptoms, which may include
depression, paranoia, delirium, and seizures.
The development of severe withdrawal syndrome is
seen only in persons who have taken high dosages for
long periods

22. When the medication is to be discontinued, the
drug must be tapered slowly (25 percent a week);
otherwise, recurrence or rebound of symptoms
is likely. Monitoring of any withdrawal symptoms
(possibly with a standardized rating scale) and
psychological support of the person are helpful
in thesuccessful accomplishment of
benzodiazepine discontinuation.

23. Signs and Symptoms of
Benzodiazepine Withdrawal
1.
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4.
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8.
9.
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11.
Anxiety Tremor
Irritability
Depersonalization
Insomnia
Hyperesthesia
Hyperacusis
Myoclonus
Nausea
Delirium
Difficulty concentrating
Seizures

24. Dosage and Clinical Guidelines
The clinical decision to treat an anxious person
with a benzodiazepine shouldbe carefully
considered. Medical causes of anxiety (e.g.,
thyroid dysfunction,caffeinism, and prescription
medications) should be ruled out.
Benzodiazepine use should be started at a low
dosage, and the person should be instructed
regarding the drug’s sedative properties and
abuse potential.

25. An estimated length of therapy should be
decided at the beginning of therapy,and the need
for continued therapy should be reevaluated at
least monthly because of the problems
associated with long-term use

26. Buspirone hydrochloride (BuSpar) is classified as
an azapirone and is chemically distinct from
other psychotropic agents. It acts on two types
of receptors, serotonin (5-HT) and dopamine (D).
Buspar, is an anxiolytic psychotropic drug of the
azapirone chemical class. It is primarily used to
treat generalized anxiety disorder (GAD).
The approved indication for this psychotropic
drug is for the treatment of GAD.

27. It was initially believed to be a better alternative
to the benzodiazepine drug group because
buspirone does not possess anticonvulsant and
muscle relaxant effects
Reports continue to appear that some patients
benefit from the addition of buspirone to their
antidepressant regimen. Its use in this role is
more common than its use as an anxiolytic.

28. Buspirone also has activity at 5-HT2 and
dopamine type 2 (D2) receptors, although the
significance of the effects at these receptors is
unknown. At D2 receptors, it has properties of
both an agonist and an antagonist.

29. Adult

30. Children

31. Therapeutic Indications
Generalized Anxiety Disorder. Buspirone is a
narrow-spectrum antianxiety agent with
demonstrated efficacy only in the treatment of
GAD.
Because buspirone does not act on the GABA–
chloride ion channel complex, the drug is not
recommended for the treatment of withdrawal
from benzodiazepines, alcohol, or sedative-
hypnotic drugs, except as treatment of comorbid
anxiety symptoms

32. Scattered trials suggest that buspirone reduces
aggression and anxiety in persons with organic brain
disease or traumatic brain injury. It is also used for
SSRI-induced bruxism and sexual dysfunction,
nicotine craving, and ADHD.
Precautions and Adverse Reactions
The most common adverse effects of buspirone
are headache, nausea, dizziness, and (rarely)
insomnia. No sedation is associated with buspirone

33. Buspirone should be used with caution by persons
with hepatic and renal impairment, pregnant women,
and nursing mothers Buspirone can be used safely by
the elderly.
Drug Interactions
The coadministration of buspirone and haloperidol
(Haldol) results in increased blood concentrations of
haloperidol. Buspirone should not be used with MAOIs
to avoid hypertensive episodes.
Drugs or foods that inhibit CYP3A4, for example,
erythromycin, itraconazole (Sporanox), nefazodone
(Serzone), and grapefruit juice, increase buspirone
plasma concentrations.

34. Laboratory Interferences
Single doses of buspirone can cause transient
elevations in growth hormone, prolactin, and
cortisol concentrations, although the effects are
not clinically significant.

35. Beta blockers are competitive antagonists that
block the receptor sites for the endogenous
catecholamines epinephrine (adrenaline) and
norepinephrine (noradrenaline) on adrenergic
beta receptors, of the sympathetic nervous
system, which mediates the fight-or-flight
response.

37. Officially, beta blockers are not approved for
anxiolytic use by the U.S. Food and Drug
Administration. However, many controlled trials
in the past 25 years indicate beta blockers are
effective in anxiety disorders, though the
mechanism of action is not known.
The physiological symptoms of the fight-or-
flight response (pounding heart, cold/clammy
hands, increased respiration, sweating, etc.) are
significantly reduced, thus enabling anxious
individuals to concentrate on the task at hand.

38. Therapeutic Indications
•
•
Anxiety Disorders. Propranolol is useful for the
treatment of social anxiety disorder. The β-
receptor antagonists are less useful for the
treatment of panic disorder than are
benzodiazepines or SSRIs.
Lithium-Induced Postural Tremor. The β-
receptor antagonists are beneficial for lithium-
induced postural tremor and other medication-
induced postural tremors—for example, those
induced by TCAs and valproate

39. 
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Neuroleptic-Induced Acute Akathisia
Aggression and Violent Behavior
Alcohol Withdrawal. Propranolol is reported to
be useful as an adjuvant tobenzodiazepines
Antidepressant Augmentation

41. Adverse Effects and Toxicity of β-
Adrenergic Receptor

44. The most common adverse effects of β-receptor
antagonists are hypotension and bradycardia.

45. The first barbiturate to be used in medicine was
barbital (Veronal), which was introduced in 1903.
It was followed by phenobarbital (Luminal),
amobarbital (Amytal), pentobarbital (Nembutal),
secobarbital (Seconal), and thiopental
(Pentothal). Many others have been synthesized,
but only a handful have been used clinically

47. Many problems are associated with these drugs,
including high abuse and addiction potential, a
narrow therapeutic range with low therapeutic index,
and unfavorable side effects.
A significant difference between the barbiturates and
the benzodiazepines is the low therapeutic index of
the barbiturates. An overdose of barbiturates can
easily prove fatal.
Because of some evidence of teratogenicity,
barbiturates should not be used by pregnant women
or women who are breastfeeding

48. Therapeutic Indications
Electroconvulsive Therapy. Methohexital
(Brevital) is commonly used as an anesthetic
agent for ECT. It has lower cardiac risks than
other barbiturate anesthetics
Seizures. Phenobarbital (Solfoton, Luminal), the
most commonly used barbiturate for treatment
of seizures, has indications for the treatment of
generalized tonic–clonic and simple partial
seizures.

49. Sleep. The barbiturates reduce sleep latency and
the number of awakenings during sleep,
although tolerance to these effects generally
develops within 2 weeks
Adverse effects of barbiturates
Some adverse effects of barbiturates are similar
to those of benzodiazepines, including
paradoxical dysphoria, hyperactivity, and
cognitive disorganization. Rare adverse effects
associated with barbiturate use include the
development of Stevens–Johnson syndrome,
megaloblastic anemia, and neutropenia.

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