This document discusses anxiolytics, or anti-anxiety drugs. It defines anxiety and differentiates it from fear. It outlines the learning objectives which are to define key terms, list classes of anxiolytic drugs, and describe the mechanisms of action, effects, pharmacokinetics, adverse effects, and interactions of anxiolytics. The major classes of anxiolytics discussed are benzodiazepines, azapirones, and beta-blockers. Benzodiazepines are described as the most important sedative-hypnotics, with properties including a wide margin of safety but risk of dependence with prolonged use. Buspirone is discussed as an azapirone anxi

1. Anxiolytics
[Antianxiety Drugs]
Dr . Archana Dhavalshankh
Prof & Head
Department of Pharmacology

2. Learning outcomes
• By the end of the lecture, students will be able to…
Define i. an anxiolytic ii. a hypnotic
List different classes of commonly used anxiolytic/hypnotic
List different classes of commonly used anxiolytic/hypnotic drugs with
examples
Describe the mechanism of action, pharmacological effects,
pharmacokinetics, adverse effects and important drug interactions of
anxiolytics/hypnotics.
Explain the clinical significance of pharmacokinetics of benzodiazepines
Describe the problems encountered with the continued use of hypnotics
and the measures that can be taken to minimize them.

3. Outline….
A. Definitions
B. Types of anxiolytics/hypnotics
Benzodiazepines (Pharmacodynamics, Pharmacokinetics, ADRs)
Azapirones (Pharmacodynamics, Pharmacokinetics, ADRs)
Propranolol (Role as anxiolytics)

4. Anxiety (Fear of Known or Unknown)
• Anxiety is a normal adaptive or physiological response
(sometimes helpful to individual to solve the problem)
• Anxiety is a disorder if:
–chronic
–disproportionate to the situation
–occurs without an identifiable stimulus
–interferes with a person’s concentration and ability to do routine tasks

5. Anxiety versus fear
Anxiety FEAR
• anxious apprehension and worry
that is a more general reaction
that is out of proportion to
threats in environment
• future oriented
• can be adaptive if not excessive
• Experienced when a person is
faced with real and immediate
danger.
• Present-oriented
• Can be adaptive

6. Anxiety
Symptom or disorder
Phobias
Stress related disorder
Panic disorder
OCD (Obsessive compulsive disorder)
GAD (Generalized Anxiety disorder)

7. Amygdala
Pathological Anxiety (No apparent external cause))
Highlighted amygdala
response
High intensity symptoms
Persis for long time
Activation threshold of
prefrontal cortex and limbic system
Lead to harmful strategies like
Avoidance / Compulsion
Impair fuctions
Controls emotion, memories and arousal.
It contains regions that detect fear

8. Symptoms – Anxiety
• Psychological Component
Fear
dread
Unpleasant anticipation
Feeling of impending doom
• Physical Component (Autonomic arousal)
Headache
Tension
Palpitation
Feeling tightness around Head
Dryness of mouth
Coldness of extremities
Spasm of back, Bodyache
Insomnia
Bowel Disturbances

9. Pathophysiology of anxious disorders
• Abnormal regulation of neurobiological substrates :
– 5-HT, GABA, Glutamate
–Autonomic nervous system
–Hypothalamo- hypophysis axis
– Neuropeptides: CCK, P substance, galanin….

10. Anxiolytic
A drug which reduces anxiety and causes calm and quietness in the
patient
1. Sedative/Hypnotics
1) Benzodiazepines (BZDs): Alprazolam, diazepam, oxazepam, triazolam
2. Azapirone – Buspirone
3. β-Blockers - Propranolol

11. Benzodiazepines
• Sedative/Hypnotics
The benzodiazepines are the most important sedative hypnotics.
Developed to avoid undesirable effects of barbiturates (abuse liability).

12. Benzodiazepines
• BDZs have a wide margin of safety if used for short periods.
• Prolonged use may cause dependence.
• BDZs have little effect on respiratory or cardiovascular function compared
to BARBS and other sedative-hypnotics.
• BDZs depress the turnover rates of norepinephrine (NE), dopamine (DA)
and serotonin (5-HT) in various brain nuclei.
• Side Effects of Benzodiazepines.
• Related primarily to the CNS depression and include: drowsiness, excess
sedation, impaired coordination, nausea, vomiting, confusion and memory
loss.
• Tolerance develops to most of these effects.
• Dependence with these drugs may develop.
• Serious withdrawal syndrome can include convulsions and death.

13. Buspirone
• An anxiolytic medicine
• Efficacy:
Similar to that of benzodiazepines in anxiolytic effect
• Mode of action:
Act as a partial agonist for serotonin 5-HT1Areceptors in the brain

14. Buspirone
• Advantages:
–No physical dependence/ withdrawal
–No abuse potential
–No abuse potential
–Less sedation and psychomotor impairment
–Lack of interaction with alcohol
• Disadvantages:
–Slow onset of action (1-2 weeks)
–Short t1/2 (∼2.5h) →b.d./ t.d.s. administration

15. Beta Blockers (adjuvant to BZDs)
• Many symptoms of anxiety
(palpitation, rise in BP, shaking, tremor, gastrointestinal hurrying, etc.)
are due to sympathetic over activity, and these symptoms reinforce anxiety.
• Propranolol and other nonselective beta blockers help anxious.
• Patients troubled by these symptoms, by cutting the vicious cycle and
provide symptomatic relief.
• They do not affect psychological symptoms such as worry, tension
and fear, but are valuable in acutely stressful situations (examination fear,
unaccustomed public appearance, etc.).