1. Drug treatment of Anxiety
Dr. Hemant D. Une
Pharmacology Department
Y. B. Chavan College of Pharmacy, Aurangabad

2. Anxiety Should I be anxious ? I have a presentation
I have a tough exam
I have an important interview
Should I be anxious ?

3. What is anxiety ?
Physical and emotional distress which interfere with normal life.

4. What are different symptoms of anxiety ?
Psychic or emotional state.
Somatic or physical symptoms.

5. Common Emotional Symptoms of anxiety
irrational and excessive fear and worry
Irritability
Restlessness
Trouble concentrating
Feeling tense

6. Common Physical Symptoms of Anxiety
Sweating
Tachycardia
Stomach upset
Shortness of breath
Frequent urination or diarrhea
Sleep disturbances (Insomnia)
Fatigue

7. Types of anxiety Generalized anxiety disorder
Post-traumatic stress disorder (PTSD).
Obsessive-compulsive disorder (OCD).
Panic disorder
Phobia

8. Generalized Anxiety Disorder (GAD)
Patients are usually and constantly worried
about health, money, work with no apparent
reasons.

9. Obsessive-Compulsive Disorder (OCD)
An anxiety disorder in which people cannot prevent themselves from unwanted thoughts or behaviors that seem impossible to stop as
Washing their hands

10. Panic disorder
An disorder in which people have sudden and intense attacks of anxiety in certain situations.

11. Post-traumatic stress disorder (PTSD)
An anxiety disorder that affects people who have experienced a severe emotional trauma, such as rape or dramatic car accident, or even war.

12. Phobia An intense, uncontrolled fear of a specific situation such as
open spaces & heights

13. Symptoms of Anxiety Anxiety is an emotion often accompanied by
various physical symptoms, including:
Twitching or trembling
Muscle tension
Headaches
Sweating
Dry mouth
Difficulty swallowing
Abdominal pain (may be the only symptom of stress especially in a child)

14. Classification of anxiolytic drugs:
Benzodiazepines ( BDZ ).
5HT1A agonists.
5HT reuptake inhibitors.
Antidepressants
beta-adrenergic blockers
MAO inhibitors

15. Additional Symptoms of Anxiety
Sometimes other symptoms accompany
anxiety:
Dizziness
Rapid or irregular heart rate
Rapid breathing
Diarrhea or frequent need to urinate
Fatigue
Irritability, including loss of your temper
Sleeping difficulties and nightmares
Decreased concentration
Sexual problems

16. Physical Reaction to Anxiety
Auditory and Visual Stimuli:
sights and sounds are processed
first by the thalamus, which filters
the incoming cues and shunts
them either directly to the
amygdala or to the other parts of
the cortex.
Olfactory and tactile stimuli:
Smells and touch sensations
Bypass the thalamus altogether,
Taking a shortcut directly to the
Amygdala. Smells, therefore,
Often evoke stronger memories
Or feelings than do sights or
Sounds.

17. Physical Reaction to Anxiety
Thalamus:
The hub for sights and sounds, The thalamus breaks down Incoming visual ques by size, Shape and color, and auditory Cues, by volume and Dissonance, and then signals The appropriate part of the Cortex.
Cortex:
It gives raw sights and sounds
meanings, enabling the brain
to become conscious of what it
Is seeing or hearing. One region, the prefrontal cortex, may be vital to turning off the anxiety response once a threat has passed.

18. Physical Reaction to Anxiety
Amygdala:
emotional core of the brain, the amygdala has the primary role of triggering the fear response. information that passes through the amygdala is tagged with emotional significance.
Bed Nucleus of Stria Terminalis:
unlike the Amygdala, which sets off an immediate burst of fear, the BNST perpetuates the fear response, causing the longer term unease typical of
anxiety.

19. Physical Reaction to Anxiety
Locus Ceruleus:
It receives signals from the
amygdala and is responsible
for initiating many of the
classic anxiety responses:
rapid heartbeat, increased
blood pressure, sweating and
pupil dilation.
Hippocampus:
This is the memory center,
vital to storing the raw
information coming in from
the senses along with the
emotional baggage attached
to the data during their trip
through the amygdala.

20. Treatment of anxiety Psychotherapy (cognitive behavioral therapy).
Anxiolytics

21. Benzodiazepines

22. Classifications of Benzodiazepines
- Short acting: (3-5 hours): triazolam
-  Intermediate: (6-24 hours)
Alprazolam
Lorazepam
Oxazepam
Estazolam
Temazepam

23. Classifications of Benzodiazepines
-  Long acting: ( hours)
Clonazepam
Chlordiazepoxide
Diazepam
Flurazepam

24. GABA (γ-aminobutyric acid): is an inhibitory neurotransmitter
Mechanism of Action
Benzodiazepines act by binding to BZ receptors
in the brain  enhance GABA action on brain  chloride channels opening   chloride influx to the cell  hyper- polarization  inhibition of brain.
GABA (γ-aminobutyric acid):
is an inhibitory neurotransmitter

26. GABA-A Receptor   d  e BDZs BARBs
Oligomeric (abdgepr) glycoprotein.
Major player in Inhibitory
Synapses.
It is a Cl- Channel
Binding of GABA
causes the channel to open and Cl- to flow into the cell with the resultant membrane hyperpolarization.
BARBs
GABA AGONISTS   d  e

27. can be given parenterally Chlordiazepoxide- Diazepam (IV only NOT IM)
PHARMACOKINETICS
are lipid soluble
well absorbed orally,
can be given parenterally
Chlordiazepoxide- Diazepam (IV only NOT IM)
widely distributed.
cross placental barrier (Fetal depression).
excreted in milk (neonatal depression).

28. metabolized in the liver to active metabolites (long
duration of action- cumulative effect).
Redistribution from CNS to skeletal muscles,
adipose tissue) (termination of action).

30. Pharmacological Actions
Anxiolytic action.
Depression of cognitive and psychomotor function
Sedative & hypnotic actions
Anterograde amnesia.

31. Pharmacological Actions
Minimal depressant effects on
Cardiovascular system
Respiratory system
Some have anticonvulsant effect:
clonazepam, diazepam.

32. Therapeutic Uses Anxiety disorders:
short term relief of severe anxiety
General anxiety disorder
Obsessive compulsive disorder
Panic attack with depression Alprazolam
(antidepressant effect)
Sleep disorders (Insomnia).
Triazolam, Lorazepam, Flurazepam

33. Therapeutic Uses Treatment of epilepsy Diazepam – Lorazepam
In anesthesia
Preanesthetic medication (diazepam).
Induction of anesthesia (Midazolam, IV)

34. Ataxia (motor incoordination)
Adverse Effects
Ataxia (motor incoordination)
Cognitive impairment.
Hangover: (drowsiness, confusion)
Tolerance & dependence
Risk of withdrawal symptoms
Rebound Insomnia, anorexia, anxiety, agitation, tremors and convulsion.

35. Adverse Effects
Toxic effects: respiratory & cardiovascular depression in large doses.

36. t ½ of benzodiazepines Drug interactions Examples CNS depressants
Alcohol & Antihistaminics of effect of benzodiazepines
Cytochrome P450 (CYT P450) inhibitors
Cimetidine & Erythromycin
t ½ of benzodiazepines
CYT P450 inducers
Phenytoin & Rifampicin
t 1/2 of benzodiazepines

37. Dose should be reduced in
Liver disease
Old people.
Precaution
Should not used in
pregnant women or breast-feeding.
People over 65.

38. 5HT1A agonists Buspirone
acts as agonist at brain 5HT1A receptors
rapidly absorbed orally.
Slow onset of action (delayed effect)
T½ : (2 – 4 h).
liver dysfunction   its clearance.
Drug Interactions with CYT P450 inducers
and inhibitors.

39. Buspirone Only anxiolytic No hypnotic effect. Not muscle relaxant.
Not anticonvulsant.
No potentiation of other CNS depressants.
Minimal psychomotor and cognitive dysfunctions.
Does not affect driving skills.
Minimal risk of dependence.
No withdrawal signs.

40. Uses of buspirone As anxiolytic in mild anxiety & generalized
anxiety disorders.
Not effective in severe anxiety/panic disorder.

41. Beta Blockers Propranolol – atenolol
act by blocking peripheral sympathetic system.
Reduce somatic symptoms of anxiety.
Decrease BP & slow HR.
Used in social phobia.
are less effective for other forms of anxiety

42. Tricyclic Antidepressants
Doxepin- imipramine
act by reducing uptake of 5HT & NA.
Used for anxiety especially associated with
depression.
Effective for panic attacks.
Delayed onset of action (weeks).
dry mouth, postural hypotension, sexual
dysfunction, weight gain.

43. Selective serotonin reuptake inhibitors (SSRIs)
Fluoxetine
acts by blocking uptake of 5HT
Orally
Delayed onset of action (weeks).
Used for panic disorder – OCD depression-
Generalized anxiety disorders - phobia.
Side Effects:
Weight gain, sexual dysfunction, dry mouth

44. MONOAMINE OXIDASE INHIBITORS
Phenelzine
Acts by blocking the action of MAO enzymes.
Used for panic attacks and phobia.
Require dietary restriction
Avoid wine, beer, fermented foods as old cheese that contain tyramine.
Side effects
Dry mouth, constipation, diarrhea, restlessness,
dizziness.

45. Conclusion of anxiolytics
CLASSES OF ANXIOLYTICS
USES
Benzodiazepines
Generalized anxiety disorders, OCD, phobia, panic attack
SSRIs
(Fluoxetine)
Tricyclic antidepressants
(doxepin, imipramine )
anxiety with depression.
panic attacks
5HT1A agonists
(Buspirone)
Mild anxiety
Not effective in panic attack
Beta blockers
(propranolol, atenolol)
Phobia (social Phobia)
MAO inhibitors
Phenelzine
Panic attack, phobia

46. Conclusion of anxiolytics
CLASSES OF ANXIOLYTICS
Adverse effects
Benzodiazepines
Ataxia, confusion, dependence, tolerance, withdrawal symptoms,
SSRIs
(Fluoxetine)
weight gain, sexual dysfunction
Dry mouth
Tricyclic antidepressants
(doxepin, imipramine )
weight gain, sexual dysfunction, atropine like actions
5HT1A agonists
(Buspirone)
Minimal adverse effects
Beta blockers
(propranolol, atenolol)
Hypotension