Antianxiety drugs

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Antianxiety drugs

• ILOs
• By the end of this lecture you will be able to
• Define different types of anxiety disorders
• Classify types of drugs used for treatment of
  anxiety
• Recognize the different characteristics of
  antianxiety drugs

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What is anxiety ?

• Physical and emotional distress which
  interfere with normal life.

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How Anxiety Affects Performance

How Anxiety Affects Performance

How Anxiety Affects Performance

How Anxiety Affects Performance

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• I always thought I was just a worrier. Id feel
  keyed up and unable to relax. At times it would
  come and go, and at times it would be constant.
  It could go on for days. Id worry about what I
  was going to fix for a dinner party, or what
  would be a great present for somebody. I just
  couldnt let something go.
• Id have terrible sleeping problems. There were
  times Id wake up wired in the middle of the
  night. I had trouble concentrating, even reading
  the newspaper or a novel.

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• Sometimes Id feel a little lightheaded. My heart
  would race or pound. And that would make me worry
  more. I was always imagining things were worse
  than they really were. When I got a stomachache,
  Id think it was an ulcer.
• I was worried all the time about everything. It
  didn't matter that there were no signs of
  problems, I just got upset. I was having trouble
  falling asleep at night, and I couldn't keep my
  mind focused at work. I felt angry at my family
  all the time.

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• Emotional Symptoms of anxiety
• irrational and excessive fear and worry
• Irritability
• Restlessness
• Trouble concentrating
• Feeling tense
• Physical Symptoms of Anxiety
• Sweating
• Tachycardia
• Stomach upset
• Frequent urination or diarrhea
• Sleep disturbances (Insomnia)
• Fatigue

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• Types of anxiety disorders
• 1- Generalized anxiety
• disorder
• 2- Panic disorder

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• 3- Phobia
• 4-Post traumatic
• stress disorder
• 5- Obsessive
• compulsive
• disorder

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Treatment of anxiety

• Psychotherapy
• Anxiolytics

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• Classification of anxiolytic drugs
• Benzodiazepines ( BDZ ).
• 5HT1A agonists.
• 5HT reuptake inhibitors.
• Tricyclic Antidepressants
• Beta-adrenergic blockers
• MAO inhibitors

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Benzodiazepines
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• Mechanism of Action
• Benzodiazepines act
• by binding to BZ
• receptors in the brain
• ? enhance GABA action
• in the brain

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• 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).

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• Can be classified according to the duration of
  action into short, medium long- acting

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• Pharmacological Actions
• Anxiolytic action.

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• Pharmacological Actions
• Depression of cognitive and
• psychomotor function
• Sedative hypnotic actions
• Anterograde amnesia
• Minimal depressant effects on
• Cardiovascular system
• Respiratory system
• Some have anticonvulsant effect
• Clonazepam, diazepam.

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• 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

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

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

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• Adverse Effects
• Toxic effects respiratory cardiovascular
  depression in large doses.

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

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Quiz?

• Which one of the following is most likely to
  result from treatment with moderate doses of
  diazepam?
  
• (A) Alleviation of the symptoms of major
  depressive disorder
• (B) Agitation and possible hyperreflexia
• with abrupt discontinuance after
  chronic use
• (C) Improved performance on tests of psychomotor
  function
• (D) Retrograde amnesia

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• 5HT1A agonists
• Buspirone
• Acts as agonist at brain 5HT1A receptors
• Rapidly absorbed orally.
• T½ (2 4 h).
• Liver dysfunction ? ? its clearance.

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• 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.

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• Uses of buspirone
• As anxiolytic in mild anxiety generalized
  anxiety disorders.

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• Disadvantages of buspirone
• Slow onset of action (delayed effect)
• Not effective in severe anxiety/panic disorder.
• GIT upset, dizziness, drowsiness
• Drug Interactions with CYT P450 inducers and
• inhibitors

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Quiz?

• Which of the following statements about buspirone
  is correct
• A. It binds to 5HT receptors in the central
  nervous system
• B. It has marked sedative activity
• C. It is chemically related to benzodiazepines
• D. It causes marked central nervous system
  depression when combined with alcohol
• E. It possesses muscle relaxant activity

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• Beta Blockers
• Propranolol atenolol
• Act by blocking peripheral sympathetic system.
• Reduce somatic symptoms of anxiety.
• Decrease BP slow HR.
• Used in performance anxiety.
• Are less effective for other forms of anxiety

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• Tricyclic Antidepressants
• Doxepin- imipramine desipramine
• Act by reducing uptake of 5HT NA.
• Used for anxiety especially associated with
• depression.
• Effective for panic attacks.
• Delayed onset of action (weeks).

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• Side effects of tricyclic antidepressants
• Atropine like actions (dry mouth-blurred
  vision).
• a-blocking activity (Postural hypotension).
• Sexual dysfunction.
• Weight gain.

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• Selective serotonin reuptake inhibitors (SSRIs)
• Fluoxetine
• acts by blocking uptake of 5HT
• Orally
• Delayed onset of action (weeks).
• Long half life
• Used for panic disorder OCD -
• Generalized anxiety disorders - phobia.

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• Side effects of SSRIs
• Nausea, diarrhea
• Weight gain or loss
• Sexual dysfunction
• Dry mouth
• Seizures
• Sleep disturbance

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• Monoamine oxidase inhibitors (MAOIs)
• Phenelzine
• act 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.

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• Synopsis of anxiolytics

CLASSES OF ANXIOLYTICS USES
Benzodiazepines Generalized anxiety disorders, OCD, phobia, panic attack
SSRIs (Fluoxetine) Generalized anxiety disorders, OCD, phobia, panic attack
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)
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• Synopsis 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
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Case
The wife of a 24-year-old computer programmer
considers him to be of a "nervous disposition. "
He is easily startled, worries about
inconsequential matters, and sometimes complains
of stomach cramps. At night he grinds his teeth
in his sleep. There is no current history of drug
abuse.
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Q1

• Assuming that the symptoms experienced by this
  young man are not related to a medical condition,
  the most appropriate drug treatment would be the
  judicious use of
• (A) Buspirone
  
• (B) Midazolam
  
• (C) Triazolam
• (D) Phenelzine

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Q2

• Regarding the characteristic properties of the
  drug prescribed for this young man, the physician
  should inform the patient to anticipate
  
• (A) Additive CNS depression with alcoholic
  beverages
• (B) A significant effect on memory
  
• (C) That the drug will take a week or so to begin
  working
• (D) A need to gradually increase drug dosage
  because of tolerance
• (E) That if he stops taking the drug abruptly he
  will experience withdrawal signs