Transcript L3-anxiet and panic disorder2014-08

Antianxiety drugs
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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
What is anxiety ?
Physical and emotional distress
which interfere with normal life.
“I always thought I was just a worrier. I’d 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. I’d worry
about what I was going to fix for a dinner
party, or what would be a great present for
somebody. I just couldn’t let something go.”
“I’d have terrible sleeping problems. There were
times I’d wake up wired in the middle of the
night. I had trouble concentrating, even
reading the newspaper or a novel.
Sometimes I’d 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, I’d 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.”
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
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
Treatment of anxiety
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Psychotherapy
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Anxiolytics
Classification of anxiolytic drugs:
1.
Benzodiazepines ( BDZ ).
2.
5HT1A agonists.
3.
5HT reuptake inhibitors.
4.
Tricyclic Antidepressants
5.
Beta-adrenergic blockers
6.
MAO inhibitors
Benzodiazepines
Mechanism of Action
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Benzodiazepines act
by binding to BZ
 receptors in the brain
 enhance GABA action
in the brain
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
Pharmacological Actions
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Anxiolytic action.
Pharmacological Actions
Depression of cognitive and
psychomotor function
 Sedative & hypnotic actions
 Anterograde amnesia
Minimal depressant effects on
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Cardiovascular system
Respiratory system
Some have anticonvulsant effect:
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Clonazepam, diazepam.
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
Therapeutic Uses
Treatment of epilepsy
Diazepam – Lorazepam
In anesthesia
 Preanesthetic medication (diazepam).
 Induction of anesthesia (Midazolam, IV)
Use of
benzodiaze
pine
Adverse Effects
• Ataxia (motor
Even
more
anxious
Reduced
anxiety
incoordination)
Effect
wears
• Cognitive impairment.
off
• Hangover:
(drowsiness, confusion)
• Tolerance & dependence
• Risk of withdrawal symptoms
Rebound insomnia, anorexia, anxiety, agitation,
tremors and convulsion.
Adverse Effects
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Toxic effects: respiratory & cardiovascular
depression in large doses.
Drug interactions
Examples
CNS depressants
Cytochrome P450
(CYT P450) inhibitors
CYT P450 inducers
Alcohol & Antihistaminics of
effect of benzodiazepines
Cimetidine & Erythromycin
t ½ of benzodiazepines
Phenytoin & Rifampicin
t 1/2 of benzodiazepines
Dose should be reduced in
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Liver disease
Old people.
Precaution
Should not be used in
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pregnant women or breast-feeding.
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People over 65.
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.
Uses of buspirone
As anxiolytic in mild anxiety & generalized
anxiety disorders.
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?
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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
Beta Blockers
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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.
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Delayed onset of action (weeks).
Side effects of tricyclic antidepressants
Atropine like actions (dry mouth-blurred vision).
 α-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.
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
Generalized anxiety disorders, OCD,
phobia, panic attack
SSRIs
(Fluoxetine)
Tricyclic antidepressants
(doxepin, imipramine )
5HT1A agonists
(Buspirone)
Beta blockers
(propranolol, atenolol)
anxiety with depression.
panic attacks
Mild anxiety
Not effective in panic attack
Phobia (social Phobia)
Synopsis of anxiolytics
CLASSES OF
ANXIOLYTICS
Benzodiazepines
SSRIs
(Fluoxetine)
Tricyclic antidepressants
(doxepin, imipramine )
5HT1A agonists
(Buspirone)
Beta blockers
(propranolol, atenolol)
Adverse effects
Ataxia, confusion, dependence,
tolerance, withdrawal symptoms,
weight gain, sexual dysfunction
Dry mouth
weight gain, sexual dysfunction,
atropine like actions
Minimal adverse effects
Hypotension
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.
Q1
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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
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
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