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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
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What is anxiety?
Physical and emotional distress which interfere with normal life.
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Emotional Symptoms of anxietyirrational and excessive fear and worry
Irritability Restlessness Trouble concentrating Feeling tensePhysical Symptoms of AnxietySweatingTachycardiaStomach upsetFrequent 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:
1. Benzodiazepines ( BDZ ).
2. 5HT1A agonists.
3. 5HT reuptake inhibitors.
4. Tricyclic Antidepressants
5. beta-adrenergic blockers
6. MAO inhibitors
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Benzodiazepines
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Can be classified according to the duration of action into short, medium & long- acting
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Mechanism of Action
Benzodiazepines act by binding to BZ receptors in the brain enhance GABA action on 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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Pharmacological Actions
Anxiolytic action.
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Pharmacological Actions
Depression of cognitive and psychomotor function Sedative & hypnotic actions Anterograde amnesiaMinimal 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 anxietyGeneral anxiety disorderObsessive compulsive disorderPanic 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 symptomsRebound 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
o Liver diseaseo Old people.
Precaution Should not be used in pregnant women or breast-feeding. People over 65.
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5HT1A agonistsBuspirone
acts as agonist at brain 5HT1A receptors rapidly absorbed orally. t½ : (2 – 4 h). liver dysfunction its clearance.
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BuspironeOnly 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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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). 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 depression- 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 effectsDry mouth, constipation, diarrhea, restlessness, dizziness.
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Conclusion 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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Conclusion of anxiolyticsCLASSES OF
ANXIOLYTICSAdverse 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