Drugs used in anxiety & panic disorder

Objectives:
 Define different types of anxiety disorders
 Classify types of drugs used for treatment of anxiety
 Recognize the different characteristics of anti anxiety drugs
 Identify the specific clinical applications of each class of anti-anxiety drugs.
 Know side effects of different classes of anti-anxiety drugs.

color index:
extra information and further explanation
important
doctors notes
Drugs names
Mnemonics

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 Anxiety
Physical and emotional distress which interferes with normal life

Emotional or psychological symptom Physical or somatic symptoms

+ attitude - attitude

• Feeling tense Sympathetic symptoms:

• Trouble concentrating • Sweating • Dr.hanan explanation :
• Irrational (without reason) • Tachycardia • Anxiety low  performance low
& excessive fear and worry • Shortness of breath (carelessness)
• ↑ Anxiety  ↑perfor a e e.g:
• Irritability • Stomach upset afraid fro be fired they work more
• Restlessness. • Frequent urination or  + attitude )
• Moderate anxiety  highest
• diarrhea performance
• Sleep disturbances (Insomnia) • After that the more anxiety
• Fatigue (feeling intense) people o ’t oped ith there life
↓ perfor a e i erse relatio
(most patient come for this  -
Physical or somatic attitude )

symptoms

Generalized anxiety disorder (GAD) Post-traumatic stress disorder

The most common type (PTSD)
Patients are usually and constantly worried about every An anxiety disorder that affects people who have
thing, health, money, work with no apparent reason. experienced a severe emotional trauma, such as rape or
dramatic car accident, or even war.

Phobias Obsessive-compulsive disorder (OCD)

An intense, uncontrolled fear of a specific situation such An anxiety disorder in which people cannot prevent
as open spaces the ’ll sta i ho e & heights. themselves from unwanted thoughts or behaviors that
seem impossible to stop e.g. washing their hands.
These thought interrupted them from work and their life

Panic Disorder
Sudden, intense and acute attacks of anxiety in certain situations. Panic attacks cannot be predicted. Remarked fear
and sometimes it’s sever and may lead to uncontrolled urination (Autonomic effect)

Antianxiety drugs :
There are drugs that can relieve
Treatment of anxiety
anxiety without interfering with Initial therapy
mental or physical function
Anxiolytics Psychotherapy (cognitive behavioral
(Anti anxiety agent ) therapy) (talk to someone)

Benzodiazepines 5HT reuptake Beta-adrenergic

5HT1A agonists Antidepressants
(BDZ) inhibitors blockers
 Classes of anxiolytics Uses Adverse effects
Benzodiazepines Generalized anxiety Ataxia, confusion,
2nd line treatment disorders, OCD, phobia, dependence, tolerance,
In panic attack. withdrawal symptoms.
severe
case SSRIs Generalized anxiety Sexual dysfunction, atropine
(fluoxetine) disorders, Obsessive- like actions.
compulsive disorder, phobia,
1st line treatment
panic attack.
Tricyclic Anxiety with depression & Weight gain, sexual
Antidepressants panic attacks. dysfunction, atropine like
(doxepin, imipramine) actions, arrythmia.
In Mild anxiety(only) Minimal adverse effects.
5HT1A agonists
Mild
(buspirone) Not effective in panic attack.
case

Beta adrenergic blockers Phobia (social Phobia). Hypotension.

(propranolol, atenolol) Control the somatic symptoms

Suffi zolam or zepam

classifications according to duration of action

Short acting Long acting

intermediate
(3-8hrs) TO
(10-20hrs (a day) late (24-72hrs)
(Average 4h)

Lorazepam (antiepileptic)
Triazolam Diazepam
Alprazolam
Oxazepam Chlordiazepoxide
Temazepam
Flurazepam
Estazolam
Clorazepate
Quazepam
 Benzodiazepines

explanation :
• Big form of benzodiazepines metabolize in the liver and transfer into
intermediate metabolize called Nordazepam which also has CNS depressant
and then it will transfer to another metabolize which is called Oxazepam
(short duration action) which enter glucuronide conjugation to be easily
execrated in urine.

• Glucuronic acid is a phase 2 (phase 1 : oxidation , reduction , hydrolysis )

studied in foundation block 

• So e on’t gi e the elderly patient long duration drugs due to :

1- They have low metabolize function + increasing in age will decrease phase 1
enzyme function so  they ill ha e hat’s called : CNS super sensiti ity =
respond more than young patient to drugs
2- Accumulation of the diazepam will cause  sever CNS depression eg :
delirium (patient can open the house door and go out without consciousness)
• Lorazepam go directly to phase 2  that’s why it is preferred
in elderly patient + it is an intermediate in action
 Benzodiazepines
1) Benzodiazepines binds
to BZ receptor in the brain

2) enhance GABA action on brain

GABA (γ-aminobutyric acid): is an
mech. Of action

inhibitory neurotransmitter

3) chloride channels opening 4) more difficult(for the stimulant) to

leading to increase CL-- influx to depolarizes which will lead to
the cell (hyperpolarization) → reduction of neural excitability.
Pharmacology Recall (page 78-79):
Benzodiazepines bind to specific receptors that are separated from but adjacent to the 𝐺
receptor, they potentiate the binding of GABA to its own receptor. The binding of GABA to its own
receptor results in increased 𝑪𝒍−conduction the ’re o e ted see the pi ture , cell membrane
hyperpolarization, & decreased initiation of action potentials.
Remember benzodiazepines do not bind to GABA receptors, they bind adjacent to them.

• Lipid solu le • idel distri uted.

• Well absorbed orally. • Can be given parenterally
• Chlordiazepoxide - Diazepam (IV only NOT IM) (IM : lead to erratic absorption (not very well
a sor ed ut if it’s the o l a ou a do it
• • ross pla e tal arrier (Fetal depression).
P.K

•e reted i ilk (neonatal depression).

•Bezodiazepines is metabolized in liver to another active metabolites  Nordazepam
again it works as CNS depressio that’s h Bezodiazepines have long duration of
action, and this mechanism called  cumulative effect & it’s e reted i urine.

• CNS depressants: (depend on the dose)

• Anxiolytic action and Sedation (1\3 of the dose):
• Hypnotic action. = sleeping pills (total dose)
•
Pharmacological Action

Anterograde amnesia .temporary impairment of memory (more increase)

Respiratory & CVS depression (over dose)
• Depression of cognitive and psychomotor function (#driving or workers in factory  give
them short acting)
• Some have skeletal muscle relaxing effect (diazepam)by increasing presynaptic
inhibition in the spinal cord
• • So e ha e a ti o ulsa t effe t e.g. clonazepam, diazepam,
lorazepam.(antiepileptic)
• Therapeutic doses have minimal depressant effects on: cardiovascular system &
respiratory system.
 Benzodiazepines
1. Anxiety disorders:
Short term relief of severe anxiety, General anxiety disorder, OCD (Obsessive- Compulsive Disorder) , Panic
Therapeutic uses

disorder with depression Alprazolam (antidepressant + anxiolytic effect)

• Be zodiazepi es are fast acting typically bringing relief within (30mins – hour).
2. Sleep disorders (Insomnia): Triazolam, Lorazepam, Flurazepam. (Triazolam not used as sleeping pills anymore due to
short action) They tend to decrease the latency to sleep onset and increase Stage II of NREM sleep.
3. Treatment of epilepsy: Diazepam – Lorazepam. (given in emergency as IV)
4. In anesthesia:
• Pre-anesthetic medication (diazepam). Before surgery
• Induction & maintenance of anesthesia (Midazolam, IV)
5. Alcohol withdrawal syndrome: (diazepam)
• Cog iti e i pair e t.
• Ata ia otor i oordi atio ith ↑ dose
• I pair e t of dri i g a ilit .
• A terograde a esia.
ADRs

• Ha go er: e ess sedation,drowsiness, confusion)

• Tolera e a d depe de e.
• Psychological & physical dependence with continuous use.
• Risk of ithdra al s pto s:
Rebound (exaggerated) insomnia, anorexia, anxiety,agitation, tremors & convulsion).
• Respirator & ardio as ular depressio i large doses o l to i effe ts .
Drug

Flumazenil (Benzodiazepine antagonist)

Given by injection, has short plasma half life
P.K

so repeated dosing is required because it is also an antidepressant

- Selective Benzodiazepine receptor antagonist.
P.D

- Bind competitively to GABA receptor  displacing benzodiazepine

1- Used in benzodiazepines overdose (antidote)
2- can precipitate withdrawal symptoms in benzodiazepines addicts Patient whose
uses

addicted to sleeping pills suddenly you stop it from it  withdrawal symptoms will
happen
• Should be used with precaution:
precaution

• Pregnant women or breast-feeding

• Dose reduction is recommended in : liver disease , old people

Drug interactions
Drugs Examples
CNS depressants e.g. alcohol & effect of benzodiazepines (Additive
antihistaminics (1st generation cross BBB effect) (synergic affect)
sedation)

Cytochrome P450 inhibitors e.g. cimetidine t ⁄ of benzodiazepines by inhibition of

& erythromycin metabolism

CYT P450 inducers phenytoin & rifampicin t1/2 of benzodiazepines (almost all epileptic
drugs are inducers)
 class 5HT1A agonists SSRIs Tricyclic Beta Blockers
( 5-hydroxytryptamine) Antidepressants

Buspirone Fluoxetine Doxepin , Propranolol (non

Drug

Imipramine , selective), Atenolol

Desipramine
• Acts as a partial agonist at brain • (SSRIs) : • act by ↓
5HT1A receptors, presynaptic
inhibiting 5HT release. Selective reducing by blocking
• Weak dopamine D2 action , but not serotonin uptake of peripheral
antipsychotic
sympathetic
Action/Mech. of action

• Rapidly absorbed orally reuptake 5HT & NA

• Slow onset of action (delayed effect) inhibitors by • Delayed system
• T½ : (2 – 4 h).
• Undergoes extensive hepatic blocking uptake onset of ↓
metabolism, some of the of 5-HT action Reduce
metabolites are active
• Its clearance is reduced by liver
• Given orally (weeks). somatic (not
dysfunction • has long half psychological)
• Adaptive changes after chronic symptoms of
life
treatment , reduction in 5HT2 anxiety.
receptors in cortex

Used As anxiolytic in (mild) generalized First line of treatment for 1. Used for • Decrease BP &
anxiety disorders cause : most anxiety disorders anxiety slow heart rate
1. It’s o l a iol ti (Panic disorder, OCD, especially  so Used in
2. No hypnotic effect. GAD, PTSD, phobia) associated performance
3. No muscle relaxant effect. because they are : with or social
4. No anticonvulsant action. 1- well tolerated, depression anxiety.
5. No alcohol additive effect. 2- low risk for
• Are less
Indication

6. Does ’t i pair e or a d dependency and abuse 2. Effective for

effective for
coordination. (can use in elderly 3- low potential for panic attacks
other forms of
patients) overdose. (CVS&
anxiety
7. Does not affect driving skills. respiration depression)
8. Minimal risk of dependence.
9. No withdrawal symptoms.
10. No potentiation of other CNS
depressants
11. Minimal psychomotor & Cognitive
dysfunctions
• Slow onset of action (delayed effect) -Delayed onset of action -Atropine like Should be used
• GIT upset, dizziness, drowsiness (weeks). actions : (dry with caution in
• Not effective in severe -Nausea, diarrhea , GIT mouth-blurred asthma, cardiac
ADRs + Contraindication

anxiety/panic disorders upset vision, urinary failure, peripheral

• Drug Interactions with CYT P450 -Weight gain or loss retention vascular disorders
inducers and inhibitors Fluoxetine cause weight Tachycardia)
• Increase blood pressure in people Loss. -α-blocking
taking MAOI. -Sexual dysfunction activity (Postural
Should be used with precaution : -Dry mouth hypotension)
• Pregnant women or breast-feeding. -Sleep disturbance or -Sexual
• People over 65 (old people) insomnia dysfunction
• Dose reduction is recommended in -Seizures -Weight gain
liver disease & old people

CYP450 3A4 Inhibitors : (verapamil, diltiazem Ca+2 blocker) ↑ buspirone level.

Buspirone CYP450 3A4 Inducers : (Rifampin) Causes fold ↓ buspirone level.
 : ‫ق دة فري ع األد ية‬
‫عبدالرحمن ذكري‬ & ‫لين التميمي‬
: ‫الشكر م ص ل ألعض ء ال ري المتميزين‬
‫شذا الغي‬
‫هي ء بن ط ل‬
‫لين ال كيل‬
‫سمر القحط ني‬
‫آم ل الشيبي‬
‫ر ان سعد القحط ني‬

References :
1- 436 doctors slides
2-435 team work
3-Pharmacology (Lippincotts Illustrated Reviews Series), 5th edition.

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