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By:-
Robin Gulati
CONTENTS

Anxiety
Symptoms and Clinical Features of
 anxiety
Causes for anxiety & Role of Receptors
Anxiety Disorders
Treatment
Prevention
ANXIETY
A psychological and physiological state
 characterized by following
 components:-
 1. Cognitive: Processing of information, applying
    knowledge, and changing preferences
 2. Somatic: Voluntary control of body
    movements via skeletal muscles, and
    with sensory reception of external
    stimuli (e.g., touch, hearing, and sight)
3. Emotional: Mood, temperament, personality
   and disposition, and motivation
4. Behavioral component: Response of the
   system or organism to various stimuli or
   inputs, whether internal or external,
   conscious or subconscious, overt or covert,
   and voluntary or involuntary.
SYMPTOMS AND CLINICAL
        FEATURES
A. Physical symptoms:
 Heart palpitations
 Muscle weakness and tension
 Fatigue
 Nausea
 Chest pain
 Shortness of breath
Stomach aches, or headaches.
Increased blood pressure and heart rate
Increased sweating
Increased blood flow to the major muscle
 groups
Immune and digestive system functions are
 inhibited (the fight or flight response).
B. External signs:
 Pale skin
 Sweating
 Trembling
 Pupillary dilation
C. Emotional symptoms:
 Feelings of apprehension or dread
 Trouble concentrating
 Feeling tense or jumpy
 Anticipating the worst
 Irritability
 Restlessness
Feeling like your mind's gone blank
Nightmares/bad dreams
Obsessions about sensations
Déjà vu
A trapped in your mind feeling, and feeling
 like everything is scary.
Can be a symptom of an underlying
 health issue such as:-
  chronic obstructive pulmonary disease
   (COPD),
  heart failure, or heart arrhythmia.
NEUROTRANSMITTER SYSTEMS

Neurotransmitter systems involved in
 anxiety generation include the
  GABA systems
  Serotonergic
  Adrenergic
  Benzodiazepine (BZD)
CAUSES & ROLE OF RECEPTORS
1. Biological
  Low levels of GABA, a neurotransmitter that
   reduces activity in the central nervous system,
   contribute to anxiety.
  GABA exhibits excitatory actions like:
    Mediating muscle activation at synapses
     between nerves and muscle cells
    Stimulation of certain glands
  A number of anxiolytics achieve their effect by
   modulating the GABA receptors.
 GABA acts at inhibitory synapses in
 the brain by binding to specific
 transmembrane receptors in the plasma
 membrane of both pre- and postsynaptic
 neuronal processes.
   GABA +                            Clˉ in and K+
                    Opening of Ion
Transmembrane                               out of the
                      Channels
   Receptors                                   cell




                                     Hyperpolarization
GABA
         RECEPTORS


GABAA Receptors   GABAB Receptors
GABAA               GABAB
• Ionotrophic       • Metabotrophic
  receptors           receptors
• Part of ligand    • Open/close via
  gated ion           intermediaries
  channel complex     (G-proteins)
GABAA
 Upon activation, the
  GABAAreceptor selectively
  conducts Cl- through
  its pore, resulting
  in hyperpolarization of
  the neuron.
 This causes an inhibitory
  effect
  on neurotransmission by
  diminishing the chance of a
  successful action
  potential occurring.
 GABAA receptors are Cl - channels so when activated by
 GABA:
  Cl moves out: excitation/ depolarization
  Cl moves in: inhibition/ hyperpolarization- inhibition of
   NT
GABAB

They can stimulate the opening of K+ channels
 which brings the neuron closer to
 the equilibrium potential of
 K+, hyperpolarizing the neuron.
This prevents sodium channels from opening,
 action potentials from firing, and VDCCs from
 opening, and so
 stops neurotransmitter release. Thus
 GABAB receptors are considered inhibitory
 receptors.
II. AMYGDALA
 The amygdala is central to the processing of fear
   and anxiety, and its function may be disrupted in
   anxiety disorders.
 Sensory information enters the amgydala through
   the nuclei of the basolateral complex (consisting of
   lateral, basal, and accessory basal nuclei).
 The basolateral complex processes sensory related
   fear memories, and communicate their threat
   importance to memory and sensory processing
   elsewhere in the brain, such as the medial prefrontal
   cortex and sensory cortices.
The adjacent central
 nucleus of the amygdala
 controls species-specific
 fear responses, via
 connections to
 the brainstem, hypotha-
 lamus,
 and cerebellum areas.
In those with general
 anxiety disorder, these
 connections functionally
 seem to be less distinct,
 with greater gray
 matter in the central
 nucleus.
III. ENVIRONMENTAL FACTORS
 Life stresses such as financial worries or
  chronic physical illness.
 Also common among older people who
  have dementia.
 On the other hand, anxiety disorder is
  sometimes misdiagnosed among older adults
  when doctors misinterpret symptoms of a
  physical ailment (for instance, racing heartbeat
  due to cardiac arrhythmia) as signs of anxiety.
Use of and withdrawal from addictive
 substances, including alcohol, caffeine,
 and nicotine.
ANXIETY DISORDERS
1. Generalized Anxiety Disorder: An ongoing
   state of excessive anxiety lacking any clear
   reason or focus
2. Panic Disorders : Sudden attacks of
   overwhelming fear occur in association with
   marked somatic symptoms, such as sweating,
   tachycardia, chest pains, trembling and choking.
3. Phobias: Strong fears of specific objects or
   situations, e.g. snakes, open spaces, flying,
   social interactions
4. Post-traumatic stress disorder: Anxiety
   triggered by recall of past stressful
   experiences
5. Obsessive compulsive disorder:
   Compulsive ritualistic behavior driven by
   irrational anxiety, e.g. fear of contamination.
GENERALIZED ANXIETY
              DISORDERS

An ongoing state of excessive anxiety lacking any
 clear reason or focus.

Characterized by excessive, uncontrollable and
 often irrational worry about everyday things that is
 disproportionate to the actual source of worry.
Interferes with daily functioning, as individuals
 suffering GAD typically anticipate disaster, and
 are overly concerned about everyday matters
 such as:-
  Health issues
  Money
  Death
   Family problems
   Friend problems
   Relationship problems or
   Work difficulties
PHYSICAL SYMPTOMS:
 Fatigue                          Difficulty concentrating

 Fidgeting                        Trembling

 Headaches                        Twitching

 Nausea                           Irritability

 Numbness in hands and            Agitation
  feet                             Sweating
 Muscle tension                   Restlessness
 Muscle aches                     Insomnia
 Difficulty swallowing            Hot flashes,
 Bouts of difficulty breathing     and rashes and
                                   Inability to fully control
                                    the anxiety
CAUSES:
Genetic predisposition and environmental factors.
Parents can model anxious behaviours to their
 children.
Stressful early life events such as early parental
 death.
Chronic experiences of fear and learned
 helplessness may cause greater chronic cortisol
 activation and increased sympathetic tone.
Traumatic experiences and abnormal prenatal
 hormonal exposures may also play a role the
 cause of this disorder.
TREATMENT:

Medication can be effective for generalized
 anxiety disorder (GAD).
Generally recommended only as a temporary
 measure to relieve symptoms at the beginning of
 the treatment process, with therapy the key to
 long-term success.
Types of medication prescribed for
  generalized anxiety disorder:
1. Benzodiazepines –
  Quick acting (usually within 30 minutes to an
   hour).
  Serious drawbacks
  Physical and psychological dependence are
   common after more than a few weeks of
   use.
  Generally recommended only for severe,
   paralyzing episodes of anxiety.
2. Buspirone –
 5-HT1A receptor antagonist.
 Safest drug for generalized anxiety
  disorder.
 Unlike the benzodiazepines, buspirone
  isn’t sedating or addictive.
 Although buspirone will take the edge off,
  it will not entirely eliminate anxiety.
3. Antidepressants –
  The relief antidepressants provide for
   anxiety is not immediate, and the full effect
   isn’t felt for up to six weeks.
  Some antidepressants can also exacerbate
   sleep problems and cause nausea.
TREATMENT OF ANXIETY
             DISORDERS
Types of anxiolytics:-
 1. Benzodiazepines

   E.g.- Alprazolam, Chlordiazepoxide,
      Clonazepam, Diazepam, Lorazepam
 2. SSRIs (Selective Serotonergic Receptor
    Inhibitors)
    E.g.- Escitalopram, Citalopram
3. Azapirones
   E.g.- Buspirone
4. Barbiturates
   E.g.- Phenobarbital, Pentobarbital
5. Miscellaneous
   E.g.- Chloral hydrate, Meprobamate,
   Methaqualone
1. BENZODIAZEPINES
Most important group, used as anxiolytic and
  hypnotic agents.
Types:
1. Ultra short acting (4-6 hrs): Triazolam,
   midazolam, Zolpidem
2. Short acting (12-18 hrs): Lorazepam,
   Oxazepam
3. Medium acting (24 hrs): Alprazolam
4. Long acting (>24 hrs): Diazepam,
   Clordiazepoxide, Flurazepam, Clonazepam
Drug(s)        Half-life of    Active        Half-life of    Main use(s)
                    parent       metabolite     metabolite
                  compound                        (Hrs)
                     (Hrs)
  Triazolam,          2-4        Hydroxylated        2            Hypnotic
  Midazolam                       derivative                     Midazolam:
                                                               I.V. anesthetic
   Zolpidem            2             No              -            Hypnotic

 Lorazepam,          8-12            No              -           Anxiolytic,
 Oxazepam                                                         hypnotic
  Alprazolam         6-12        Hydroxylated        6           Anxiolytic,
                                  derivative                   antidepressant
  Diazepam,          20-40       Nordazepam         60           Anxiolytic,
Chlordiazepoxid                                                muscle relaxant
       e                                                        Dzpam: I.V.
                                                               anticonvulsant
 Flurazepam            1         Desmethyl-         60           Anxiolytic
                                 flurazepam
 Clonazepam           50             no              -         Anticonvulsant,
                                                                 anxiolytic
                                                                   (mania)
MECHANISM OF ACTION
       Selectively act on GABAA receptors




 Increase affinity of GABA for the receptor



    Opening of GABA activated Cl‾ channels




Inhibition of synaptic transmission throughout CNS
MOA
PHARMACOLOGICAL EFFECTS AND
USES OF BZD :-

1. Reduction of anxiety and aggression.
2. Sedation and induction of sleep.
3. Reduction of muscle tone and coordination.
4. Anticonvulsant effect.
UNWANTED EFFECTS OF BZD

Divided into:
  1. Toxic effect resulting from acute overdose
     (antagonist- flumazenil).
  2. Unwanted effects during normal
     therapeutic dose: drowsiness, confusion,
     amnesia, impaired coordination.
  3. Tolerance and dependence.
2. SSRI

Lower levels of serotonin (5-HT) produces
 depression.
Inhibit serotonin reuptake.
Serotonin stays at the synapse for a longer
 duration, as a result, longer action.
Produce little or no sedation.
Do not interfere with psychomotor functions or
 anticholinergic side effects.
 Do not inhibit cardiac conduction- overdose
  arrhythmias are not a problem.
 Used along with BZD to cover exacerbations
a) Citalopram:
    T1/2 : 33 hrs
    No active metabolite
    Overdose: suicide


b) Escitalopram:
    Active S(+) enantiomer of citalopram.
    Effective at half dose
    Less side effects and improved safety.
b) Fluoxetine
   Longest acting
   T1/2 for parent compound: 2 days and active
    demethylated metabolite: 7-10 days.
   Slow onset of action
MECHANISM
OF ACTION
SIDE EFFECTS

 Nausea
 Interference with ejaculation and orgasm
 Nervousness
 Restlessness
 Insomnia
 Anorexia
 Headache
 Diarrhoea
3. AZAPIRONES: BUSPIRONE

Does not produce significant sedation or
 cognitive/ functional impairment.
Does not interact with BZD receptor or modify
 GABAnergic transmission.
Does not produce tolerance or physical
 dependence.
Has no muscle relaxant or anticonvulsant
 activity.
Used in mild to moderate GAD. Ineffective in
 severe cases.
Slow therapeutic effect. Delayed up to 2
 weeks.
T1/2 : 2-3.5 hrs
MOA:
  Stimulates presynaptic 5-HT1A
    autoreceptors.
  Activity of dorsal raphe serotonergic
    neurons decreases.
  Agonist action on 5-HT1A receptors.
SIDE EFFECTS:

Dizziness
Nausea
Headache
Light-headedness
Excitement (rarely)
4. BARBITURATES
Non-selective CNS depressants.
Effects range from sedation and reduction of
 anxiety to unconsciousness and death from
 respiratory and cardiac failure.
Dangerous in overdose.
Act by enhancing action of GABA, but less
 specific than BZD.
Use as sedative/ hypnotic agent is no longer
 recommended.
Can cause drug interactions as it is a potent
 inducer of hepatic drug metabolizing enzymes.
Tolerance and dependence occur.
PANIC DISORDER

SIGNS AND SYMPTOMS:
Shortness of breath or hyperventilation
Heart palpitations or a racing heart
Chest pain or discomfort
Trembling or shaking
Choking feeling
Feeling unreal or detached from your
 surroundings
Sweating
Nausea or upset stomach
Feeling dizzy, lightheaded, or faint
Numbness or tingling sensations
Hot or cold flashes
Fear of dying, losing control, or going crazy
CAUSES:

The exact causes of panic disorder are
 unclear,.
Major life transitions such as graduating from
 college and entering the workplace, getting
 married, and having a baby.
Severe stress, such as the death of a loved
 one, divorce, or job loss can also trigger a
 panic attack.
Medical conditions and other physical causes.
  Mitral valve prolapse, a minor cardiac
   problem that occurs when one of the heart’s
   valves doesn't close correctly.
  Hyperthyroidism
  Hypoglycaemia
  Stimulant use (amphetamines, cocaine,
   caffeine)
  Medication withdrawal
TREATMENT

Antidepressants: SSRIs
benzodiazepines
PHOBIAS
Phobias are known as an emotional response
 learned because of difficult life experiences.
Occur when fear produced by a threatening
 situation is transmitted to other similar
 situations, while the original fear is often
 repressed or forgotten.
The individual attempts to avoid that situation
 in the future, a response that, while reducing
 anxiety in the short term, reinforces the
 association of the situation with the onset of
 anxiety.
ANATOMICAL CAUSE
The amygdala triggers secretion
 of hormones that affect fear and aggression.
When the fear or aggression response is
 initiated, the amygdala may trigger the release
 of hormones into the body to put the human
 body into an "alert" state, in which they are
 ready to move, run, fight, etc.
This defensive "alert" state and response is
 generally referred to in psychology as the fight-
 or-flight response.
TYPES OF PHOBIAS

i. Social phobia- fears involving other people
   or social situations such as performance
   anxiety or fears of embarrassment by
   scrutiny of others, such as eating in public.
Overcoming social phobia is often very difficult
 without the help of therapy or support groups.
Social phobia may be further subdivided into:
  a) Generalized social phobia (also known as
     social anxiety disorder or simply social
     anxiety) and
  b) Specific social phobia: Anxiety is triggered
     only in specific situations.
  The symptoms may extend to
    psychosomatic manifestation of physical
    problems.
  E.g.- Sufferers of paruresis find it difficult or
    impossible to urinate in reduced levels of
    privacy.
ii.  Specific phobias - Fear of a single specific
     panic trigger such as spiders, snakes, dogs,
     water, heights, flying, catching a specific
     illness, etc.
iii. Agoraphobia - A generalized fear of leaving
     home or a small familiar 'safe' area, and of
     possible panic attacks that might follow.
Agoraphobia may also be caused by various
 specific phobias such as:-
  Fear of open spaces
  Social embarrassment (social agoraphobia)
  Fear of contamination (fear of germs,
   possibly complicated by obsessive-
   compulsive disorder) or PTSD (post
   traumatic stress disorder).
TREATMENT

Cognitive behavioural therapy (CBT): CBT lets
 the patient understand the cycle of negative
 thought patterns, and ways to change these
 thought patterns.
SSRIs
Benzodiazepines
POST-TRAUMATIC STRESS DISORDER

Classified as an anxiety disorder and usually
 develops as a result of a terribly frightening,
 life-threatening, or otherwise highly unsafe
 experience.
PTSD sufferers re-experience the traumatic
 event or events in some way, tend to avoid
 places, people, or other things that remind
 them of the event (avoidance), and are
 exquisitely sensitive to normal life experiences
 (hyperarousal).
SIGNS AND SYMPTOMS

Explosive anger, or passive aggressive
 behaviours.
A tendency to forget the trauma or feel
 detached from one's life (dissociation) or body
 (depersonalization).
Persistent feelings of helplessness, shame,
 guilt, or being completely different from others.
Feeling the perpetrator of trauma is all-
 powerful and preoccupation with either
 revenge against or allegiance with the
 perpetrator.
Severe change in those things that give the
 sufferer meaning, like a loss of spiritual faith or
 an ongoing sense of helplessness,
 hopelessness, or despair.
TREATMENT
Cognitive Behavioural Therapy
Alpha-adrenergic agonist: Clonidine
Beta blockers (Propranolol): These may inhibit
 the formation of traumatic memories by
 blocking adrenaline's effects on the amygdala.
Glucocorticoids: Corticosterone
Buspirone
Benzodiazepines
SSRIs
OBSESSIVE-COMPULSIVE DISORDER

Characterized by intrusive thoughts that
 produce uneasiness, apprehension, fear, or
 worry, by repetitive behaviours aimed at
 reducing anxiety, or by a combination of such
 thoughts (obsessions) and behaviours
 (compulsions).
SIGN AND SYMPTOMS
Obsessive:-
 Fear of being contaminated by germs or dirt or
  contaminating others
 Fear of causing harm to yourself or others
 Intrusive sexually explicit or violent thoughts and images
 Excessive focus on religious or moral ideas
 Fear of losing or not having things you might need
 Order and symmetry: the idea that everything must line
  up “just right.”
 Superstitions; excessive attention to something
  considered lucky or unlucky
Compulsive:
 Excessive double-checking of things, such as locks,
  appliances, and switches.
 Repeatedly checking in on loved ones to make sure
  they’re safe.
 Counting, tapping, repeating certain words, or doing
  other senseless things to reduce anxiety.
 Spending a lot of time washing or cleaning.
 Ordering, evening out, or arranging things “just so.”
 Praying excessively or engaging in rituals triggered by
  religious fear.
 Accumulating “junk” such as old newspapers,
  magazines, and empty food containers, or other things
  you don’t have a use for.
ETIOLOGY
A. Psychological:
Obsessions are:
  Recurrent and persistent thoughts,
   impulses, or images that are intrusive and
   inappropriate. The thoughts cause severe
   anxiety or distress.
  The person tries to ignore or suppress the
   thoughts, impulses, or images, or to
   neutralize them with some other thought or
   action.
Compulsions are:
  Repetitive behaviours or mental acts that
   the person feels they must perform in
   response to an obsession, or according to
   rigid rules.
  The behaviours or mental acts to prevent or
   reduce distress or prevent some dreaded
   event or situation.

B. Biological: Serotonin receptors of OCD
  sufferers may be relatively under-stimulated.
TREATMENT

Cognitive behavioural therapy (CBT):
SSRIs
Anxiety disorders

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Anxiety disorders

  • 2. CONTENTS Anxiety Symptoms and Clinical Features of anxiety Causes for anxiety & Role of Receptors Anxiety Disorders Treatment Prevention
  • 3. ANXIETY A psychological and physiological state characterized by following components:- 1. Cognitive: Processing of information, applying knowledge, and changing preferences 2. Somatic: Voluntary control of body movements via skeletal muscles, and with sensory reception of external stimuli (e.g., touch, hearing, and sight)
  • 4. 3. Emotional: Mood, temperament, personality and disposition, and motivation 4. Behavioral component: Response of the system or organism to various stimuli or inputs, whether internal or external, conscious or subconscious, overt or covert, and voluntary or involuntary.
  • 5. SYMPTOMS AND CLINICAL FEATURES A. Physical symptoms: Heart palpitations Muscle weakness and tension Fatigue Nausea Chest pain Shortness of breath
  • 6. Stomach aches, or headaches. Increased blood pressure and heart rate Increased sweating Increased blood flow to the major muscle groups Immune and digestive system functions are inhibited (the fight or flight response).
  • 7. B. External signs: Pale skin Sweating Trembling Pupillary dilation
  • 8. C. Emotional symptoms: Feelings of apprehension or dread Trouble concentrating Feeling tense or jumpy Anticipating the worst Irritability Restlessness
  • 9. Feeling like your mind's gone blank Nightmares/bad dreams Obsessions about sensations Déjà vu A trapped in your mind feeling, and feeling like everything is scary.
  • 10. Can be a symptom of an underlying health issue such as:- chronic obstructive pulmonary disease (COPD), heart failure, or heart arrhythmia.
  • 11. NEUROTRANSMITTER SYSTEMS Neurotransmitter systems involved in anxiety generation include the GABA systems Serotonergic Adrenergic Benzodiazepine (BZD)
  • 12. CAUSES & ROLE OF RECEPTORS 1. Biological Low levels of GABA, a neurotransmitter that reduces activity in the central nervous system, contribute to anxiety. GABA exhibits excitatory actions like: Mediating muscle activation at synapses between nerves and muscle cells Stimulation of certain glands A number of anxiolytics achieve their effect by modulating the GABA receptors.
  • 13.  GABA acts at inhibitory synapses in the brain by binding to specific transmembrane receptors in the plasma membrane of both pre- and postsynaptic neuronal processes. GABA + Clˉ in and K+ Opening of Ion Transmembrane out of the Channels Receptors cell Hyperpolarization
  • 14. GABA RECEPTORS GABAA Receptors GABAB Receptors
  • 15. GABAA GABAB • Ionotrophic • Metabotrophic receptors receptors • Part of ligand • Open/close via gated ion intermediaries channel complex (G-proteins)
  • 16. GABAA  Upon activation, the GABAAreceptor selectively conducts Cl- through its pore, resulting in hyperpolarization of the neuron.  This causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring.
  • 17.  GABAA receptors are Cl - channels so when activated by GABA:  Cl moves out: excitation/ depolarization  Cl moves in: inhibition/ hyperpolarization- inhibition of NT
  • 18.
  • 19. GABAB They can stimulate the opening of K+ channels which brings the neuron closer to the equilibrium potential of K+, hyperpolarizing the neuron. This prevents sodium channels from opening, action potentials from firing, and VDCCs from opening, and so stops neurotransmitter release. Thus GABAB receptors are considered inhibitory receptors.
  • 20. II. AMYGDALA  The amygdala is central to the processing of fear and anxiety, and its function may be disrupted in anxiety disorders.  Sensory information enters the amgydala through the nuclei of the basolateral complex (consisting of lateral, basal, and accessory basal nuclei).  The basolateral complex processes sensory related fear memories, and communicate their threat importance to memory and sensory processing elsewhere in the brain, such as the medial prefrontal cortex and sensory cortices.
  • 21.
  • 22.
  • 23. The adjacent central nucleus of the amygdala controls species-specific fear responses, via connections to the brainstem, hypotha- lamus, and cerebellum areas. In those with general anxiety disorder, these connections functionally seem to be less distinct, with greater gray matter in the central nucleus.
  • 24. III. ENVIRONMENTAL FACTORS Life stresses such as financial worries or chronic physical illness. Also common among older people who have dementia. On the other hand, anxiety disorder is sometimes misdiagnosed among older adults when doctors misinterpret symptoms of a physical ailment (for instance, racing heartbeat due to cardiac arrhythmia) as signs of anxiety.
  • 25. Use of and withdrawal from addictive substances, including alcohol, caffeine, and nicotine.
  • 26. ANXIETY DISORDERS 1. Generalized Anxiety Disorder: An ongoing state of excessive anxiety lacking any clear reason or focus 2. Panic Disorders : Sudden attacks of overwhelming fear occur in association with marked somatic symptoms, such as sweating, tachycardia, chest pains, trembling and choking.
  • 27. 3. Phobias: Strong fears of specific objects or situations, e.g. snakes, open spaces, flying, social interactions 4. Post-traumatic stress disorder: Anxiety triggered by recall of past stressful experiences 5. Obsessive compulsive disorder: Compulsive ritualistic behavior driven by irrational anxiety, e.g. fear of contamination.
  • 28. GENERALIZED ANXIETY DISORDERS An ongoing state of excessive anxiety lacking any clear reason or focus. Characterized by excessive, uncontrollable and often irrational worry about everyday things that is disproportionate to the actual source of worry.
  • 29. Interferes with daily functioning, as individuals suffering GAD typically anticipate disaster, and are overly concerned about everyday matters such as:- Health issues Money Death  Family problems  Friend problems  Relationship problems or  Work difficulties
  • 30. PHYSICAL SYMPTOMS:  Fatigue  Difficulty concentrating  Fidgeting  Trembling  Headaches  Twitching  Nausea  Irritability  Numbness in hands and  Agitation feet  Sweating  Muscle tension  Restlessness  Muscle aches  Insomnia  Difficulty swallowing  Hot flashes,  Bouts of difficulty breathing and rashes and  Inability to fully control the anxiety
  • 31. CAUSES: Genetic predisposition and environmental factors. Parents can model anxious behaviours to their children. Stressful early life events such as early parental death. Chronic experiences of fear and learned helplessness may cause greater chronic cortisol activation and increased sympathetic tone. Traumatic experiences and abnormal prenatal hormonal exposures may also play a role the cause of this disorder.
  • 32. TREATMENT: Medication can be effective for generalized anxiety disorder (GAD). Generally recommended only as a temporary measure to relieve symptoms at the beginning of the treatment process, with therapy the key to long-term success.
  • 33. Types of medication prescribed for generalized anxiety disorder: 1. Benzodiazepines – Quick acting (usually within 30 minutes to an hour). Serious drawbacks Physical and psychological dependence are common after more than a few weeks of use. Generally recommended only for severe, paralyzing episodes of anxiety.
  • 34. 2. Buspirone – 5-HT1A receptor antagonist. Safest drug for generalized anxiety disorder. Unlike the benzodiazepines, buspirone isn’t sedating or addictive. Although buspirone will take the edge off, it will not entirely eliminate anxiety.
  • 35. 3. Antidepressants – The relief antidepressants provide for anxiety is not immediate, and the full effect isn’t felt for up to six weeks. Some antidepressants can also exacerbate sleep problems and cause nausea.
  • 36. TREATMENT OF ANXIETY DISORDERS Types of anxiolytics:- 1. Benzodiazepines E.g.- Alprazolam, Chlordiazepoxide, Clonazepam, Diazepam, Lorazepam 2. SSRIs (Selective Serotonergic Receptor Inhibitors)  E.g.- Escitalopram, Citalopram
  • 37. 3. Azapirones  E.g.- Buspirone 4. Barbiturates  E.g.- Phenobarbital, Pentobarbital 5. Miscellaneous  E.g.- Chloral hydrate, Meprobamate, Methaqualone
  • 38. 1. BENZODIAZEPINES Most important group, used as anxiolytic and hypnotic agents. Types: 1. Ultra short acting (4-6 hrs): Triazolam, midazolam, Zolpidem 2. Short acting (12-18 hrs): Lorazepam, Oxazepam 3. Medium acting (24 hrs): Alprazolam 4. Long acting (>24 hrs): Diazepam, Clordiazepoxide, Flurazepam, Clonazepam
  • 39. Drug(s) Half-life of Active Half-life of Main use(s) parent metabolite metabolite compound (Hrs) (Hrs) Triazolam, 2-4 Hydroxylated 2 Hypnotic Midazolam derivative Midazolam: I.V. anesthetic Zolpidem 2 No - Hypnotic Lorazepam, 8-12 No - Anxiolytic, Oxazepam hypnotic Alprazolam 6-12 Hydroxylated 6 Anxiolytic, derivative antidepressant Diazepam, 20-40 Nordazepam 60 Anxiolytic, Chlordiazepoxid muscle relaxant e Dzpam: I.V. anticonvulsant Flurazepam 1 Desmethyl- 60 Anxiolytic flurazepam Clonazepam 50 no - Anticonvulsant, anxiolytic (mania)
  • 40. MECHANISM OF ACTION Selectively act on GABAA receptors Increase affinity of GABA for the receptor Opening of GABA activated Cl‾ channels Inhibition of synaptic transmission throughout CNS
  • 41. MOA
  • 42. PHARMACOLOGICAL EFFECTS AND USES OF BZD :- 1. Reduction of anxiety and aggression. 2. Sedation and induction of sleep. 3. Reduction of muscle tone and coordination. 4. Anticonvulsant effect.
  • 43. UNWANTED EFFECTS OF BZD Divided into: 1. Toxic effect resulting from acute overdose (antagonist- flumazenil). 2. Unwanted effects during normal therapeutic dose: drowsiness, confusion, amnesia, impaired coordination. 3. Tolerance and dependence.
  • 44. 2. SSRI Lower levels of serotonin (5-HT) produces depression. Inhibit serotonin reuptake. Serotonin stays at the synapse for a longer duration, as a result, longer action. Produce little or no sedation. Do not interfere with psychomotor functions or anticholinergic side effects.
  • 45.  Do not inhibit cardiac conduction- overdose arrhythmias are not a problem.  Used along with BZD to cover exacerbations a) Citalopram:  T1/2 : 33 hrs  No active metabolite  Overdose: suicide b) Escitalopram:  Active S(+) enantiomer of citalopram.  Effective at half dose  Less side effects and improved safety.
  • 46. b) Fluoxetine  Longest acting  T1/2 for parent compound: 2 days and active demethylated metabolite: 7-10 days.  Slow onset of action
  • 48. SIDE EFFECTS  Nausea  Interference with ejaculation and orgasm  Nervousness  Restlessness  Insomnia  Anorexia  Headache  Diarrhoea
  • 49. 3. AZAPIRONES: BUSPIRONE Does not produce significant sedation or cognitive/ functional impairment. Does not interact with BZD receptor or modify GABAnergic transmission. Does not produce tolerance or physical dependence. Has no muscle relaxant or anticonvulsant activity.
  • 50. Used in mild to moderate GAD. Ineffective in severe cases. Slow therapeutic effect. Delayed up to 2 weeks. T1/2 : 2-3.5 hrs MOA: Stimulates presynaptic 5-HT1A autoreceptors. Activity of dorsal raphe serotonergic neurons decreases. Agonist action on 5-HT1A receptors.
  • 52. 4. BARBITURATES Non-selective CNS depressants. Effects range from sedation and reduction of anxiety to unconsciousness and death from respiratory and cardiac failure. Dangerous in overdose. Act by enhancing action of GABA, but less specific than BZD.
  • 53. Use as sedative/ hypnotic agent is no longer recommended. Can cause drug interactions as it is a potent inducer of hepatic drug metabolizing enzymes. Tolerance and dependence occur.
  • 54. PANIC DISORDER SIGNS AND SYMPTOMS: Shortness of breath or hyperventilation Heart palpitations or a racing heart Chest pain or discomfort Trembling or shaking Choking feeling Feeling unreal or detached from your surroundings
  • 55. Sweating Nausea or upset stomach Feeling dizzy, lightheaded, or faint Numbness or tingling sensations Hot or cold flashes Fear of dying, losing control, or going crazy
  • 56. CAUSES: The exact causes of panic disorder are unclear,. Major life transitions such as graduating from college and entering the workplace, getting married, and having a baby. Severe stress, such as the death of a loved one, divorce, or job loss can also trigger a panic attack.
  • 57. Medical conditions and other physical causes. Mitral valve prolapse, a minor cardiac problem that occurs when one of the heart’s valves doesn't close correctly. Hyperthyroidism Hypoglycaemia Stimulant use (amphetamines, cocaine, caffeine) Medication withdrawal
  • 59. PHOBIAS Phobias are known as an emotional response learned because of difficult life experiences. Occur when fear produced by a threatening situation is transmitted to other similar situations, while the original fear is often repressed or forgotten. The individual attempts to avoid that situation in the future, a response that, while reducing anxiety in the short term, reinforces the association of the situation with the onset of anxiety.
  • 60. ANATOMICAL CAUSE The amygdala triggers secretion of hormones that affect fear and aggression. When the fear or aggression response is initiated, the amygdala may trigger the release of hormones into the body to put the human body into an "alert" state, in which they are ready to move, run, fight, etc. This defensive "alert" state and response is generally referred to in psychology as the fight- or-flight response.
  • 61. TYPES OF PHOBIAS i. Social phobia- fears involving other people or social situations such as performance anxiety or fears of embarrassment by scrutiny of others, such as eating in public. Overcoming social phobia is often very difficult without the help of therapy or support groups.
  • 62. Social phobia may be further subdivided into: a) Generalized social phobia (also known as social anxiety disorder or simply social anxiety) and b) Specific social phobia: Anxiety is triggered only in specific situations. The symptoms may extend to psychosomatic manifestation of physical problems. E.g.- Sufferers of paruresis find it difficult or impossible to urinate in reduced levels of privacy.
  • 63. ii. Specific phobias - Fear of a single specific panic trigger such as spiders, snakes, dogs, water, heights, flying, catching a specific illness, etc. iii. Agoraphobia - A generalized fear of leaving home or a small familiar 'safe' area, and of possible panic attacks that might follow.
  • 64. Agoraphobia may also be caused by various specific phobias such as:- Fear of open spaces Social embarrassment (social agoraphobia) Fear of contamination (fear of germs, possibly complicated by obsessive- compulsive disorder) or PTSD (post traumatic stress disorder).
  • 65. TREATMENT Cognitive behavioural therapy (CBT): CBT lets the patient understand the cycle of negative thought patterns, and ways to change these thought patterns. SSRIs Benzodiazepines
  • 66. POST-TRAUMATIC STRESS DISORDER Classified as an anxiety disorder and usually develops as a result of a terribly frightening, life-threatening, or otherwise highly unsafe experience. PTSD sufferers re-experience the traumatic event or events in some way, tend to avoid places, people, or other things that remind them of the event (avoidance), and are exquisitely sensitive to normal life experiences (hyperarousal).
  • 67. SIGNS AND SYMPTOMS Explosive anger, or passive aggressive behaviours. A tendency to forget the trauma or feel detached from one's life (dissociation) or body (depersonalization). Persistent feelings of helplessness, shame, guilt, or being completely different from others.
  • 68. Feeling the perpetrator of trauma is all- powerful and preoccupation with either revenge against or allegiance with the perpetrator. Severe change in those things that give the sufferer meaning, like a loss of spiritual faith or an ongoing sense of helplessness, hopelessness, or despair.
  • 69. TREATMENT Cognitive Behavioural Therapy Alpha-adrenergic agonist: Clonidine Beta blockers (Propranolol): These may inhibit the formation of traumatic memories by blocking adrenaline's effects on the amygdala. Glucocorticoids: Corticosterone Buspirone Benzodiazepines SSRIs
  • 70. OBSESSIVE-COMPULSIVE DISORDER Characterized by intrusive thoughts that produce uneasiness, apprehension, fear, or worry, by repetitive behaviours aimed at reducing anxiety, or by a combination of such thoughts (obsessions) and behaviours (compulsions).
  • 71. SIGN AND SYMPTOMS Obsessive:-  Fear of being contaminated by germs or dirt or contaminating others  Fear of causing harm to yourself or others  Intrusive sexually explicit or violent thoughts and images  Excessive focus on religious or moral ideas  Fear of losing or not having things you might need  Order and symmetry: the idea that everything must line up “just right.”  Superstitions; excessive attention to something considered lucky or unlucky
  • 72. Compulsive:  Excessive double-checking of things, such as locks, appliances, and switches.  Repeatedly checking in on loved ones to make sure they’re safe.  Counting, tapping, repeating certain words, or doing other senseless things to reduce anxiety.  Spending a lot of time washing or cleaning.  Ordering, evening out, or arranging things “just so.”  Praying excessively or engaging in rituals triggered by religious fear.  Accumulating “junk” such as old newspapers, magazines, and empty food containers, or other things you don’t have a use for.
  • 73. ETIOLOGY A. Psychological: Obsessions are: Recurrent and persistent thoughts, impulses, or images that are intrusive and inappropriate. The thoughts cause severe anxiety or distress. The person tries to ignore or suppress the thoughts, impulses, or images, or to neutralize them with some other thought or action.
  • 74. Compulsions are: Repetitive behaviours or mental acts that the person feels they must perform in response to an obsession, or according to rigid rules. The behaviours or mental acts to prevent or reduce distress or prevent some dreaded event or situation. B. Biological: Serotonin receptors of OCD sufferers may be relatively under-stimulated.