The document discusses anxiety, including its symptoms, causes, role of neurotransmitters like GABA and receptors, and various anxiety disorders. It provides details on generalized anxiety disorder and its physical symptoms and treatment options involving medication like benzodiazepines, buspirone, and antidepressants, as well as therapy. The goal of treatment is to relieve symptoms and achieve long-term success through therapeutic methods rather than just temporary medication use.

1. By:-
Robin Gulati

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

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.

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

47. MECHANISM
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.

51. SIDE EFFECTS:
Dizziness
Nausea
Headache
Light-headedness
Excitement (rarely)

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

58. TREATMENT
Antidepressants: SSRIs
benzodiazepines

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.

75. TREATMENT
Cognitive behavioural therapy (CBT):
SSRIs