By:Robin Gulati

CONTENTS
fAnxiety fSymptoms and Clinical Features of anxiety fCauses for anxiety & Role of Receptors fAnxiety Disorders fTreatment fPrevention

ANXIETY
fA 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:
fHeart palpitations fMuscle weakness and tension fFatigue fNausea fChest pain fShortness of breath

fStomach aches, or headaches. fIncreased blood pressure and heart rate fIncreased sweating fIncreased blood flow to the major muscle

groups fImmune and digestive system functions are inhibited (the fight or flight response).

B. External signs:
fPale skin fSweating fTrembling fPupillary dilation

C. Emotional symptoms:
fFeelings of apprehension or dread fTrouble concentrating fFeeling tense or jumpy fAnticipating the worst fIrritability fRestlessness

fFeeling like your mind's gone blank fNightmares/bad dreams fObsessions about sensations fDj vu fA trapped in your mind feeling, and feeling like

everything is scary.

fCan be a symptom of an underlying health

issue such as:fchronic obstructive pulmonary disease (COPD), fheart failure, or heart arrhythmia.

NEUROTRANSMITTER SYSTEMS
fNeurotransmitter systems involved in

anxiety generation include the

fGABA systems fSerotonergic fAdrenergic fBenzodiazepine (BZD)

CAUSES & ROLE OF RECEPTORS

1. Biological
fLow levels of GABA, a neurotransmitter that

reduces activity in the central nervous system, contribute to anxiety. fGABA exhibits excitatory actions like:
fMediating muscle activation at synapses between

nerves and muscle cells fStimulation of certain glands fA number of anxiolytics achieve their effect by modulating the GABA receptors.

f 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 + Transmembrane Receptors Opening of Ion Channels Cl in and K+ out of the cell

Hyperpolarization

GABA RECEPTORS

GABAA Receptors

GABAB Receptors

GABAA
Ionotrophic receptors Part of ligand gated ion channel complex

GABAB
Metabotrophic receptors Open/close via intermediaries (Gproteins)

GABAA
f Upon activation, the

GABAAreceptor selectively conducts Cl- through its pore, resulting in hyperpolarization of the neuron. f This causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring.

f GABAA receptors are Cl

- channels so when activated by

GABA: f Cl moves out: excitation/ depolarization f Cl moves in: inhibition/ hyperpolarization- inhibition of NT

GABAB
fThey can stimulate the opening of K+ channels

which brings the neuron closer to the equilibrium potential of K+, hyperpolarizing the neuron. fThis 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 f The amygdala is central to the processing of fear and anxiety, and its function may be disrupted in anxiety disorders. f Sensory information enters the amgydala through the nuclei of the basolateral complex (consisting of lateral, basal, and accessory basal nuclei). f 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.

fThe adjacent central

nucleus of the amygdala controls species-specific fear responses, via connections to the brainstem, hypothalamus, and cerebellum areas. fIn those with general anxiety disorder, these connections functionally seem to be less distinct, with greater gray matter in the central nucleus.

III. ENVIRONMENTAL FACTORS

fLife stresses such as financial worries or chronic

physical illness. fAlso common among older people who have dementia. fOn 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.

fUse 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

fAn ongoing state of excessive anxiety lacking any clear

reason or focus.
fCharacterized by excessive, uncontrollable and often

irrational worry about everyday things that is disproportionate to the actual source of worry.

fInterferes with daily functioning, as individuals

suffering GAD typically anticipate disaster, and are overly concerned about everyday matters such as:fHealth issues fMoney fDeath f Family problems f Friend problems f Relationship problems or f Work difficulties

PHYSICAL SYMPTOMS:
f Fatigue f Fidgeting f Headaches f Nausea f Numbness in hands and feet f Muscle tension f Muscle aches f Difficulty swallowing f Bouts of difficulty breathing f Difficulty concentrating f Trembling f Twitching f Irritability f Agitation f Sweating f Restlessness f Insomnia f Hot flashes, and rashes and f Inability to fully control the

anxiety

CAUSES:
fGenetic predisposition and environmental factors. fParents can model anxious behaviours to their children. fStressful early life events such as early parental death. fChronic experiences of fear and learned helplessness

may cause greater chronic cortisol activation and increased sympathetic tone. fTraumatic experiences and abnormal prenatal hormonal exposures may also play a role the cause of this disorder.

TREATMENT:
fMedication can be effective for generalized anxiety

disorder (GAD). fGenerally recommended only as a temporary measure to relieve symptoms at the beginning of the treatment process, with therapy the key to long-term success.

fTypes of medication prescribed for

generalized anxiety disorder: 1. Benzodiazepines

fQuick acting (usually within 30 minutes to an

hour). fSerious drawbacks fPhysical and psychological dependence are common after more than a few weeks of use. fGenerally recommended only for severe, paralyzing episodes of anxiety.

2. Buspirone
f5-HT1A receptor antagonist. fSafest drug for generalized anxiety disorder. fUnlike the benzodiazepines, buspirone isnt

sedating or addictive. fAlthough buspirone will take the edge off, it will not entirely eliminate anxiety.

3. Antidepressants fThe relief antidepressants provide for anxiety is

not immediate, and the full effect isnt felt for up to six weeks. fSome antidepressants can also exacerbate sleep problems and cause nausea.

TREATMENT OF ANXIETY DISORDERS

fTypes of anxiolytics:1. Benzodiazepines

fE.g.- Alprazolam, Chlordiazepoxide, Clonazepam,

Diazepam, Lorazepam 2. SSRIs (Selective Serotonergic Receptor Inhibitors)

f E.g.- Escitalopram, Citalopram

3. Azapirones
f E.g.- Buspirone

4. Barbiturates
f E.g.- Phenobarbital, Pentobarbital

5. Miscellaneous
f E.g.- Chloral hydrate, Meprobamate, Methaqualone

1. BENZODIAZEPINES
fMost important group, used as anxiolytic and

hypnotic agents. fTypes: 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 parent compound (Hrs) 2-4

Active metabolite

Half-life of metabolite (Hrs) 2

Main use(s)

Triazolam, Midazolam Zolpidem Lorazepam, Oxazepam Alprazolam Diazepam, Chlordiazepoxide

Hydroxylated derivative No No Hydroxylated derivative Nordazepam

Hypnotic Midazolam: I.V. anesthetic Hypnotic Anxiolytic, hypnotic Anxiolytic, antidepressant Anxiolytic, muscle relaxant Dzpam: I.V. anticonvulsant Anxiolytic Anticonvulsant, anxiolytic (mania)

2 8-12 6-12 20-40

6 60

Flurazepam Clonazepam

1 50

Desmethylflurazepam no

60 -

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

fDivided 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
fLower levels of serotonin (5-HT) produces

depression. fInhibit serotonin reuptake. fSerotonin stays at the synapse for a longer duration, as a result, longer action. fProduce little or no sedation. fDo not interfere with psychomotor functions or anticholinergic side effects.

f Do not inhibit cardiac conduction- overdose

arrhythmias are not a problem. f Used along with BZD to cover exacerbations a) Citalopram:
f T1/2 : 33 hrs f No active metabolite f Overdose: suicide

b) Escitalopram: f Active S(+) enantiomer of citalopram. f Effective at half dose f Less side effects and improved safety.

b) Fluoxetine
f Longest acting f T1/2 for parent compound: 2 days and active

demethylated metabolite: 7-10 days. f Slow onset of action

MECHANISM OF ACTION

SIDE EFFECTS
f Nausea f Interference with ejaculation and orgasm f Nervousness f Restlessness f Insomnia f Anorexia f Headache f Diarrhoea

3. AZAPIRONES: BUSPIRONE
fDoes not produce significant sedation or cognitive/

functional impairment. fDoes not interact with BZD receptor or modify GABAnergic transmission. fDoes not produce tolerance or physical dependence. fHas no muscle relaxant or anticonvulsant activity.

fUsed in mild to moderate GAD. Ineffective in

severe cases. fSlow therapeutic effect. Delayed up to 2 weeks. fT1/2 : 2-3.5 hrs MOA: fStimulates presynaptic 5-HT1A autoreceptors. fActivity of dorsal raphe serotonergic neurons decreases. fAgonist action on 5-HT1A receptors.

SIDE EFFECTS:
fDizziness fNausea fHeadache fLight-headedness fExcitement (rarely)

4. BARBITURATES
fNon-selective CNS depressants. fEffects range from sedation and reduction of

anxiety to unconsciousness and death from respiratory and cardiac failure. fDangerous in overdose. fAct by enhancing action of GABA, but less specific than BZD.

fUse as sedative/ hypnotic agent is no longer

recommended. fCan cause drug interactions as it is a potent inducer of hepatic drug metabolizing enzymes. fTolerance and dependence occur.

PANIC DISORDER
SIGNS AND SYMPTOMS: fShortness of breath or hyperventilation fHeart palpitations or a racing heart fChest pain or discomfort fTrembling or shaking fChoking feeling fFeeling unreal or detached from your surroundings

fSweating fNausea or upset stomach fFeeling dizzy, lightheaded, or faint fNumbness or tingling sensations fHot or cold flashes fFear of dying, losing control, or going crazy

CAUSES:
fThe exact causes of panic disorder are unclear,. fMajor life transitions such as graduating from

college and entering the workplace, getting married, and having a baby. fSevere stress, such as the death of a loved one, divorce, or job loss can also trigger a panic attack.

fMedical conditions and other physical causes. fMitral valve prolapse, a minor cardiac problem

that occurs when one of the hearts valves doesn't close correctly. fHyperthyroidism fHypoglycaemia fStimulant use (amphetamines, cocaine, caffeine) fMedication withdrawal

TREATMENT
fAntidepressants: SSRIs fbenzodiazepines

PHOBIAS
fPhobias are known as an emotional response

learned because of difficult life experiences. fOccur when fear produced by a threatening situation is transmitted to other similar situations, while the original fear is often repressed or forgotten. fThe 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
fThe amygdala triggers secretion of hormones that

affect fear and aggression. fWhen 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. fThis defensive "alert" state and response is generally referred to in psychology as the fight-orflight response.

TYPES OF PHOBIAS
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. fOvercoming social phobia is often very difficult without the help of therapy or support groups.
i.

fSocial 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. fThe symptoms may extend to psychosomatic manifestation of physical problems. fE.g.- Sufferers of paruresis find it difficult or impossible to urinate in reduced levels of privacy.

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.
ii.

fAgoraphobia may also be caused by various specific

phobias such as:fFear of open spaces fSocial embarrassment (social agoraphobia) fFear of contamination (fear of germs, possibly complicated by obsessive-compulsive disorder) or PTSD (post traumatic stress disorder).

TREATMENT
fCognitive behavioural therapy (CBT): CBT lets the

patient understand the cycle of negative thought patterns, and ways to change these thought patterns. fSSRIs fBenzodiazepines

POST -TRAUMATIC STRESS DISORDER

fClassified as an anxiety disorder and usually

develops as a result of a terribly frightening, lifethreatening, or otherwise highly unsafe experience. fPTSD 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

fExplosive anger, or passive aggressive behaviours. fA tendency to forget the trauma or feel detached

from one's life (dissociation) or body (depersonalization). fPersistent feelings of helplessness, shame, guilt, or being completely different from others.

fFeeling the perpetrator of trauma is all-powerful

and preoccupation with either revenge against or allegiance with the perpetrator. fSevere 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
fCognitive Behavioural Therapy fAlpha-adrenergic agonist: Clonidine fBeta blockers (Propranolol):These may inhibit the

formation of traumatic memories by blocking adrenaline's effects on the amygdala. fGlucocorticoids: Corticosterone fBuspirone fBenzodiazepines fSSRIs

OBSESSIVE-COMPULSIVE DISORDER
fCharacterized 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:f Fear of being contaminated by germs or dirt or contaminating

others f Fear of causing harm to yourself or others f Intrusive sexually explicit or violent thoughts and images f Excessive focus on religious or moral ideas f Fear of losing or not having things you might need f Order and symmetry: the idea that everything must line up just right. f Superstitions; excessive attention to something considered lucky or unlucky

Compulsive:
f Excessive double-checking of things, such as locks,

appliances, and switches. f Repeatedly checking in on loved ones to make sure theyre safe. f Counting, tapping, repeating certain words, or doing other senseless things to reduce anxiety. f Spending a lot of time washing or cleaning. f Ordering, evening out, or arranging things just so. f Praying excessively or engaging in rituals triggered by religious fear. f Accumulating junk such as old newspapers, magazines, and empty food containers, or other things you dont have a use for.

ETIOLOGY
A. Psychological: fObsessions are: fRecurrent and persistent thoughts, impulses, or

images that are intrusive and inappropriate.The thoughts cause severe anxiety or distress. fThe person tries to ignore or suppress the thoughts, impulses, or images, or to neutralize them with some other thought or action.

fCompulsions are: fRepetitive behaviours or mental acts that the

person feels they must perform in response to an obsession, or according to rigid rules. fThe 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
fCognitive behavioural therapy (CBT): fSSRIs