1. By:-Robin Gulati

2. CONTENTSAnxietySymptoms and Clinical Features of anxietyCauses for anxiety & Role of ReceptorsAnxiety DisordersTreatmentPrevention 3. ANXIETYA psychological and physiological state characterized by following components:- 1. Cognitive: Processing of information, applyingknowledge, and changing preferences 2. Somatic: Voluntary control of bodymovements via skeletal muscles, andwith sensory reception of externalstimuli (e.g., touch, hearing, and sight) 4. 3. Emotional: Mood, temperament, personality and disposition, and motivation4. 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 CLINICALFEATURESA. 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 rateIncreased sweatingIncreased blood flow to the major muscle groupsImmune 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 minds gone blankNightmares/bad dreamsObsessions about sensationsDj vuA 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 SYSTEMSNeurotransmitter systems involved in anxiety generation include theGABA systemsSerotonergicAdrenergicBenzodiazepine (BZD) 12. CAUSES & ROLE OF RECEPTORS1. BiologicalLow 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 cellsStimulation of certain glandsA 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 +Cl in and K+Opening of IonTransmembrane out of theChannels Receptors cell Hyperpolarization 14. GABA RECEPTORSGABAA Receptors GABAB Receptors 15. GABAA GABAB Ionotrophic Metabotrophicreceptors receptors Part of ligand Open/close viagated ion intermediarieschannel complex (G-proteins) 16. GABAA Upon activation, theGABAAreceptor selectivelyconducts Cl- throughits pore, resultingin hyperpolarization ofthe neuron. This causes an inhibitoryeffecton neurotransmission bydiminishing the chance of asuccessful actionpotential 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. GABABThey 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. 19. 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. 20. 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. 21. III. ENVIRONMENTAL FACTORS Life stresses such as financial worries orchronic physical illness. Also common among older people whohave dementia. On the other hand, anxiety disorder issometimes misdiagnosed among older adultswhen doctors misinterpret symptoms of aphysical ailment (for instance, racing heartbeatdue to cardiac arrhythmia) as signs of anxiety. 22. Use of and withdrawal from addictive substances, including alcohol, caffeine, and nicotine. 23. ANXIETY DISORDERS1. Generalized Anxiety Disorder: An ongoing state of excessive anxiety lacking any clear reason or focus2. Panic Disorders : Sudden attacks of overwhelming fear occur in association with marked somatic symptoms, such as sweating, tachycardia, chest pains, trembling and choking. 24. 3. Phobias: Strong fears of specific objects or situations, e.g. snakes, open spaces, flying, social interactions4. Post-traumatic stress disorder: Anxiety triggered by recall of past stressful experiences5. Obsessive compulsive disorder: Compulsive ritualistic behavior driven by irrational anxiety, e.g. fear of contamination. 25. GENERALIZED ANXIETYDISORDERSAn 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. 26. Interferes with daily functioning, as individuals suffering GAD typically anticipate disaster, and are overly concerned about everyday matters such as:-Health issuesMoneyDeath Family problems Friend problems Relationship problems or Work difficulties 27. PHYSICAL SYMPTOMS: Fatigue Difficulty concentrating Fidgeting Trembling Headaches Twitching Nausea Irritability Numbness in hands and Agitationfeet Sweating Muscle tension Restlessness Muscle aches Insomnia Difficulty swallowing Hot flashes, Bouts of difficulty breathing and rashes and Inability to fully controlthe anxiety 28. 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. 29. 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. 30. Types of medication prescribed forgeneralized anxiety disorder:1. Benzodiazepines Quick acting (usually within 30 minutes to an hour).Serious drawbacksPhysical and psychological dependence are common after more than a few weeks of use.Generally recommended only for severe, paralyzing episodes of anxiety. 31. 2. Buspirone 5-HT1A receptor antagonist. Safest drug for generalized anxietydisorder. Unlike the benzodiazepines, buspironeisnt sedating or addictive. Although buspirone will take the edge off,it will not entirely eliminate anxiety. 32. 3. Antidepressants The relief antidepressants provide for anxiety is not immediate, and the full effect isnt felt for up to six weeks.Some antidepressants can also exacerbate sleep problems and cause nausea. 33. TREATMENT OF ANXIETY DISORDERSTypes of anxiolytics:- 1. Benzodiazepines E.g.- Alprazolam, Chlordiazepoxide,Clonazepam, Diazepam, Lorazepam 2. SSRIs (Selective Serotonergic ReceptorInhibitors) E.g.- Escitalopram, Citalopram 34. 3. Azapirones E.g.- Buspirone4. Barbiturates E.g.- Phenobarbital, Pentobarbital5. Miscellaneous E.g.- Chloral hydrate, Meprobamate, Methaqualone 35. 1. BENZODIAZEPINESMost important group, used as anxiolytic andhypnotic agents.Types:1. Ultra short acting (4-6 hrs): Triazolam, midazolam, Zolpidem2. Short acting (12-18 hrs): Lorazepam, Oxazepam3. Medium acting (24 hrs): Alprazolam4. Long acting (>24 hrs): Diazepam, Clordiazepoxide, Flurazepam, Clonazepam 36. Drug(s)Half-life ofActiveHalf-life ofMain use(s)parent metabolite metabolitecompound(Hrs) (Hrs)Triazolam,2-4Hydroxylated2HypnoticMidazolam derivative Midazolam: I.V. anesthetic Zolpidem2 No-Hypnotic Lorazepam,8-12No- Anxiolytic, Oxazepam hypnoticAlprazolam 6-12Hydroxylated6 Anxiolytic,derivative antidepressantDiazepam,20-40 Nordazepam 60 Anxiolytic,Chlordiazepoxidmuscle relaxant eDzpam: I.V. anticonvulsant Flurazepam1 Desmethyl- 60 Anxiolytic flurazepam Clonazepam 50 no- Anticonvulsant, anxiolytic (mania) 37. MECHANISM OF ACTION Selectively act on GABAA receptors Increase affinity of GABA for the receptorOpening of GABA activated Cl channelsInhibition of synaptic transmission throughout CNS 38. MOA 39. PHARMACOLOGICAL EFFECTS ANDUSES OF BZD :-1. Reduction of anxiety and aggression.2. Sedation and induction of sleep.3. Reduction of muscle tone and coordination.4. Anticonvulsant effect. 40. UNWANTED EFFECTS OF BZDDivided 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. 41. 2. SSRILower 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. 42. Do not inhibit cardiac conduction- overdosearrhythmias are not a problem. Used along with BZD to cover exacerbationsa) Citalopram: T1/2 : 33 hrs No active metabolite Overdose: suicideb) Escitalopram: Active S(+) enantiomer of citalopram. Effective at half dose Less side effects and improved safety. 43. b) Fluoxetine Longest acting T1/2 for parent compound: 2 days and activedemethylated metabolite: 7-10 days. Slow onset of action 44. MECHANISMOF ACTION 45. SIDE EFFECTS Nausea Interference with ejaculation and orgasm Nervousness Restlessness Insomnia Anorexia Headache Diarrhoea 46. 3. AZAPIRONES: BUSPIRONEDoes 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. 47. Used in mild to moderate GAD. Ineffective in severe cases.Slow therapeutic effect. Delayed up to 2 weeks.T1/2 : 2-3.5 hrsMOA:Stimulates presynaptic 5-HT1Aautoreceptors.Activity of dorsal raphe serotonergicneurons decreases.Agonist action on 5-HT1A receptors. 48. SIDE EFFECTS:DizzinessNauseaHeadacheLight-headednessExcitement (rarely) 49. 4. BARBITURATESNon-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. 50. 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. 51. PANIC DISORDERSIGNS AND SYMPTOMS:Shortness of breath or hyperventilationHeart palpitations or a racing heartChest pain or discomfortTrembling or shakingChoking feelingFeeling unreal or detached from your surroundings 52. SweatingNausea or upset stomachFeeling dizzy, lightheaded, or faintNumbness or tingling sensationsHot or cold flashesFear of dying, losing control, or going crazy 53. 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. 54. Medical conditions and other physical causes.Mitral valve prolapse, a minor cardiac problem that occurs when one of the hearts valves doesnt close correctly.HyperthyroidismHypoglycaemiaStimulant use (amphetamines, cocaine, caffeine)Medication withdrawal 55. TREATMENTAntidepressants: SSRIsbenzodiazepines 56. PHOBIASPhobias 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. 57. ANATOMICAL CAUSEThe 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. 58. TYPES OF PHOBIASi. 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. 59. Social phobia may be further subdivided into:a) Generalized social phobia (also known as social anxiety disorder or simply social anxiety) andb) Specific social phobia: Anxiety is triggered only in specific situations.The symptoms may extend topsychosomatic manifestation of physicalproblems.E.g.- Sufferers of paruresis find it difficult orimpossible to urinate in reduced levels ofprivacy. 60. 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. 61. Agoraphobia may also be caused by various specific phobias such as:-Fear of open spacesSocial embarrassment (social agoraphobia)Fear of contamination (fear of germs, possibly complicated by obsessive- compulsive disorder) or PTSD (post traumatic stress disorder). 62. TREATMENTCognitive behavioural therapy (CBT): CBT lets the patient understand the cycle of negative thought patterns, and ways to change these thought patterns.SSRIsBenzodiazepines 63. POST-TRAUMATIC STRESS DISORDERClassified 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). 64. SIGNS AND SYMPTOMSExplosive anger, or passive aggressive behaviours.A tendency to forget the trauma or feel detached from ones life (dissociation) or body (depersonalization).Persistent feelings of helplessness, shame, guilt, or being completely different from others. 65. 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. 66. TREATMENTCognitive Behavioural TherapyAlpha-adrenergic agonist: ClonidineBeta blockers (Propranolol): These may inhibit the formation of traumatic memories by blocking adrenalines effects on the amygdala.Glucocorticoids: CorticosteroneBuspironeBenzodiazepinesSSRIs 67. OBSESSIVE-COMPULSIVE DISORDERCharacterized 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). 68. SIGN AND SYMPTOMSObsessive:- Fear of being contaminated by germs or dirt orcontaminating 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 lineup just right. Superstitions; excessive attention to somethingconsidered lucky or unlucky 69. Compulsive: Excessive double-checking of things, such as locks,appliances, and switches. Repeatedly checking in on loved ones to make suretheyre safe. Counting, tapping, repeating certain words, or doingother 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 byreligious fear. Accumulating junk such as old newspapers,magazines, and empty food containers, or other thingsyou dont have a use for. 70. ETIOLOGYA. 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. 71. 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 OCDsufferers may be relatively under-stimulated. 72. TREATMENTCognitive behavioural therapy (CBT):SSRIs