Anxiety disorders

1. ANXIETY disorders 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:- Cognitive: Processing of information, applying knowledge, and changing preferences Somatic: V oluntary  control of body movements via skeletal muscles, and with sensory reception of external stimuli  (e.g., touch, hearing, and sight )

4. Emotional: Mood, temperament, personality and disposition , and motivation 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 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. External signs: Pale skin Sweating Trembling Pupillary dilation

8. 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 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 + Transmembrane Receptors Opening of Ion Channels Cl ˉ in and K+ out of the cell Hyperpolarization

14. gaba a Upon activation, the GABA A receptor 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.

15. GABA A receptors are Cl - channels so when activated by GABA: Cl moves out: excitation/ depolarization Cl moves in: inhibition/ hyperpolarization- inhibition of NT

16. Gaba b 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 GABA B  receptors are considered inhibitory receptors.

17. 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 .

18. T he 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.

19. ENVIRONMENTAL FACTORS Life stresses such as financial worries or chronic physical illness. A lso 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 .

20. U se of and withdrawal from addictive substances, including alcohol,  caffeine , and  nicotine.

21. Anxiety disorders Generalized A nxiety Disorder: An ongoing state of excessive anxiety lacking any clear reason or focus Panic D isorders : Sudden attacks of overwhelming fear occur in association with marked somatic symptoms, such as sweating, tachycardia, chest pains, trembling and choking.

22. Phobias: Strong fears of specific objects or situations, e.g. snakes, open spaces, flying, social interactions Post-traumatic stress disorder: Anxiety triggered by recall of past stressful experiences Obsessive compulsive disorder: Compulsive ritualistic behavior driven by irrational anxiety, e.g. fear of contamination.

23. 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.

24. 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

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

26. 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 .

27. 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.

28. Types of medication prescribed for generalized anxiety disorder : 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.

29. Buspirone  – 5-HT 1A 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.

30. 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 .

31. Treatment OF ANXIETY DISORDERS Types of anxiolytics:- Benzodiazepines E.g .- Alprazolam, Chlordiazepoxide , Clonazepam, Diazepam, Lorazepam SSRIs (Selective Serotonergic Receptor Inhibitors) E.g.- Escitalopram , Citalopram

32. Azapirones E.g.- Buspirone Barbiturates E.g.- Phenobarbital, Pentobarbital Miscellaneous E.g.- Chloral hydrate, Meprobamate , Methaqualone

33. benzodiazepines Most important group, used as anxiolytic and hypnotic agents. Types: Ultra short acting (4-6 hrs ): Triazolam , midazolam, Zolpidem Short acting (12-18 hrs ): Lorazepam , Oxazepam Medium acting (24 hrs ): Alprazolam Long acting (>24 hrs ): Diazepam, Clordiazepoxide , Flurazepam , Clonazepam

34. Drug(s) Half-life of parent compound ( Hrs ) Active metabolite Half-life of metabolite ( Hrs ) Main use(s) Triazolam , Midazolam 2-4 Hydroxylated derivative 2 Hypnotic Midazolam: I.V. anesthetic Zolpidem 2 No - Hypnotic Lorazepam , Oxazepam 8-12 No - Anxiolytic, hypnotic Alprazolam 6-12 Hydroxylated derivative 6 Anxiolytic, antidepressant Diazepam, Chlordiazepoxide 20-40 Nordazepam 60 Anxiolytic, muscle relaxant Dzpam : I.V. anticonvulsant Flurazepam 1 Desmethyl-flurazepam 60 Anxiolytic Clonazepam 50 no - Anticonvulsant, anxiolytic (mania)

35. Mechanism of action

36. MOA

37. Pharmacological effects and uses of bZD :- Reduction of anxiety and aggression. Sedation and induction of sleep. Reduction of muscle tone and coordination . Anticonvulsant effect.

38. Unwanted effects of BZD Divided into: Toxic effect resulting from acute overdose (antagonist- flumazenil). Unwanted effects during normal therapeutic dose: drowsiness, confusion, amnesia, impaired coordination. Tolerance and dependence.

39. 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.

40. Do not inhibit cardiac conduction- overdose arrhythmias are not a problem. Used along with BZD to cover exacerbations Citalopram : T 1/2 : 33 hrs No active metabolite Overdose: suicide Escitalopram : Active S(+) enantiomer of citalopram. Effective at half dose Less side effects and improved safety.

41. Fluoxetine Longest acting T 1/2 for parent compound: 2 days and active demethylated metabolite: 7-10 days. Slow onset of action

42. MECHANISM OF ACTION

43. Side effects Nausea Interference with ejaculation and orgasm Nervousness Restlessness Insomnia Anorexia Headache Diarrhoea

44. 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.

45. Used in mild to moderate GAD. Ineffective in severe cases. Slow therapeutic effect. Delayed up to 2 weeks. T 1/2 : 2-3.5 hrs MOA: Stimulates presynaptic 5-HT 1A autoreceptors . Activity of dorsal raphe serotonergic neurons decreases. Agonist action on 5-HT 1A receptors.

46. Side effects: Dizziness Nausea Headache Light-headedness Excitement (rarely)

47. 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.

48. 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.

49. 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

50. 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

51. 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 .

52. 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

53. treatment Antidepressants: SSRIs benzodiazepines

54. 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.

55. 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.

56. 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. Overcoming social phobia is often very difficult without the help of therapy or support groups.

57. Social phobia may be further subdivided into: Generalized social phobia (also known as social anxiety disorder or simply social anxiety) and 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 .

58. Specific phobias - Fear of a single specific panic trigger such as spiders, snakes, dogs, water, heights, flying, catching a specific illness, etc. Agoraphobia - A generalized fear of leaving home or a small familiar 'safe' area, and of possible panic attacks that might follow.

59. 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).

60. 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

61. 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 ). 

62. 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 .

63. 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.

64. 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: C orticosterone Buspirone Benzodiazepines SSRIs

65. 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).

66. 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

67. 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 .

68. etiology 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.

69. 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 . Biological: S erotonin receptors of OCD sufferers may be relatively under-stimulated.

70. treatment Cognitive behavioural therapy (CBT ): SSRIs