CONTENTSAnxietySymptoms and Clinical Features of anxietyCauses for anxiety & Role of ReceptorsAnxiety DisordersTreatmentPrevention
ANXIETYA 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 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.
SYMPTOMS AND CLINICAL FEATURESA. Physical symptoms: Heart palpitations Muscle weakness and tension Fatigue Nausea Chest pain Shortness of breath
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).
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 minds gone blankNightmares/bad dreamsObsessions about sensationsDéjà vuA 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 SYSTEMSNeurotransmitter systems involved in anxiety generation include the GABA systems Serotonergic Adrenergic Benzodiazepine (BZD)
CAUSES & ROLE OF RECEPTORS1. 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 IonTransmembrane out of the Channels Receptors cell Hyperpolarization
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
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.
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 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.
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.
GENERALIZED ANXIETY DISORDERSAn 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.
1. BENZODIAZEPINESMost important group, used as anxiolytic and hypnotic 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
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‾ channelsInhibition of synaptic transmission throughout CNS
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.
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.
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.
Do not inhibit cardiac conduction- overdose arrhythmias 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.
b) Fluoxetine Longest acting T1/2 for parent compound: 2 days and active demethylated metabolite: 7-10 days. Slow onset of action
SIDE EFFECTS Nausea Interference with ejaculation and orgasm Nervousness Restlessness Insomnia Anorexia Headache Diarrhoea
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.
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-HT1A autoreceptors. Activity of dorsal raphe serotonergic neurons decreases. Agonist action on 5-HT1A receptors.
SIDE EFFECTS:DizzinessNauseaHeadacheLight-headednessExcitement (rarely)
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.
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 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
SweatingNausea or upset stomachFeeling dizzy, lightheaded, or faintNumbness or tingling sensationsHot or cold flashesFear 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 doesnt close correctly. Hyperthyroidism Hypoglycaemia Stimulant use (amphetamines, cocaine, caffeine) Medication withdrawal
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.
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.
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.
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).
TREATMENTCognitive behavioural therapy (CBT): CBT lets the patient understand the cycle of negative thought patterns, and ways to change these thought patterns.SSRIsBenzodiazepines
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).
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.
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.
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
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).
SIGN AND SYMPTOMSObsessive:- 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.
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.
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.