Mania

Introduction to Mania/Psychiatric Disorders

  • Disordered functioning in the areas of emotions, perception, thinking and memory, and have no clearly established biological basis.

Etiology of Psychiatric Disorders:

  • Genetic
  • Brain Structure and Functions:
    • The brain structure remains largely normal
    • The functioning of the brain Is commonly altered with, for example, changes in neurotransmitters such as dopamine, norepinephrine and serotonin activity of specific areas of the brain
  • Environmental Factors:
    • Early childhood abuse and emotional deprivation
    • Personality
    • Behavior such as alcoholism, anorexia nervosa and phobias
    • Social isolation
    • Stressors such as anxiety, loss in life, threat etc.

Types of Physchiatric Disorders

Neurosis: there is no radical loss from the surrounding, this is less serious and may be precipitated by surroundings

  • Anxiety: it is the exaggerated response to stress, there is excessive fear which is unrealistic
  • Phobic states
  • Obsessive-compulsive disorder: recurrent intrusive thoughts or ritual like behaviors which are abnormal
  • Post-traumatic stress disorder
  • Hysteria
  • Eating disorders
    • Anorexia nervosa
    • Bulimia nervosa
  • Body dysmorphic disorder
  • Psychosis: These are severe psychiatric illness with serious distortion of thought, capacity to recognize reality and of perception

Mania

  • Mood (affective) disorders: The primary symptom is change in mood state.
  • The exact pathophysiology of mania is unknown
  • Genetic predisposition:
    • 80% higher chances in mono zygotic twins
    • It is autosomal dominant
  • Drug induced: drugs with elevate Dopamine or serotonin levels
    • Cocaine
    • L DOPA
    • SSRI??
  • The exact aetiology is unclear

Clinical Features:

  • Excessive joviality
  • Over-activity
  • lack of sleep and appetite
  • Undue optimism
  • over-talkativeness
  • Irritability
  • Recklessness in spending

Lithium Chloride

  • Lithium is an effective mood stabilizer .
  • 1940, lithium chloride was introduced in salt as a replacement to NaCl for hypertensive patients
    • It cause tmprovement in symptoms of MDA
    • Deaths were reported due to serious lithium toxicity

Mechanism of Action

  • It has been hypothesized that in mania following neurotransmitters are effected:
    • Dopamine
    • Nor epinephrine
    • Serotonin
  • Inhibits hydrolysis of inositel-1-phosphiate by incsitol monophosphate. -> The supply of free inositol for regeneration of membrane phosphatidylinasitides is reduced

Other mechanisms:

  • Lithium decreases the presynaptic release of NA and DA in the brain of treated animals without affecting 5-HT release
  • Uncoupling receptors from the G protein
  • Inhibits protein Kinase C levels

Actions of Lithium

  • The hyperacfive neurons involved in the manic state are preferentially affected
  • It has no effect on normal individuals
  • It has no acute changes in patients of mania
    • Manic episodes are supressed within 1-2 weeks
    • Continuous treatment prevents cyclic mood changes
    • Sleep is also normalized

Other actions:

  • Lithium inhibits the action of ADH on distal tubules in the kidney and causes a diabetes insipidus like state.
  • Produces hypoglycaemia -> insulin like action
  • Increases leucocyte counts
  • Inhibits thyroid hormone release (feedback action)

Pharmacokinetics:

  • Itis neither metabolised and not bound to plasma protein
  • It gets into the extracellular fluid and then into the cells
  • The margin of safety is narrow, monitoring of serum lithium
    concentration is essential for optimizing therapy
    • Serum lithium level is measured 12 hours after the last dose to reflect the steady-state concentration

Adverse effects

  • Toxicity occur at tevels only marginally higher than therapeutic levels
  • Gastrointestinal: can be minimised by starting low dose
    • Nausea
    • Vomiting
    • Diarrhoea
  • Fine tremors are noted even at therapeutic concentrations
  • Thirst and polyuria
  • Renal Diabetes insipidus
  • Hypothyroidism and Goitre

Toxicity

  • CNS toxicity:
    • coarse tremors
    • giddiness, ataxia, motor incoordination,
    • nystagmus
    • Mental confusion, slurred speech, hyper-reflexia.
    • Convuisions
    • Coma
  • Vomiting, severe diarrhea, albuminuria, hypotension and cardiac
    arrhythmias
  • No Specific Treatment
    • Osmotic Diuresis
    • Sodium Bicarbonate Promotes lithium excretion
    • Haemodialysis

Interactions:

  • Diuretics:
    • Promote Na Loss
    • Increases Proximal reabsorption of ti
    • Toxicity may occur
  • Tetracycline, NSAIDs and ACE inhibitors can also cause lithium
    retention

Uses

  • Acute mania:
    • It is characterised by inappropriate cheerfulness or irritability, motor restlessness, high energy level, nonstop talking, flight of ideas, little need for sleep and progressive loss of contact with reality; sometimes violent behavior
    • Lithium is a good drug but not used routinely due to narrow margin of safety
    • Newer drugs are used b
  • Prophylaxis in bipolar disorder:
    • It is the preferred drug
    • Gradually dose increment is preferred
  • Cancer chemotherapy induced leukopenia and agranulocytosis

Limitations of Lithium

  • Narrow therapeutic margin
  • Chronic Adverse effects
  • Diabetes Insipidus
  • Hypothyroidism
  • 30% patients do not respond to Li+ therapy

Alternatives to Lithium

Summary

  • Mood disorders
    • Depression
    • Mania
    • Bipolar disorders
  • Li+ is a monovalent ion was found beneficial in Bipolar episode
  • It acts by decreasing inositol generation in the second messenger pathway
  • Follows a narrow therapeutic margin
  • Adverse effects -> Diabetes insipidus and Hypothyroidism
  • Alternative drugs are preferred

Other Pharmacology Notes:-

General Anaesthetics

Hypnotics – Sedative

Depression

Antiparkinsonian Drugs

Alzheimer’s Disease

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