LITHIUM.pptx use history mechanism of action

LITHIUM PPT PRESENTATRION

1. LITHIUM Dr DIVY RANA

2. Agenda - Introduction to Lithium - History of Lithium in Psychiatry - Mechanism of Action - Indications - Dosing and Administration - Side Effects - Monitoring and Toxicity - Contraindications and Precautions - Benefits and Future Directions - Conclusion

3. HISTORY YEAR NAME DISCOVERED In 1817 Johan August Arfvedson Lithium was discovered as a chemical element In 1847 Garrod Lithium treatment for gout In 1870 Silas weir Lithium bromide as an anticonvulsant and a hypnotic In 1871, William Hammond First recorded use of lithium for mania In 1894 Fredrick Used in the prevention of melancholic depression In 1949 John Cade Rediscovered the use of lithium for mania In 1970 FDA Approved the use of lithium for mania

4. INTRODUCTION - Lithium carbonate (Li2CO3): Alkali metal, first-line mood stabilizer for bipolar I disorder - Adjunct in treatment-resistant major depressive disorder (MDD); reduces suicide risk by up to 80%. - Underutilized due to side effects, monitoring needs, and newer agents.

5. PHARMACOKINETICS Half life – 18 – 24hrs Lithium is readily absorbed with peak plasma levels occuring 2 – 4 hours after a single oral dose of lithium carbonate Lithium is distributed rapidly in liver, kidney, muscle, bone and brain. Elimination is predominantly 95% via kidneys and is influenced by sodium balance

6. MECHANISM OF ACTION BRAIN STRUCTURE NEUROTRANSMITTER MODULATIONS INTRACELLULAR CHANGES MULTIPLE LEVELS OF ACTION OF LITHIUM But the exact mechanism of action of lithium is unknown.

7. MECHANISM OF ACTION Exact mechanism unclear; acts via multiple pathways. Alters sodium transport, affecting Catecholamine/ serotonin metabolism.reduce absorption of NEP and serotonin. Inhibits inositol monophosphatase (IMPase), reducing phosphoinositide signaling (overactive in mania). Reduce protein kinase C activity, possibly affecting genomic expression associated with neurotransmission.

8. MOA Enhances BDNF(brain derived neurotrophic factor), Bcl-2, supporting neuronal survival; explains anti-suicidal effects. Immunomodulatory: Reduces pro-inflammatory cytokines, ATP-induced cell death. Neuroprotective: Increases gray matter, reduces dementia risk.

9. INDICATIONS FDA-Approved: Acute mania/mixed episodes, maintenance in bipolar I disorder; prevents relapses.(age 7 and older) Adjunctive: Augmentation in treatment-resistant MDD, schizoaffective disorder. Anti-Suicidal: Reduces suicide attempts in bipolar/unipolar depression. Other: Cyclothymia prophylaxis, aggression in personality disorders, potential in Alzheimer’s.

10. INDICATIONS ACUTE MANIA PROPHYLAXIS FOR BIPOLAR AND UNIPOLAR MOOD DISORDER SCHIZOAFFECTIVE DISODER BOARDERLINE PERSONALITY DISORDER

11. indications BULLIMIA NERVOSA BINGE DRINKING CLUSTER HEADACHE NEUTROPENIA

12. TRICHOTILLOMANIA OTHER INDICATIONS CYCLOTHYMIA IMPULSIVITY AND AGGRESSION

13. DOSES Lithium is available in the form of following preparation: Lithium carbonate 300mg (slow release), capsule 150mg,300mg, 600mg. 450mg sustained release tablets Lithium citrate 8mEq/5ml liquid

14. DOSES Forms: Immediate-release (IR) capsules/tablets (300 mg), extended-release (ER) tablets (300-450 mg), solut Adults - Acute Mania: 600-900 mg/day (IR, divided) or 900 mg BID (ER); target 0.8-1.2 mEq/L, max 1.8 g/day. Adults - Maintenance: 300-600 mg 2-3 times/day (IR) or 600-900 mg BID (ER); target 0.6-1.0 mEq/L.

15. DOSES Pediatrics (7+, 20-30 kg): Acute: 15-20 mg/kg/day; maintenance: 10-15 mg/kg/day. Adjust for elderly/renal impairment; take with food; maintain hydration/sodium intake. Taper over 3+ months to avoid relapse; once-daily dosing may reduce renal risk.

16. SIDE EFFECTS L – Leucocytosis I – Insipidus (Diabetic) T – Tremors, teratogenicity H – Hypothyroidism I – Increased weight gain U – Vomiting(GI disturbances) M - Miscellaneous – ECG changes, Acne

17. NEUROLOGICAL Tremors, motor hyperactivity, muscular weakness, cogwheel rigidity, seizures, neurotoxicity. cognitive dulling; treat with propranolol (10-40 mg). 2. RENAL Polydipsia, polyuria, tubular eenlargement, nephritic syndrome, Nephrogenic diabetes insipidus (20-40%); CKD risk (1-5% after 10+ years). 3. CARDIOVASCULAR: T – WAVE depression

18. 4. GATROINTESTINAL Nausea, vomiting, diaarhoea , abdominal pain and metallic taste(10-20%) manage with ER or dose splitting. 5. ENDOCRINE Abnormal thyroid function, goitre , weight gain 5-35% 6. DERMATOLOGICAL A cniform eruptions, populareruptions and exacerbation of psoriasis 7. PREGNANCY & LACTATION Teratogenic possibility Increased incidence of ebstein’s anomaly Secretes in milk and causes toxiity in infant

19. CONTRAINDICATIONS Contraindications: Severe renal failure (eGFR <30 mL/min), acute MI, hypersensitivity, Brugada syndrome. Precautions: Cardiovascular disease, dehydration, hyponatremia, thyroid disorders, pregnancy, elderly. Interactions: Increase levels: Thiazides, NSAIDs, ACE inhibitors; Neurotoxicity risk: Antipsychotics, SSRIs.

20. MONITORING - Baseline: Renal (eGFR >50 mL/min), thyroid (TSH, T4), ECG (>50 years), CBC, weight, electrolytes. - Ongoing: Serum levels ( 12h post-dose): Weekly initially, then every 3-6 months; renal/thyroid every 6 months. - Pregnancy: Category D, Ebstein’s anomaly risk (0.05-0.1%); monitor fetal echo.

21. Lithium toxicity

22. Lithium toxicity is another term for a lithium overdose or poisoning Lithium is similar to sodium. In addition, lithium may inhibit the release of monoamines from nerve endings and increase their uptake.

23. TYPES OF POISONING: ACUTE POISONING –voluntary or accidental ingestion in untreated patient ACUTE ON CHRONIC – Voluntary or accidental ingestion in patient currently using lithium CHRONIC OR THERAPEUTIC – progressive lithium toxicity in a patient on lithium therapy.

24. signs and symptoms MILD – MODERATE TOXICITY: Generalized weakness Fine resting tremor Mild confusions MODERATE – SEVERE TOXICITY: Severe tremors Muscle fasciculations Stupor Seizures COMA Signs of cardiovascular collapse

25. SYMPTOMS WITH CHRONIC TOXICITY SYMPTOMS NONE MILD TREMOR COARSE TREMOR HYPERREFLEXIA DYSARTHRIA MYOCLONIA, ATAXIA,CONFUSION DELIRIUM, COMA, SEIZURES LEVEL 0.5 mEq /L 1.0 mEq /L 1.5 mEq /L 2.0 mEq /L 2.5 mEq /L > 3.0 mEq /L

26. complications Truncal and gait ataxia Nystagmus Hypertonicity Short term memory deficits Dementia( rare) PROGNOSIS: Most cases of lithium toxicity result in a favourable outcome; however up to 10% of individuals are with severe toxicity.

27. MANAGEMENT There is no specific antidote for lithium toxicity Vital signs monitoring – unusual signs Lab studies – serum lithium level, electrolytes, RFT and ECG as soon as possible Gastric lavage or bowel irrigation – if have taken lithium within one hour. IV fluids – to restore electrolyte balance Hemodialysis – to remove excess lithium from blood Medication – if seizure occurs

28. - Benefits: Reduces mania relapses (40-60%), suicide risk; cost-effective; neuroprotective. - May lower dementia risk, support brain health. - Future Research: Low-dose for neurodegenerative diseases, biomarkers for response, minimizing renal/thyroid risks.

29. Lithium: Gold-standard mood stabilizer with rich history, unique anti-suicidal and neuroprotective benefits. Requires vigilant monitoring due to narrow therapeutic index More affective in treating maniac episode than depressive May be the best for euphoric mania lithium is one of the most usefull adjunctive agent to augment antidepressent for treatment resistant unipolar depression.

30. REFRENCES - Cade JFJ. Lithium salts in the treatment of psychotic excitement. Med J Aust. 1949;2:349-352. - Schou M. Lithium treatment of mood disorders: A practical guide. 6th ed. Basel: Karger; 2004. - Shorter E. The history of lithium therapy. Bipolar Disord. 2009;11(Suppl 2):4-9. - Lithobid (lithium carbonate) [package insert]. Baudette, MN: ANI Pharmaceuticals; 2023. - Stahl SM. Stahl’s Essential Psychopharmacology. 4th ed. Cambridge University Press; 2017.