1. Lithium Toxicity Robert Nashat, Pharm.D, CDE Medical Place Pharmacy 20 Emma St, Chatham, On

2. Roadmap Lithium Background Pharmokinetics of Lithium – Lithium Toxicity Lithium Side-effects – Acute and Long Term Lithium Toxicity – Factors leading to Toxicity – Drug Interactions Treating Lithium Toxicity Case Conclusion

3. Background on Lithium Has been used since the 1870s. – Initially used to gout Also used in the treatment of symptoms associated with depression independent of gout. Fell out of favor because of side effects. Banned by FDA in 1940s because of fatalities John Cade

4. Lithium Considered Standard of Therapy For Bipolar Disease

5. Lithium Pharmokinetics Taken Orally ( Liquid and Capsule) Absorption – Complete Absorption from the GI Tract 2-4 Hours Post-ingestion – Long Half-life 12-27 Hours Elimination – Excreted from the Kidney but undergoes a lot of reabsorption (80%) – Works very similar to Sodium in the body and is linked to sodium concentrations. Levels between 0.6-1.2 meq/L – Narrow Therapeutic Index

6. Lithium Toxicity Severe Toxicity- Seizures, loss of consciousness, coma, death Mild Toxicity- Nausea, vomiting, Tremor, Slurred Speech, Confusion We have to be very careful of Drug Interactions and other Influencing factors ( Salt Intake, Caffeine, Hydration Status)

7. Factors Predisposing To Lithium Toxicity Renal failure Volume depletion CHF Caffeine Intake Decreased Na intake Dehydration

8. Drug Interactions and Lithium Levels ACE Inhibitors/ARB – Increase lithium levels Diuretics – Especially HCTZ, triamterene, spironolactone Caffeine NSAIDs – Advil, Aleve – Increase lithium levels Serotonergic agents

10. Drug Interactions and Lithium Levels ACE Inhibitors/ARB – Increase lithium levels Diuretics – Especially HCTZ, Lasix Caffeine NSAIDs – Advil, Aleve – Increase lithium levels Serotonergic agents

11. Diuretics and the Kidney Direutics Increase

12. Lithium Toxicity (chronic Ingestion) Levels[Li] mEq/LClinical Manifestations Treatment Grade 11.5-2.5Nausea Vomitting Tremor Hyperreflexia Ataxia Agitation Muscular Weakness Hydration (x 4-6h) Kayexalate Grade 22.5 -3.5Stupor Rigidity Hypertonia Hypotension Hydration, Kayexalate, +/- dialysis Grade 3> 3.5Coma Seizures Hemodialysis

13. What Else Should Be Done? Consult Renal Service Consult psychiatric Service Consult poison control/toxicology service

14. Lithium Side Effects Long Term Side Effects – Hypothyroidism – Cardiac Effects – Weight Gain – Leukocytosis – Dermatological Effects Acne, Psoriasis Acute effects – Nausea, Diarrhea – Lethargy – Impaired Cognitive Functioning – Hand Tremor

15. Putting It All Together- Case 1 The Patient Mr. X 53 years old Presented to the ER with – Loose Stools from the last 2 days – Nausea – Loss of Energy – Fatigue Known Patient of Bipolar Disorder and under treatment by Psychiatry Care. Patient is on Lithium Carbonate

16. Examination Pulse: 108 Bp 100/70 Dehydrated CNS: Irritable, Confused, Mild Tremor, Ataxia CVS: Tachycardia Lithium Levels: 3.17 mmol/L ( Ref:0.50-1.2 mmol/L)

17. Diagnosis

18. Management Admit in ward I/V Fluids Stop the Lithium Supportive Care Lithium repeated after 4 days is 0.68 mmol/L Discharged via psychiatry after one week.

19. Conclusion Important to be educated about the side effects of Lithium. – Mortality rate Approximately 25 percent with an acute overdose 9 percent in patients intoxicated during maintenance therapy. Presentation is available on our website www.medicalplacepharmacy.com Online Medication Reconciliation Program Available

20. Questions?