Lithium Toxicity

Robert Nashat, Pharm.D, CDEMedical Place Pharmacy

20 Emma St, Chatham, On

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

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

Lithium

• Considered Standard of Therapy For Bipolar Disease

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

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)

Factors Predisposing To Lithium Toxicity

• Renal failure• Volume depletion• CHF• Caffeine Intake• Decreased Na intake• Dehydration

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

Drug Interactions and Lithium Levels

• ACE Inhibitors/ARB– Increase lithium levels

• Diuretics– Especially HCTZ, Lasix

• Caffeine• NSAIDs– Advil, Aleve– Increase lithium levels

• Serotonergic agents

Diuretics and the Kidney

Direutics Increase

Lithium Toxicity(chronic Ingestion)

Level s[Li] mEq/L Clinical Manifestations

Treatment

Grade 1 1.5-2.5 NauseaVomittingTremorHyperreflexiaAtaxiaAgitationMuscular Weakness

Hydration (x 4-6h)Kayexalate

Grade 2 2.5 -3.5 StuporRigidityHypertoniaHypotension

Hydration, Kayexalate,+/- dialysis

Grade 3 > 3.5 ComaSeizures

Hemodialysis

What Else Should Be Done?

• Consult Renal Service• Consult psychiatric Service• Consult poison control/toxicology service

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

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

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)

Diagnosis

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.

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

Questions?

Thank you