JD is a 31-year old male with bipolar disorder that presents to the emergency department with symptoms of confusion, nausea, vomiting, and blurred vision. JD has been stable on lithium therapy for many years but was recently started on several new medications. His current medication list and vitals are listed below.
Medication List:
Lithium ER 600mg PO BID
Sertraline 50mg PO daily
Ibuprofen 800mg PO TID
Omeprazole 20mg PO daily
Metoprolol succinate 25mg PO daily
Labs/Vitals:
Ht: 6’0" ft
Wt: 211 lbs
BP: 146/91 mmHg
HR: 83 BPM
Temp: 98.6 F
Lithium level: 2.5 mEq/L (0.8-1.0 mEq/L)
Glucose: 103 mg/dL (70-130 mg/dL)
Scr: 0.8 mg/dL (0.5-1.2 mg/dL)
Na: 139 mEq/L (135-145 mEq/L)
Cl: 99 mEq/L (95-105 mEq/L)
K: 2.9 mEq/L (3.5-5 mEq/L)
Ca: 9.2 mg/dL (8.5-10.5 mg/dL)
Mg: 1.9 mg/dL (1.7-2.2 mg/dL)
Which of the following medications could be the culprit for JD’s lithium toxicity?
A. Omeprazole
B. Sertraline
C. Metoprolol
D. Ibuprofen
Answer with rationale:
Lithium is a primary treatment option for bipolar disorder and effective mood stabilization. However, its narrow therapeutic index requires careful monitoring because small changes in the serum levels can result in toxicity. Lithium is primarily eliminated by the kidneys and therefore it is susceptible to interactions with medications with similar excretion routes. When patients are stable on lithium therapy and present with symptoms like confusion, vomiting, or blurry vision it is crucial to review any recent medication changes. More severe toxicity could lead to seizures, hypotension, or coma. Lithium is unique in that it is one of the few medications that if toxic can be readily removed by dialysis treatments. It is important to have an understanding of which specific drugs can affect lithium levels for safe long-term management.
Answer A is incorrect. Omeprazole is a proton pump inhibitor used in the treatment of gastroesophageal reflux disease (GERD) and does not have a known drug-drug interaction with lithium. A number of medications that require an acidic environment for absorption, such as atazanavir, iron products, or certain azole antifungals (e.g. ketoconazole), could be impacted by proton pump inhibitor or any acid suppressing therapy.
Answer B is incorrect. Sertraline is a selective serotonin reuptake inhibitor (SSRI) that does not cause an increase in lithium levels. In rare cases, lithium at normal concentrations has been associated with increased serotonergic effects (e.g. agitation) in addition with SSRI therapy. Notably SSRIs are associated with hyponatremia through inappropriately high antidiuretic hormone secretion, especially in the elderly. Therefore sodium concentrations should be monitored regularly in patients receiving long-term SSRI therapy.
Answer C is incorrect. Metoprolol is a beta-1 selective blocker used for the treatment of hypertension, heart failure (succinate salt form) and many other diseases. Beta blockers are actually a preferred treatment option for patients on lithium compared to angiotensin converting enzyme (ACE) inhibitors, potassium sparing diuretics, and angiotensin receptor antagonists-all of which are known to potentially increase lithium levels. Speaking of diuretics, a good rule of thumb is that any medication or condition (e.g. dehydration) that affects sodium or water concentrations (e.g. diuretic) could also potentially lead to lithium toxicity.
Answer D is correct. Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that reduces lithium clearance and could result in a buildup of lithium concentrations. This is due to NSAID's ability to inhibit prostaglandins at the afferent arteriole, which could lead to increased lithium levels and toxicity. The patient in the case above is experiencing symptoms of lithium toxicity most likely from a drug-drug interaction with ibuprofen.
Brand/generics Covered:
Lithium (Lithobid), Omeprazole (Prilosec), Sertraline (Zoloft), Metoprolol (Lopressor), Ibuprofen (Advil, Motrin)
Naplex Content Outline Topics Covered:
3. C. 1 - Signs or symptoms of medical conditions
3. C. 2 - Appropriateness of therapy
3. C. 6 - Toxicologic exposure and overdoses
3. D. 2 - Safety