What is the most likely underlying mechanism of this patient's condition, who presents with slurred speech, coarse tremor, and ataxic gait, with a history of bipolar disorder managed with lithium (lithium carbonate) and ziprasidone, and borderline hypertension managed with amlodipine, and currently experiencing severe nausea, vomiting, and diarrhea?

From the Guidelines

The most likely underlying mechanism of this patient's condition is lithium toxicity, which is closely related to serum lithium concentrations and can occur at doses close to therapeutic concentrations, as stated in the black box warning for lithium 1. The patient's neurological symptoms, such as slurred speech, coarse tremor, and ataxic gait, combined with gastrointestinal symptoms like severe nausea, vomiting, and diarrhea, strongly suggest elevated lithium levels in the blood. This toxicity has likely been precipitated by dehydration from the gastrointestinal symptoms, which reduces lithium excretion by the kidneys.

• Key factors contributing to this condition include:
  • Dehydration from severe nausea, vomiting, and diarrhea, leading to reduced renal clearance of lithium
  • Narrow therapeutic window of lithium, making it easy for levels to rise to toxic ranges when fluid balance is disrupted
  • The patient's history of bipolar disorder managed with lithium carbonate, which increases the risk of lithium toxicity
• The patient's borderline hypertension managed with amlodipine is not directly related to these symptoms, though dehydration could affect blood pressure control. Immediate management should include:
• Stopping lithium temporarily to prevent further toxicity
• Obtaining serum lithium levels to confirm the diagnosis
• Correcting fluid and electrolyte imbalances to restore proper renal function
• Monitoring renal function closely, as lithium toxicity can affect kidney function Lithium toxicity affects the central nervous system progressively, starting with mild symptoms like tremor and progressing to more severe manifestations including ataxia, dysarthria, and potentially seizures or coma if not addressed, as noted in the study on lithium treatment for Kleine-Levin syndrome 1. Once the patient is stabilized and lithium levels return to therapeutic range, a reassessment of their medication regimen for bipolar disorder may be necessary, possibly considering alternative mood stabilizers or adjusting the lithium dosage with more frequent monitoring, to prevent future episodes of toxicity.

From the FDA Drug Label

The distribution space of lithium approximates that of total body water. Lithium is primarily excreted in urine with insignificant excretion in feces. Renal excretion of lithium is proportional to its plasma concentration Decreased tolerance to lithium has been reported to ensue from protracted sweating or diarrhea and, if such occur, supplemental fluid and salt should be administered. Caution should be used when lithium and diuretics or angiotensin converting enzyme (ACE) inhibitors are used concomitantly because sodium loss may reduce the renal clearance of lithium and increase serum lithium levels with risk of lithium toxicity.

The most likely underlying mechanism of this patient's condition is reduction of renal clearance. The patient is experiencing severe nausea, vomiting, and diarrhea, which can lead to dehydration and decreased renal function, resulting in reduced renal clearance of lithium. This can cause an increase in serum lithium levels, leading to toxicity, as evidenced by the patient's symptoms of slurred speech, coarse tremor, and ataxic gait 2.

From the Research

Patient's Condition

The patient presents with slurred speech, coarse tremor, and ataxic gait, along with a history of bipolar disorder managed with lithium (lithium carbonate) and ziprasidone, and borderline hypertension managed with amlodipine. The patient is also experiencing severe nausea, vomiting, and diarrhea.

Possible Mechanisms

The following mechanisms could be contributing to the patient's condition:

• Reduction of renal clearance: Lithium is primarily excreted by the kidneys, and any decrease in renal function can lead to increased lithium levels 3, 4. The patient's symptoms, such as slurred speech, coarse tremor, and ataxic gait, are consistent with lithium toxicity.
• Dehydration: The patient's severe nausea, vomiting, and diarrhea can lead to dehydration, which can further decrease renal function and increase lithium levels 5, 4.
• Drug interactions: The patient is taking multiple medications, including lithium, ziprasidone, and amlodipine. Drug interactions can affect lithium levels and increase the risk of toxicity 3.

Key Points

• Lithium toxicity can occur due to various factors, including reduced renal clearance, dehydration, and drug interactions 5, 3, 4.
• Monitoring of serum lithium levels and clinical conditions is essential in patients taking lithium, especially when introducing new medications or experiencing dehydration 3, 4.
• The patient's symptoms, such as slurred speech, coarse tremor, and ataxic gait, are consistent with lithium toxicity, and reduction of renal clearance is a possible underlying mechanism 5, 4.

Most Likely Underlying Mechanism

Based on the patient's symptoms and medical history, the most likely underlying mechanism of this patient's condition is:

• Reduction of renal clearance: This is due to the patient's dehydration caused by severe nausea, vomiting, and diarrhea, which can lead to increased lithium levels and toxicity 5, 3, 4.