Pharmacology
Central Nervous System
Which of the following classes of drugs may predispose to lithium toxicity:
Answer:
Excretion of lithium may be reduced by thiazide diuretics, NSAIDs, and ACE inhibitors thus predisposing to lithium toxicity. Loop diuretics also cause lithium retention but are less likely to result in lithium toxicity.Lithium
Pharmacology / Central Nervous System
Last Updated: 23rd May 2023
Indications
Lithium salts are used in the prophylaxis and treatment of mania, hypomania and depression in bipolar disorder and in the prophylaxis and treatment of recurrent unipolar depression.
Contraindications
Lithium is contraindicated in:
- Addison’s disease
- Cardiac disease associated with rhythm disorders
- Family or personal history of Brugada syndrome
- Low sodium (including people that are dehydrated and those on low sodium diets)
- Untreated hypothyroidism
- Clinically significant renal impairment
Cautions
Lithium should be used with caution in:
- Cardiac disease
- Concurrent ECT (may lower seizure threshold)
- Diuretic treatment (risk of toxicity)
- Elderly (reduce dose)
- Epilepsy (may lower seizure threshold)
- Myasthenia gravis
- Psoriasis (risk of exacerbation)
- QT interval prolongation
Interactions
Caution with concomitant use of drugs and any therapy that may lower seizure threshold.
Caution with concomitant use of drugs that prolong the QT interval.
Lithium toxicity is made worse by sodium depletion, therefore concurrent use of diuretics (particularly thiazides) is hazardous and should be avoided. Thiazide diuretics also cause a rapid increase in serum lithium levels by reducing clearance of lithium.
Concomitant NSAIDs may increase serum lithium levels.
Side Effects
Initial adverse effects of lithium therapy include nausea, diarrhoea, vertigo, muscle weakness, and a dazed feeling. These effects often resolve with continued therapy. Fine hand tremors, polyuria, and polydipsia may persist. Adverse effects tend to be directly related to plasma levels. Longer-term adverse effects include thyroid dysfunction (hyperthyroidism and hypothyroidism), hyperparathyroidism, nephrotoxicity, renal tumours and rhabdomyolysis.
Lithium Monitoring
Lithium has a narrow therapeutic index. Samples should be taken 12 hours after the dose to achieve a serum-lithium concentration of 0.4 – 1 mmol/litre (lower end of the range for maintenance therapy and elderly patients).
Routine serum-lithium monitoring should be performed weekly after initiation and after each dose change until concentrations are stable, then every 3 months thereafter. Additional serum-lithium measurements should be made if a patient develops significant intercurrent disease or if there is a significant change in a patient’s sodium or fluid intake.
Renal function should be monitored at baseline and every 6 months thereafter (more often if there is evidence of deterioration or if the patient has other risk factors, such as starting ACE inhibitors, NSAIDs, or diuretics).
A lithium treatment pack should be given to patients on initiation of treatment with lithium. The pack consists of a patient information booklet, lithium alert card, and a record book for tracking serum-lithium concentration.
Lithium Toxicity
Most cases of lithium intoxication occur as a complication of long term therapy and are caused by reduced excretion of the drug because of a variety of factors including dehydration, deterioration of renal function, infections, and co-administration of diuretics or NSAIDs (or other drugs that interact).
Lithium toxicity occurs at serum lithium concentrations of approximately 1.5 mmol/L and above, but may occur despite an apparently normal plasma level.
Features of toxicity include:
- Gastrointestinal disturbances (vomiting, diarrhoea, anorexia)
- Muscle weakness
- Lethargy, drowsiness
- Dizziness
- Ataxia
- Tinnitus
- Visual disturbances
- Coarse tremor of the extremities and lower jaw
- Muscle hyperirritability
- Choreoathetoid movements
- Dysarthria
- Severe toxicity (serum-lithium concentration > 2 mmol/L)
- Hyperreflexia, myoclonus and hyperextension of limbs
- Syncope
- Toxic psychosis
- Seizures
- Polyuria, dehydration and renal failure
- Electrolyte imbalance e.g. hypernatraemia
- Cardiac arrhythmias (including sinoatrial block, bradycardia and first-degree heart block)
- Circulatory failure
- Coma
There is no specific antidote to lithium toxicity. In secondary care the treatment is supportive and lithium levels are normally rechecked every 6 – 12 hours. Osmotic or forced alkaline diuresis may be required, however peritoneal or haemodialysis may be used if levels are above 3 mmol/L.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
