Discuss the possible mechanisms of action of Lithium

• Lithium can substitute sodium in generating action potentials
• Lithium also has effects on the second messengers. It influences specifically IP₃ and DAG 2^nd messenger systems by decreasing various enzymes that are important for the conversion and recirculation of membrane phosphoinositides. IP₃ and DAG is important in monoamine and cholinergic neurotransmission

What is the therapeutic index of lithium, and what is its clinical significance?

• Lithium has a very narrow therapeutic index of 0.5-1.5 mM. Anything higher than 2mM can have toxic effects. Lithium toxicity can have severe side effects like Tremors, Muscle weakness, Polydipsia, Nephrogenic diabetes insipidus, Thyroid enlargement, Leucocytosis etc.

When is lithium used as a single drug, and in which cases and with which type of drug is Lithium combined?

• Lithium can be used as monotherapy with acute major depression
• It is often used in combination with an antipsychotic drug in the treatment of Schizophrenia
• Benzodiazepines and Lithium are used together in the treatment of Bipolar Disorder

Name 3 clinically significant interactions lithium may have with other drugs. Illustrate your answer with suitable examples of drugs.

• Drugs like Thiazides (Diuretics), ACE inhibitors (Enalapril) and Fluoxetine increase the levels of Lithium in the body, which could lead to lithium toxicity.
• Theophylline and caffeine increases the renal excretion of Lithium
• Carbamazepine, Ca²⁺ blockers, Losartan, Methyldopa, Metronidazole and Phenytoin in combination with Lithium can have serious neurotoxic side effects

Name the major side effects of lithium

• Tremors, sedation, ataxia, aphasia
• Muscle weakness, fatigue
• Polydipsia, polyuria, nocturia
• Nephrogenic diabetes insipidus
• Thyroid enlargement
• Leucocytosis
• Oedema
• Weight gain
• Acne, Alopecia
• Sexual dysfunction   

What is the status of the use of lithium during pregnancy and lactation?

• Patients can continue taking Lithium whilst pregnant. It could help to reduce the risk for post-partem psychosis. If patients do decide to stop taking Lithium, they need to resume the treatment as soon as possible after giving birth.
• Lithium moves into the breastmilk and passes into the baby’s body, causing high concentrations of Lithium in the baby’s bloodstream. Lithium should be used with caution in women who are breastfeeding.

Name 3 other important indications for lithium

• Prophylaxis of manic and hypomanic episodes
• Treatment of resistant or recurrent (unipolar) depression to increase the effects of the antidepressants
• Aggressive or self-mutilating behaviour

Evaluate the case and motivate your recommendations.

The lithium falls in the therapeutic index, and her dose is correct for her weight according to the SAMF (20mg/kg/day). The lithium should not cause any adverse effects on its own, but by drinking her mother’s water pill (Diuretic), the levels of Lithium in her body has increased. Due to this increase, she is experiencing symptoms that can be seen with lithium toxicity, such as fatigue and the shakiness she is experiencing. She needs to stop using her mother’s water pills (diuretics) in an attempt to lose weight and drink more water to compensate for the effects caused by the water pill. By keeping herself hydrated and the cessation of the water pill, her lithium levels should return to normal, and the toxic effects will fade. If she is concerned about her weight, other options should be considered, like talking to her pharmacists about changes she can make to her lifestyle to lose weight in a healthy and controlled manner.