• Discuss the possible mechanisms of action of lithium.

Mechanism of action of lithium: Lithium influences the IP3 and DAG 2nd messenger systems by decreasing the various enzymes which are very important for conversion and re-circulation of membrane phosphoinositide’s.

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

The therapeutic index of lithium is 0,5-1.5mM which is very small and therefore the dosing of lithium should be done very carefully, and blood levels must be monitored to prevent lithium toxicity.

• When is lithium used as single drug and in which cases and with which type of drugs is lithium combined?

Lithium as monotherapy is used for prophylaxis of manic and hypomanic episodes and treatment of an acute manic episode. Lithium is used in combination with antidepressants for the treatment of resistant or recurrent unipolar depression and self-mutilating or aggressive behaviour.

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

The renal clearance may be decreased by thiazide diuretics, new NSAIDs, ACE inhibitors, and fluoxetine. Renal clearance of lithium is increased by theophylline and caffeine. Lithium is neurotoxic in combination with carbamazepine, calcium-blockers, losartan, methyldopa, metronidazole, and phenytoin.

• 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, and sexual dysfunction.

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

Lithium has been associated with an increased incidence of congenital cardiovascular abnormalities, but the incidence is very low, keep the risk-benefit in mind. Lithium is excreted into the breastmilk in high concentrations and thus breastfeeding is not suggested.

• Name three other important indications for lithium.

Lithium as monotherapy is used for prophylaxis of manic and hypomanic episodes and treatment of an acute manic episode.

• Evaluate the following case and fully motivate your recommendations:
• Ms B. Polar (21 years, 60 kg) is a student and used the following medication for the past two months: Camcolith 600mg bd. The plasma levels after two weeks were 0.8mmol/l. She sustained a muscle injury and has been using Indocid® 75mg nocte for the past 10 days. On questioning she reveals that “she had picked up a lot of weight” and is now using some of her mother’s “water pills” in the hope of losing a few of the extra kilos. However, she complains of fatigue, that she has difficulty in keeping her eyes open in class, remains thirsty and constantly feels shaky and nauseous.

The NSAID is causes decreased clearance of the lithium and therefore can cause an increase in the patient’s weight and other side effects of lithium. I would rather recommend Tylenol, acetaminophen, for pain. It does not have any drug interactions with lithium.