• Discuss the possible mechanisms of action of lithium.

Lithium suppresses IP3 and DAG second messenger systems by decreasing various enzymes important for conversion and re-circulation of phosphoinositides thus leading to an effect on monoamine and cholinergic neurotransmission

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

It has a narrow therapeutic index of 0.5-1.5Mm ,anything >2mM = toxic

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

Monotherapy: prophylaxis of manic and hypomanic episodes and for treatment of acute mania.

Combination therapy: treatment of resistant depression and aggressive behaviour.

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

In combination with a diuretic, NSAID, ACE inhibitor and fluoxetine it increases lithium levels and leads to toxicity.

In combination with caffeine, it increases renal excretion of lithium

In combination with a typical APs it worsens EPS.

• Name the major side effects of lithium.

GIT disturbance ,increase in QT Intervals ,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?

Category D drug. The use of lithium during lactation is not encouraged.

• Name three other important indications for lithium.

Bipolar disorder

Schizoaffective disorder

Major depression

• 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.

NSAIDS and the water pills that the patient is taking is increasing levels of lithium making it toxic and can be the reason for her side effects thus it explains the side effects she has been experiencing. Therefore I suggest is a replacement of the medication for the injury with something such as Cyclobenzaprine (antispasmodic) or paracetamol to help relieve the pain. Stopping the water pills and increasing physical activity and following correct eating habits may assist in the weight loss. The other symptoms that she is facing are side effects of using lithium.