• Discuss the possible mechanisms of action of lithium.

The MOA is mediated by Li⁺. Lithium inhibits 2 signal transduction pathways where it suppresses IP₃ and glycogen synthase kinase-3. It influences IP₃ and DAG 2^nd messenger system by decreasing various enzymes which are important for conversion and re-circulation of membrane phosphoinositide. IP₃ and DAG are important in 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; >2mM = toxic

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

Lithium is used in monotheraphy for prophylaxis of manic and hypomanic episodes and for treatment of acute mania.

And in combination therapy it is used 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.

When used in combination with a diuretic, NSAID, ACE I and fluoxetine it increases lithium levels and leads to toxicity.

In combination with caffeine, it increases renal excretion of lithium

And in combination with a typical APs it worsens EPS.

• Name the major side effects of lithium.

Tremors, sedation, ataxia, aphasia, muscle weakness, fatigue, polydipsia, polyuria, nocturia, nephrogenic diabetes insipidus, thyroid enlargement, leucocytosis, edema 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

The NSAID she is currently taking has an interaction with the lithium treatment that she is taking. NSAIDS are known to cause increase levels of lithium making it toxic thus it explains the side effects she has been experiencing like. I would suggest that she replaces the medication she is taking for her muscle injury with something like Cyclobenzaprine which is an antispasmodic or paracetamol to help relieve the pain. I would also suggest to her to try physical activities to try and reduce the weight she has been gaining.