BLOG #13

1. Discuss the possible mechanisms of action of lithium.

Lithium affects the IP3 and DAG 2nd messenger systems by reducing the activity of certain enzymes that are critical for the conversion and recirculation of membrane phosphoinositides.

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

Lithium has a therapeutic index of 0,5-1.5mM, which is very low. As a result, lithium dosing should be performed very carefully, and blood levels must be controlled to avoid lithium toxicity.

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

Lithium is used as a monotherapy for the prevention of depressive and hypomanic episodes, as well as the treatment of acute manic episodes. For the treatment of resistant or chronic unipolar disorder, as well as self-mutilating or destructive behaviour, lithium is combined with antidepressants.

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

Thiazide diuretics, new NSAIDs, ACE inhibitors, and fluoxetine can all lower renal clearance. Theophylline and caffeine improve lithium clearance in the kidneys. In combination with carbamazepine, calcium-blockers, losartan, methyldopa, metronidazole, and phenytoin, lithium is neurotoxic.

5. 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.

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

While lithium has been linked to an increased risk of congenital cardiovascular defects, the risk-benefit ratio is still favourable. Since lithium is excreted in high amounts in breastmilk, breastfeeding is not recommended.

7. Name three other important indications for lithium.

Lithium is used as a monotherapy for the prevention of depressive and hypomanic episodes, as well as the treatment of acute manic episodes.

8. Evaluate the following case and fully motivate your recommendations:

Ms B. Polar (21 years old, 60 kg) is a student who has been taking Camcolith 600mg bd for the past two months. After two weeks, the plasma levels were 0.8mmol/l. She has been taking Indocid® 75mg nocte for the past ten days due to a muscle injury. When questioned, she admits that she "had gained a lot of weight" and that she is now taking some of her mother's "water pills" in the hopes of losing a few pounds. She does, however, complain of exhaustion, having trouble holding her eyes open in class, being thirsty, and feeling weak and nauseous all of the time.