Name of Blog: Blog #13

Answer the following for a Blog Summary:

Q. Discuss the possible mechanisms of action of lithium.

MOA is mediated by Li⁺. The drug inhibits several enzymes involved in recycling of neuronal membrane phospholipids. This action result in the depletion of the 2^nd messenger source, phosphatidylinositol bisphosphate (PIP₂), which in turn decreases the generation of inositol trisphosphate (IP₃) and diglycerol (DAG). These 2^nd messengers are IMP in amine neurotransmission including those mediated by central adrenoreceptors and muscarinic receptors. It also inhibits glycogen synthase kinase-3 (GSK-3).GSK-3 is a component of diverse intracellular signalling pathways. 

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

Small therapeutic index of 0.5 – 1.5mM; >2mM = toxic.

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

Monotherapy for acute major depression.

Bipolar disorder it is used, but Benzodiazepines or antipsychotic agents are often required at the initiation of treatment because lithium has a slow onset of action.

Schizoaffective disorders used in combination with other APDs.

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

1. When used in combination with diuretics it decreases Lithium clearance = lithium toxicity due to increased Lithium plasma levels Ex. Chlorothiazide.

2. When used in combination with other APDs it worsens EPS.

3. When used in combination with NSAIDs (Diclofenac) it decreases Lithium clearance which leads to lithium toxicity due to increased Lithium plasma levels.

4. When used in combination with Phenytoin or carbamazepine it causes neurotoxicity.

Q. Name the major side effects of lithium.

Leucocytosis, Nephrogenic Diabetes Insipidus, Thyroid enlargement, sexual dysfunction, weight gain, oedema, acne & alopecia, tremors, dysarthria, aphasia, ataxia, polyuria, polydipsia & nocturia, muscle weakness and fatigue.

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

Category D drug. There is evidence that show human foetal risk. The use of lithium during lactation is not encouraged however there have been many woman who have breastfed their babies while on lithium who have not experienced any negative side effects. 

Q. Name three other important indications for lithium.

- Bipolar disorder (manic phase), Schizoaffective disorder, acute Major depression

Q. 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.

Ms B.Polar is showing clear side effects of Lithium with the weight gain, thirst, polyuria, fatigue, tremors, nausea and water retention (oedema). I would recommend her dosage be decreased to relive of the side effects or give a propranolol for the tremors and recommend regular physical activity for the weight gain it usually also helps with better motor functioning and overall wellbeing (thus fatigue might be improved).