1. Possible mechanism of action of Lithium:

Lithium inhibits several enzymes involved in the recycling of neuronal membrane phosphoinositides. This action may result in depletion of the second messenger source, phosphatidylinositol biphosphate (PIP2), which, in turn would decrease generation of IP3 and DAG. These second messengers are important in amine neurotransmission, including that mediated by central adrenoreceptors and muscarinic receptors. 

2. Therapeutic index of lithium and its clinical significance:

The therapeutic index of Lithium is very small, it ranges between 0.5-1.5 mM. >2mM is toxic. It is for this reason that plasma levels should be monitored. 

3. When is Lithium used as a single drug and in which cases and with which drugs is it combined?

Lithium is used as a single drug /monotherapy for the treatment of manic, hypomanic, and acute-manic episodes. Lithium is used in combination with anti-depressants in the treatment of resistant or unipolar depression. 

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

• Diuretics (thiazides), NSAIM's, ACE inhibitors and fluoxetine: increase Li levels = toxicity
• Theophylline and caffeine increase the renal excretion of lithium.
• Neurotoxic combination with carbamazepine, CA2+ blockers, losartan, methyldopa, metronidazole and phenytoin. 
• Traditional anti-depressants worse EPS when used in combination with lithium 

5. Name the major side effects of Lithium:

Tremors, sedation, ataxia, aphasia, muscle weak\ness, fatigue, polydipsia, polyuria, nocturia, nephrogenic diabetes insipidus, thyroid enlargement, leukocytosis, edema, weight gain, acne, alopecia, sexual dysfunction. 

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

During pregnancy, Lithium is safe in the lowest possible dose. However, breastfeeding is not allowed at all. 

7. Name 3 other important indications of lithium

Lithium is used to treat acute mania, manic episodes, hypomanic episodes and is used to prevent relapse in depression. 

8. Case study recommendations: 

The patient's weight gain, fatigue, nausea, shaking and thirst are all adverse effects of lithium due to drug interactions. The "water pills" and the non-steroidal anti-inflammatory Indocid both have adverse interactions with lithium and increase the concentration of lithium. This is what is causing the lithium toxicity and side effects. IO would recommend that the patient stops using her moms water pills and instead of using a NSAIM, she should rather use a different painkiller such as acetaminophen.