Discuss the possible mechanisms of action of lithium.
The possible mechanism of action of lithium is that it influences the secondary messengers (cAMP,IP3, and DAG) through the lowering of enzymes which is important for the conversion and re-circulation of membrane phospoinositides.IP3 and DAG is important in monoamine and cholinergic neurotransmission.

What is the therapeutic index of lithium and what is its clinical significance?
It has a small therapeutic index and therefor plasma concentration should be monitored carefully. Toxic levels could be reached easily. Lithium is not metabolised bu the liver and is safe in patients with liver problems. The half life for lithium is 20 hours daily doses are sufficient. 

When is lithium used as single drug and in which cases and with which type of drugs is lithium combined?
Clonazepam , Lorasepam and Lithium is used in combination for Bipolar disorder.
Lithium is used as monotherapy can be used for preventing mood instability or acute mania. 

Name 3 clinically significant interactions lithium may have with other drugs. Illustrate your answer with suitable examples of drugs.
Lithium has interactions with theophylline which increases the renal excretion of Lithium
Lithium in combination with Carbamazepine or Ca2+ blockers , losartan, methyldopa, metronidazole and pehnytoin can be neurotoxic.
Lithium in combination with Anti-psychotic drugs worsen extra pyramidal effects. 

Name the major side effects of lithium.
Tremors, aphasia and Sexual dysfunction.

What is the status of the use of lithium during pregnancy and lactation?
Lithium is effective for Bipolar disorder during pregnancy but it is not safe. The Baby's heart might not develop properly.

Name three other important indications for lithium.
Manic disorders (Such as manic depressive illness), anxiety, mood stabilizer or even suicidal.

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.

Camcolit is a controlled release lithium carbonate drug and Indocin is an NSAID (indomethacin). NSAIDS has an interaction with lithium. It increases Lithium levels and toxicity could be reached.One of the Lithium toxicity symptoms is weight gain. Water pills = Diuretic. Diuretic drugs are mainly for high blood pressure, there are no significant evidence for weight loss. That being said the diuretic lowerd her blood pressure and it lead to fatique due to low cerebral blood flow hence why she cant focus in class. NSAIDS and Lithium is the same as Diuretics and Lithium- both lead to toxic levels of lithium. Toxic levels of lithium causes tremors (shake of student), the body notice the toxic levels in the body and want to get rid of it (stimulating CTZ- Vomiting centre) which makes her feel nauseous.