1. Discuss the possible mechanisms of action of lithium.

Lithium ion: Affects cAMP, IP3 and DAG second messenger systems, the latter by lowering several enzymes that are important in the conversion and recycling of membrane phosphinocytes. IP3 and DAG are important in monoamine and cholinergic neurotransmission.

2. What is lithium's therapeutic index and what is its clinical significance?

The therapeutic index is 0.5 - 1.5 mM and anything more than 2 mM can be toxic. It therefore possesses a very narrow or small therapeutic index and can very quickly lead to toxic plasma concentrations. It is therefore important to monitor and monitor blood plasma levels regularly to prevent toxicity due to Lithium.

3. When is lithium used as a single agent and in what cases and with what type of agents is lithium combined?

Lithium is used as a single agent for anti-manic and anti-depressant effects during acute or maintenance phases.

Valproate is used in combination with Lithium for acute manic phase, when the patient does not respond to Lithium.

4. Name 3 clinically significant interactions that lithium may have with other drugs. Illustrate your answer with appropriate drug examples.

• Interactions with diuretics (thiazides), NSAIDs, ACE inhibitors and Fluoxetine increase Lithium levels and may lead to toxicity.
• Interactions with antacids (eg na - bicarbonate), theophylline and caffeine increase renal excretion of lithium in other words decrease the effectiveness of lithium.
• Interactions with Carbamazepine, Calcium channel blockers, Losartan, Methyldopa, Metronidazole and Phenitoin lead to neurotoxicity.
• Interactions with traditional antipsychotics exacerbate extra pyramidal effects in combination with Lithium.

5. Name the most important side effects of lithium.

• Tremore
• Sedation
• Ataxia
• Aphasia
• Muscle weakness
• Fatigue
• Polydipsia
• Polyuria
• Nocturne
• Nephrogenic diabetes insipidus
• Thyroid enlargement
• Leukositoses
• Edema
• Mass increase
• Acne
• Alopecia
• Sexual dysfunction

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

Lithium can lead to lithium toxicity in unborn baby and cause abnormalities such as underdeveloped heart, or affect development of unborn baby's heart.

7. Name 3 other important indications for lithium.

• Anti - depressant
• Schizophrenia
• Mood Stabilizers

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

Ms B. Polar (21 years, 60kg) is a student and has been using the following medication for the past 2 months:

Camcolit 600mg bd. Plasma levels taken after two weeks were 0.8mmol / L. She suffered a muscle injury and has also been using Indocid R® 75mg for the past 10 days. Upon further inquiry, she states that she has "gained an awful lot of weight" and is now simply drinking from her mother's "water pills" in the hope that she can get rid of the extra kilos. However, she complains that she is very tired, struggling to keep her eyes open in class, staying thirsty and constantly shaking and feeling nauseous.

Recommendations:Blood plasma levels fall within the range of the therapeutic index, from 0.5 - 1.5 mmol per liter. My suggestion would be to stop taking the diuretics immediately as it interacts with the Lithium medication. This can lead to an elevated blood plasma level of Lithium which can eventually lead to toxicity. Weight gain is one of the side effects of using Lithium. The non-steroidal anti-inflammatory (NSAIDs) medication, such as Indocid, also interacts with Lithium. It increases blood plasma levels of Lithium and can lead to toxicity. The diuretics therefore increase the excretion of water in the body and her fatigue, nausea, shakiness and dry mouth symptoms can therefore be attributed to it due to some degree of dehydration.