• Discuss the possible mechanisms of action of lithium.

It is a small monovalent cation that does not produce any acute effect but on prolonged use, acts as a mood stabilizer. It has no psychotropic effect in normal persons. The drug influences the secondary messengers (cAMP,IP3, and DAG) through the lowering of enzymes which is important for the conversion and re-circulation of IP3 and DAG is important in monoamine and cholinergic neurotransmission..

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

Very narrow therapeutic index,monitor carefuly. Plasma concentration of lithium should be 0.5-0.8 mEq/L for maintenance therapy of bipolar disorder and 0.8-1.2 mEq/L for acute mania. Toxic symptoms are seen if plasma concentration exceeds 1.5mEq/L. Lithium is not metabolised by the liver and is as a result safe in patients with liver problems. The half life for lithium is 20 hours.

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

Single

It is the drug of choice for the prophylaxis of bipolar disorder.

Combined

It can be used in acute mania but benzodiazepines like lorazepam must be added (due to the slow action of Li). In patients not controlled by BZDs, antipsychotics like olanzapine may be added.

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

Thiazides - Increased plasma levels of lithium due to decreased total body water. 

ACE inhibitors, angiotensin II receptor antagonists (sartans), diuretics, and non-steroidal anti-inflammatory drugs (NSAIDs).

Medications for depression (Antidepressant drugs) interacts with LITHIUM

Lithium increases a brain chemical called serotonin. Some medications for depression also increase the brain chemical serotonin. Taking lithium along with these medications for depression might increase serotonin too much and cause serious side effects including heart problems, shivering, and anxiety. Do not take lithium if you are taking medications for depression.
Some of these medications for depression include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), amitriptyline (Elavil), clomipramine (Anafranil), imipramine (Tofranil), and others.

Medications for depression (MAOIs) interacts with LITHIUM

Lithium increases a chemical in the brain. This chemical is called serotonin. Some medications used for depression also increase serotonin. Taking lithium with these medications used for depression might cause there to be too much serotonin. This could cause serious side effects including heart problems, shivering, and anxiety.
Some of these medications used for depression include phenelzine (Nardil), tranylcypromine (Parnate), and others.

• Name the major side effects of lithium.
  • Increased tremors (Most common side effect)
  • Hypothyroidism
  • Increased urine - Nephrogenic diabetes insipidus, can be used for the treatment of SIADH.  Amiloride is DOC for lithium-induced DI.

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

Should be avoided in expectant Mothers as it causes Ebstein’s anomaly. 

• Name three other important indications for lithium.

Leucocytes are Useful in the treatment of cancer chemotherapy-induced leucopenia.

• 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:

My recommendation is to immediately  stop the NSAIM and diuretic treatment to prevent further side-effects. Decrease the current dose to only once per day, or if it is possible for the patient, change treatment to Valproate or Carbamasepine seeing as both are mood stabilisers