• Discuss the possible mechanisms of action of lithium.

The mechanism of action is not well defined. This drug inhibits the action of several enzymes involved in the recycling of neuronal membrane phosphoinositides. This results in the depletion of the second messenger source, PIP2, which will decrease the generation of IP3 and DAG which are important in amine neurotransmission.

 

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

The therapeutic index of Lithium is 0.5-1.5 mM which is very small.

It is used to stabilize the mood swings experienced in patients with Bipolar Disorder.

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

Monotherapy of Lithium is used for Bipolar disorder. Lithium may be combined with Valproate for the treatment of psychiatric symptoms when the patient shows no improvement with monotherapy.

• Name 3 clinically significant interactions lithium may have with other drugs. Illustrate your answer with suitable examples of drugs.
  • Drugs such as diuretics, NSAID’s, ACE inhibitors, and Fluoxetine may increase the Lithium ion levels and can cause toxicity.
  • Theophylline and caffeine can increase the renal excretion of Lithium.
  • Can have neurotoxic effects when used in combination with Carbamazepine, Ca-blockers, Losartan, Methyldopa, Metronidazole, and Phenytoin.

 

• Name the major side effects of lithium.
  • Tremors
  • Sedation
  • Ataxia
  • Aphasia
  • Muscle weakness, fatigue
  • Polidypsia, polyuria, nocturia
  • Nephrogenic diabetes insipidus
  • Thyroid enlargement
  • Leucocytosis
  • Edema
  • Weight gain
  • Acne, alopecia
  • Sexual dysfunction

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

Its use is contraindicated in nursing mothers and the use thereof should be withheld 24-48 hours before delivery. During pregnancy, use of Lithium is thought to increase the incidence of congenital cardiogenic anomalies. The risk for the development of teratogenic effects is low but can contribute to low Apgar scores in neonates.

• Name three other important indications for lithium.
  • Depression
  • Schizophrenia
  • Mania

• 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.

Camcolith is a controlled release Lithium Carbonate drug, her plasma levels were 0.8mMol/L which lies within the therapeutic range (0.5-1.5mMol/L). The weight gain is a common side effect that comes with the use of the Lithium tablets. the diuretics (water pills) can cause an interaction with the Lithium tablets which may cause toxicity. The fatigue, constant thirst, nausea and feeling shaky may be due to dehydration caused by the diuretic tablets due to the increased excretion of water. Indocid is a Non-steroidal anti-inflammatory drug, is also known to have an interaction with Lithium tablets which may increase the plasma levels and cause toxicity. Thus, my recommendation would be to stop the Diuretic tablets (water pills), since the Camcolith shows no toxicity, the patient can continue with usage thereof but should be monitored for toxic effects for the duration of the Indocid therapy. Otherwise the patient should be given a different medication to treat her injury.

Brand, L.Prof.  2021.  Study Unit 9:Anti-psychotic Drugs and Lithium.  Unpublished lecture notes on efundi, FKLG 312.  Potchefstroom: NWU.  [PowerPoint presentation].

Katzung, B.G.  2018.  Basic & Clinical Pharmacology.  14^th ed.  California, San Francisco: McGraw-Hill Companies, Inc.