• Discuss the possible mechanisms of action of lithium.

• Mediated by Li+
• Suppresses IP3 & DAG 2^nd messenger systems by decreasing various enzymes important for conversion & re-circulation of membrane phosphoinositide’s

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

narrow therapeutic index of 0.5-1.5mM, anything more than 2mM = toxic

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

Single Drug: prophylaxis of manic and hypomanic episodes and for treatment of acute mania.

Combined: treatment of resistant depression and aggressive behaviour

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

• In combination with a Thiazides, NSAID, ACE inhibitor and fluoxetine it increases lithium levels and leads to toxicity.
• In combination with xanthine’s, can increases renal excretion of lithium and decrease its effect.
• In combination with antipsychotic drugs, it worsens EPS.

• Name the major side effects of lithium.

• Tremor
• Sedation
• Ataxia, aphasia, m weakness, fatigue, choreoathetosis, motor hyperactivity
• Polyuria, polydipsia & nocturia
• Oedema
• Hypothyroidism
• Li-induced diabetes insipidus
• Transient acneiform eruptions
• Leucocytosis
• Folliculitis, Acne, Alopecia
• Sexual dysfunction
• Increase weight
• Renal dysfunction & Dysrhythmias

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

• The use of lithium during lactation is not encouraged. Pregnancy category D

• Name three other important indications for lithium.

• Bipolar disorder
• Schizoaffective disorder
• Major depression

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.

 

The patient has increasing levels of Lithium because of the use of the NSAIDS and water pills creating toxic levels of Lithium which could explain the side effects she is facing. Therefore, I would prescribe another drug for her muscle injury such as paracetamol or Mephenesin. Stopping the water pills and a correct monitored diet could help with the weight loss. Lithium could be causing the fatigue thirstiness and other side effects

Brand, L. 2021. Antipsychotic drugs and lithium salts. SU. 9 [PowerPoint Presentation]. Unpublished Lecture Notes on eFundi, FKLG 312. Potchefstroom, NWU.

Katzung, B.G. 2018. Basic and Clinical Pharmacology. 14^th ed. United States of America: McGraw-Hill Education