Blog #13 (SU 9.5)

• Discuss the possible mechanisms of action of lithium.

Lithium influences the second messenger systems decreasing their sources and thus decreases the generation of IP₃ and DAG. These second messengers are important for amine neurotransmission and influences multiple neurotransmission processes.

 

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

The therapeutic index of lithium is between 0.5 – 1.5millimolar. Lithium has a narrow therapeutic index. The clinical significance of this is that the drug is only effective between the limit of the therapeutic index, if the plasma level of lithium is below the therapeutic index no clinical effect is seen and if the plasma level of lithium is above the therapeutic index a toxic effect will be seen at as little as 2millimolar. 

 

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

Lithium is used as a single drug in the treatment of bipolar disorder.

Lithium is used in combination with valproate or carbamazepine in the treatment of psychiatric symptoms.

Lithium is also used in combination with olanzapine or quetiapine for treatment of acute mania.

 

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

• Lithium in combination with diuretics (e.g. thiazides), NSAIDs, ACE inhibitors and fluoxetine can cause dehydration and electrolyte imbalances causing toxic levels of lithium.
• Lithium in combination with caffeine, theophylline or anti-acids cause increased excretion of lithium in the urine, decreasing plasma lithium and lowering the clinical effects of lithium.
• Lithium in combination with typical antipsychotics (e.g. chlorpromazine) increase extrapyramidal side effects.
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• Name the major side effects of lithium.

• Sedation
• Tremor
• 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?

Lithium is not safe to use during pregnancy and lactation. Taking lithium during early stages of pregnancy increases the risk that your baby’s heart does not develop properly. Breastfeeding while on lithium can cause heard defects in your baby.

 

• Name three other important indications for lithium.

Schizophrenia

Depression

Psychosis

 

• 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 600mg tablets contain lithium carbonate, which is used to treat and prevent mania, bipolar disorder and depression in adults. For acute symptoms the target plasma therapeutic concentration is 8-12mmol/L and maintenance is 0.4-0.7mmol/L. The plasma levels of Ms Polar is 0.8mmol/L, this plasma concentration exceeds the prescribed therapeutic index of lithium. This can be a result of the NSAI-drug, Indocid® (Indocid® is used for pain, swelling and joint stiffness caused by arthritis or gout. It is an anti-inflammatory drug), she is taking, the NSAID together with the lithium causes electrolyte changes and dehydration and thus also an increase in lithium plasma levels.

This increase in the lithium ion plasma levels and cause adverse side effects, such as weight gain, fatigue, sedation, polydipsia (thirsty) and tremors.

The “water pill” (a diuretic) of her mother’s she is taking in hopes that it will help her lose weight only worsens her symptoms because diuretics increase the lithium ion levels and cause adverse side effects.

Therefore, Ms Polar’s physician needs to re-evaluate her antipsychotic as to not cause adverse effects with her NSAID or she needs to use an alternative pain killer (not a NSAID) and she needs to stop using the diuretic if she remains on the lithium.

 

Reference list.

Brand, L. 2021. SU 9 Antipsychotic Drugs and Lithium. https://efundi.nwu.ac.za/access/lessonbuilder/item/6005036/group/dd46f2da-d3be-402e-9ba7-2c5955cedd9d/English%20power%20point/English%20PP%202021/SU%209.pdf Date of access: 26 Apr. 2021. [PowerPoint presentation]

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