Lithium Pharmacology - Indications, Mechanism Of Action, Adverse Effects & Toxicity

Wed, 20 Aug 2025 18:24:01 +0000

Lithium, is a medication used as a mood stabilizer in the treatment of bipolar disorder.
In addition, it is used in the management of acute manic episodes, treatment of resistant depression and resistant schizophrenia.
Bipolar disorder is a condition characterized by periods of lowered mood and depression, as well as periods of heightened mood and mania.
In bipolar disorder, individuals can have dramatic shifts in emotions, mood, and energy levels.
Lithium is one of the oldest and most effective medications in the treatment of bipolar disorder.
It decreases the frequency and magnitude of these ups and downs.
The exact mechanism by which lithium does this is not known.
However, it is thought that it regulates the release of neurotransmitters within the brain.
So, let’s first discuss the mechanism of neurotransmitter release at a synapse.
First, inositol, a carboxylic sugar is converted into phospho-inositol by adding a phosphate group.
Phospho-inositol is then converted to phospho-inositol-4-phosphate by adding another phosphate group.
Then, a 3rd phosphate group is added to form phospho-inositol-4,5-bisphosphate.
Then, a membrane-bound enzyme called phospho-lipase C, splits phospho-inositol-4,5-bisphosphate into diacylglycerol, or DAG, and inositol triphosphate, or IP3.
IP3 increases the intracellular calcium levels, which triggers the release of neurotransmitters to the synaptic cleft.
However, IP3 should be converted back to inositol before it can be used again.
IP3 is dephosphorylated to form IP2, and then into IP1, by an enzyme called inositol phosphate phosphatase, and ultimately into inositol by the enzyme inositol mono-phosphatase.
It is postulated that lithium inhibits these enzymes and prevents recycling of inositol, which will lead to decreased neurotransmitter release.
Lithium is taken orally, and it is absorbed rapidly into the blood.
It is not metabolized by the liver and eliminated exclusively by the kidneys.
Lithium has a narrow therapeutic window.
Therefore, blood levels should be monitored closely.
Some common adverse effects of lithium include the following.
Gastrointestinal disturbances such as nausea and vomiting, and diarrhea.
Tremors.
Nephrogenic diabetes insipidus, where the individuals have increased urine output, also known as polyuria, and increased thirst, also called polydipsia.
This adverse effect of lithium is due to the inhibition of ADH hormone by the drug.
Lithium also blocks the hormone TSH, which stimulates the thyroid gland to secrete thyroid hormones.
This will lead to hypothyroidism.
Lithium also causes increased white blood cells, more specifically lymphocytes.
Lithium is not safe to use during pregnancy since it increases the risk of congenital heart defects in the baby.
Finally, if lithium in blood rises to toxic levels, it can cause acute renal failure, and severe neurological complications like ataxia, confusion, inability to speak, coma, and even death.

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