Pharmacology
Summary
Bipolar disorder, once referred to as manic-depressive illness, is distinctly separate from schizophrenia and is characterized by manic and depressive periods. Lithium, known for its mood-stabilizing effects, was the first treatment used to manage these swings. Regarded as the "lithium lift-ium", it sees use both in treating acute mania and as a prophylaxis to prevent mania and depression in bipolar patients. Lithium's mood-stabilizing effect originates from its ability to inhibit certain signal transduction pathways, such as the inositol triphosphate pathway and protein kinase pathways.
Lithium comes with a narrow therapeutic index, necessitating frequent monitoring of therapeutic levels to avoid toxicity. Toxic levels can induce GI symptoms, tremors, confusion, and ataxia. Furthermore, extended use of lithium has been associated with thyroid function disruption, leading to symptoms such as weight gain, dry skin, hair loss, and constipation. Lithium can also cause a condition known as diabetes insipidus because it reduces the kidney's ability to concentrate urine. Notably, lithium is not metabolized; rather, it is substantially excreted in the urine, so factors affecting kidney function, like diuretics and NSAIDs, can affect lithium levels. Lithium has also been linked to fetal malformations, such as Ebstein's anomaly. Other treatments for bipolar disorder include valproate, carbamazepine, lamotrigine, and antipsychotics, which can be used to manage acute mania.
Lesson Outline
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FAQs
Bipolar disorder can be effectively managed with mood stabilizers such as lithium, valproate, carbamazepine, and lamotrigine. Additionally, both first-generation (e.g. haloperidol) and second-generation antipsychotics (e.g., quetiapine) are prescribed for acute mania. Notably, while lithium, valproate, and carbamazepine are used for acute mania and maintenance, lamotrigine is typically reserved for maintenance therapy alone.
Lithium serves as a pivotal mood stabilizer for acute mania episodes and long-term maintenance in bipolar disorder. Because of its very narrow therapeutic index, the dosage and blood levels need meticulous monitoring to avoid potential toxicity.
Acute lithium toxicity primarily presents with gastrointestinal symptoms, notably nausea, vomiting, and diarrhea. Chronic toxicity, on the other hand, leads to neurological complications such as tremors and ataxia. It's imperative to recognize and manage these symptoms early, given lithium's narrow therapeutic window.
Lithium therapy can induce hypothyroidism, characterized by symptoms like weight gain, dry skin, hair loss, and constipation. In terms of renal effects, lithium can precipitate nephrogenic diabetes insipidus. This effect is further compounded when co-administered with medications like thiazide diuretics, which elevate lithium levels, or NSAIDs, which reduce lithium clearance by decreasing GFR.
Lithium is teratogenic and is associated with Ebstein's anomaly, a congenital heart defect marked by atrialization of the right ventricle. Given the potential risks, it's recommended to be cautious with lithium use during pregnancy, especially in the first trimester.
