LITHOSUN SR

Indications

• Treatment of mania
• Treatment of bipolar disorder
• Prophylaxis of recurrent depression
• Prophylaxis of aggressive or self-harming behavior

Dosage

Children: Dose adjusted according to serum-lithium concentration; doses are initially divided throughout the day, but once daily administration is preferred when serum-lithium concentration is stabilized.

Adults: Initially 450–675 mg twice daily, adjusted according to serum-lithium concentration; doses are initially divided throughout the day, but once daily administration is preferred when serum-lithium concentration is stabilized.

Mechanism of action

Lithium exerts its therapeutic effects primarily through the inhibition of inositol monophosphatase and the modulation of glutamate levels in the brain. It influences intracellular signaling pathways, particularly those involving phosphoinositide metabolism, which plays a crucial role in synaptic transmission and neuroprotection. Additionally, lithium affects the serotoninergic and dopaminergic systems, contributing to mood stabilization.

Pharmacodynamics

Lithium's pharmacodynamic profile includes mood stabilization, reduction in the frequency and severity of manic episodes, and prevention of recurrent depressive episodes. Its effects are attributed to alterations in neurotransmitter levels and synaptic function, particularly through increased serotonin receptor sensitivity and decreased norepinephrine release.

Pharmacokinetics

Lithium is absorbed quickly from the gastrointestinal tract, with peak plasma concentrations occurring within 1-3 hours post-administration. It has a volume of distribution of about 0.7 L/kg and is primarily excreted unchanged by the kidneys. The half-life of lithium varies but is approximately 24 hours in patients with normal renal function. Serum lithium levels must be monitored to avoid toxicity, with therapeutic ranges typically between 0.6 and 1.2 mmol/L.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Dizziness
• Tremors
• Weight gain
• Thyroid dysfunction
• Nephrotoxicity
• Cardiac arrhythmias
• Cognitive impairment

Interactions

• Diuretics may increase the risk of lithium toxicity
• Non-steroidal anti-inflammatory drugs (NSAIDs) may increase lithium levels
• Antidepressants may interact with lithium, especially SSRIs
• Antiepileptic drugs may alter lithium levels

Precautions

• Monitor renal function regularly
• Assess thyroid function periodically
• Use caution in patients with cardiovascular disease
• Monitor sodium intake as it affects lithium levels
• Adjust dosage in elderly patients due to decreased renal function

Pregnancy

Lithium should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Risks include teratogenic effects, particularly during the first trimester.

Breast-feeding

Lithium is excreted in human milk. Caution is advised when administering to nursing mothers, and monitoring of the infant for signs of lithium toxicity is recommended.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Lithium citrate 250 mg tablets
• Lithium citrate liquid formulation

Mechanism of action

Carbonate ions participate in buffering reactions that help maintain pH homeostasis in biological systems. They can react with acids to form bicarbonate and carbon dioxide, thus neutralizing excess acidity in the body. This mechanism is crucial in processes such as respiration and metabolism.

Pharmacodynamics

As a buffer, carbonate helps to stabilize pH levels in different biological environments, preventing excessive acidity or alkalinity that could impair cellular functions. It is involved in the transport of carbon dioxide in the blood and plays a role in maintaining the acid-base equilibrium necessary for physiological processes.

Pharmacokinetics

Carbonate ions are readily absorbed in the gastrointestinal tract when ingested and can be found in various body fluids. They are involved in the bicarbonate buffering system, where they are converted to bicarbonate (HCO3-) and carbon dioxide (CO2) through reactions with acids. The kidneys regulate the levels of bicarbonate and carbonate in the body, excreting or reabsorbing them as needed to maintain homeostasis.

Pregnancy

There is no specific information available regarding the use of carbonate compounds during pregnancy. Consult a healthcare provider for advice.

Breast-feeding

There is no specific information available regarding the use of carbonate compounds while breastfeeding. Consult a healthcare provider for advice.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Bipolar disorder
• Acute mania
• Adjunctive treatment for depression

Dosage

Children: Refer to the BNF for Children for specific dosing information for paediatric patients, as it varies based on age and weight.

Adults: The usual starting dose for the treatment of acute mania is 900 to 1200 mg per day, divided into two or three doses. Maintenance doses usually range from 600 to 900 mg per day, adjusted based on serum lithium levels.

Mechanism of action

The exact mechanism of action of lithium is not fully understood. However, it is believed to influence neurotransmitter release and receptor sensitivity, particularly in relation to serotonin and norepinephrine. Lithium also affects second messenger systems, particularly inositol monophosphate and cyclic AMP, which play critical roles in neuronal signaling and mood regulation.

Pharmacodynamics

Lithium exhibits mood-stabilizing effects, decreasing the severity and frequency of mood swings in individuals with bipolar disorder. It has anti-manic effects that can lead to a reduction in symptoms such as euphoria, irritability, and hyperactivity. Lithium also has neuroprotective properties and may enhance neuronal survival and function.

Pharmacokinetics

Lithium is absorbed from the gastrointestinal tract and achieves peak plasma concentrations within 1 to 3 hours after oral administration. It has a volume of distribution of approximately 0.7 L/kg and is primarily excreted unchanged by the kidneys. The half-life of lithium can vary from 18 to 36 hours, and it requires careful monitoring to maintain therapeutic levels, as the therapeutic range is narrow.

Contra-indications

• Severe renal impairment
• Cardiovascular disease
• Dehydration
• Hypersensitivity to lithium

Adverse effects

• Nausea
• Diarrhea
• Tremors
• Weight gain
• Polyuria
• Thyroid dysfunction
• Cognitive impairment
• Kidney damage

Interactions

• mexiletine: Severe (affects exposure)
• ace inhibitors: Moderate (increases concentration)
• metronidazole: Moderate (increases concentration)
• tetracyclines: Moderate (increases risk of lithium toxicity)
• theophylline: Moderate (decreases concentration)
• acetazolamide: Unknown (affects concentration)
• aminophylline: Unknown (decreases concentration)
• sodium bicarbonate: Unknown (decreases concentration)
• zuclopenthixol: Unknown (increases risk of neurotoxicity)
• eplerenone: Unknown (increases concentration)

Precautions

• Monitor renal function regularly
• Assess thyroid function prior to treatment
• Careful use in patients with cardiovascular conditions
• Ensure adequate hydration
• Monitor for signs of lithium toxicity

Pregnancy

Use with caution, potential risk of teratogenic effects. Monitor closely if used during pregnancy.

Breast-feeding

Lithium is excreted in breast milk. Caution is advised; monitor infant for signs of toxicity.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Oral tablets
• Oral solution