lithium

Actions and Spectrum: 

lithium is a highly reactive alkali metal found in the periodic table with the atomic number 3. It exhibits a range of fascinating chemical and physical properties. From an action perspective, lithium is known for its powerful reducing properties. It readily donates its single valence electron, making it highly reactive and capable of forming ionic solid bonds with other elements.

This reactivity is most notable when lithium reacts with water, as it vigorously reacts to produce lithium hydroxide and hydrogen gas. The reaction is so exothermic that it can ignite the hydrogen gas, resulting in a fiery display. In terms of its spectrum, lithium displays a distinctive emission spectrum when excited. lithium atoms become excited and transition to higher energy states when subjected to a flame or electrical discharge. As they return to their ground state, they release energy in the form of light.

The emitted light corresponds to specific wavelengths, producing a characteristic spectrum with bright lines. In the case of lithium, these lines appear in the red portion of the electromagnetic spectrum. The red emission lines of lithium are commonly used in spectroscopy and flame tests to identify the presence of lithium in compounds or solutions. This unique spectrum allows for the identification and analysis of lithium in various scientific and industrial applications. 

DRUG INTERACTION

Frequency defined 

>10% 

Headache  

Dry mouth  

Leukocytosis 

Polyuria 

Nausea, vomiting, diarrhea 

Hand tremor 

Electrocardiographic changes 

Confusion  

Muscle twitch 

Vertigo 

Hyperreflexia 

Diminished memory  

Muscle weakness 

1-10% 

Hair thinning  

Extrapyramidal symptoms, goiter  

Acne  

Hypothyroidism 

Frequency not defined 

lithium-induced polyuria 

Ataxia/gait disturbance 

Renal toxicity 

Coma 

Lethargy 

Seizures 

Acute lithium toxicity 

Black Box Warning: 

• lithium Toxicity: lithium has a narrow therapeutic index, meaning there is a slight difference between the practical and toxic doses. Excessive levels of lithium in the blood can lead to lithium toxicity, which can be life-threatening.  
• Kidney Function: Long-term use of lithium can be associated with kidney damage, especially if high lithium levels persist in the blood.  
• Thyroid Disorders: lithium can interfere with thyroid function and may lead to hypothyroidism (underactive thyroid) in some individuals.

Contraindication/Caution: 

Contraindication 

• Renal Impairment: lithium is primarily excreted by the kidneys. Therefore, individuals with significant renal impairment or a history of renal disease may be at higher risk of lithium toxicity due to decreased drug clearance. It is important to monitor kidney function regularly in patients taking lithium. 
• Cardiovascular Disease: lithium has been associated with specific cardiovascular effects, including changes in heart rhythm. Individuals with pre-existing cardiovascular conditions, such as heart disease or arrhythmias, may be at increased risk of adverse cardiovascular effects when taking lithium. 
• Thyroid Disorders: lithium can interfere with thyroid function and may cause hypothyroidism (underactive thyroid) in some individuals. Patients with a history of thyroid disorders or those taking medications for thyroid conditions should be closely monitored when prescribed lithium. 
• Pregnancy and Breastfeeding: The use of lithium during pregnancy and breastfeeding is a complex topic. lithium has been associated with potential risks to the developing fetus, including cardiovascular malformations. It is generally recommended to weigh the potential benefits against the risks and consult a healthcare professional to determine the best action for pregnant or breastfeeding individuals. 
• Sodium Imbalance: lithium can affect sodium levels in the body. Individuals with hyponatremia (low sodium levels) or conditions that may lead to electrolyte imbalances should exercise caution when using lithium as it may exacerbate these conditions. 

Caution 

• Kidney Function: lithium is primarily eliminated through the kidneys, so it is essential to monitor kidney function regularly. Impaired renal function can lead to increased lithium levels in the blood, which may result in toxicity. Therefore, individuals with compromised kidney function should be closely monitored and may require lower doses of lithium. 
• Dehydration: Dehydration can affect lithium levels in the blood, leading to increased toxicity. Staying adequately hydrated while taking lithium is essential, especially during hot weather, exercise, or illnesses that cause fluid loss. 
• Sodium Levels: lithium can affect sodium balance in the body. Low sodium levels (hyponatremia) can increase the risk of lithium toxicity, while high sodium levels (hypernatremia) can decrease lithium effectiveness. Sodium levels should be monitored regularly, and any imbalances should be addressed appropriately. 
• Drug Interactions: lithium can interact with various medications, including diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), and certain antidepressants. These interactions can alter lithium levels in the blood or increase the risk of adverse effects. Before starting lithium, it is crucial to inform healthcare providers about all medications, including over-the-counter drugs and supplements. 
• Thyroid Function: lithium can interfere with thyroid function, leading to hypothyroidism in some individuals. Thyroid function should be monitored regularly, especially in individuals with a history of thyroid disorders or those taking other medications that affect thyroid function. 
• Pregnancy and Breastfeeding: As mentioned earlier, the use of lithium during pregnancy and breastfeeding requires careful consideration. The potential risks and benefits should be evaluated, and healthcare providers should be involved in making decisions regarding lithium use in these situations. 
• Elderly Population: Elderly individuals may be more susceptible to lithium’s side effects, including neurological symptoms and kidney impairment. Dose adjustments and close monitoring are essential when prescribing lithium to older adults. 

Pregnancy consideration:  

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk: Yes 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category 

Pharmacology: 

lithium exerts its pharmacological effects through various mechanisms. It is thought to modulate neurotransmitter systems, including serotonin and norepinephrine, and inhibit the enzyme glycogen synthase kinase-3 (GSK-3). These actions contribute to the mood-stabilizing properties of lithium. lithium alters intracellular signaling pathways, such as the inositol phosphate pathway, leading to changes in neuronal excitability and synaptic plasticity. It also influences neuroprotective mechanisms, mitochondrial function, and gene expression.  

Pharmacodynamics: 

Mechanism of action: The exact mechanism of action of lithium in the treatment of bipolar disorder and other types of mental health conditions is not fully understood.  

• Modulation of Neurotransmitters: lithium may modulate the activity of neurotransmitter systems, including serotonin and norepinephrine. It is thought to enhance the reuptake of these neurotransmitters, leading to increased availability and regulation of their signaling pathways. This modulation of neurotransmitter activity may contribute to the mood-stabilizing effects of lithium. 
• Inhibition of Glycogen Synthase Kinase-3 (GSK-3): lithium inhibits the enzyme GSK-3, which plays a crucial role in various cellular processes, including signaling pathways related to mood regulation, neuronal development, and synaptic plasticity. By inhibiting GSK-3, lithium may influence these pathways, leading to changes in neuronal function and mood stabilization. 
• Modification of Intracellular Signaling Pathways: lithium affects intracellular signaling pathways, such as the inositol phosphate pathway. It reduces inositol triphosphate (IP3) levels, leading to alterations in neuronal excitability and neurotransmitter release. These changes in signaling pathways may contribute to the therapeutic effects of lithium. 
• Neuroprotective Effects: lithium has been shown to exhibit neuroprotective properties, potentially influencing neuronal viability, cellular resilience, and the maintenance of neuronal structure and function. It may enhance cellular defense mechanisms against oxidative stress and inflammation, promoting neuronal health and survival. 
• Gene Expression Regulation: lithium has been found to affect gene expression and the activity of various transcription factors. It may modulate gene expression in neuroplasticity, cell survival, and mood regulation. These effects on gene expression can contribute to the long-term therapeutic actions of lithium. 

Pharmacokinetics: 

Absorption 

lithium is well-absorbed after oral administration. It is primarily absorbed in the small intestine, with peak plasma concentrations achieved within 2 to 4 hours after ingestion. Food intake can affect the rate and extent of absorption, with higher absorption occurring when lithium is taken with meals. 

Distribution 

lithium is widely distributed throughout the body due to its small size and ionic nature. It readily crosses cell membranes, including the blood-brain barrier, and distributes into various tissues, including the brain, muscles, and kidneys. It does not bind extensively to plasma proteins, allowing it to exist in a free and ionized form in the blood. 

Metabolism 

lithium is not extensively metabolized in the body. It undergoes minimal hepatic metabolism and primarily undergoes renal excretion unchanged. However, it is essential to note that the pharmacological actions of lithium are not solely dependent on metabolic transformation but rather on its direct interactions with cellular components. 

Elimination and Excretion 

The primary route of lithium excretion is via the kidneys. The glomerulus filters it and undergoes reabsorption and secretion along the renal tubules. The renal clearance of lithium is influenced by factors such as renal function, sodium intake, and fluid balance. Any impairment in renal function can lead to reduced lithium clearance, potentially increasing the risk of lithium accumulation and toxicity. 

Administration: 

Oral administration 

lithium is typically administered orally as lithium carbonate or lithium citrate. Following the prescribed dosage and administration instructions a healthcare professional provides is essential.  

• Dosage: lithium dosage varies depending on the individual’s condition, age, kidney function, and other factors. Following the prescribed dosage and not exceeding or reducing it without medical guidance is crucial. 
• Timing: lithium is usually divided throughout the day to maintain stable blood levels. This helps to minimize fluctuations and reduce the risk of side effects. The daily dose may be divided into two to three doses, taken with meals or as directed by a healthcare professional. 
• Regular Monitoring: Regular monitoring of lithium blood levels is essential to ensure the medication’s effectiveness and safety. Blood tests are typically performed every few months initially and then periodically to maintain therapeutic levels and avoid toxicity. Compliance with blood testing is crucial for adjusting the dosage as needed. 
• Hydration: Adequate hydration is essential while taking lithium. Maintaining a consistent and appropriate fluid intake is recommended to avoid dehydration, especially during periods of increased physical activity, hot weather, or illness. Dehydration can affect lithium levels in the blood, potentially leading to toxicity. 
• Food and Sodium Intake: Taking lithium with meals can help reduce gastrointestinal side effects. Additionally, maintaining a consistent sodium intake is vital as both low and high sodium levels can affect lithium levels in the body. Following dietary recommendations regarding sodium intake is advisable, and consult with a healthcare professional if any significant dietary changes are planned. 
• Adherence: It is crucial to adhere to the prescribed treatment plan and not discontinue or adjust the lithium dosage without consulting a healthcare professional. Suddenly stopping lithium or making significant changes can lead to a recurrence of symptoms or other complications. 

Patient information leaflet 

Generic Name: lithium 

Pronounced: [ LITH-ee-um ] 

Why do we use lithium? 

lithium has several medical and industrial uses.  

• Treatment of Bipolar Disorder: lithium is one of the primary drug used to treat bipolar disorder. It helps to stabilize mood, reducing the frequency and severity of manic and depressive episodes. lithium can be an effective mood stabilizer in both acute and maintenance therapy of bipolar disorder. 
• Depression Augmentation: In some cases, lithium is also used as an augmentation strategy for treating depression that has not responded adequately to other antidepressant medications. It can be prescribed alongside antidepressants to enhance their effectiveness. 
• Other Mental Health Conditions: lithium may treat other mental health conditions, like schizoaffective disorder and certain types of recurrent depression. A healthcare professional determines its specific use in these conditions based on individual patient needs. 
• Research and Therapy: lithium is also used in scientific research to investigate its mechanisms of action and potential therapeutic applications. Studies are ongoing to explore its potential benefits in neuroprotection, Alzheimer’s disease, and other neurological disorders.