Talk about Lithium Clinical Considerations in Internal Medicine.
Lithium, the third element in the periodic table, shares some properties with elements like sodium and potassium (1 2, 14).
Majorly, lithium is used in hospitals for the treatment of mental disorders. It is used as a mood stabilizer in the treatment and maintenance of bipolar disease (1, 2, 3, 4, 12, 14-16).
In 1949, bipolar disorder therapy was first discovered to be effective.
Because lithium is believed to lower suicide risk in bipolar patients (4, 6, 9,), it has been a preferred drug in bipolar treatment.
Additionally, lithium can be used to treat schizophrenia, depression, schizoaffective disorder, and other mental illnesses (1 2, 3, 6, 7, 8, 9).
This drug profile aims to show the mechanism of lithium’s action, side effects, and toxicities, as well as clinical uses, drug composition, chemical structure, pharmacokinetics and requirements for therapeutic drug monitoring.
Mechanism of Action
It is unclear what the exact mechanism of action of lithium, especially as mood stabilizer (2- 4, 7, 9, 12).
The sodium transport across cell membranes can be altered by lithium. It can also alter serotonin, catecholamine metabolism, and intracellular signaling via the second messengers (9).
The activity of proteins kinase B can be decreased by lithium, which may affect neurotransmission-related genome expression (12).
The cytoprotective protein activity of lithium may be increased, activating a series of growth factors that might enhance neurogenesis activation. This could also increase gray matter and in turn increase neurogenesis activation.
Monoamine neurotransmitters mediate lithium’s synaptic transmission. This can increase the presynaptic degradation of catecholamines, thereby inhibiting transmitters from reaching the synapse, and reduce postsynaptic receptor sensitivity (9, 12).
Numerous studies have demonstrated that lithium can increase brain neuronal serotonin release.
Lithium has been shown to increase the release of serotonin from the synapse by inhibiting 5HT1A/5HT1B receptors. This makes it an antidepressant.
It has been shown that lithium interacts with Nitric Oxide, which signals the pathway in our neural system that plays an important role in neural plasticity (12-13).
Long-term mood stabilization is possible through the modulation of glutamate levels.
Its competing actions with magnesium toward glutamate receptors are the reason for this.
Dopamine transmission can increase during manic episodes. This can lead to depression if it is not controlled using hemostasis (12, 16).
Postsynaptic actions of dopamine are usually controlled by the G-proteins receptors.
As part of the mechanism, lithium may alter certain G-proteins subunits that are linked with dopamine (12).
Hyperreflexia, which is characterized by a patient with highly responsive reflexes and increased muscle strength, white blood cell count, nausea, vomiting, increase thirst, urination, weight gain, confusion, low memory and constipation, are the most common side effects of lithium.
Hypothyroidism and hair loss are some of the side effects that lithium can have on patients.
Other side effects are rare and usually occur in a small percentage of patients who are treated with lithium. These include seizures, renal toxicities, sinus node dysfunction, and coma. Brugada syndrome is a condition that causes abnormal heart rhythms, high levels of magnesium, calcium and thyroid hormones, and an increase in intracranial pressure (1 3, 13, 15).
Bipolar disorders are the most prevalent clinical use of lithium. It is used to stabilize moods ( 1, 2, 3, 4, 5).
Acute manic episodes, treatment for bipolar depression, and bipolar prophylaxis are all common uses of lithium.
Lithium can be used to stabilize mood in acute manic episodes without the need for additional treatments such as antipsychotics or benzodiazepines (13).
Lithium can be used as a mood stabilizer in acute bipolar depression.
When a rapid effect is needed, antidepressants should only be combined with lithium ( 8).
As a prophylaxis, lithium can be continued to treat bipolar disorder episodes that have resolved.
Lithium can also be used to treat resistant depression by augmenting antidepressants (14).
Bipolar disorder sufferers have reported a decrease in suicide attempts due to lithium.
Dosage and available formulation
Tablet form is the most common form of Lithium medicine. They come in different milligrams.
Common milligrams are 300mg (150mg), 450mg, 600mg, and 450mg.
A 5 ml vial of lithium can contain 300mg of lithium (4/5).
The patient’s age and condition will determine the dosage of lithium.
Children under 12 years old receive the full dose.
Acute mania patients usually take 1800mg daily. They are given 600mg orally three times per day, and 900mg twice per day.
A maintenance dose of 900mg daily is recommended for long-term control. The conventional formulation of 300mg oral four times per day ( 4, 5, 6) is also recommended.
Adulthood in bipolar disorder is treated similarly to acute mania.
Dosing should be adjusted to the response to treatment and the lithium serum levels (5).
For long-term control, an alternative dose of 600mg is available in an extended formulation (5).
For children aged 12 and older, the dosage is identical to an adult ( 4).
There is an alternative extended formulation that is 300mg, which is used for long-term control.
Only extended-release formulations are available for severe renal impairment patients.
Avoiding lithium during pregnancy is important (5).
Pharmacokinetic Parameters: Chemical Structures
Above a is the Lithium chemical structure, which is commonly found as Lithium carbonate. The chemical structure can be seen at b) (6)
The gastrointestinal tract absorbs all of the lithium ion.
After 8 hours, the complete absorption occurs. The serum peak at the highest concentration is reached after 2 to 4 hours (7).
Slow-release lithium carbonate preparations have a slower rate of absorption, which quickly decreases the plasma serum peak.
Before it enters the tissues, lithium ions are distributed first to extracellular fluids (7).
Lithium lactate, and lithium salicylate are two other structures that can be used to make lithium salts.
Lithium lactate and Lithium salticylate
When lithium lactate is absorbed into the gastrointestinal tract, it reaches plasma levels in 2 hours. However, the peak of lithium salicylate is typically at 24 hours and is then eliminated quickly (8).
The peak of lithium salicylate, however, is reached 48 hours after it has been absorbed in the gastrointestinal tract and is then eliminated slowly(8).
Smith et.al. conducted a study.
Smith et al. found that lithium carbonate has a higher bioavailability than the other high-quality Lithium salts (8).
Amazing Pharmacokinetic Parameters and Clinical Implications
The serum pick period for slow and controlled lithium releases is approximately 4 to 5 hours after absorption in your gastrointestinal tract (13,15).
Regular preparations of lithium are fast absorbed, with serum levels peaking around 2 hours.
The drug is not metabolized by the liver so it is not affected by any past effects in the alimentary tube (14).
Lithium is not metabolized in the liver and has no clinically important binding properties to proteins (9).
Because most of the Lithium is absorbed in the proximal convoluted tubes, the renal clearance is approximately 20%.
The kidney excretes almost all of the lithium, but some traces are excreted via sweat and feces (2,3,).
The lithium half-life is approximately 24 hours.
Due to a lower infiltration rate at Bowman’s capsule, the half-life of lithium in older patients is slightly longer. It is shorter for youths (3).
It does not have a protein bound characteristic and approximately 80% of the drug is absorbed in proximal convoluted tubes ( 1).
When serum sodium levels drop, the levels of Lithium usually rise. This is due to dehydration (1,3).
Therapeutic Drug Monitoring (TDM), Requirements
Ratanajamit and colleagues wrote a report.
Ratanajamit et al. reported in 2008 that therapeutic drug monitoring of lithium was possible between 2005 and 2006. This report discussed the appropriateness of such monitoring (3).
Study results showed that 41.8 percent of participants suspected toxicities, while 27% required tests. No specific indications were given for the remaining 27%. Serum lithium levels were also reported in 91.
2.2% of patients had not received lithium drug for at least five days during treatment(3).
These dosage modifications (3) are required for 6%.
Before administering the Lithium treatment, it is important to check certain parameters, such as complete blood count, electrocardiogram, baseline creatinine and thyroxin-stimulating hormones.
If the first trimester of pregnancy is associated with Ebstein anomaly, where 1 in 1000 women are affected by lithium, then it should not be used.
Patients receiving lithium treatment should have regular serum levels and kidney function tests. Thyroid hormones can also interfere with the body’s water and sodium regulation.
This is the main cause of lithium-treated patients becoming dehydrated.
Normally, the body’s lithium levels increase when there is dehydration(8).
This is due to the inhibition of antidiuretic hormone through an increase in lithium levels, which inhibits water reuptake by the kidney (11,13).
This led to thirst and a loss of water.
Monitoring lithium can be done by measuring the lithium concentration in serum and blood. The results can then be used as a guide for therapy.
The average serum level of Lithium ranges from 0.5 to 1.44 mmol/l.
It can build up over time. Usually, it takes between 0.5 and 1.4 mmol/l. Typically, this happens after five days.
Overdoses can lead to levels up to 3-10 mmol/l.
The patient should be monitored in facilities that allow for easy monitoring of the plasma ratio.
The normal doses are adjusted to reach the correct levels, which tend to be lower for older patients and higher for young patients.
The absence of psychosis and classic mania, as well as no adverse effects, are indicators that lithium therapy is correct.
Consideration of Lithium in Special Populations
Mild and moderate renal conditions do not require dosage adjustments in renal dose adjustments.
Only severe renal problems will require the extended release formulation. This allows small doses to be started slowly and closely monitored for toxicity (4, 5, 6).
In severe renal dysfunction, immediate release formulations should not be used.
Before the next dose, it is important to check your serum levels.
This can be done within 10 to 12 hours of the last dose.
After three days, the dose is adjusted to correct acute lithium spikes.
After two months, the long-term dose adjustment can be made (5).
Patients with cardiovascular problems should be cautious and their doses must be adjusted (4,5).
Avoiding lithium during pregnancy is a good idea, as it can cause cardiovascular problems, particularly in the first trimester.
Lithium should be avoided in infants as it can cause drowsiness, heart problems, and other side effects that are permanent to the child(2).
Because lithium has metabolic effects on carbohydrates, weight gain can be a serious side effect (2, 9).
Patients with obesity should be cautious as lithium can increase their weight.
Extended-release formulations are recommended (13)
Clinical Considerations in Internal Medicine: Lithium
Oruch R e. Lithium – A review of pharmacology and clinical uses as well as toxicity.
Ratanajamit, C. E. Appropriateness for therapeutic drug monitoring of lithium.
2017 Lithium: Side Effects, Dosage, and Drug Uses.
Lithium Dosage guide with Precautio. 2017.
Lithium – DrugBank 2017 [Internet].
Smith A, Kim S. Tan J, Sneed k, Sanberg P. Borlongan C, et al.
The plasma and brain pharmacokinetics previously unknown lithium salts.
Gitlin M. Lithium toxicities and side effects: Prevalence and management strategies.
International Journal of Bipolar Disorders.
New data on the effects of lithium beyond mood stabilization
Herve D. Inhibition of glycogen synthase Kinase-3 by lithium (GSK-3),: Possible mechanism for therapeutic action of lithium.
Lum G. Lithium Self Intoxication Treatable with Hemodialysis
Toker L, Belmaker RL, Agam G. Gene expression studies to understand the mechanism of lithium’s action.
Expert Review of Neurotherapeutics.
Oruch R. Elderbi M. Khattab H., Pryme 1 and Lund A. Lithium. A review of pharmacology as well as clinical uses and toxicology.
European Journal of Pharmacology.
Hu Q. Lithium. The Literature Concerning Its Uses In Chemistry, Psychiatry and the Engineering of Materials and Batteries.
Science & Technology Libraries.