Pharmacology of methotrexate | methotrexate mechanism of action | methotrexate adverse effects

 Pharmacology of Methotrexate 

Methotrexate is a commonly prescribed medication for various medical conditions, such as cancer, rheumatoid arthritis, and psoriasis. In this article, we will discuss the pharmacokinetics and pharmacodynamics of methotrexate.

1. Pharmacokinetics

a. Absorption mechanism

Methotrexate can be taken orally, intravenously, intramuscularly, or subcutaneously. Oral absorption is limited and highly variable. The medication is rapidly absorbed through intramuscular and subcutaneous routes. Intravenous administration of methotrexate results in complete bioavailability.

b. Distribution in body

Methotrexate is highly protein-bound and is distributed to body tissues such as the liver, kidneys, lungs, and bone marrow. It does not cross the blood-brain barrier efficiently.

c. Metabolism mechanism

Methotrexate undergoes hepatic metabolism through various enzyme systems, such as dihydrofolate reductase and polyglutamation. Polyglutamation is a process that increases the intracellular retention of methotrexate, thereby prolonging its therapeutic effect.

d. Excretion mechanism

Methotrexate is primarily eliminated through renal excretion. In patients with renal impairment, the dosage should be adjusted to prevent toxicity.

2. Pharmacodynamics

a. Mechanism of action

Methotrexate acts by inhibiting the synthesis of nucleotides, thereby interfering with DNA synthesis and cell proliferation. It also has immunosuppressive properties and decreases the production of inflammatory cytokines.

b. Dose required

The dosage of methotrexate varies depending on the medical condition being treated. It is usually administered once weekly for rheumatoid arthritis and once every 2-3 weeks for cancer.

c. Adverse effects

Methotrexate can cause various adverse effects, such as gastrointestinal disturbances, bone marrow suppression, and liver toxicity. Long-term use of methotrexate can also cause pulmonary fibrosis.

d. Contraindications

Methotrexate is contraindicated in pregnant women, patients with hepatic or renal impairment, and those with a history of alcohol abuse.

e. Interactions

Methotrexate interacts with various medications, such as non-steroidal anti-inflammatory drugs, penicillins, and sulfonamides, which can increase the risk of toxicity. It should not be used in combination with other immunosuppressive medications without proper medical supervision.

In conclusion, methotrexate is a widely used medication for various medical conditions. Understanding its pharmacokinetics and pharmacodynamics is crucial to ensure safe and effective use of the medication. Patients taking methotrexate should be closely monitored for adverse effects and should follow their doctor's instructions regarding dosage and administration.