Methotrexate – a double edged sword
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This document discusses the risks of methotrexate toxicity and ways to prevent it. It notes that methotrexate can cause severe side effects like mucositis, stomatitis, and myelosuppression. Risk factors for toxicity include increased free plasma levels due to drug interactions or protein deprivation, and decreased renal elimination in older patients or those with renal failure. To prevent toxicity, the document recommends careful counseling of patients about dosages, emphasizing the weekly schedule, and using tools like daily pill containers to help patients track their doses correctly. Close monitoring of patients and involving relatives can help reduce medication errors.
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This document discusses immunosuppressant drugs. It begins by defining immunosuppression and immunosuppressants. The primary use of immunosuppressants is to prevent rejection after organ transplantation by lowering the body's immune response. The document then categorizes immunosuppressants and discusses their mechanisms of action. The main categories are selective inhibitors of cytokine production/function, immunosuppressive antimetabolites, antibodies, and corticosteroids. Examples like cyclosporine, tacrolimus, sirolimus, azathioprine, and prednisone are explained in terms of how they suppress immune responses.
Immunosuppressive Drugs
Immunosuppressive drugs used to treat transplant rejection include calcineurin inhibitors like cyclosporine and tacrolimus, mTOR inhibitors like sirolimus and everolimus, anti-proliferatives like azathioprine and mycophenolic acid, corticosteroids like prednisolone and hydrocortisone, and antibodies like the monoclonal anti-IL-2Rα receptor antibodies basiliximab and daclizumab or polyclonal anti-T-cell antibodies like anti-thymocyte globulin. The IL-2 receptor antagonist daclizumab is approved for use in renal, cardiac transplant, and multiple sclerosis.
medicinal chemistry of Anticancer agents
1) Cancer is caused by abnormal cells dividing uncontrollably and spreading to other tissues. Chemotherapy uses drugs to kill cancer cells or slow their growth.
2) There are several types of chemotherapy drugs that work through different mechanisms such as alkylating agents, antimetabolites, plant-derived products, and monoclonal antibodies.
3) Alkylating agents work by adding alkyl groups to DNA, damaging its structure and preventing cell division. Common alkylating agents include cyclophosphamide, cisplatin, and carmustine.
Anticancer drugs 3 antimetabolites
Methotrexate is a folate antagonist antimetabolite drug that works by inhibiting the enzyme dihydrofolate reductase, depleting tetrahydrofolate cofactors needed for DNA synthesis. It is used to treat cancers like acute lymphocytic leukemia, breast cancer, and rheumatoid arthritis. 5-Fluorouracil and capecitabine are pyrimidine antagonist antimetabolites that inhibit the enzyme thymidylate synthase, blocking DNA synthesis. They are used for cancers like colon cancer. Cytarabine is also a pyrimidine antagonist that incorporates into DNA, inhibiting its synthesis, and is used for acute leukemias. 6-Mercap
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Antineoplastic agents
Antineoplastic agents can be classified as cytotoxic drugs, hormones, or miscellaneous agents. Cytotoxic drugs include alkylating agents, antimetabolites, plant derivatives, and antibiotics. They work by directly damaging DNA or interfering with cell division and metabolism. Combination therapy is more effective than single agents to increase response rates and decrease resistance development.
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This document provides information on methotrexate, including its history, mechanism of action, pharmacokinetics, uses, dosage, interactions, and adverse effects. Methotrexate was initially used to treat childhood leukemias in 1948 and is now approved by the FDA to treat psoriasis. It works by inhibiting dihydrofolate reductase and interfering with DNA synthesis. Its uses include psoriasis, rheumatoid arthritis, and some cancers. Adverse effects include hepatotoxicity, myelosuppression, gastrointestinal upset, and potential teratogenicity.
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This document discusses various immunosuppressive agents used in dermatology, including their mechanisms of action, indications, contraindications, side effects, and monitoring guidelines. It covers systemic corticosteroids, methotrexate, and azathioprine. Corticosteroids suppress inflammation through regulating gene transcription. Methotrexate and azathioprine suppress immune responses by inhibiting DNA synthesis. They are used for various inflammatory and autoimmune dermatological conditions. Monitoring includes checking for side effects like infections, myelosuppression, and hepatotoxicity.
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This document discusses various immunosuppressive agents used in dermatology, including their mechanisms of action, indications, contraindications, side effects, and monitoring guidelines. It covers systemic corticosteroids, methotrexate, and azathioprine. Corticosteroids suppress inflammation through regulating gene transcription. Methotrexate and azathioprine suppress immune responses by inhibiting DNA synthesis. These agents are used to treat various inflammatory and autoimmune skin conditions. Monitoring is needed due to potential serious side effects like infections, malignancies, and myelosuppression.
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This document discusses classifications and mechanisms of action of various anti-cancer drugs. It describes how anti-cancer drugs can be classified based on their mechanisms, which include alkylating agents, antimetabolites, natural products, and steroid hormones. It also discusses how anti-cancer drugs can be classified based on their effects on the cell cycle. The document outlines some common adverse effects of chemotherapy like nausea, vomiting, alopecia, and bone marrow depression. It provides examples of specific adverse effects of different anti-cancer drugs and notes some important drug interactions to be aware of like between methotrexate and salicylates or 6-mercaptopurine and allopurinol.
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1) The document is about the drug methotrexate, which is a disease-modifying anti-rheumatic drug used to reduce immune system activity for certain conditions like rheumatoid arthritis and psoriasis.
2) It works by inhibiting dihydrofolate reductase and decreasing DNA, RNA, and protein synthesis in rapidly dividing cells. This leads to its effectiveness in treating cancers and autoimmune diseases.
3) However, by suppressing the immune system, methotrexate can cause several toxicities and side effects involving the liver, kidneys, bone marrow, gastrointestinal tract, lungs, and skin. Close monitoring is required when using this drug.
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This document provides information on the treatment of rheumatoid arthritis (RA). It discusses that RA is an autoimmune disease causing joint inflammation and damage. The goals of treatment are to reduce pain, swelling, stiffness, and prevent further joint damage. Non-pharmacological treatments include lifestyle changes while pharmacological treatments include NSAIDs, steroids, and disease-modifying antirheumatic drugs (DMARDs) like methotrexate, azathioprine, and gold compounds. DMARDs work to suppress the immune system and inflammatory process of RA but have side effects so must be carefully monitored. Biological DMARDs may be used if other options lose effectiveness. Surgery is considered for severe cases with joint damage and loss
Antirheumatoid drugs
1) Rheumatoid arthritis is an autoimmune disorder characterized by joint inflammation and cartilage destruction, causing pain, swelling, and loss of function. It affects around 1-2% of the population and is more common in women over age 55.
2) Disease-modifying antirheumatic drugs (DMARDs) like methotrexate, sulfasalazine, and hydroxychloroquine are used to suppress the rheumatoid process and bring remission, in addition to nonsteroidal anti-inflammatory drugs (NSAIDs) for symptom relief. Biologic response modifiers targeting tumor necrosis factor alpha are also used.
3) Methotrexate is one of the most effective and commonly used
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Methotrexate – a double edged sword
- 1. Methotrexate – A double edged sword Dr.Yogesh kalyanpad, Department of dermatology, Seth G.S.M.C.&K.E.M.Hospital
- 2. Severe clinical manifestations of toxicity : Mucositis Stomatitis Esophagitis Acute Renal failure Myelosuppression Neurologic dysfunction Erosions all over body specially on psoriatic plaques Diarrhea RISK FACTORS FOR METHOTREXATE TOXICITY : 1. Increased Free plasmatic levels due to: • Displacement of protein bound methotrexate by other drugs : sulfonamides , tetracycline, aspirin, phenytoin • Displacement by protein deprivation 2. Renal elimination decreased: • Old age • Pre-existing renal failure • Drugs : salicylates, cyclosporinA, colchicine, sulfonamides.
- 3. Physician level- 1. Inadequate counselling about drug dosage 2.Lack of re-emphasis about weekly dosage system 3. Use of confusing brand names(eg –metz=metoprolol) Medication errors during methotrexate toxicity Patient level- •Confusion among various drugs •Misinterpretation about dosage •Daily methotrexate and weekly folic acid •For faster relief self administration of larger dosage •Forgetfulness of ingested dosage in old patients Pharmacy- 1. Modification of dosage prescribed 2. Over the counter availability Other- Idiosyncrasy reaction
- 4. Mistakes while taking some tablet forms
- 5. Can be simply prevented by converting into
- 7. Prevention is better than cure • Involvement of close relative during counselling • Initiate with small dose with gradual escalation • Creating awareness among patient as well relatives about possible side effects • Use of supervised injectable forms of methotrexate
- 8. Thank you