Antimetabolites: Sulfonamides and trimethoprim
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Antimetabolites: Sulfonamides and trimethoprim
Prerequisite basic sciences
Prerequisite basic sciences
Childhood and early-onset psychological disorders: Pathology review
Prerequisite basic sciences
Attributable risk (AR)
Bias in interpreting results of clinical studies
Bias in performing clinical studies
Clinical trials
Confounding
DALY and QALY
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Acyanotic congenital heart defects: Pathology review
Adrenal masses: Pathology review
Bacterial and viral skin infections: Pathology review
Bone tumors: Pathology review
Coagulation disorders: Pathology review
Congenital neurological disorders: Pathology review
Cyanotic congenital heart defects: Pathology review
Extrinsic hemolytic normocytic anemia: Pathology review
Eye conditions: Inflammation, infections and trauma: Pathology review
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Platelet disorders: Pathology review
Renal and urinary tract masses: Pathology review
Seizures: Pathology review
Viral exanthems of childhood: Pathology review
Pharmacodynamics: Agonist, partial agonist and antagonist
Pharmacodynamics: Desensitization and tolerance
Pharmacodynamics: Drug-receptor interactions
Pharmacokinetics: Drug absorption and distribution
Pharmacokinetics: Drug elimination and clearance
Pharmacokinetics: Drug metabolism
Prerequisite basic sciences
Adrenal masses: Pathology review
Cystic fibrosis: Pathology review
Diabetes mellitus: Pathology review
HIV and AIDS: Pathology review
Intrinsic hemolytic normocytic anemia: Pathology review
Leukemias: Pathology review
Nasal, oral and pharyngeal diseases: Pathology review
Obstructive lung diseases: Pathology review
Papulosquamous and inflammatory skin disorders: Pathology review
Pediatric brain tumors: Pathology review
Renal and urinary tract masses: Pathology review
Seizures: Pathology review
Prerequisite basic sciences
Developmental and learning disorders: Pathology review
Prerequisite basic sciences
Growth hormone and somatostatin
Prerequisite basic sciences
Ectoderm
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Human development days 4-7
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Hardy-Weinberg equilibrium
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Acyanotic congenital heart defects: Pathology review
Autosomal trisomies: Pathology review
Congenital neurological disorders: Pathology review
Cyanotic congenital heart defects: Pathology review
Cystic fibrosis: Pathology review
Disorders of sex chromosomes: Pathology review
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Prerequisite basic sciences
Breastfeeding
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Shock: Pathology review
Supraventricular arrhythmias: Pathology review
Traumatic brain injury: Pathology review
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Prerequisite basic sciences
Androgens and antiandrogens
Estrogens and antiestrogens
Miscellaneous cell wall synthesis inhibitors
Protein synthesis inhibitors: Tetracyclines
Cell wall synthesis inhibitors: Penicillins
Antihistamines for allergies
Acetaminophen (Paracetamol)
Non-steroidal anti-inflammatory drugs
Antimetabolites: Sulfonamides and trimethoprim
Antituberculosis medications
Cell wall synthesis inhibitors: Cephalosporins
Cell wall synthesis inhibitors: Penicillins
DNA synthesis inhibitors: Fluoroquinolones
DNA synthesis inhibitors: Metronidazole
Miscellaneous cell wall synthesis inhibitors
Miscellaneous protein synthesis inhibitors
Protein synthesis inhibitors: Aminoglycosides
Protein synthesis inhibitors: Tetracyclines
Bronchodilators: Beta 2-agonists and muscarinic antagonists
Bronchodilators: Leukotriene antagonists and methylxanthines
Pulmonary corticosteroids and mast cell inhibitors
Glucocorticoids
Bronchodilators: Beta 2-agonists and muscarinic antagonists
Bronchodilators: Leukotriene antagonists and methylxanthines
Azoles
Glucocorticoids
Pulmonary corticosteroids and mast cell inhibitors
Acetaminophen (Paracetamol)
Non-steroidal anti-inflammatory drugs
Antimetabolites: Sulfonamides and trimethoprim
Cell wall synthesis inhibitors: Cephalosporins
Cell wall synthesis inhibitors: Penicillins
Miscellaneous protein synthesis inhibitors
Protein synthesis inhibitors: Tetracyclines
Pharmacodynamics: Agonist, partial agonist and antagonist
Pharmacodynamics: Desensitization and tolerance
Pharmacodynamics: Drug-receptor interactions
Pharmacokinetics: Drug absorption and distribution
Pharmacokinetics: Drug elimination and clearance
Pharmacokinetics: Drug metabolism
Cell wall synthesis inhibitors: Cephalosporins
Glucocorticoids
Miscellaneous protein synthesis inhibitors
Anticonvulsants and anxiolytics: Barbiturates
Anticonvulsants and anxiolytics: Benzodiazepines
Nonbenzodiazepine anticonvulsants
Cell wall synthesis inhibitors: Cephalosporins
Cell wall synthesis inhibitors: Penicillins
Miscellaneous cell wall synthesis inhibitors
Assessments
Antimetabolites: Sulfonamides and trimethoprim
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Antimetabolites: Sulfonamides and trimethoprim
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External References
First Aid
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2018
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2016
Agranulocytosis p. 597
sulfa drug allergies p. 253
Anemia
sulfa drug allergies as cause p. 253
Chlamydia spp. p. 146
sulfonamides for p. 191
Hemolysis
sulfonamides as cause p. 191
Hemolytic anemia p. 429
sulfa drug allergies p. 253
Hypersensitivity reactions p. 110-111
sulfonamides p. 191
Nephrotoxicity
sulfonamides p. 191
Nocardia spp.
sulfonamides for p. 191
Photosensitivity (cutaneous)
sulfonamides p. 191
Stevens-Johnson syndrome p. 191, 494, 565
sulfa drug allergies p. 253
Sulfa drugs p. 253
acute pancreatitis p. 406
erythema multiforme p. 494
G6PD deficiency from p. 417
megaloblastic p. 251
rash p. 251
Sulfonamides p. 191
acute interstitial nephritis from p. 626
cytochrome P-448 and p. 253
hemolysis in G6PD deficiency p. 251
hypothyroidism p. 250
mechanism p. 184
Nocardia spp. p. 137
photosensitivity p. 251
pregnancy contraindication p. 201
trimethroprim p. 191
vitamin BNaN deficiency p. 66
Thrombocytopenia p. 415
sulfa drug allergies p. 253
Urinary tract infections (UTIs) p. 179, 625
sulfa drugs for p. 253
sulfonamides for p. 191
Urticaria p. 487, 489
sulfa drug allergies p. 253
Transcript
Content Reviewers
Contributors
Antimetabolites are medications that interfere with the synthesis of DNA.
Some antimetabolites are used in chemotherapy to kill cancer cells, while others are used as antibiotics since they inhibit bacterial folate synthesis.
Folate, or folic acid, also known as vitamin B9, is necessary for the synthesis of nucleic acids, which are the building blocks of DNA and RNA.
Simply put, a lack of folate results in a lack of nucleic acids, which then results in decreased DNA and RNA synthesis, leading to hindered cell division and function.
Now, a key difference between our cells and bacterial cells is that we get all of our folate through our diet, while bacteria can make their own folate from scratch.
Because of this, we can target the bacterial folate synthesis pathway to minimize the damage done to our cells.
So in order to synthesize folate, the bacteria will first use the host’s para-aminobenzoic acid, or pABA, and convert it to dihydropteroic acid via the enzyme dihydropteroate synthetase, or DHPS.
In the second step, dihydropteroic acid is converted into dihydrofolic acid by dihydrofolate synthetase.
The third step is the conversion of dihydrofolic acid into tetrahydrofolic acid via dihydrofolate reductase.
Tetrahydrofolic acid is a folic acid derivative and can be used to synthesize purines like adenine and guanine, which are used to build DNA and RNA, as well as thymidine, which is only used in DNA.
Now, the first group of antimetabolite antibiotics are the sulfonamides, which include sulfamethoxazole, or SMX, sulfisoxazole, and sulfadiazine.
These medications bind to dihydropteroate synthetase, or DHPS, in the first step of folate synthesis and prevents the bacteria from making dihydropteroic acid.
These medications can be given peroral or injected into a vein, but they need to be metabolized by the liver in order to work.
Now, they are broad spectrum and can treat a variety of gram positive and gram negative bacteria, as well as chlamydia and nocardia species.
Next we have trimethoprim, which inhibits the 3rd step of folate synthesis by inhibiting dihydrofolate reductase, or DHFR, preventing the formation of tetrahydrofolic acid.
Now humans also have dihydrofolate reductase, but the bacterial version of this enzyme is 4-5 times more sensitive to this medication.
Trimethoprim is also broad spectrum and is effective against both gram positive and gram negative bacteria.
Sources
- "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
- "Rang and Dale's Pharmacology" Elsevier (2019)
- "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
- "Methotrexate, and trimethoprim-sulfamethoxazole: toxicity from this combination continues to occur" Can Fam Physician (2014)
- "Prophylactic Trimethoprim-Sulfamethoxazole Does Not Affect Pharmacokinetics or Pharmacodynamics of Methotrexate" Journal of Pediatric Hematology/Oncology (2016)
- "Medication Use and the Risk of Stevens–Johnson Syndrome or Toxic Epidermal Necrolysis" New England Journal of Medicine (1995)
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