DRUG SUMMARY TABLE: CHAPTER 33 Principles of Antimicrobial and Antineoplastic Pharmacology
DRUG CLINICAL APPLICATIONS
ANTIMICROBIAL DIHYDROPTEROATE SYNTHASE INHIBITORS
Mechanism—PABA analogues that competitively inhibit microbial dihydropteroate synthase and thereby prevent the synthesis of folic acid
Sulfonamides: Susceptible vaginal infections
 Sulfanilamide (sulfanilamide)
 Sulfadiazine Toxoplasmosis, Haemophilus
 Sulfamethoxazole influenzae, chancroid, inclusion
 Sulfadoxine (See conjunctivitis, meningococcal
Chapter 36) meningitis, nocardiosis, recurrent
 Sulfalene (See rheumatic fever, trachoma
Chapter 36) (sulfadiazine)
Atypical mycobacterial infection,
chancroid (sulfamethoxazole)
Pneumocystis jiroveci pneumonia,
shigellosis, traveler’s diarrhea,
urinary tract infection, granuloma
inguinale, acute otitis media
(sulfamethoxazole/trimethoprim)
Sulfones: Acne vulgaris
 Dapsone Leprosy
Dermatitis herpetiformis
ANTIMICROBIAL DIHYDROFOLATE REDUCTASE INHIBITORS
Mechanism—Folate analogues that competitively inhibit microbial dihydrofolate reductase (DHFR) and thereby prevent the regeneration of tetrahydrofolate
from dihydrofolate
Trimethoprim Urinary tract infection
SERIOUS & COMMON ADVERSE EFFECTS CONTRAINDICATIONS THERAPEUTIC CONSIDERATIONS
Kernicterus in newborns, crystalluria,
Stevens-Johnson syndrome,
agranulocytosis, aplastic anemia, hepatic
failure
Gastrointestinal disturbance, rash
Hemolytic anemia, methemoglobinemia,
aplastic anemia, agranulocytosis, toxic
epidermal necrolysis, pancreatitis, toxic
hepatitis, suicidal ideation
Stevens-Johnson syndrome, erythema
multiforme, anaphylaxis, megaloblastic
anemia
Hypersensitivity to Because of the high incidence of
sulfonamides sulfonamide resistance,
Infants less than 2 sulfonamides are commonly
months old administered in combination with
Pregnant women at a synergistic drug such as
term trimethoprim or pyrimethamine.
Breastfeeding Sulfonamides compete with
Megaloblastic anemia bilirubin for binding sites on
due to folate serum albumin and can cause
deficiency kernicterus in newborns.
Avoid co-administration with
PABA, which is the natural
substrate for dihydropteroate
synthase.
Hypersensitivity to Dapsone and trimethoprim or
dapsone pyrimethamine can be used as a
Glucose-6-phosphate synergistic drug combination.
dehydrogenase Patients susceptible to hemolytic
(G6PD) deficiency anemia and methemoglobinemia
are typically deficient in the
erythrocyte enzyme G6PD.
Hypersensitivity to Selectively inhibits bacterial
trimethoprim DHFR.
 See above for applications of
sulfamethoxazole/trimethoprim
combination therapy
Pyrimethamine (See Toxoplasmosis
Chapter 36) Malaria
ANTINEOPLASTIC DIHYDROFOLATE REDUCTASE INHIBITOR
Mechanism—Folate analogue that competitively inhibits mammalian DHFR and thereby prevents the regeneration of tetrahydrofolate from dihydrofolate
Methotrexate Many tumor types, including
carcinomas of the breast, lung,
head and neck; acute
lymphoblastic leukemia;
choriocarcinoma
Autoimmune diseases including
psoriasis, rheumatoid arthritis
Rash, pruritus
Stevens-Johnson syndrome, leukopenia,
megaloblastic anemia, anaphylaxis
Rash
Thromboembolic disorder, erythema
multiforme, Stevens-Johnson syndrome,
myelosuppression, hepatotoxicity, kidney
disease, interstitial pulmonary disease,
leukoencephalopathy, seizure, malignant
lymphoma, opportunistic infection
Gastrointestinal disturbance, stomatitis,
alopecia, photosensitivity, rash,
headache, bronchitis, nasopharyngitis
Megaloblastic anemia Trimethoprim is bacteriostatic
due to folate and can be used as a single agent
deficiency to treat uncomplicated urinary
tract infection.
Typically used in combination
with sulfamethoxazole.
Hypersensitivity to Selectively inhibits parasitic
pyrimethamine DHFR.
Megaloblastic anemia Typically used in combination
due to folate with sulfadiazine for treatment of
deficiency toxoplasmosis.
Folic acid may interfere with the
efficacy of pyrimethamine.
Hypersensitivity to The use of high-dose
methotrexate methotrexate in cancer
Pregnancy chemotherapy has been
Breastfeeding broadened by the application of
Patients with psoriasis folinic acid rescue.
or rheumatoid Methotrexate toxicity to the
arthritis who also have gastrointestinal mucosa and bone
alcoholism, alcoholic marrow is generally reversible
liver disease, chronic after therapy is discontinued.
liver disease, Extremely toxic to the fetus
preexisting blood because folic acid is essential for
dyscrasia, or differentiation of fetal cells and
laboratory evidence of for neural tube closure.
immunodeficiency Avoid co-administration of polio
syndrome vaccine in immunosuppressed
patients receiving methotrexate
as a component of
chemotherapy.
Avoid concurrent alcohol intake.
Use extreme caution with co-
administration of naproxen and
phenylbutazone due to sporadic
case reports of deaths.
Co-administration with
trimethoprim may result in
severe methotrexate toxicity.
Oral absorption of methotrexate
can be decreased by up to 50% in
patients receiving oral antibiotic
mixtures containing
paromomycin, neomycin,
nystatin, and vancomycin.