Pharm 32 Antimicrobial and Antineoplastic Mechanisms

Question 1

PABA analogues that competitively inhibit microbial dihydropteroate synthase and thereby prevent the synthesis of folic acid (typically bacteriostatic)

Answer 1

• SULFA DRUGS (Sulfonamides and Sulfones)
• Sulfonamides: Sulfanilamide, Sulfadiazine, Sulfamethoxazole, Sulfadoxine, Sulfalene
• Sulfones: Dapsone

Question 2

Folate Analogues that competitively inhibit microbial dihydrofolate reductase (DHFR) and thereby prevent the regeneration of tetrahydrofolate (THF) from dihydrofolate (DHF).

Answer 2

• Trimethoprim (Specifically Bacterial)
• Pyrimethamine (Specifically Parasitic)
• Methotrexate (Everything, very toxic)

Question 3

Use of high dose (blank) in caner chemo has been broadened by the application of (blank) rescue

Answer 3

• Methotrexate

- Folinic Acid

Question 4

Which sulfa drugs can be used in combination trimethoprim and Pyrimethamine for Sequential Blockade?

Answer 4

• Sulfamethoxazole (Trimethoprim) for bacterial infections.

- Sulfadiazine (Pyrimethamine) for Parasitic Infections.

Question 5

What is the advantage of Sequential Blockage with Dihydropteroate (Sulfa) Drugs and Dihydrofolate Reductase Inhibitors?

Answer 5

• The sulfonamide decreases intracellular concentration of dihydrofolate; this increases the effectiveness of the DHFR inhibitor, which competes with dihydrofolate for binding to the enzyme.
• Also the combination decreases the rate of resistance development.

Question 6

Serious/Common Adverse Effects and Contraindications of Sulfonamides

Answer 6

KERNICTERUS in Newborns, crystalluria, Stevens-Johnson syndrome/GI disturbance, RASH
- Newborns! (Less than 2 months), Pregnant women at term, Breastfeeding

Question 7

Applications, Serious/Common Adverse Effects and Contraindications of Sulfones

Answer 7

• Leprosy and Pneumocystis Carinii
• Hemolytic Anemia, methemoglobinemia, toxic epidermal necrolysis, erythema nodosum/ Abdominal Pain
• Glucose-6-phosphate Dehydrogenase deficiency

Question 8

Applications, Serious/Common Adverse Effects and Contraindications of Trimethoprim

Answer 8

• UTIs
• Stevens-Johnson Syndrome, leukopenia, megaloblastic anemia/RASH, Pruritus
• Megaloblastic Anemia due to folate deficiency

Question 9

Applications, Serious/Common Adverse Effects and Contraindications of Pyrimethamine

Answer 9

• TOXOPLASMOSIS
• Stevens-Johnson Syndrome, leukopenia, megaloblastic anemia/RASH
• Megaloblastic Anemia due to folate deficiency

Question 10

Applications, Serious/Common Adverse Effects and Contraindications of Methotrexate

Answer 10

• Tumors (breast, lung, head, neck, leukemia, etc), Autoimmune Diseases (psoriasis, RA), Early Ectopic Pregnancy
• Myelosuppression, GI Hemorrhage, Mucous Membrane Disease/GI Disturbance, stomatitis, alopecia, photosensitivity, rash
• Pregnancy, Breastfeeding, Patients with RA or psoriasis w/alcoholism (can cause liver disease.