11. Chloramphenicol. Polymyxins. Antifolate drugs

Question 1

Chloramphenicol

Answer 1

• binds reversibly to 50s ribosome, inhibiting peptide bond formation and halting translation
• bacteriostatic
• empiric treatment for meningitis in developing countries (S. Pneumo, H Flu, N Meningitidis)
• alternative agent in serious rickettsial infections (rocky mountain spotted fever) useful in pregnant women

• anemia due to dose related reversible suppression of RBC production
• aplastic anemia

-accumulation of the drug in newborns-grey baby syndrome
(due to ineffective glucuronic acid conjugation system)

-causes flaccidity, hypothermia, shock (floatation device looks like a liver)

Question 2

Polymyxins

Answer 2

bind LPS in the outer membrane of Gram-negative and disrupt both the outer and inner membranes.
causing membrane damage, suggesting a detergent-like mode of action. bactericidal

Polymyxin B- I​V, otic, ophthalmic, topical

• G (-)
• *​Pseudomonas ​**

Polymyxin E (colistin) -​IV, aerosol

• Pseudomonas ​(Cystic fibrosis) → given aerosol
• do not enter CNS
• Neuro/nephro toxicity

Question 3

Antifolate drugs

Answer 3

Sulfamethoxazole (SMX)
Trimethoprim (TMP)

• Bactrim = SMX/TMP

PABA → Dihydrofolate →tetrahydrofolate → purines → DNA

-SMX is a PABA analog that blocks dihydropterate synthetase

• TMP /Pyrimethamine blocks **dihydrofolate reductase
• ——————————————————————————--1st linetreatment forUTI**
• Treats acute prostatitis
• activity against gram (-) GI and urinary tract bacteria
• activity against MRSA

activity against nocardia

activity against gram positives

-treats pneumocystis jirovecii pneumonia (PJP)

• PJP prophylaxis for cd4<200
• toxoplasmosis prophylaxis with TMP/SMX for CD4 <100

-Pyramethamine/sulfadizine treat toxoplasmosis caused by toxoplasma gondii

Question 4

Antifolate drugs
side effects

Answer 4

• pancytopenia
• megaloblastic fireworks
• teratogen in the 1st trimester anti-folate effects cause neural tube defects

- sulfa allergy – fever, urticarial, rash

• Hemolytic anemia in G6PD deficiency
• Bite cells and Heinz bodies seen in RBC’s
• stevens-johnson syndrome

type IV renal tubular acidosis →hyperkalemia

-interstitial nephritis

-photosensitivity

-kernicterus in the neonate
(sulfonamides when used in the lath month of pregnancy displace bilirubin in the neonate)

• sulfonamides displace warfarin from albumin causing over anticoagulation and bleeding
• inhibition of cytochrome 450
• causes drug induced lupus