11. Chloramphenicol. Polymyxins. Antifolate drugs

Question 1

Chloramphenicol

Answer 1

Protein synthesis inhibitor S50 subunit - reversible inhibition (inhibits peptide bond formation)

Bacteriostatic depends on dose and the organism can be cidal

Spectrum: WIDE G+ive, G-ive, Anaerobes, Rickettsiae, chlamydia, Spirochetes

Administration: IV
Distribution: wide, enters CNS
Metabolism: hepatic (glucuronidation) - inhibits CYP450 (blocks metabolism of warfarin, phenytoin)
Elimination: Kidney (tubular excretion) | Breast milk

Adverse effect: Aplastic anemia, gray baby syndrome

Question 2

Polymyxins

Answer 2

Polymyxin B 
Polymyxin E (colistin)

Question 3

Antifolate drugs

Answer 3

Sulfonamides

Trimethoprim

Question 4

Polymyxin E

Answer 4

colistin

Question 5

Polymyxin B

Polymyxin E

Answer 5

Cation polypeptides that bind to the membrane altering permeability
Bactericidal (dose dependant)

Spectrum: G-ive, Pseudomonas (Not effective: proteus, serretia)
Polymyxin E (colistin) can treat Pseudomonas (Cystic fibrosis) → given aerosol

Distribution: poor, do not enter CNS
Adverse effect: Neurotoxicity | Nephrotoxicity

Question 6

adminstration of Polymyxin E & B

Answer 6

Polymyxin B: IV, otic, ophthalmic, topical

Polymyxin E: IV, aerosol

Question 7

Sulfonamides

Answer 7

Sulfadoxine 
Sulfasalazine 
Sulfamethoxazole 
Sulfadimidine 
Sulfadiazine (Silver sulfadiazine)

Question 8

Sulfadoxine 
Sulfasalazine 
Sulfamethoxazole 
Sulfadimidine 
Sulfadiazine (Silver sulfadiazine)

Answer 8

Sulfonamides
Synthetic analog of PABA
Inhibits dihydropteroate synthase (found only in bacteria)
Bacteriostatic

Spectrum: Nocardia, enteric bacteria, proteus
given with Pyrimethamine can treat - Leishmaniasis, toxoplasmosis, Pl. falciparum

Mechanism of resistance:
Overproduction of PABA
Decreased permeability
Altered dihydropteroate

Distribution: WIDE (including CSF, Placenta, urinary tract) | Binds albumin (increased activity of warfarin)
Metabolism: Acetylation (lowers solubility), glucuronidation
Excretion: Kidney (glomerular filtration) and breast milk

Adverse effect: Allergic reaction (stevens-johnson syndrome) | photosensitivity | nephrotoxicity (crystalluria) | Kernicterus | Hematotoxicity (megaloblastic anemia, hemolytic anemia in G6PD)

Question 9

differences between ….

Sulfasalazine
Sulfamethoxazole
Sulfadiazine (Silver sulfadiazine)

Answer 9

the Administration:

Oral
Medium acting: Sulfamethoxazole, Sulfadiazine
Long acting: Sulfadoxine
Non absorbable: Sulfasalazine (for U.colitis)

Topical:
Silver sulfadiazine For burn wounds

Question 10

Trimethoprim

Answer 10

Inhibits dihydrofolate reductase (found also in human)

Adverse effect: Folic acid deficiency

Monotherapy → rapid resistance
For UTI’s

usually given in combination (synergic) with → Cotrimoxazole

Question 11

Cotrimoxazole

Answer 11

Sulfamethoxazole + Trimethoprim
has synergic effect
Bactericidal

Use: Pneumocystis jiroveci, toxoplasmosis, nocardiosis, resistance salmonella, UTI.

Adverse effect: Skin rash, hepatotoxicity, Nausea