Topic 11-Chloramphenicol. Polymyxins. Antifolate drugs

Question 1

What is the mechanism of action of Chloramphenicol?

Answer 1

Binds reversibly to the bacterial 50s ribosomal subunit

Question 2

What is Chloramphenicol’s spectrum?

Answer 2

Broad spectrum (Examples include enterococci, pseudomonas, acinetobacter, shigeela, bacteria fragilis, H. influenzae, klebsiella, etc)
Including anaerobes, rickettsiae, chlamydia, and spirochetes

Question 3

Pharmacokinetics of Chloramphenicol
Bacteriocidal/bacteriostatic?
Administration?
Penetration?
Metabolism?
Administration?

Answer 3

Bacteriostatic but can become bactericidal depending on bacteria susceptibility
Administered orally, available as eye cream
Great tissue penetration (CNS, eye, peritoneal cavity, breast milk, everywhere)
Metabolism by glucuronidation, inhibits CYP450
Administered 4x times a day

Question 4

Indications for chloramphenicol (4)

Answer 4

1. ) Brain abscess if metronidazole is not effective
2. )Mixed infection if have no other drug
3. )Menigo/pneumococci meningitis in case of beta lactam allergy
4. )rickettsiae in children (severe below age of 9, if older then we use tetracycline since tetra side effects will cause bone and teeth issues)

Question 5

Adverse effects of chloramphenicol

Answer 5

1. )Gray baby syndrome-babies have immature glucuronidation so chloramphenicol builds up leading to flaccidity, poor feeding and breathing, cyanosis, hypothermia, and shock
2. )Aplastic anemia (two types)
   - 100% of patients get it at 720 gram does for 2 week treatment, leading to suppression of blood cell production and leukocytopenia (this is reversible if treatment is stopped)
   - idiosyncratic aplastic anemia that is irreversible, happens in 1/20000 patients, dose independent (patient will require bone marrow transplant, this is why the drug is not used in 1st world countries anymore)
3. )CYP450 inhibitor blocking warfarin and phenytoin degradation, elevating their concentration and potentiating their effects

Question 6

Bacterial resistance to Chloramphenicol

Answer 6

bacterial enzymatic degradation and decreased permeability

Question 7

What are the two Polmyxin drugs?

Answer 7

B and E colistin

Question 8

Mechanism of action of E-colistin

Answer 8

Binds to the membrane by interacting with phospholipids altering their permeability

Question 9

Pharmacokinetics of E-colistin
bacteriocidal or bacteriostatic?
Kinetics?
Administration?

Answer 9

bacteriocidal
poor distribution, doesn't enter CNS 
Administered parenterally (IV), also as topical (drops) and aerosal( used for children with cystic fibrosis
Possible to do UTI flush via catheter
Given 3 times a day

Question 10

Spectrum of E-colistin

Answer 10

Narrow
Gram negative bacteria (pseudomonas aeruginosa and acintobacter
NOT effective against B. fragilis, proteus, Gram positive, serratia, and klebsiella

Question 11

Indications of E-colistin

Answer 11

Pseudomonas aeruginosa or other gram negative if nothing else is active (last choice in severe life threatening infection)

Question 12

Adverse effects of E-colistin

Answer 12

nephrotoxic and neurotoxic

Question 13

What are the 2 drug classes part of the antifolate drugs

Answer 13

Sulfonamides and Trimethoprim

Question 14

What is the mechanism of action of antifolate drugs

Answer 14

Sulfonamides inhibits formation of the dihydropteroic acid and Trimethoprim inhibits the formation of the tetrahyrofolic acid

Question 15

Spectrum of sulfonamides

Answer 15

Gram +/-
Nocardia, trachomatis (chlamydia), some protozoa, toxoplasma gondii, pneumocystis jirovecii
No action agains rickettsia and poor against anaerobes

Question 16

Pharmacokinetics of sulfonamides
Administered?
Absorption?
Distribution?
Pregnancy?
Protein binding?
Metabolized?
Excreted?

Answer 16

Administered orally, topically
Good absorption in GI
Wide distribution (CSF, placenta, fetus, urinary tract, and liver)
Contraindicated in pregnancy
High protein bind
metabolized in liver (acetylation, glucuronidation)
Excretion in urine

Question 17

Two short acting oral sulfonamides

Answer 17

sulfamethoxazole

sulfadiazine

Question 18

Long acting oral sulfonamides

Answer 18

sulfadoxine

Question 19

Non-absorbable sulfonamides agents

Answer 19

sulfasalazine (for ulcerative colitis)

Question 20

Topical sulonamide agents

Answer 20

sulfacetamide (for conjunctivitis, trachoma)
silver sulfadiazine (burn wounds)
sulfadimidine (ophthalmological cream)

Question 21

Adverse effects of sulfonamides

Answer 21

allergic reaction
photosensitivity
GI effects
Nephrotoxicity (patient must hydrate)
hematotoxicity (hemolytic anemia, aplastic anemia, granulocytopenia, thrombocytopenia)
In newborns: competition with bilirubin leading to risk of kernicterus (bilirubin building up in the brain)

Question 22

Trimethoprim pharmacokinetics

bactericidal or bacteriostatic

Answer 22

The same as sulfonamides and is bacteriostatic

Question 23

what combination of antifolate drugs makes them bactericidal

Answer 23

trimethoprim and sulfamethoxazole

Question 24

What is trimethoprim and sulfamethoxazole used in

Answer 24

pneumocystitis jiroveci and toxoplasmosis, nocardia mainly

but also respiratory pathogens, shigella enteritis, some salmonella infections, and UTI

Question 25

What combination of antifolate drugs are used to treat leishmaniasis, toxoplasmosis, and plasmodium falciparum
How is it given?

Answer 25

Pyrimethamine and sulfadiazine