Topic 11-Chloramphenicol. Polymyxins. Antifolate drugs Flashcards
What is the mechanism of action of Chloramphenicol?
Binds reversibly to the bacterial 50s ribosomal subunit
What is Chloramphenicol’s spectrum?
Broad spectrum (Examples include enterococci, pseudomonas, acinetobacter, shigeela, bacteria fragilis, H. influenzae, klebsiella, etc) Including anaerobes, rickettsiae, chlamydia, and spirochetes
Pharmacokinetics of Chloramphenicol Bacteriocidal/bacteriostatic? Administration? Penetration? Metabolism? Administration?
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
Indications for chloramphenicol (4)
- ) Brain abscess if metronidazole is not effective
- )Mixed infection if have no other drug
- )Menigo/pneumococci meningitis in case of beta lactam allergy
- )rickettsiae in children (severe below age of 9, if older then we use tetracycline since tetra side effects will cause bone and teeth issues)
Adverse effects of chloramphenicol
- )Gray baby syndrome-babies have immature glucuronidation so chloramphenicol builds up leading to flaccidity, poor feeding and breathing, cyanosis, hypothermia, and shock
- )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) - )CYP450 inhibitor blocking warfarin and phenytoin degradation, elevating their concentration and potentiating their effects
Bacterial resistance to Chloramphenicol
bacterial enzymatic degradation and decreased permeability
What are the two Polmyxin drugs?
B and E colistin
Mechanism of action of E-colistin
Binds to the membrane by interacting with phospholipids altering their permeability
Pharmacokinetics of E-colistin
bacteriocidal or bacteriostatic?
Kinetics?
Administration?
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
Spectrum of E-colistin
Narrow
Gram negative bacteria (pseudomonas aeruginosa and acintobacter
NOT effective against B. fragilis, proteus, Gram positive, serratia, and klebsiella
Indications of E-colistin
Pseudomonas aeruginosa or other gram negative if nothing else is active (last choice in severe life threatening infection)
Adverse effects of E-colistin
nephrotoxic and neurotoxic
What are the 2 drug classes part of the antifolate drugs
Sulfonamides and Trimethoprim
What is the mechanism of action of antifolate drugs
Sulfonamides inhibits formation of the dihydropteroic acid and Trimethoprim inhibits the formation of the tetrahyrofolic acid
Spectrum of sulfonamides
Gram +/-
Nocardia, trachomatis (chlamydia), some protozoa, toxoplasma gondii, pneumocystis jirovecii
No action agains rickettsia and poor against anaerobes
Pharmacokinetics of sulfonamides Administered? Absorption? Distribution? Pregnancy? Protein binding? Metabolized? Excreted?
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
Two short acting oral sulfonamides
sulfamethoxazole
sulfadiazine
Long acting oral sulfonamides
sulfadoxine
Non-absorbable sulfonamides agents
sulfasalazine (for ulcerative colitis)
Topical sulonamide agents
sulfacetamide (for conjunctivitis, trachoma)
silver sulfadiazine (burn wounds)
sulfadimidine (ophthalmological cream)
Adverse effects of sulfonamides
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)
Trimethoprim pharmacokinetics
bactericidal or bacteriostatic
The same as sulfonamides and is bacteriostatic
what combination of antifolate drugs makes them bactericidal
trimethoprim and sulfamethoxazole
What is trimethoprim and sulfamethoxazole used in
pneumocystitis jiroveci and toxoplasmosis, nocardia mainly
but also respiratory pathogens, shigella enteritis, some salmonella infections, and UTI
What combination of antifolate drugs are used to treat leishmaniasis, toxoplasmosis, and plasmodium falciparum
How is it given?
Pyrimethamine and sulfadiazine
