Macrolides & Chloramphenicol

Question 1

List the drugs for 50s protein synthesis inhibitors

Answer 1

1. Macrolides : Erythromycin, Clarithromycin, Azithromycin
2. Ketolides: Telithromycin
3. Lincosamide: Clindamycin
4. Streptogramin: quinupristin-dalfopristin
5. Oxazolidinones: Linezolid
6. Chloramphenicol

Question 2

Does administration of macrolides can harm human?

Answer 2

No.
Ribosomal subunit in bacteria are 30s and 50s which are different than human ribosomal subunit which are 40s and 60s.
Macrolides disrupt protein synthesis in bacteria and not the mammalian hosts cells.

Question 3

Macrolides is bacteriostatic or bactericidal?

Answer 3

Macrolides is bacteriostatic.

However, in higher doses, it can be bactericidal.

Question 4

MOA of Macrolides

Answer 4

-Macrolides binds irreversibly to a site of 50s ribosomal subunits of bacteria, thus inhibiting the translocation steps of protein synthesis.

Question 5

Therapeutic application of macrolides

Answer 5

1. Atypical pneumonia cause by mycoplasma pneumoniae
2. Community acquired pneumonia (CAP) cause by Mycoplasma pneumoniae & Legionella pneumoniae.
3. Whooping cough cause by bordetella pertussis
4. Corynebactrium diphtheria
5. Chlamydia infections

Question 6

Mechanism of resistance of Macrolides

Answer 6

1. Inability of the organisms to take up the antibiotics.
2. Presence of efflux pumps
3. A decreased affinity of the 50s ribosomal subunit for antibiotics
4. Presence of plasmid-associated erythromycin esterases in gram negative organism such as enterobacteria.

Question 7

Adverse effects of macrolides

Answer 7

1. Gastrointestinal distress & motility: Nausea, Vomitting, diarrhea & abdominal cramps.
2. Cholestatic jaundice
3. Ototoxicity (loss of hearing)
4. QTc prolongation: cardiac proarrythmia

Question 8

Macrolides is contraindicated to?

Answer 8

-patient with hepatic dysfunction (drugs can accumulate in the liver)

Question 9

Indication of ketolides

Answer 9

• Community acquired pneumonia (CAP) cause by streptococcus pneumoniae.
• no longer used for respiration tract infection because it can cause liver failure & hepatitis

Question 10

Adverse effect of Clindamycin (lincosamide)

Answer 10

1. Diarrhea
2. Nausea
3. Skin rashes
4. Impaired liver function
5. Pseudomembranous colitis (due to overgrowth of clostridium difficile)

Question 11

Clinical use of quinupristin-dalfopristin

Answer 11

-treatment for severe infection caused by staphylococcal or Vancomycin-resistant Enterococcus faecium (VRE)

Question 12

Adverse effect of quinupristin-dalfopristin

Answer 12

1. Venous irritation
2. Hyperbilirubinemia
3. Arthralgia & Myalgia in high doses

Question 13

Adverse effect of linezolid

Answer 13

1. Gastrointestinal upset
2. Nausea
3. Headache
4. Rash
5. Thrombocytopenia

Question 14

Chloramphenicol is bacteriostatic or bactericidal?

Answer 14

• Chloramphenicol is bacteriostatic. But, in high doses or according to organism, it can be bactericidal.

Question 15

MOA of chloramphenicol

Answer 15

-Chloramphenicol bind irreversibly of 50s ribosomal subunit of bacteria and inhibit protein synthesis at the peptidyl transferase reaction

Question 16

Adverse effects of chloramphenicol

Answer 16

1. Hemolytic anemia & aplastic anemia (due to bone marrow depression)
2. Gastrointestinal disturbances: Nausea, Diarrhea, Vomitting
3. Grey baby syndrome
   - newborn/premature infants received relatively in high doses
   - lack of an effective glucuronic acid conjugation mechanism for degradation & detoxification of drugs
   - thus, drugs accumulate to concentration that interfere the function of mitochondrial ribosome.
4. Superinfections: Oropharyngeal candidiasis & acute staphylococcal enterocolitis