Macrolides

Question 1

MOA

Answer 1

Bind reversibly to 23s RNA in the 50s ribosomal subunit and prevent translocation which leads to blocking peptide bond formation

Question 2

Resistance

Answer 2

4 ways
1. lactone ester hydrolyse on the first carbon
2. Drug induced methylation of adenine A2058 on 23s RNA which blocks the ability for macrolides to bind
3. Mutation of Adenine A2058 which greatly reduces affinity of binding
4. Increased efflux pumps

Question 3

Chemical reactivity

Answer 3

Inactivated under acidic conditions due to intramolecular acid-catalyzed ketal formation between 6-OH and 12-OH

Question 4

Clarithromycin - what allows it to be oral

Answer 4

6-OCH derivative enhances oral absorption as it avoids ketal formation at low pH

Question 5

Azithromycin - why is it stable in lower pH

Answer 5

The ketone at C-9 is replaced which means ketal formation is no longer possible

Question 6

drug interactions

Answer 6

Bind and inhibit CYP3A and related p450 isozymes

Question 7

Clinical use of Erythromycins
Drug of choice for the following

Answer 7

Mycoplasma pneumoniae infections
Group A streptococcal upper respiratory tract infection (penicillin-allergic patient) Legionella infection
Bordetella pertussis
Campylobacter jejuni
Corynebacterium

Question 8

Side effects

Answer 8

Vomiting, gastric cramps, and abdominal pain, minor and severe allergic skin reactions
Stevens-johnson syndrome
toxic epidermal necrolysis
reversible cholestatic hepatitis

Also Pyloric stenosis in childrens whos mothers took the drug in late stages of pregnancy

Question 9

Pharmacokinetics

Answer 9

inactivated by gastric acids (ketal formation) (given as either enteric coated capsules or tablets)

Rapidly absorved and diffuses into most tissues and phagocytes