Macrolide Anti Flashcards

Question 1

Q

Generations of All antimicrobials

Question 2

Q

General Background macrolides

Which portion of the drug is responsible for Causing SEs?

Which portion is key for interactions?

Predominantly used for the treatment of? and some?

Hgih concentrations in?

Key structural features?

Answer

A

Cladinose- GI effects
Desosamine- Interaction with target
Used for gram (+) strains, but also some gram (-)
levels in bronchial tree
14-member ring lactone and basic amino groups

Question 3

Q

Macrolide static or cidal?

Answer

A

Static blocks peptide escape tunnel

Question 4

Q

Macrolide MOA?

key binding sites?

Erythromycin

Bacterio___

Inhibits?

Binds to?

Binding dose?

Incompletely formed?

Answer

A

Static
Inhibits bacterial protein biosynth
Binds rRNA bases in 23SrRNA of the 50S bacterial ribosome
Binding of macrolide in the groove blocks the exit route for growing peptide
Incompletley formed peptides (di or tri) dissociate

Question 5

Q

ERM resistance

Resistance (MLSb cross resistance)

Major:

Moderate:

Common clinically in?

Genes for methylation

Answer

A

Extends to drugs with overlapping binding sites (lincosamides, Streptogrammin B)
Major ERM enzymes that methylate - loss of key H-binding interactions
Moderate: Mutation in A2058–>G reduction in binding
Genes can be encoded on plasmids and chromosomes —>spreading gene
Staph, Strep, atypicals (no cell wall)

Question 6

Q

Less common Erythromycin modes of resistance

Answer

A

Resistance due to export or poor uptake (gram -) known, but less common
Resistance due to lactone hydrolysis, efflux, or phophorylation are rare
R- Factor mediated self-methylation of A2503 residue of ribosome
1. prevents macrolide binding
2. Extends to clindamycin, chloramphenicol, pleuromutilin, streptogramin A, Linezolid

Question 7

Q

Stability and ADME/DMPK for Erythromycin

Interactions

Answer

A

Major usage: Upper respiratory infections (also consider spectrum) Desosamine causes high concentration in bronchials

Minor: GI/motility/ prokinetic effect (cladinose)

CYP3A4 interaction lead to arrhythmias

Question 8

Q

Instability of erythromycins to acid (stomach)

What is the fix for this?

Answer

A

spiroketal formation in the presence of acid is an inactive metabolite of erythromycin, this also causes GI cramps

Enteric coating gets the drug to the small intestine

Question 9

Q

Erythromycin salts and esters

Question 10

Q

Erythromycin products with better water solubility

Answer

A

Gluceptate salt (IV)

Lactrobionate (IV)

Question 11

Q

Clarithromycin

Whats changed and what does this mean?

Drug is linked with?

Answer

A

C6-OMe

Increased acid stability and less GI cramping, more lipophilic

Increased CV risk

Question 12

Q

Azithromycin

Presently?

Improved?

And?

Answer

A

Drug of choice
Improved PK AUC/MIC- Lower acid sensitivity, rapid absorption from GI: better serum levels than Ery, longer t1/2, CYP interactions less, high levels in respiratory, significant PAE
PD- Broader spectrum (good vs gram +, enhanced against gram (-)
Recently linked with prolonged QT interval and cardia arrhythmias