Macrolide AB - 5Qs Flashcards
Explain the meaning of Macrolides AB
Macro = large (14-16 memebered ring)
Lied = lactose glycoside
MOA of Macrolide AB
ALL are bacterioSTATIC
Are Macrolide ABs acidic or basic?
Bases
Name the most common Macrolide ABs used.
Salts and esters of erythromycin
Which Macrolide ABs is produced naturally?
Erythromycin (Saccharopolyspora erythraea)
All the rest are semi-synthetic
Name the target of Macrolide ABs
Inh of protein biosynthesis
Following binding to the 50s ribosomal subunit
What other ABs do Macrolide ABs share a common target with?
What’s the result of this similarity?
Lincosamides and chloramphenicol
They are CLINICALLY CROSS RESISTANT with one another
Name agents that are Macrolide ABs
Erythromycin
Clarothromycin
Azithromycin
Dirithromycin
What other ABs are equivalent to Macrolide ABs
1st gen Cephalosporin and 2nd gen Penicillin
What m.o. is most susceptible to Macrolide ABs
Legionella (gram -ve)
Mycoplasma (miscellaneous m.o.)
What m.o. are susceptible to Macrolide ABs
Gram tve - strep, staphy, Corneybacterium, B. anthracis
Gram -ve - Legionella, Haemophilis
Anaerobes - propionibacteria
Miscellaneous m.o. - Mycoplasma, Ureoplasma, Chlamydia, Rickettisiae
When do Macrolide ABs find special utility?
In pts allergic to Penicillin
List clinical uses of oral Macrolide ABs
Upper and lower respiratory tract inf. (Strep Pneumonia)
Upper and lower respiratory tract and otitis media (H. Influenza + sulfonamide)
Mycoplasmal pneumonia
Skin and soft tissue (streptococcus pyrogenes)
Legionnaires dx (Legionella)
What is Macrolide ABs used for PROPHYLAXIS?
Bacterial endocarditis (Strep viridans)
Similar to Pen G
What’s Macrolide ABs combo with to treat Mycobacterium avium complex inf in. AIDS, and somewhere STDs?
Rifabutin
What Macrolide ABs is used to treat gastric ulcer due to H. Pylori?
Clarithromycin
How does resistance dev to Macrolide ABs
Alteration of ribosomal target (50S ribosome) by METHYLATION of a ribosomal DNA base leading to weaker binding of AB
What mediates the resistance?
R-factor mediated.
Name alternate resistance to Macrolide ABs
Efflux pump
Reduced uptake
By destroying enzymes e.g. esterases and phosphotransferases
Effect of food on Erythromycin
Absorption is irregular with food.
Propulsive agent (Motilin agonist) causing GI upset
What does liver metabolism of the ff entail
A. Erythromycin
B. Clarithromycin
A. N-demethylation
B. C-hydroxylation at C-14
Effect of erythromycin on CP450
Erythromycin can inh P-450 enzymes t4 affecting several drugs e.g.
Carbamazepine, cyclosporine, terfernadine, midazolam, warfarin
What is the effect of erythromycin on astemizole and terfernadine?
Could lead to v serious CV effect e.g. fibrillation and Arrythmias
What’s the effect of acid medium on erythromycin?
Erythromycin is unstable in acid medium due to internal KETAL formation
Does erythromycin have a bitter taste?
Yes
What may happen after prodrug form of erythromycin?
HIGHER blood levels can occur
Some pts get idiosyncratic and reversible cholestatic jaundice damaging the liver
List erythromycin pdts with enhanced water solubility
Gluceptate salt used by IV infusion
Lactobionate salt used by IV infusion
How’s Clarithromycin made?
6-O-Methylerythromycin
Note: Clarithromycin has NO cl
Is erythromycin more lipophilic than Clarithromycin?
No.
Clarithromycin is more lipophilic
Effect of acid medium on Clarithromycin
Acid stability is enhanced becuz of lack of internal KETAL formation
T4, no stomach cramps
What’s the effect of extensive 1st pass metabolism at C-14 (hydroxylation)
Produces at active metabolite that’s active against H. Influenza
What differentiates Azithromycin from the others?
M-methyl Grp is inserted btw C-9 & C-10
How’s the stability of Azithromycin?
Increased stability, t/4 no Ketal formation
How’s the spectrum of Azithromycin
Broad spectrum
Enhanced gram -ve activity
Does Azithromycin exhibit postantibiotic effect?
Yes
What’s dirithromycin hydrolysed to?
Erythromycyclamine
Is drug-drug interaction a concern with dirithromycin?
Appears to be less than erythromycin
Becuz dirithromycin is not a good substrate for P-450
What’s the diff btw Ketolides and Erythromycin?
A. No sugar at C-3 (erythromycin has 2 sugars)
B. oxidation occurs at C-3 from an alcohol to a ketone.
What’s the effect of the oxidation at C-3?
Reduced polarity, high lipophilicity => increased bioavailability and reduced degradation in acid medium
Whats the Target of Ketolides?
50s subunit, inh protein synthesis
Resistant and Ketolides
Ketolides retain activity against macrolide resistant strains that are resistant due to METHYLATION process
What are Ketolides most useful against?
Respiratory tract infection
Are Ketolides and Macrolides cross-allergenic?
Yes
What may cuz the drug-drug int btw Ketolides and telithromycin?
Ketolides is metabolized by P-450 3A4
Telitnromycin is a 3A4 inhibitor
List agents that fall under Lincosamides
Lincomycin
Clindamycin
Clindamycin phosphate
What unusual about lincomycin structure?
Contains an unusual thiomethyl amino-octoside
How’s the stability of Lincosamides?
Very unstable, should be refrigerated
Which of the Lincosamides is a natural pdt?
Lincomycin
What’s the effect of the addition of Cl to clindamycin?
More lipophilic, more active, and better absorbed than lincomycin
Whats the Target of clindamycin?
50s ribosome subunit
MOA of clindamycin
BacterioSTATIC
Is clindamycin cross-resistant with Macrolides?
Yes
Compare clindamycin and erythromycin in terms of
A. Parental use
B. absorption after oral admin
Clindamycin is much less irritating
And about 90% is absorbed after oral admin
Which clindamycin is used for
A. Parental admin
B. PO admin
A. Clindamycin C-2 phosphate pro-drug
B. the palmitate hydrochloride is a pro-drug for PO
Main GI compliant of clindamycin?
Diarrhea
Is clindamycin metabolite inactive?
No
It’s active.
List main clinical uses of clindamycin
Gram tve cocci
Anaerobic bacterial inf
What has recently reduced the popularity of clindamycin and lincomycin?
PMC
