PHARMACO - Macrolides Flashcards
Large cyclic lactone ring structure with attached sugars
Erythromycin , azithromycin, and clarithromycin
Good oral bioavailability
Erythromycin , azithromycin, and clarithromycin
oral bioavailability of Erythromycin , azithromycin, and clarithromycin
good
tissue distribution of Erythromycin , azithromycin, and clarithromycin
wide: Distributed to most body tissues
macrolide whose Absorption is impeded by food
azithromycin
macrolide which is Eliminated slowly in the urine mainly as unchanged drug
azithromycin
half-life of azithromycin
2-4 days
macrolide whose levels in tissues and phagocytes are higher than in plasma
azithromycin
macrolideS whose Elimination of intact drug is rapid
Erythromycin and clarithromycin
mode of excretion of Erythromycin
biliary excretion
mode of excretion of Hepatic metabolism and urinary excretion
Clarithromycin
half-life of Clarithromycin
2-5 hours
half-life of Erythromycin
2-5 hours
macrolide used against chlamydia
erythromycn
Preparations erythromycin
Erythromycin stearate
Erythromycin lactobionate
Erythromycin estolate
-Best absorbed oral preparation of erythromycin
Erythromycin estolate
spectra of activity of azithromycin and clarithromycin
same with erythro but with GREATER activity
Mode of resistance of macrolides in gram +
Efflux pump mechanisms
Production of methylase that adds methyl group to the ribosomal binding site
Mode of resistance of macrolides to enterobacteriaceae
Formation of drug-metabolizing esterases
Cross-resistance between individual macrolides is complete incomplete partial?
complete
if a microorganism is resistant to erythromycin, will it also be resistant to clarithromycin or azithromycin
yes because cross-resistance between individual macrolides is complete
cross-resistance with other drugs that bind to the same site occur in methylase-producing strains especially Clindamycin and streptogramins, complete incomplete partial?
PARTIAL
enzyme found in the liver
needed to metabolize other drugs
cytochrome P450
capable of inhibiting cytochrome P450
erythromycin
and clarithyromycin
antibiotic not capable of inhibiting cytochrome P450
azithromycin
is erytho still commonly used?
not anymore because of azithro and clarithro
antibiotic that promotes the effect of other drug because it inhibits Cyt P450
erythromycin
and clarithyromycin
drug against
Gram (+) cocci like pneumococci (not penicillin-resistant S. pneumoniae [PRSP])
Beta-lactamase-producing staphylococci (not Methicillin-resistant S. aureus [MRSA] strains)
erythromycin
drug of choice for the Prophylaxis against and treatment of M. avium complex
clarithromycin
Component for drug regimens for ulcers caused by H. pylori
clarithromycin
macrolide for neisseria
azithromycin
Long half-life, single dose is effective
Urogential infections caused by C. trachomatis
azithromycin
4-day course is effective for community-acquired pneumonia (CAP
azithromycin
identify which antibiotic causes this toxicity GI irritation is common Stimulation of motolin receptors Skin rashes Eosinophilia
macrolides
toxicity caused by Erythromycin estolate
Hypersensitivity-based acute cholestatic hepatitis
Hypersensitivity-based acute cholestatic hepatitis is rare in
children
there is increased risk of Hypersensitivity-based acute cholestatic hepatitis
pregnant patients
Inhibits several forms of cytochrome P450
Erythromycin and clarithromycin
Increases the plasma levels
Anticoagulants Carbamazepine
Cisapride Digoxin
Theophylline
Erythromycin and clarithromycin
macrolide whose similar drug interactions of erythromycin can occur
clarithromycin
Structure of lactone ring is slightly different
azithromycin
Drug interactions are uncommon because it Does not inhibit hepatic cytochrome P450
azithromycin
why are drug interactions uncommon for azithromycin
because it Does not inhibit hepatic cytochrome P450
prototype drug of ketolides
Telithromycin
Structurally related to macrolides
Telithromycin
Same MOA as erythromycin
Similar spectrum of antimicrobial activity
Telithromycin
advantage of Telithromycin over macrolides
Some macrolide-resistant strains are susceptible to telithromycin because it binds more tightly to ribosomes
why are Some macrolide-resistant strains susceptible to telithromycin (2)
because it binds more tightly to ribosomes
because it is a Poor substrate for bacterial efflux pump that mediate resistance
dosing regimen for telithromycin
orally once daily
mode of elimination for telithromycin
bile and urine
Inhibitor of cytochrome CYP3A4 isozyme
telithromycin
used for CAP and other upper respiratory tract infections
telithromycin
drugs (2) for community acquired pneumonia
telithromycin and azithromycin
prototype of lincosamides
clindamycin
MoA of clindamycine
Inhibit bacterial protein synthesis
Mechanism similar to macrolides but are not chemically related
Mechanism similar to macrolides but are not chemically related
clindamycin
Resistance to clindamycin (2)
Methylation of the binding site on 50S
Enzymatic inactivation
Cross-resistance with macrolides is —–
common
is clindamycin orally absorbed
yes
tissue penetration of clindamycin
good
mode of elimination of clindamycin
partly by metabolism and partly by biliary and renal excretion
clinical use of clindamycin
severe infections caused by anaerobes like bacteriodes
drug for severe infections caused by anaerobes like bacteriodes
clindamycin
Backup drug against gram (+) cocci
clindamycin
Prophylaxis for endocarditis in valvular heart disease who are allergic to penicillin
clindamycin
Active against P. carinii and T. gondii
clindamycin
Superinfection such as C. difficile and pseudomembranous colitis caused by clindamycin is Treated by
oral vancomycin
identify which antibiotic has these toxicities
GI irritation Skin rashes
Neutropenia Hepatic dysfunction
clindamycin
toxicities of clindamycin
GI irritation Skin rashes
Neutropenia Hepatic dysfunction
Antibiotic used for gram (-) anaerobe
clindamycin
Combination of 2 streptogramins
Quinupristin-dalfopristin
MoA of Quinupristin-dalfopristin
BACTERICIDAL
has a postantibiotic effect
Quinupristin-dalfopristin (and aminoglycosides)
Duration of bacterial activity is longer than the half-lives of the 2 compounds
Postantibiotic effect of Quinupristin-dalfopristin
Used for PRP, MRSA and vancomycin-resistant staphylococci (VRSA) and resistant E. faecium
Quinupristin-dalfopristin
First of a new class of antibiotics
linezolid
a class of a new antibiotics
oxazolidinone
newest antibiotic in the market
linezolid
for Gram (+) cocci, including strains resistant to beta-lactams and vancomycin
linezolid
Binds to a unique site on the 23S ribosomal RNA of 50S
linezolid
No cross-resistance with other protein synthesis inhibitors
linezolid
does linezolid have cross-resistance with other protein synthesis inhibitors
no
med preparationsof linezolid
oral and parenteral forms
drug with RARE resistance
linezolid
toxicity of linezolid
Thrombocytopenia and neutropenia occur in immunocompromised patients
resistance to linezolid
Decreased affinity of the drug for its binding site
prototype drug of macrolides
erythromycin
mode of elimination of azithromycin
urinary excretion
a macrolide that can be given to treat chlamydia
azithromycin, erythromycin, clarithromycin
which drug to give between doxycycline and azithromycin for chlamydia
azithromycin because you only give 1 dose
causes severe epigastric pain
erythromycin
advantage of linezolid
no cross resistance with other protein synthesis inhibitors
if allergic to penicillin and cephalosporin, what drug must be given next
macrolides since they are protein synthesis inhibitors
not aminoglycosides since they do not have oral preparation
not chloramphenicol since they are toxic
not tetracycline because not very common
