Pharmacology Exam II

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A group of closely related compounds characterized by a macrocyclic lactone ring to which deoxy sugars are attached

Macrolides
Macrolides contain ___-___ carbon atoms

14-16
Erythromycin
- macrolide
- wider spectrum than PCN
- used in people with PCN allergy
Erythromycin consists of
- two sugar moieties attached to a 14-atom lactone ring
- sugars are desosamine and cladinose
Erythromycin stability
- poorly water soluble
- solutions unstable at room temp
- lose activity rapidly in acidic pH
Reason why erythromycins are usually dispensed as various esters

to increase solubility
Erythromycin is active against
- gram-positive organisms
- gram-negative organisms
- Mycoplasma
- haemophilus influenzae somewhat less susceptible
Mechanism of Erythromycin
- inhibitory or bacteriocidal
- binds 50s ribosomal subunit
- blocks the aminoacyl translocation preventing transfer of tRNA at the A site from moving to the P site
Three mechanisms of resistance to macrolides
- reduced cell membrane permeability or active efflux
- production of esterases that hydrolize macrolides
- modification of the ribosomal binding site (ribosomal protection)
Most important resistance mechanisms against macrolides in gram positive organisms
- efflux
- methylase production
Cross resistance exists between

erythromycing and other macrolides
Erythromycin absorption
- erythromycin is destroyed in stomach acid and needs an enteric coating
- food interferes with absorption
- large amounts excreted in bile and feces, 5% in urine
Fairly acid-resistant, better absorbed forms of erythromycin
- stearates
- erythromycin ethylsuccinate
Distribution of erythromycin

widely distributed except CNS
Erythromycin is taken up by
- polymorphonuclear leukocytes
- macrophages
Will erythromycin cross the placenta?

yes
Erythromycin t1/2 is increased in patients with____ and is not removed via____.
- anuria
- dialysis
Erythromycin dosing must be done for patients with renal failure

A. True
B. False

B. False
Erythromycin is the drug of choice for

corynebacterial infections
Erythromycin is also used for
- respiratory infections
- neonatal/ocular/genital infections
- community aquired pneumonia
Erythromycin is recommended as prophylaxis against
- endocarditis during dental procedures
- largely replaced by clindamycin
ADRs with erythromycin
- N/V/D
- anorexia
- direct stimulation of GI motility
Forms of Erythromycin less likely to have adverse effects
- stearate
- succinate salt
Liver and Erythromycin
- can produce acute cholestatic hepatitis
- hepatitis recurs when the pt is given e-mycin again
Drug interactions with Erythromycin
- Erythromycin inhibits CYP3A4
- statin levels will ^^
- ergotamine and dihydroergotamnie levels ^^
- digoxin levels will ^^
Simvastatin + erythromycin

can cause rhabdomyolysis
clarithromycin
- derived from erythromycin by addition of 1 methyl group
- improved acid stability
- improved oral absorption
Uses of clarithromycin
- upper RTIs
- chronic bronchitis
- pneumonia
- skin infections
- legionellosis
- lyme disease
Mechanism of action for clarithromycin
- same as erythromycin
- binds 50s subunit and inhibits translocation of peptides
clarithromycin is metabolized by the _____ to _____.
- liver
- active metabolites (14-hydroxy clarithromycin)
14-hydroxy clarithromycin
- active metabolite of clarithromycin
- almost twice as active with a longer half life
Clarithromycin and metabolites are excreted via
- urinary
- biliary
Dosage reduction is recommended for patients with creatinine clearance less than ____ who are taking clarithromycin

30mL/min
Clarithromycin compared to erythromycin
- similar drug interactions
- cross resistance
- clarithromycin has a longer half life permiting bid dosing
- Cl. has lower incidence of GI intolerance
Clarithromycin is more effective than erythromycin against

certain gram negative bacteria including legionella pneumophila
Clarithromycin has bacteriostatic and bacteriocidal effects against
- H. Influenzae
- S. pneumonia
- N. Gonorrhoeae
Azithromycin
- zithromax
- 15 atom lactone macrolide
- additional methylated nitrogen added into the lactone ring of erythromycin
Mechanism of action for Azithromycin
- prevents bacterial growth
- binds 50s subunit of ribosome inhibiting translovation of mRNA
- nucleic acid synthesis is not affected
Azithromycin activity compared to Clarithromycin and Erythromycin

same spectrum
Active against M Avium complex and T gondii

azithromycin
More effective against staph and strep
- erythromycin
- clarithromycin
more active against H. influenzae

azithromycin
Highly active against chlamydia

azithromycin
Kinetics of Azithromycin
- low serum concentration
- absorbed into tissues and released slowly with a half life of 3 days
- once daily dosing
A single 1 gram dose of azithromycin is as effective as _____ for chlamydial cervictis and urethritis.

a 7 day course of doxycycline
Azithromycin administration with reguard to meals

1 hour before or 2 hrs after
Azithromycin CYP interaction

because it has a 15 membered ring it does not inactivate CYP enzymes
Ketolides
- semisynthetic 14 membered ring macrolides
- substitution of a 3-keto group for cladinose
Example of a ketolide

telithromycin
Mechanism of action for telithromycin
- prevents bacterial protein synthesis
- binds 50s ribosomal subunit
- can also inhibit formation of ribosomal complex formed between 50s and 30s
Telithromycin vs. erythromycin

telithromycin has over 10x higher affinity for the 50s subunit than erythromycin
Many macrolide resistant strains are succeptible to ketolides because
- poor substrates for efflux pumps
- bind ribosome with higher affinity
Absorption and excretion of telithromycin
- 57% oral bioavailability
- metabolized in the liver
- eliminated by biliary and urinary routes
Clinical uses for telithromycin
- Respiratory tract infetions
- non-tuberculosis mycobacteria
Telithromycin toxicities

rare cases of hepatitis and liver failure

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Card Set

Pharmacology Exam II

Description

Macrolides

Updated

2011-02-09T15:41:47Z

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