32 Questions
What is the mechanism of action of macrolides in inhibiting protein synthesis?
Reversibly binding to the 50s ribosomal subunit
Which macrolide has a similar antimicrobial spectrum as erythromycin but is more effective against certain gram-negative bacteria?
Roxithromycin
What is the primary site of metabolism for erythromycin?
Liver
Which statement best describes the pharmacokinetics of macrolides?
Widespread distribution with higher concentrations in most tissues than in the serum
What effect does macrolide binding have on the ribosome?
Stimulates dissociation of peptidyl tRNA from the ribosome
What is the half-life (t½) of erythromycin?
1.6 hours
What is the primary route of excretion for erythromycin?
Excretion in bile
Which enzyme does erythromycin strongly inhibit?
P450 3A4 isoenzymes
What are some of the potential life-threatening drug interactions associated with erythromycin?
Midazolam, quinidine, warfarin
What percentage of patients may experience gastrointestinal adverse effects from erythromycin?
~30%
In which patients is hepatic cholestatic toxicity from erythromycin more common?
Patients with pre-existing liver dysfunction
Which macrolide antibiotic has a longer half-life compared to erythromycin?
Clarithromycin
Which macrolide antibiotic is extraordinarily well-tolerated and has very few drug interactions?
Azithromycin
Which mechanism of antibiotic resistance involves methylation of the 23s rRNA of the 50s ribosomal subunit?
Target site alteration
Which resistance mechanism for macrolides is associated with enzymatic inactivation of erythromycin by esterases or phosphotransferases?
Antibiotic modification
What types of microorganisms belong to the Gram-negative group that shows primary resistance to macrolides due to decreased permeability?
Haemophilus inf.
Which bacterial protein synthesis inhibitor reversibly binds to the 50s ribosomal subunit and interferes with the elongation phase?
Streptogramins
What is a general characteristic of erythromycin's metabolism?
Catalyzed by CYP3A enzymes in the liver
Which macrolide antibiotic has a similar antimicrobial spectrum as erythromycin and is more effective against certain gram-negative bacteria?
Dirithromycin
What is the primary route of excretion for erythromycin?
Biliary excretion
Which resistance mechanism for macrolides is associated with enzymatic inactivation of erythromycin by esterases or phosphotransferases?
Enzymatic inactivation of the drug
What effect does macrolide binding have on the ribosome?
Stimulates peptidyl-tRNA dissociation
What is the mechanism of action of azithromycin in inhibiting protein synthesis?
Inhibiting 50S ribosomal subunit
What factor contributes to macrolide resistance among most Gram-negative bacteria?
Decreased permeability
Which macrolide antibiotic is most likely to inhibit cytochrome P450 enzymes?
Erythromycin
What adverse effect is more common with higher doses of clarithromycin?
Taste disturbances
Which antibiotic has a longer half-life compared to azithromycin?
Clarithromycin
What is the primary route of excretion for azithromycin?
Excreted by the kidneys
Which macrolide antibiotic is associated with lifethreatening drug interactions such as with midazolam, quinidine, and warfarin?
Erythromycin
What is the primary site of metabolism for clarithromycin?
Metabolized by the liver (N demethylation)
What percentage of patients may experience gastrointestinal adverse effects from azithromycin?
~10%
In which patients is hepatic cholestatic toxicity from erythromycin more common?
Patients with pre-existing liver dysfunction
Study Notes
Mechanism of Action
- Macrolides inhibit protein synthesis by binding to the 50s ribosomal subunit, interfering with the elongation phase.
Azithromycin
- Has a similar antimicrobial spectrum as erythromycin but is more effective against certain gram-negative bacteria.
- Has a longer half-life compared to erythromycin.
Erythromycin
- Primary site of metabolism is in the liver.
- Half-life (t½) is 1.5-2 hours.
- Primary route of excretion is through the bile.
- Strongly inhibits cytochrome P450 enzymes.
- Can cause gastrointestinal adverse effects in up to 30% of patients.
- Hepatic cholestatic toxicity is more common in elderly patients.
Macrolide Resistance
- Can occur through methylation of the 23s rRNA of the 50s ribosomal subunit.
- Can occur through enzymatic inactivation of erythromycin by esterases or phosphotransferases.
- Decreased permeability contributes to primary resistance in Gram-negative bacteria.
Clarithromycin
- Has a longer half-life compared to azithromycin.
- Is associated with life-threatening drug interactions such as with midazolam, quinidine, and warfarin.
- Primary site of metabolism is in the liver.
- Higher doses can cause gastrointestinal adverse effects.
- Can cause hepatic cholestatic toxicity, more common in elderly patients.
Pharmacokinetics
- Macrolides have a narrow therapeutic window and are metabolized in the liver.
Ribosome Binding
- Macrolide binding causes a conformational change in the ribosome, blocking the exit tunnel and inhibiting protein synthesis.
Test your knowledge on protein synthesis inhibitors such as Macrolides, Lincosamides, Aminoglycosides, Streptogramins, and Oxazolidinones. Learn to differentiate between antimicrobials based on mechanism of action, spectrum of activity, resistance mechanisms, toxicity, and appropriate use.
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