Pharmacology
Summary
The macrolide class of antibiotics--- which includes erythromycin, azithromycin, clarithromycin, and fidaxomicin--- exerts its bacteriostatic action by binding to the 50S ribosomal subunit within bacterial cells. This binding obstructs protein synthesis, which effectively halts bacterial replication and growth.
Along with their antimicrobial applications, macrolides exhibit strong anti-inflammatory properties in the lungs, making them suitable for managing chronic lung diseases. Additionally, these antibiotics enhance smooth muscle motility in the gut, imparting a prokinetic effect that aids gastrointestinal movement.
Macrolides, owing to their broad bacterial coverage, find utility in an array of clinical scenarios. These include treating community-acquired pneumonias, atypical pneumonias, pertussis, mycobacterial infections like mycobacterium avium complex (MAC), sexually transmitted infections, neonatal eye infections, and H. pylori-related ulcers. Additionally, macrolides are unique for their use against Mycoplasma, Babesia, and Bartonella infections.
Different types of macrolides offer distinct advantages; for instance, fidaxomicin is ideal for C. difficile colitis due to its bactericidal nature and high retention in the gut. While effective, however, macrolides use is not without its drawbacks. Potential adverse effects include hepatotoxicity, potentially fatal cardiac dysrhythmias, heightened risks in patients with coronary artery disease, and skin rashes. Drug interaction is also an important consideration for patients on macrolides due to their inhibitory effect on cytochrome P450 and P-glycoprotein.
Lesson Outline
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FAQs
Macrolides function by binding to the 50S subunit of the bacterial ribosome, which prevents ribosomal translocation and thus inhibits protein synthesis. This action primarily renders them bacteriostatic antibiotics, meaning they inhibit bacterial growth and reproduction. Note, however, that fidaxomicin is an exception as it is bactericidal, meaning it kills bacteria directly.
One unique characteristic of macrolides is their ability to decrease respiratory inflammation, which makes them useful agents for preventing flare-ups and/or infections in chronic lung disease such as COPD, CF, and bronchiectasis. Additionally, macrolides can increase gastrointestinal motility, making them effective GI prokinetic agents.
Macrolides are broad-spectrum antimicrobials, which means they are effective against a wide variety of bacteria including gram-positive, gram-negative, and atypical bacteria. Examples of bacterial infections treated by certain macrolides include community-acquired pneumonia, atypical pneumonia caused by Legionella and Chlamydia, Mycoplasma pneumonia, Bordetella pertussis (whooping cough), Bartonella henselae infections (cat-scratch fever), Babesia infection, and infections caused by Corynebacterium diphtheriae and the Mycobacterium avium complex (MAC).
Macrolides can potentially cause hepatotoxicity, which includes mild to severe liver damage and even liver failure. They can also trigger an intrahepatic biliary duct injury that may result in biliary obstruction, acute cholestatic hepatitis, and jaundice. These antibiotics can also cause a prolongation of the Q-T interval which can increase the risk for fatal dysrhythmia like torsades de pointes. Additionally, rare but severe delayed hypersensitivity skin reactions like DRESS or SJS (Steven Johnson's Syndrome) can potentially occur.
Macrolides are known to inhibit cytochrome P450, an enzyme that plays a crucial role in the body's ability to metabolize a wide variety of drugs. This inhibition can potentially lead to drug-drug interactions that may affect the safety or efficacy of other medications. Furthermore, macrolides are strong inhibitors of the P-glycoprotein efflux pump, a protein that helps transport various molecules across intracellular and extracellular membranes. This could affect absorption, distribution, metabolism, or excretion of other drugs.
