أسئلة الـ 17 فارما PPPM (قبل التعديل)

Protein Synthesis Inhibitors (50S Subunit Inhibitors)

• Macrolides are a type of protein synthesis inhibitor.
• Other protein synthesis inhibitors are Clindamycin, Linezolid, Quinupristin + Dalfopristin, and Chloramphenicol.

Macrolides

• Erythromycin, Clarithromycin, and Azithromycin are examples of macrolides.
• Macrolides are bacteriostatic at low doses but can be cidal at high doses.
• Whether a macrolide is cidal depends on the organism.
• Their mechanism of action involves inhibiting protein synthesis by targeting the 50S ribosomal subunits.
• Macrolides are active against Gram-positive bacteria.
• Some Gram-negative bacteria that macrolides are effective against are H. pylori (Clarithro > azithro), H. influenzae (Azithromycin is the most active), B. pertussis, Nisseria, and Enterobacteriaceae.
• Macrolides are also effective against atypical bacteria like Mycoplasma, Chlamydia, and Legionella.

Erythromycin

• Acid labile, so it is available in enteric-coated tablets to protect it from stomach acid.
• Absorption is incomplete, and food delays absorption but its esters are better absorbed.
• Distribution is wide, entering cells, abscesses, and the placenta, but it does not cross the blood-brain barrier (BBB).
• Excretion occurs mainly in bile.

Clarithromycin & Azithromycin

• These are more acid-stable and have better absorption compared to erythromycin.
• They exhibit larger tissue distribution and intracellular penetration
• Metabolism and excretion mainly occur in bile.
• Clarithromycin gets metabolized into an active metabolite, and 30% of it is excreted unchanged in urine.
• Azithromycin is largely excreted unchanged.

Therapeutic Uses

• Macrolides serve as an alternative to penicillin for those allergic to it.
• They can be used in the treatment of streptococcal pharyngitis, tonsillitis, upper and lower respiratory infections, and skin and soft tissue infections.
• Azithromycin is useful in treating infections caused by atypical bacteria like atypical pneumonia (Mycoplasma, Chlamydia, and Legionella).
• Macrolides can be used in the treatment of Chlamydial infections such as urethritis, genital infections in men and women, and eye infections.
• Macrolides are used in the treatment of whooping cough.
• Clarithromycinis used against H. pylori, which causes peptic ulcers.
• Macrolides are effective against toxoplasmosis (a protozoal infection).

Adverse Effects

• Macrolides can cause gastrointestinal upset, abdominal pain, and diarrhea, especially with erythromycin.
• Macrolides can cause hepatitis and cholestatic jaundice.
• Erythromycin inhibits liver microsomal enzymes (CYP3A4), causing drug interactions that increase the levels of warfarin and second-generation antihistamines; azithromycin does not inhibit.
• Macrolides can cause QT prolongation and ventricular arrhythmia.
• Macrolides can cause thrombophlebitis if administered intravenously, as well as hypersensitivity reactions.

Clindamycin

• Clindamycin has a similar mechanism of action and spectrum to erythromycin.
• Clindamycin is active against Gram-positive bacteria and anaerobic infections (Bacteroides fragilis).
• Clindamycin serves as an alternative to penicillin for individuals with allergies.
• It treats anaerobic (Bact. fragilis) and mixed infections, including abdominal, pelvic, and lung abscesses, especially when combined with an aminoglycoside or a cephalosporin.
• Topical clindamycin is used for acne treatment.
• Side effects can include superinfection by Clostridium difficile (colitis).

Linezolid

• Linezolid exhibits bacteriostatic properties.
• It inhibits protein synthesis by targeting the 50S ribosomal subunits.
• Linezolid is effective against resistant Gram-positive bacteria, including MRSA, some VRSA, and VRE.
• Its use is restricted to serious and multidrug-resistant bacterial infections, such as hospital-acquired pneumonias and bacteremia.

Quinupristin + Dalfopristin

• This combination exerts synergistic inhibition of bacterial protein synthesis and considered bactericidal.

Chloramphenicol

• Inhibits protein synthesis by binding 50S subunits
• Has a broad spectrum
• Due to toxicity, its use is restricted
• Used topically for eye infections.
• Used for typhoid fever (though ampicillin and quinolones are better choices).
• Dose-dependent bone marrow depression can occur.
• Can cause gray baby syndrome.
• Newborns have difficulty metabolizing it.
• This syndrome is fatal in 40% of cases.

Fusidic Acid

• Inhibits bacterial protein synthesis.
• Spectrum is narrow.
• Active against penicillinase-producing Staphylococci and other G + Ve bacteria.
• Used topically for cutaneous infections (boils, folliculitis)
• Available as ointment and cream.