ANTIMICROBIAL DRUGS-2

Presented by: Sarbeel Al Mosddar

Drugs that act on 50S subunit

Chloramphenicol

Antimicrobial Activity: • Chloramphenicol has a wide spectrum of antimicrobial activity bacteriostatic . Some strains of H influenzae, N meningitidis, and bacteroides chloramphenicol bactericidal.. It is not active against chlamydia The drug is commonly used as a topical antimicrobial

Toxicity: • Gastrointestinal disturbances: Gray baby syndrome: Aplastic anemia:

MACROLIDES

erythromycin, azithromycin, and clarithromycin) • chlamydia, mycoplasma, legionella, gram-positive cocci, and some gram-negative organisms. Azithrornycin has a similar spectrum of activity but is more active against H influenzae, Adverse effects include gastrointestinal irritation (common), skin rashes,

CLINDAMYCIN

inhibit bacterial protein synthesis via a mechanism similar to that of the macrolides,

treatment of severe infec tions due to certain anaerobes such as bacteroides.

prophylaxis of endocarditis in valvular disease patients who are penicillin-allergic. toxicity of clindamycin includes gastrointestinal irrita tion, skin rashes, neutropenia

LINEZOLID

drug-resis tant gram-positive cocci, including • strains resistant to beta-lactams and vancomycin - resistant Enterococcusfaecium). • Linezolid binds to a unique site on the 50S ribosomal sub unit,

Telithromycin

Ketolide group • Similar in structure and action to macrolide Gram-positive and gram -negative bacteria • • Treatment of community acquired pneumonia •

STREPTOGRAMIN S

Quinupristin-dalfopristin combination of two streptogramins, penicillin-resistant pneumococci, ° a is bactericidal • methicillin-resistant) and vancomycin-resistant staphylococci resistant Entero coccus faecium.

Inhibition of nucleic acid synthesis

Inhibition of precursor

• Sulfonamides: active against gram-positive and gram-negative bacteria. nocardia. Shigella.Escherichia

Selective action in blocking folic acid synthesis

Trimethoprim:

Trimethoprim is a selective inhibitor of bacterial dihydrofolate reductase • dihydrofolate reductase is four to five orders of magnitude mammalian enzyme. Trimethoprim plus sulfamethoxazole:

Inhibition of DNA synthesis

Quinolones Bactericidal Inhibit DNA GYRASE

ciprofloxacin, ofloxacin, levofloxacin, lomefloxacin, and sparfloxacin. Fluoroquinolones are effective in the treatment of infections urogenital and gastrointestinal tracts caused by gram-negative respiratory tract, skin, and soft tissue infections,

Flucytosine

pyrimidine antimetabolite • Flucytosine is accumulated in fungal cells by the action of a membrane permease converted by cytosine deaminase to 5-FU, an inhibitor of thymidylate synthase The antifungal spectrum of 5-FC is narrow; Cryptococcus neofor roans and possibly systemic candidal infections.

Inhibition of mRNA synthesis

Rifampin: • bactericidal against M tuberculo sis. The drug inhibits DNA-dependent RNA polymerase InTP rifampin is always used in combination with other drugs. prophylaxis against tuberculosis in 1NH-intolerant patients

Alternation of bacterial cell membrane

Polymyxins • Polypeptid • Polymyxin E most clinically useful AGAINST gram-negative bacteria • • Cationic detergent for phospholipids in plasma membrane •

daptomycin

Lipopeptide that disrupt the cell membrane of gram – positive bacteria •

Alternation of fungal cell membrane

Amphotericin B: • Amphotericin B is the most important of the drugs in treatment of systemic mycoses widest antifungal spectrum the drug of choice for most systemic infections caused by aspergillus, Candida albicans, cryptococcus, bind to ergosterol, a sterol specific to fungal cell membranes, and cause the formation of artificial pores

Amphotericin B decreases the glomemlar filtration rate • tubular acidosis with magnesium and potassium wasting. Anemia Liposomal formulations of amphotericin B have reduced nephrotoxic effects,

Nystatin • Only used topically for infection caused by Candidad The azoles interfere with fungal cell membrane permeability hibiting the synthesis of ergosterol. -demethylation of lanosterol  These drugs act at the step of 14c , which is catalyzed by a cytochrome P450 isozyme. Adverse effects of the azoles include vomiting, diarrhea, rash,

Ketoconazole:

narrow antifungal spectrum • backup drug for systemic infections caused by certain blastomyces, coccidioides, and histoplasma. commonly for chronic mucocutaneous candidiasis

Fluconazole:

Fluconazole is a drug of choice in esophageal and oropharyngeal can didiasis

Additional drug mechanisms

Antibacterial activity

Isoniazid

• • the single most important drug used in tuberculosis inhibition of enzymes required for the synthesis of mycolic acid Neurotoxic effects are common and include peripheral neuritis, restlessness, muscle twitching, and insomnia. administration of pyridoxine. hepatotoxic

Metronidazole:

activity against protozoa and bacteria. metronidazole is the drag of choice in trichomoniasis treatment of in- testinal amebiasis and amebic hepatic abscess. HAVE 2 mechanismes of action Electron sink Inhibit DNAsynthysis

Ethambutol

Bacteriostatic • Ethambutol inhibits arabinosyl transferases involved in the synthesis of arabinogalactan, a component of mycobacterial cell walls. The only use of ethambutol is in tuberculosis, The most common adverse effects are dose-dependent visual disturbances,

Antifungal activity

Griseofulvin Treatment of hair and nail infection Bind to tubulin

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Chemoprophylaxis • probiotics •

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