Antibiotics PDF

BACTERIOSTATIC Folic acid pathway: folic acid synthesis is necessary for the synthesis of nucleotides in bacterial and mammalian cells ○ Sulfamethoxazole (SMZ) ○ Trimethoprim (TMP): excellent drug for MRSA ○ SMZ-TMP (Bactrim): synergistic against a wide spectrum of bacterial species Used for UTIs if...

BACTERIOSTATIC Folic acid pathway: folic acid synthesis is necessary for the synthesis of nucleotides in bacterial and mammalian cells ○ Sulfamethoxazole (SMZ) ○ Trimethoprim (TMP): excellent drug for MRSA ○ SMZ-TMP (Bactrim): synergistic against a wide spectrum of bacterial species Used for UTIs if the patient is not allergic to sulfa medications Polytrim is a polymixin and is used as a first line of treatment for bacterial conjunctivitis Tetracyclines: broad drug meaning takes care of a wide variety of microbial species ○ Penetrates wall by passive diffusion and there the cytoplasmic membrane by ATP-dependent active transport system ○ Active against staphylococcus species and chlamydia and H. pylori ○ Tetracycline and oxytetracycline 60-70% absorbed Interfered by bivalent cations 40-80% protein bound ○ Doxycycline and minocycline: used more because of less food interference 95% absorption Less protein bound Renal and biliary excretion ○ Adverse effects: GI, Pseudomembranous colitis, Teratogenic defects (cause congenital disorders in a developing embryo or fetus), premature epiphysis closure (defective bone formation), and teeth discoloration in children under 12 years old, pseudotumor cerebri ○ Resistance: impaired diffusion, bacteria protein synthesis interferes with binding of tetracyclines, enzymatic inactivation 50S Ribosome Subunit: inhibits protein synthesis at 50s which is important for replication/growth ○ Macrolides: GI absorption is variable and does not cross the BBB barrier Adverse effects: (MACRO) M: Motility disturbances A: Arrhythmia C: Cholestatic (canalicular) hepatitis, Colitis R: Rash O: Eosinophilia Resistance: alteration in cell membrane permeability and modification of 50s subunit binding site Azithromycin: Zithromax (Z-pack) Semi-synthetic form of erythromycin by adding a methylated nitrogen group Better spectrum (Haemophilus influenzae disease) than the other macrolides and better activity: ½ life is 2-4 days Not metabolized by cytochrome P450 ○ Erythromycin Base, estolate, stearate, and ethyl succinate Activity: (MCS) -> Mycobacterium, Chlamydia, Staphylococcus and streptococcus Biliary excretion Do not give erythromycin if patient has hepatic dysfunction Clarithromycin (Biaxin) Synthetic form of erythromycin by adding a methyl group to the chemical structure of erythromycin - provides GI acid stability Used in tx for H. pylori (inhibits protein synthesis) Same spectrum as erythromycin Hydroxyclarithromycin (active metabolite) Renal and biliary excretion (dosage adjustment) Linezolid (Zyrox) Considered bacteriostatic against most organisms but has some bactericidal activity against streptococci, pneumococci, GAS, and anaerobes Inhibit of bacterial protein synthesis by blocking the formation of the 70s ribosomal initiation complex Oxazolidinone- used for gram + infections, can be bacteriostatic or bactericidal depending on bacteria being treated Lincosamide: Clindamycin Binds to 50s ribosomal binding site as other macrolides At low concentrations, clindamycin inhibits the production of toxic shock and other toxins by GAS and S. aureus A bacteriostatic agent but has a concentration-dependent bactericidal activity against staphylococci, streptococci, anaerobes, and H. pylori BACTERIOCIDAL Antibiotics that interfere with DNA synthesis ○ DNA Integrity Metronidazole: Increases formation of reactive oxygen species (free radicals) to produce breaks in bacteria’s DNA Enters bacteria via cell diffusion Contraindicated in patients with renal or liver impairment Can kill anaerobes ○ Protozoans- Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis ○ Most gram-negative and gram-positive anaerobic bacteria Used often due to bacterial resistance to amoxicillin and tetracycline or due to intolerance (H. pylori) ○ mRNA synthesis Rifampicin Used for treatment of TB ○ DNA gyrase function Fluoroquinolones: concentration dependent Nicks and relaxes DNA supercoiled for DNA replication and is believed to have activity on supercoiling after replication Topoisomerases II: Gram-negative Topoisomerases IV: Gram-positive 1st gen: Ciprofloxacin & ofloxacin (broad-spectrum drug) 2nd gen: Levofloxacin & moxifloxacin (newer gen & better for gram + bacteria) Parent drug: Nalidixic acid (a quinolone) Inhibitors of cell wall synthesis: beta-lactams are time-dependent killing ○ [I]: Peptidoglycan synthesis Vancomycin- (time-dependent) glycopeptides: inhibit the second stage of cell wall peptidoglycan synthesis by binding to the (D-alanyl-D-alanine precursor) peptide side chain, which fits into a “pocket” in the vancomycin molecule and that prevents assemble of the murein monomer into peptidoglycan Good for MRSA infections Penicillin allergic and has resistance to gram + Used for osteomyelitis as well Contraindicated in patients with renal impairment ○ [II]: Cross-linking of peptidoglycans Natural PCN’S: great for internal hordeolum Penicillin G potassium Penicillin V phenoxy methyl ○ Penicillinase-resistant (CONDOM) Oxacillin, Nafcillin, Dicloxacillin Cloxacillin Methicillin ○ Amino-PCN’S: extended drugs, effective against gram + and - organisms and used for H. pylori Ampicillin Amoxicillin: used in tx of H. pylori (disrupts cell wall) ○ Antipseudomonal PCN’S Ureidopenicillin -> Piperacillin ○ Cephalosporins: rx oral cephalosporins for internal hordeolum 1st gen Cefazolin 2nd gen Cefuroxime Cefoxitin 3rd gen Cefotaxime Ceftriaxone Ceftazidime 4th gen Cefepime Cefpirome ○ Carbapenems: used for the treatment of severe infections of resistant bacteria, subclass of beta-lactams, “beast agents” kill both + and - organisms D.I.M.E Doripenem (Doribax) Imipenem (Primaxin) High affinity to high molecular weight PBPs Meropenem (Merem) Ertapenem (Invanz) ○ Monobactams Aztreonam 30S Ribosome subunit ○ Aminoglycosides: concentration-dependent, mainly IV admin, main activity against a gram - bacilli and staph. species Systemic administration may lead to ototoxicity, nephrotoxicity, and respiratory depression Reserved for severe systemic gram - infections Excreted in topical ophthalmic use, but only for short therapy (5-7 days) Resistance: alteration of 30s subunit binding site, change cell membrane permeability, enzymatic inactivation Adverse effects: vestibular and auditory dysfunction, nephrotoxicity (tubular necrosis), respiratory depression (neuromuscular paralysis) Tobramycin Gentamycin Beta-lactamase inhibitors: protects from the hydrolytic activity of beta-lactamases by “suicide” inactivation (inhibitor is hydrolyzed) ○ Amoxicillin-clavulanate ○ Piperacillin-tazobactam ○ Ampicillin-sulbactam