Pharm_Antibiotics Flashcards
Aminoglycosides: Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
Mechanism: Bactericidal; inhibit formation of initiation complex and cause misreading of mRNA. Requite O2 for uptakel therefore ineffective against anaerobes. Clinical use: Severe gram-negative rod infections. Synergistic with β-lactam antibiotics. Neomycin for bowel surgery. Toxicity: Nephrotoxicity (+ cephalosporins), Ototoxicity (+ loop diuretics). Teratogen.
Ampicillin, amoxicillin (aminopenicillins)
Mechanism: Same as penicillin. Wider spectrum; penicillinase sensitive. Also combine with clavulanic acid to enhance spectrum. Amoxicillin has greater oral bioavailability than ampicillin. Clinical use: Extended-spectrum penicillin - certain gram-positive bacteria (Listeria monocytogenes, Enterococci) and gram-negative rods (Haemophilus influenza, E.coli, Proteus mirabilis, Salmonella) Toxicity: Hypersensitivity reactions; ampicillin rash; pseudomembranous colitis
Anti-TB drugs (5)
1st line - Streptomycin, Pyrazinamide, Isoniazid (INH), Rifampin, Ethambutol 2nd line - Cycloserine Important side effect of ethambutol is optic neuropathy (red-green color blindness). For other drugs, hepatotoxicity.
Antimycobacterial drugs
M.tuberculosis Prophylaxis: Isoniazid; Treatment: Rifampin, Isoniazid, Pyrazinamide, Ethambutol M.avium-intracellulare Prophylaxis: Azithromycin; Treatment: Azithromycin, rifampin, ethambutol, streptomycin M.leprae Prophylaxis: N/A; Treatment: Dapsone, rifampin, clofazimine
Aztreonam
Mechanism: A monobactam resistant to β-lactamases. Inhibits cell wall synthesis (binds to PBP3). Synergistic with aminoglycosides. No cross-allergenicity with penicillins. Clinical use: Gram-negative rods only - No activity against gram-positive anaerobes. For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides. Toxicity: Usually nontoxic; occasional GI upset. No cross-sensitivity with penicillin or cephalosporins
Bactericidal antibiotics (6)
Vancomycin, Fluoroquinolones, Penicillin, Aminoglycosides, Cephalosporins, Metronidazole
Bacteriostatic antibiotics (6)
Erythromycin, Clindamycin, Sulfamethoxazole, Trimethoprim, Tetracyclines, Chloramphenicol
Cephalosporins: 1st generation (cefazolin, cephalexin)
Mechanism: β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal. Clinical use: gram-positive cocci, Proteus mirabilis, E.coli, Klebsiella pneumoniae Toxicity: Hypersensitivity reactions, vitamin K deficiency. Cross-hypersensitivity with penicillins occurs in 5-10% of patients. ↑nephrotoxicity of aminoglycosides; disulfiram-like reaction with ethanol (in cephalosporins with a methylthiotetrazole group, e.g., cefamandole)
Cephalosporins: 2nd generation (cefoxitin, cefaclor, cefuroxime)
Mechanism: β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal. Clinical use: gram-positive cocci, Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E.coli, Klebsiella pneumoniae, Serratia marcescens Toxicity: Hypersensitivity reactions, vitamin K deficiency. Cross-hypersensitivity with penicillins occurs in 5-10% of patients. ↑nephrotoxicity of aminoglycosides; disulfiram-like reaction with ethanol (in cephalosporins with a methylthiotetrazole group, e.g., cefamandole)
Cephalosporins: 3rd generation (ceftriaxone, cefotaxime, ceftazidime)
Mechanism: β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal. Clinical use: serious gram-negative infections resistant to other β-lactams Toxicity: Hypersensitivity reactions, vitamin K deficiency. Cross-hypersensitivity with penicillins occurs in 5-10% of patients. ↑nephrotoxicity of aminoglycosides; disulfiram-like reaction with ethanol (in cephalosporins with a methylthiotetrazole group, e.g., cefamandole)
Cephalosporins: 4th generation (cefepime)
Mechanism: β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal. Clinical use: ↑ activity against Pseudomonas and gram-positive organisms Toxicity: Hypersensitivity reactions, vitamin K deficiency. Cross-hypersensitivity with penicillins occurs in 5-10% of patients. ↑nephrotoxicity of aminoglycosides; disulfiram-like reaction with ethanol (in cephalosporins with a methylthiotetrazole group, e.g., cefamandole)
Chloramphenicol
Mechanism: Inhibits 50S peptidyltransferase activity. Bacteriostatic. Clinical use: Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae). Conservative use owing to toxicities but often still used in developing countries due to low cost. Toxicity: Anemia (dose dependent), aplastic anemia (dose dependent), gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase)
Clavulanic acid
β-lactamase inhibitors
Clindamycin
Mechanism: Blocks peptide bond formation at 50S ribosomal subunit. Bacteriostatic. Clinical use: Anaerobic infections (e.g., Bacterioides fragilis, Clostridium perfrigens) in aspiration pneumonia or lung abscesses. Toxicity: Pseudomembranous colitis (C. difficile overgrowth), fever, diarrhea PS: Treats anaerobes above the diaphragm vs. metronidazole (anaerobic infections below the diaphragm)
Contraindication: Tetracyclines
in pregnancy
Contraindications: Fluoroquinolones
in pregnant women and in children because animal studies show damage to cartilage
Demeclocycline
ADH antagonist; acts as a diuretic in SIADH
DOC: Candida albicans
Nystatin for superficial infection; amphotericin B for serious systemic infection
DOC: Chlamydiae
azithromycin or doxycycline
DOC: Gardnerella vaginalis
metronidazole
DOC: Haemophilus influenzae
Treat meningitis with ceftriaxone. Rifampin prophylaxis in close contacts.
DOC: Helicobacter pylori (3)
Triple therapy: (1) metronidazole, bismuth, tetracycline / amoxicillin; (2) metronidazole, omeprazole, clarithromycin (3) PPI, clarithromycin, amoxicillin / metronidazole
DOC: Legionella pneumophila
erythromycin
DOC: Leprosy (Hansen’s disease)
Long-term oral dapsone; toxicity is hemolysis and methomoglobinemia. Alternate treatments include rifampin and combination of clofazimine and dapsone.
DOC: Lyme disease - Borrelia burgdorferi
doxycycline, ceftriaxone
DOC: Mycoplasma pneumoniae
tetracycline or erythromycin
DOC: Neonatal Chlamydia trachomatis
azithromycin
DOC: Pneumocystis jiroveci (formerly carinii)
TMP-SMX, pentamidine, dapsone
DOC: Pseudomembranous colitis - Clostridia difficile
Metronidazole
DOC: Pseudomonas aeruginosa
Aminoglycoside + extended-spectrum penicillin (e.g., piperacillin, ticarcillin)
DOC: Rickettsiae
Doxycycline
DOC: Sporothrix schenckii
Itraconazole or potassium iodide
DOC: Syphilis
penicillin G
DOC: Systemic mycoses (Histoplasmosis, Blastomycosis, Coccidioidomycosis, Paracoccidioidomycosis)
fluconazole or ketoconazole for local infection; amphotericin B for systemic infection
DOC: Tinea pedis (foot), Tinea cruris (groin), Tinea corporis (ringworm on body), Tinea capitis (head, scalp) - Microsporum, Trichophyton, and Epidermophyton
treated with topical azoles
DOC: Tinea versicolor - Malassezia furfur
topical miconazole, selenium sulfide (Selsun)
Ethambutol
↓ carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
Fluoroquinolones: Ciprofloxacin, norfloxacin, ofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, enoxacin (fluoroquinolones), nalidixic acid (a quinolone)
Mechanism: Inhibit DNA gyrase (topoisomerase II). Bactericidal. Must not be taken with anticids. Clinical use: Gram-negative rods of urinary and GI tracts (including Pseudomonas), Neisseria, some gram-positive organisms. Toxicity: GI upset, superinfections, skin rashes, headache, dizziness. Tendonitis and tendon rupture in adults; leg cramps and myalgias in kids
Imipenem / cilastatin, meropenem
Mechanism: Imipenem is a broad-spectrum, β-lactamase-resistant carbapenem. Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to ↓ inactivation of drug in renal tubules. Clinical use: Gram-positive cocci, gram-negative rods, and anaerobes. Wide spectrum, but the significant side effects limit use of life threatening infections, or after other drugs have failed. Meropenem, however, has a reduced risk of seizures and is stable to dihydropeptidase I. Toxicity: GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels
Isoniazid (INH)
Mechanism: ↓ synthesis of mycolic acids. Bacteria catalase-peroxidase needed to convert INH to active metabolite Clinical use: Mycobacterium tuberculosis. The only agent used as solo prophylaxis against TB. (Different INH half-lives in fast vs. slow acetylators) Toxicity: Neurotoxicity, hepatotoxicity, lupus. Pyridoxine (vitamin B6) can prevent neurotoxicity, lupus
Macrolides: Erythromycin, azithromycin, clarithromycin
Mechanism: Inhibit protein synthesis by blocking translocation; bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic. Clinical use: Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), URIs, STDs, gram-positive cocci (streptococcal infections in patients allergic to penicillin), and Neisseria Toxicity: Prolonged QT interval (especially erythromycin), GI discomfort (most common cause of noncompliance), acute cholestatic hepatitis, eosinophilia, skin rashes. Increases serum concentration of theophyllines, oral anticoagulants.
Mechanism in resistance: Fluoroquinolones
Chromosome-encoded mutation in DNA gyrase
Mechanism of action: Block cell wall synthesis by inhibition of peptidoclycan cross-linking
Drugs: Penicillin, ampicillin, ticarcillin, piperacillin, imipenem, aztreonam, cephalosporins
Mechanism of action: Block DNA topoisomerases
Drugs: Fluoroquinolones
Mechanism of action: Block mRNA synthesis
Drugs: Rifampin
Mechanism of action: Block nucleotide synthesis
Drugs: Sulfonamides, trimethoprim
Mechanism of action: Block peptidoglycan synthesis
Drugs: Bactitracin, vancomycin
Mechanism of action: Block protein synthesis at 50S ribosomal subunit
Drugs: Chloramphenicol, macrolides, clindamycin, streptogramins (quinupristin, dalfopristin), linezolid
Mechanism of action: Blocks protein synthesis at 30S ribosomal subunit
Drugs: Aminoglycosides, tetracyclines
Mechanism of action: Disrupt bacterial cell membranes
Drugs: Polymyxins
Mechanism of resistance: Aminoglycosides
Transferase enzymes that inactivate the drug by acetylation, phosphorylation, or adenylation
Mechanism of resistance: Chloramphenicol
Plasmid-encoded acetyltransferase that inactivates drug
Mechanism of resistance: Macrolides
Methylation of 23S rRNA binding site
Mechanism of resistance: Sulfonamides
Altered enzyme (bacterial dihydropteroate synthetase), ↓ uptake, or ↑PABA synthesis
Mechanism of resistance: Tetracyclines
↓ uptake into cells or ↑ efflux out of cell by plasmid-encoded transport pumps
Mechanism of resistance: Vancomycin
Occurs with amino acid change of D-ala D-ala to D-ala D-lac
Methicillin, nafcillin, dicloxacillin (penicillinase-resistant penicillins)
Mechanism: Same as penicillin. Narrow spectrum; penicillinase resistant because of bulkier R group. Clinical use: S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site) Toxicity: Hypersensitivity reactions; methicillin - interstitial nephritis
Metronidazole
Mechanism: Froms free radical toxic metabolites in the bacterial cell that damage DNA. Bactericidal, antiprotozoal. Clinical use: Treats Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, Clostridium). Used with bismuth and amoxicillin (or tetracycline) for “triple therapy” against H.Pylori Toxicity: Disulfiram-like reaction with alcohol; headache, metallic taste
Nonsurgical antimicrobial prophylaxis: Endocarditis with surgical or dental procedures
Penicillins
Nonsurgical antimicrobial prophylaxis: Gonorrhea
Ceftriaxone
Nonsurgical antimicrobial prophylaxis: History of recurrent UTIs
TMP-SMX
Nonsurgical antimicrobial prophylaxis: Meningococcal infection
Rifampine (drug of choice), minocycline
Nonsurgical antimicrobial prophylaxis: Mycobacterium avium-intracellulare
Azithromycin
Nonsurgical antimicrobial prophylaxis: Pneumocystis jiroveci pneumonia
TMP-SMX (drug of choice), aerosolized pentamidine
Nonsurgical antimicrobial prophylaxis: Syphilis
Benzathine penicillin G
Penicillin: Penicillin G (IV form), Penicillin V (oral). Prototype β-lactam antibiotics.
Mechanism: 1. Bind penicillin-binding proteins 2. Block transpeptidase cross-linking of cell wall 3. Activate autolytic enzymes Clinical use: Mostly used for gram-positive organisms (S.pneumoniae, S.pyogenes, Actinomyces) and syphilis. Not penicillinase resistant. Toxicity: Hypersensitivity reactions, hemolytic anemia.
Polymyxins: Polymyxin B, colistimethate (polymyxin E)
Mechanism: Bind to cell membrane of bacteria and disrupt their osmotic properties. Polymyxins are cationic, basic proteins that act like detergents Clinical use: Resistant gram-negative infections. Toxicity: Neurotoxicity, acute renal tubular necrosis
Prophylaxis: Mycobacteria avium-intracellulare
azithromycin
Prophylaxis: Neisseria Meningococci
Rifampin prophylaxis in close contacts
Protein synthesis 30S inhibitors
Aminoglycosides [bactericidal] Tetracyclines [bacteriostatic]
Protein synthesis 50S inhibitors
Chloramphenicol, Clindamycin [bacteruistatic] Erythromycin [bacteriostatic] Lincomycin [bacteriostatic] Linezolid [variable]
Pyrazinamide
Effective in acidic pH of phagolysosomes, where TB engulfed by macrophages is found
Rifampin
Mechanism: Inhibits DNA-dependent RNA polymerase Clinical use: Mycobacterium tuberculosis; delays resistance to dapsone when used for leprosy. Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with Haemophilus influenzae type B. Toxicity: Minor hepatotoxicity and drug interaction (↑P-450); orange body fluids (nonhazardous side effect)
Rifampin’s 4 R’s
RNA polymerase inhibitor Revs up microsomal P-450 Red/orange body fluids Rapid resistance if used alone
Sulbactam
β-lactamase inhibitors
Sulfa drug allergies
Patients who do not tolerate sulfa drugs should not be given sulfonamides or other sulfa drugs, such as sulfasalazine, sulfonylureas, thiazide diuretics, acetazolamide, furosemide, celecoxib, or probenecid
Sulfonamides: Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
Mechanism: PABA antimetabolites inhibit dihydropteroate synthetase. Bacteriostatic. Clinical use: Gram-positive, gram-negative, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI. Toxicity: Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g., warfarin)
Tazobactam
β-lactamase inhibitors
Tetracyclines: Tetracycline, doxycycline, demeclocycline, minocycline
Mechanism: Bacteriostatic; bind to 30S and prevent attachment of aminoacyl-tRNA; limited CNS penetration. Doxycycline is fecally eliminated and can be used in patients with renal failure. Must NOT take with milk, antacids, or iron-containing preparations because divalent cations inhibit its absorption in the gut. Clinical use: Borrelia burgdorferi, H.pylori, M.pneumoniae. Drug’s ability to accumulate intracellularly makes it very effective against Rickettsia and Chlamydia Toxicity: GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity.
Ticarcillin, carbenicillin, piperacillin (antipseudomonals)
Mechanism: Same as penicillin. Extended spectrum Clinical use: Pseudomonas spp. and gram-negative rods; susceptible to penicillinase; use with clavulanic acid Toxicity: Hypersensitivity reactions
Treatment of MRSA
Vancomycin
Treatment of VRE
Linezolid and streptogramins (quinupristin / dalfopristin)
Trimethoprim
Mechanism: Inhibits bacterial dihydrofolate reductase. Bacteriostatic. Clinical use: Used in combination with sulfonamides (trimethroprim-sulfamethoxazole [TMP-SMX]), causing sequential block of folate synthesis. Combination used for recurrent UTIs, Shigella, Salmonella, Pneumocystis jiroveci pneumonia. Toxicity: Megaloblastic anemia, leukopenia, granulocytopenia (May alleviate with supplemental folinic acid [leucovorin rescue])
Vancomycin
Mechanism: Inhibits cell wall mucopeptide formation by binding D-ala D-ala portion of cell wall precursors. Bactericidal. Clinical use: Gram positive only - serious, multidrug-resistant organisms, including S.aureus, enterococci and Clostridium difficile (pseudomembranous colitis) Toxicity: Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing - “red man syndrome”. Well tolerated in general.
β-lactamase inhibitors
Include clavulanic acid, sulbactam, tazobactam. Often added to penicillin antibiotics to protect the antibiotic from destruction by β-lactamase (penicillinase)
