Term
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Definition
Tetracyclines spectrum Gram positive and negative plus Rickettsia, Mycoplasma and Chlamydiae. Not used too much though. Other drugs are better.
Mechanism of Tetracyclines Binds 30S ribosome. Blocks amino-acyl-tRNA binding.
Absorption of tetracyclines Incomplete except for doxycycline and minocycline. Dairy and divalent cations chelate and prevent absorption (except doxy and mino).
Distribution of tetracyclines Widely distributed, BBB, placenta etc.. Minocylcine is very lipophilic and can have sufficient concentration in saliva/tears to treat meningococcal carrier states.
Tetracycline side effects Gastrointestinal(most frequent) Superinfections(Candida, staph, C. diff, esp in diabetics, leukemia or SLE) Phototoxicity(esp w doxy and demeclocycline) Bone defects (esp children, contraindicated in pregnancy) Hepatotoxicity(pregno, liver diseased) Renal Toxicity(Fanconi syndrome=prox tubule) Vestibular toxicity(minocycline)
Chloramphenicol Spectrum Bacteroides fragilis and amp resistant H. influ/CNS anaerobes and life threatening meningitis. Gram + and -, Rickettsia, mycoplasma and Chlamydiae.
Chloramphenicol mechanism Inhibits protein synthesis by binding 50S. Bacterial static except for highly susceptible strains of H. flu, N.men, and Strep. p.
Chloramphenicol Therapeutic uses 1. Life threatening meningitis 2. Severe CNS Bacteroides 3. Alternate to tetracyclines for Rickettsial and brucellosis
Absorption and distribution of Chloramphenicol Rapid oral absorption and high distribution(lipophilic, crosses BBB placenta, CSF)
Chloramphenicol excretion. inactivated by liver glucuronyl transferase(90%) some active drug is excreted VIA urine.
Adverse effects of Chloramphenicol Dose related anemia/bone marrow suppression. Aplastic irreversible anemia (often fatal) Gray Baby Syndrome
Aminoglycosides spectrum Aerobic gram (-) bacilli
Aminoglycosides chemistry and mechanism Basic cations can react w acidic penicillins and deactivate each other. Binds 30S ribosome and causes mRNA misreads. Bad proteins can insert into membrane and destroy membrane integrity.
Aminoglycosides spectrum Severe aerobic gram (-) nosocomial infections. Ineffective against anaerobes.
Aminoglycosides 3 mechanisms of resistance 1. Inactivation by plasmid-mediated enzymes that acetylate, phosporylate or adenylate(Amikacin is less susceptible) 2. Alteration of transport system (energy and oxygen dependent) 3. Mutation in Ribosome that binds drug
Aminoglycosides absorption and distribution Poor absorption and only 20% distribution, does not enter CSF or cross placenta
Excretion of Aminoglycosides Glomerular filtration. Elderly, neonates and renally compromised are at risk for toxicity.
Aminoglycosides adverse effects 1. Neurotoxicity: irreversible damage to hair cells in cochlea and vestibule 2. Nephrotoxicity: (proximal tubule) inhibits phospholipases in lysosomes which burst and release hydrolases into the cytoplasm 3. Neuromuscular blockade: respiratory depression(myasthenia gravis and hypoglycemic are susceptible) Antidote: Calcium gluconate or neostigmine
Drug interactions of Aminoglycosides Penicillins, nephrotoxic drugs(diuretics, cisplatin, cyclosporine, amphotericin B, and Vancomycin).
What combinations are used against Psuedomonas and some gram (-) nifections Aminoglycosides and either penicillin or cephalosporins.
Aminoglycoside prototypes Gentamicin (systemically) Amikacin (systemically) Neomycin (topical or oral prior to surgery) Streptomycin (used for TB)
tetracycline prototypes tetracycline doxycycline minocycline tigecycline
Mechanism of Macrolides Inhibits protein synthesis by binding 50S ribosome. Only bacteriostatic.
Therapeutic uses of Macrolides 1. Common strep URI 2. H. infl otitis media 3. Pneumonias due to Chlamyophillia, mycoplasma and legionella 4. Bordetella (whooping cough, chronic bronchitis, sinusitus.) 5. H. pylori (clarithromycin) 6. Mycobacterium avium in AIDS patients (Clar/azith) 7. Diptheria carriers
Resistance to Macrolides 1. Decreased drug penetration through cell envelope 2. Methylation of ribosome target 3. Hydrolysis of drug (enteric gram (-)) 4. Ribosome mutation
Macrolides absorption erythromycin-acid labile Clarithromycin-acid stable take w food Azithromycin-acid stable
Macrolides distribution Good into tissue but not CSF. Azithromycin concentrates in Phagocytes, macrophages and fibroblasts
Macrolides excretion E: CYP3A metabolism A: unchanged in feces t1/2 = 68hrs C: 30% in urine, remainder in feces D: t1/2 = 30-44 hrs
Macrolides adverse effects E: GI upset, ototoxicity, and hepatotoxicity w estolate ester
Drug interactions of Macrolides E and C: inhibit CYP3A4 which can cause build up of carbamazepime, glucocorticoids, cyclosporin, digoxin, theophylline, triazolam, valproate and warfarin. E: Cardiac arrhythmias and QT prolongation
Macrolide prototypes Erythromycin Clarithromycin Azithromycin telithromycin
Sulfonamides are only effective against what kind of microorginisms Those that require PABA to synthesize folic acid.
Sulfonamides mechanism of action Competively inhibits dihydropteroate synthase, can serve as an alternate substrate causing inactive produts. Bacteriostatic
Mechanism of trimethoprim Blocks dihydrofolate reductase
Sulfasoxazole 1. Oral sulfamide of choice 2. High water solubility 3. can be combined with erythromycin to treat otitis media or URI's
sulfadiazine High CSF levels, therapeutic within 4 hrs, t1/2=10 hrs, problems with crystalluria
sulfamethoxazole Similar to sulfasoxazole, longer t 1/2 = 11 hrs due to slower absorption/excretion. More likely to cause crystaluria
TMP-SMX Synergistic effect. Net result makes it bacteriocidal.
Sulfasalazine Prodrug, Poorly absorbed, broken down into sulfapyridine(active) and mesalamine(COX inhibitor). Treats IBD, ulcerative colitis, and regional enteritis. Absorption of high doses of sulfapyridine can be toxic
Silver sulfadiazine Topical, drug of choice for 2nd and 3rd degree burns. Can cause photosensitivity. Preferred over mafenide.
sulfacetamide sodium Ophthlamic topical, treats Chlamydia trachomatis
sulfadoxine-pyramethamine Pyramethamine is similar to TMP in action, sometimes prescribed for parasites
trimethoprim Highly selective for bacterial dihydrofalate reductase
Sulfonamides absorption rapid except sulfasalizine
Sulfonamides distribution widely distributed, crosses placenta and can be toxic
Sulfonamides metabolism and excretion Acetylated in liver excreted by glomerular filtration, so renal function is required
Sulfonamides adverse effects 1. UTI(crystalluria) 2. Hypersensitivity(rash, erythema multiforme, drug fevers, PT) 3. Hematopoetic (rare, bloody dyscrasias, anemia, contraindicated w porphyria patients) 4. Kernicterus (bilirubin displced from albumin in neonates, also passes in breast milk)
Sulfonamides drug interactions Displaces drugs from albumin. Including Sulfonylurea, hypoglycemic drugs, anticoagulants, phenytoin and methotrexate.
TMP-SMX sensitive organisms 1. Gram (-) bacilli 2. Actinomyces, Nocardia 3. Three parasites (AIDs patients) Cyclospora, Isospora, Toxoplasma. 4. One fungus: Pnuemocystis jiroveci 5. Back up drug for 24 others
TMP-SMX therapeutic uses 1. Oral Rx for UTI 2. MRSA backup 3. Pneumocystis in AIDs patients 4. URI due to H. flu Strep. P. 5. GI infections (Shigella, Salm., EHEC may increase HUS though)
TMP-SMX Distribution Widely distributed
TMP-SMX adverse effects 1. Hypersensitivity (fever, rash, etc) 2. CNS effects (headache, depression and hallucination) 3. Contraindicated in renal disease 4. Megaloblastic anemia in folate deficient patients.
Methenamine Prodrug, decomposes to formaldehyde and ammonia in acidic conditions. Used for chronic cystitis.
Methenamine toxicities 1. GI (take with food) 2. Contraindicated with renal or liver disfunction 3. Rashes, hematuria, almbuminuria, and painful/frequent micturition 4. Formaldehyde forms precipitates with sulfamethizole 5. Don't use with drugs that Alkanize urine
What bacteria can alkalize urine Proteus and Pseudomonas can split urea thus alkalizing urine
Nitrofurantoin Reduced by bacteria to products that mediate cell damage. Static at low, cidal at high, needs acidic urine
Nitrofurantoin resistant bacteria Klebsiella, enterobacter and those that alkalize urine (Proteus and Psuedomonas)
Nitrofurantoin absorption and excretion Rapidly absorped and excreted. never reaches high plasma levels, don't give with probenecid due to toxicicity.
What UTI drugs should never be mixed Any methenamine + Any sulfa ▬► An insoluble ppt
Which UTI drug is given with an organic acid? When is this contraindicated? Methenamine, renally impaired.
Nitrofurantoin Toxicities GI irritation – common N/V. Pulmonary and hepatic
Nitrofurantoin Toxicities Turns Urine brown, contraindicated in pregnancy and with decreased renal function. Can have sensory/nueral problems in which case the drug is discontinued.
Fosfomycin Blocks cell wall synthesis by inactivating bacterial enolpyruvyl transferase. Single dose adequate for Cystitis, Effective against many enteric gram (-) organisms but *not useful against Pseudomonas
Phenazopyridine An analgesic for symptomatic relief of UTI pain
Fluoroquinolone’s Mechanism of Action They target two enzymes needed for replication of double-stranded DNA: DNA gyrase (Topoisomerase II) Topoisomerase IV
Fluoroquinolones spectrum and limitations Wide spectrum of both Gram + and -. Limitations: *Spirochetes are completely resistant *Anaerobes are mostly resistant: only moderately sensitive to moxifloxacin *Penicillin-resistant Strep. pneumoniae are mostly resistant *Resistance is increasing in Staph. aureus and is frequent in MRSA *Neisseria gonorrhoeae is now likely to be resistant.
Therapeutic Uses of Fluoroquinolones *Cipro is #1 for UTIs due to Pseudomonas *Cipro & levofloxacin are drugs of choice for uncomplicated pyelonephritis *They are backups to TMP-SMX for commonly occurring uncomplicated cystitis; Bactrim is preferred to minimize development of resistance to FQs.
What drug would be used to treat prostatitis Any FQ
What drugs are used to treat travelers diarrhea *Cipro or Levaquin are good & preferred to TMP-SMX in adults *Azithromycin (the FQ backup) is preferred in India, Thailand where Campylobacter is resistant to FQs. *Bactrim is preferred for TD in kids
Prophylaxis after exposure to meningococcus or anthrax Cipro
Toxicities of the Fluoroquinolones CNS agitation *Responses range from headache to seizures (1-10%) *Inhibits by displacing GABA from CNS receptors. *Agitation more common in elderly patients. *Insomnia occurs more often in young children*Prolongation of the QT Interval in the heart*FQs contraindicated in pregnant, nursing mothers & children
First generation FQs to know Ciprofloxacin, lomefloxacin
Second generation FQ's to know Gemifloxacin, Levofloxacin, Moxifloxacin
Drug Interactions with FQs **FQs are very well absorbed (70-100%) in the absence of multivalent cations. **Antacids, iron, multivitamins, sucralfate (Al), or didanosine (Al, Mg) chelate FQs & decrease bioavailability by up to 90%; must be staggered in dosing by 2+ hr
Two ways to treat TB 6-month course of treatment that involves 4 drugs for the first 2 months (isoniazid, rifampin, ethambutol, and pyrazinamide), Followed by isoniazid and rifampin for the remaining 4 months. Rifampin in combination with isoniazid for 9 months also is effective therapy for strains susceptible to both agents
Isoniazid TB, primary drug in all regimens, also prophylaxis
Rifampin excellent tuberculcidal drug, most rapid acting, useful for other bacterial infections
What drugs are used when there is resistance to first line TB drugs Pyrazinamide and Streptomycin
Clinical problems with TB drugs Isoniazid (peripheral neuritis, hepatitis) Rifampin (hepatic toxicity, GI effects, red-orange urine and tears, flu-like symptoms) Ethambutol (altered visual acuity and impaired ability to peceive green) Pyrazinamide (hepatic necrosis, precipitate gout) Streptomycin (ototoxicity, vestibular toxicity, and nephrotoxicity
Adverse effects of Clindamycin Diarrhea* (8%) potential antibiotic associated colitis (overgrowth of C. difficile) skin rashes* (10%) Thrombophlebitis* with IV admin.
Adverse effects of Vancomycin Nephrotoxicity* Ototoxicity* (reversible) Thrombophlebitis* Red man syndrome
Adverse effects of metronidazole frequent GI disturbances* and metallic taste Neurotoxicity* (dizziness and vertigo) blood dyscrasias* or neutropenia
Bacitracin Topical, used vs. gram positive cocci
Polymixin B used vs. aerobic gram-neg. bacilli Topical treatment of infections of skin, mucous membranes, eye and ear
Which drug is limited by crystalluria and should be taken with lots of water and bicarbonate. Urine should be >1200 ml per day Sulfadiazine
Oncogenes ras, EGF receptor, PDGF receptor, BRAF, kit, and abl. There is a specific treatment imatinib (Gleevec) for kit and abl. |
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