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24 Cards in this Set
- Front
- Back
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Sulfonamides
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First synthetic antimicrobial agents (Prontosil, 1935)
Synthesized in Germany: chemical industry made many dyes and pigments Some used in histological and microbiological staining Specificity of stains inspired the theory of the “magic bullet” (Paul Ehrlich” |
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Mechanism of action
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Para-aminobenzoic acid----Dihydrofolate synthetase---> dihydrofolic acid (sulfonamides)
dihydrofolic acid ----Dihydrofolate reductase---> tetrahydrofolic acid (trimethoprim) |
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Sulfonamides: mechanism of action
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Spectrum: both G+ and G- including S. pyogenes, S. pneumoniae, H. influenzae
Bacteriostatic action Prevent synthesis of folic acid required for synthesis of purines and nucleic acid Does not affect human cells or certain bacteria - they can use preformed folic acid (nutrition) |
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Classification: sulfonamides
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Absorbed rapidly and excreted rapidly: sulphamethoxazole, sulfadiazine: orally for systemic infections.
Absorbed slowly and excreted slowly: sulfadoxine, long acting, 7-9 days: used for treatment of malaria along with pyrimethamine Not absorbed orally: sulfasalazine: gets broken down into 5-ASA and sulfapyridine in large intestine, 5-ASA acts locally in IBD. Topically used: silver sulfadiazine (Flammazine, for dressing of burn wound infection), sulfacetamide eye drops, mafenide |
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Sulfonamides: sulfamethoxazole
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Therapeutic uses:
Combined with trimethoprim. Used to treat UTIs, Pneumocystis carinii pneumonia, ear infections, bronchitis, gonorrhea Nocardiosis (pulmonary, systemic, Nocardia spp) Toxoplasmosis: combination of pyrimethamine (also DHFR inhibitor) and sulfadiazine is treatment of choice |
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Adverse reactions
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Hypersensitivity reactions, phototoxicity, fixed drug eruption, Stevens-Johnson syndrome (erythema multiforme)
Urinary tract disturbances: crystalluria, hemorrhagic cystitis: adequate diuresis (> 1200ml/day), alkaline urine Haematopoietic disturbances: hemolytic anemia (G6PD deficiency), aplastic anemia Interactions: can increase effects of coumarins, phenytoin Non-hemolytic jaundice Contraindicated in pregnancy, G6PD deficiency |
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Co-trimoxazole
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Fixed dose combination of trimethoprim and sulfamethoxazole (1:5, e.g. “Forte” = 960mg, 160 mg trimethoprim, 800 mg sulfamethoxazole)
Combination becomes bactericidal, also widens the spectrum to include Salmonella spp Sequential blockade: synergistic Optimum plasma ratio 1:20 (differences in kinetics) Good penetration in tissue: especially in lungs and kidneys higher concentration than in plasma. Therapeutic concentrations achievable in gall, prostate, saliva, sputum, vaginal secretions, liquor cerebrospinalis, interstitial fluid and the middle ear |
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Uses of co-trimoxazole
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U.T.I
Bacterial respiratory tract infections G.I.infections caused by Shigella, Salmonella Pneumocystis carinii infections: treatment and prophylaxis of PCP pneumonia (HIV) Nocardiosis Brucellosis: DOC is combination of doxycycline and streptomycin / gentamicin. Triple therapy of doxycycline, rifampin, co-trimoxazole in neurobrucellosis . |
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Adverse effects of co-trimoxazole
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Same as sulfamethoxazole plus:
Itch and rash GI upset Aseptic meningitis Allergic reactions including anafylaxia Thrombocytopenia, leukopenia, megaloblastic anemia |
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Quinolones: classification
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First‑generation drugs: nalidixic acid achieves minimal serum levels: not used (much?) clinically
Second‑generation quinolones: ciprofloxacin, ofloxacin, norfloxacin: excellent activity against G- aerobic organisms including Enterobacteria, Pseudomonas, Neisseria, Hemophilus Third‑generation drugs: levofloxacin, sparfloxacin, gatifloxacin, moxifloxacin expanded activity against gram‑positive bacteria and atypical pathogens, Chlamydia, Mycoplasma, Legionella, Brucella, Mycobacterium. Fourth‑generation quinolone drugs (garenoxacin, gemifloxacin) add significant activity against anaerobes |
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Mechanism of action
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Inhibit DNA gyrase enzyme (for Gram negative bacteria) and topo-isomerase IV (for Gram positive bacteria)
Well absorbed orally, widely distributed Dose adjustment in renal failure Resistance is due to alterations in the DNA gyrase, decreased outer membrane permeability or the development of efflux mechanisms. |
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Fluoroquinolones: adverse effects
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Phototoxicity (more common with lomefloxacin (Maxaquin®) and sparfloxacin (Zagam®))
Sparfloxacin and moxifloxacin: prolongation of the QT interval Ciprofloxacin, pefloxacin: enzyme inhibitors, can increase concentrations of warfarin Achilles tendon rupture or tendinitis occurs rarely, especially with concommitant use of corticosteroids and in the elderly. Not recommended for use in patients younger than 18 years or in pregnant or lactating women: cartilage damage and arthropathy has been demonstrated in animals. |
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Fluoroquinolones: 2nd generation
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Ciprofloxacin exhibits good activity against Pseudomonas aeruginosa and strong gram‑negative activity that may be superior to that of ofloxacin.
Coverage against Streptococcus pneumoniae is inadequate, ciprofloxacin inappropriate in patients with community‑acquired pneumonia. Ciprofloxacin and ofloxacin are effective in treating: urinary tract infections caused by susceptible organisms respiratory tract infections caused by susceptible gram‑negative organisms skin and soft‑tissue infections osteomyelitis (ciprofloxacin only) |
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Fluoroquinolones: 3rd generation
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The third‑generation fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin) have expanded coverage against streptococci and atypical organisms.
This attribute has improved the usefulness of fluoroquinolones in treating patients with community‑acquired pneumonia, acute sinusitis and acute exacerbations of chronic bronchitis, which are their primary FDA‑labeled indications. Activity against Haemophilus influenzae and Moraxella catarrhalis is high, Activity against other gram‑negative bacteria, especially P. aeruginosa, is less than that of ciprofloxacin Gatifloxacin has FDA‑labeled indications for urinary tract infections and gonorrhea. |
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Fluoroquinolones
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Recently withdrawn :
Temafloxacin: immune hemolytic anemia Trovafloxacin: hepatotoxicity Grepafloxacin: cardiotoxicity Clinafloxacin: phototoxicity |
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Therapeutic uses of fluoroquinolones: summary
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UTI: caused by Pseudomonas: ciprofloxacin
Bacterial diarrheas by Salmonella, Shigella, E.coli Typhoid fever: Know other drugs that can be used. Infection of soft tissues, bones and joints STD's caused by gonococci, Chlamydia trachomatis, Haemophilis ducreyi (chancroid) Community acquired pneumonias: 3rd generation Ciprofloxacin: wide usage for the prophylaxis of anthrax and effective for treatment of tularemia. Second line drug in TB |
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A 75 year old woman is seen in her nursing home because of cough, shortness of breath, and fever. She has mild Alzheimer's disease and type II diabetes mellitus controlled with oral hypoglycemic agents. On physical examination, her temperature is 37.8 °C (100 °F), pulse rate is 85/min, respiration rate is 24/min, and blood pressure is 145/75 mm Hg. She denies headache. Her neck is supple. Bibasilar crackles and decreased breath sounds are auscultated at the right lung base. Cardiac examination shows an S4 gallop rhythm but no murmur. The abdominal examination is unremarkable. There is mild edema of both ankles. Chest radiograph shows an infiltrate in the right lower lobe without a pleural effusion. The patient is unable to produce sputum for examination. Leukocyte count is 16,000/µL with 93% polymorphonuclear neutrophils, 5% band forms, and 2% lymphocytes. Results of blood cultures are pending.
Which of the following is the most appropriate therapy for this patient? 1.Oral trimethoprim-sulfamethoxazole 2.Oral azithromycin 3. Oral levofloxacin 4. Oral cefuroxime axetil 5. Intravenous vancomycin |
ANSWER-
Predictive criteria suggest that this patient with community-acquired pneumonia can be safely managed out of the hospital, so that oral medications should be chosen preferentially. The principal pathogens causing community-acquired pneumonia are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and atypical pathogens such as Legionella spp. A nursing-home patient also has an increased risk of gram-negative pathogens, such as Klebsiella pneumoniae. All of these potential pathogens are likely to be covered by levofloxacin, which is well absorbed orally. Trimethoprim-sulfamethoxazole and cefuroxime axetil would cover H. influenzae and M. catarrhalis, but would not have activity against atypical pathogens. In addition, 20% of strains of S. pneumoniae in the United States are resistant to trimethoprim-sulfamethoxazole and to cefuroxime. Azithromycin provides good coverage for atypical pathogens, H. influenzae, and M. catarrhalis. Its coverage for S. pneumoniae may be adequate in an outpatient, although as many as 50% of penicillin-resistant strains of S. pneumoniae are also resistant to macrolides such as azithromycin. Azithromycin and vancomycin would not cover gram-negative bacteria such as K. pneumoniae in this nursing-home patient. |
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A 27-year-old male presents with complaints of a painless ulcer on his penis. He admits to having unprotected intercourse with a woman he met in a bar during a conference 2 weeks ago. A scraping of the lesion, visualized by dark field microscopy, demonstrates spirochetes and a diagnosis of syphilis is made. Which of the following is the treatment of choice assuming the patient has no known allergies?
A. Benzathine Penicillin G B. Penicillin G C. Penicillin V D. Doxycycline E. Bacitracin |
The answer is A. Patients with primary syphilis require a single intramuscular dose of benzathine penicillin G. Oral preparations of Pen G or Pen V are not sufficient. Doxycycline for 14 days is an alternative treatment in penicillin-allergic patients. Bacitracin is only topical and not sufficient for syphilis.
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A 19-year-old military recruit living in the army barracks develops a severe headache, photophobia, and a stiff neck, prompting a visit to the emergency room. A lumbar puncture reveals a diagnosis of bacterial meningitis. Which of the following cephalosporins is likely to be given to this patient?
A. Cefazolin B. Cefuroxime axetil C. Ceftriaxone D. Cefoperazone E. Cefepime |
The answer is C. Ceftriaxone is a third-generation cephalosporin that has excellent CNS penetration. All the third- generation cephalosporins, except cefoperazone, enter the CNS. The first- and second-generation agents, cefazolin and cefuroxime, respectively, do not enter the CNS. There are limited data on the effectiveness of the fourth-generation agent, cefepime, in meningitis.
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A 27-year-old intravenous drug abuser is admitted for fever and shortness of breath. Multiple blood cultures drawn demonstrate S. aureus. The cultures further suggest resistance to methicillin. The attending physician also orders a transesophageal echocardiogram that shows tricuspid vegetations consistent with endocarditis. Which of the following is an appropriate antibiotic?
A. Aztreonam B. Imipenem C. Gentamicin D. Vancomycin E. Ceftriaxone |
The answer is D. Vancomycin is the drug of choice for serious infections due to methicillin-resistant S. aureus (MRSA). In the case of endocarditis, the treatment is usually 6 weeks. MRSA's resistance is often due to altered penicillin-binding proteins, not β-lactamases, so aztreonam, imipenem, and ceftriaxone would not be useful. Gentamicin is often used in conjunction with penicillins in a non-MRSA setting.
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A 27-year-old African American female is seen in the emergency room with complaints of urinary frequency, urgency, and dysuria. A urinary analysis demonstrates bacteria and white blood cells, and she is given trimethoprim-sulfamethoxazole. She now returns with sores and blisters around her mouth and the inside of her mouth. Given her history and findings, what should you include in the differential of her current complaint?
A. Glucose-6-phosphate dehydrogenase (G-6-P DH) deficiency B. Steven-Johnson syndrome C. Red man syndrome D. Aplastic anemia E. Disseminated M. avium-intracellulare infection |
The answer is B. Steven-Johnson syndrome is a form of erythema multiforme, rarely associated with sulfonamide use. Patients with G-6-P dehydrogenase deficiency are at risk of developing hemolytic anemia. Red man syndrome is associated with vancomycin. Aplastic anemia is a rare complication of clindamycin use. Disseminated Mycobacterium avium-intracellulare infection, more common in AIDS patients, is treated with macrolides.
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A 43 year old HIV positive female with a CD4+ count of 150 presents with shortness of breath. An arterial blood gas determination indicates hypoxia, and a chest x-ray shows bilateral interstitial infiltrates. A suspected diagnosis of Pneumocystis carinii pneumonia (PCP) is confirmed with bronchoscopy and silver staining of bronchial washings. Which of the following therapies should be started?
A. Isoniazid B. Clindamycin C. Azithromycin D. Miconazole E. Trimethoprim/sulfamethoxazole |
The answer is E. Trimethoprim/sulfamoxazole is not only the treatment for PCP but also should be considered for prophylaxis in patients undergoing immunosuppressive therapy or with HIV. Azithromycin can be use in Mycobacterium avium-intracellulare (MAC complex) in AIDS patients. Isoniazid is used for tuberculosis, yet another illness more common in AIDS patients. Miconazole is an antifungal used for vulvovaginal candidiasis.
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A 35-year-old diabetic female presents to the emergency room with signs and symptoms of urinary tract infection, including fever, dysuria, and bacteriuria. Given that she is diabetic, she is admitted for treatment with intravenous ciprofloxacin. What is the mechanism of this drug?
A. Inhibition of the 30s ribosome B. Inhibition of the 50s ribosome C. Inhibition of bacterial cell wall synthesis D. Inhibition of RNA synthesis E. Inhibition of DNA gyrase |
The answer is E. Ciprofloxacin is a quinolone, a group of antibiotics that inhibit bacterial topoisomerase II (DNA gyrase). The antibiotic classes that inhibit the 30S ribosome include aminoglycosides and tetracycline. Inhibitors of the 50S ribosome include chloramphenicol, erythromycin, and clindamycin. Bacterial cell wall inhibitors include penicillins, cephalosporins, and vancomycin. Rifampin inhibits DNA-dependent RNA polymerase (RNA synthesis).
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A 42-year-old AIDS patient presents to the emergency room with mental status changes and a headache. A computed tomography (CT) scan is ordered and demonstrates a ring enhancing lesion. You decide to treat him empirically due to the possibility of Toxoplasmosis gondii abscess. Which agent should be included in his treatment?
A. Ivermectin B. Praziquantel C. Pyrimethamine plus sulfadiazine D. Niclosamide E. Pyrantel pamoate |
The answer is C. Toxoplasmosis is treated with a combination of pyrimethamine and sulfadiazine. Ivermectin is used to treat filariasis, whereas praziquantel is used to treat schistosomiasis. Niclosamide can be used to treat tapeworm infections, and pyrantel pamoate is used to treat many helminth infections.
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