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253 Cards in this Set
- Front
- Back
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Beta lactam and other cell wall or membrane active antibiotics Members and mechanism and resistance |
- Narrow spectrum penicillins Penicillin G and V - Anti staphylococcal Beta lactamase Methicillin , Nafcillin, Oxacillin - Extended spectrum and anti-pseudomonas Ampicillin, amoxicillin, Piperacillin, ticarcillin - Cephalocporins - Monobactam - Beta-lactamase inhibitor - Carbapenems - Glycopeptide - Lipopeptide (ALL mentioned are Bactericidal) Their functions: - Prevent bacterial cell wall synthesis by binding to and inhibiting cell wall transpeptidases - Inhibit cell wall synthesis by binding to the D-Ala-D-Ala terminus of nascent peptidoglycan - Bind to cell membrane, causing depolarization and rapid cell death |
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Penicillin G Penicillin V Benzathine and Procaine penicillin G |
Penicillin G - IV - Bactericidal - Inhibited by B lactamase - Non-beta lactamase producing staphylococci - Streptococci - Meningococci - Syphillis Penicillin V - Oral - Minor infection - Oropharyngeal infection Benzathine and Procaine Penicillin G - IM - Low effect - Prolong drug level - Streptococcal, meningococcal and gram + bacilli |
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Penicillin resistant to staphylococcal Beta lactamase |
Methicillin, Nafcillin, oxacillin - Beta lactamase producing staphylococci - Penicillin susceptible streptococci and pneumococci Methicillin is rarely used - nephrotoxicity |
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Extended spectrum penicillins Antipseudomonas |
Ampicillin, Amoxicillin, Piperacillin, Ticarcillin Amoxicillin orally: UTIs Sinusitis Otitis Lower respiratory tract infections Ampicillin and amoxicillin are most active oral B-lactam antibiotics against pneumoocci IV ampicillin: - Enterococci and Listeria monocytogenes - synergistic with aminoglycosides - Cocci, bacilli, E coli and salmonella (gastroenteritis) - Shigellosis - Non B lactamase producing H influenza Ampicillin - amoxicillin - Piperacillin - ticarcillin - Can be used in combo with one of B lactamase inhibitors - enhance activity against B lactamases Piperacillin and Ticarcillin Gram negative rods - Pseudomonas - Enterobacter - Some Klebsiella species Often used in combo with penicillinase inhibitors |
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Adverse effects of Penicillins |
Allergy Cross Hypersensitivity Gastrointestinal disturbances |
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Cephalosporins are not active against... |
Enterococci and Listeria monocytogenes |
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1. Generation Cephalosporins |
Cefazolin (IV) Cephalexin Oral Skin, soft tissue and UTI (and surgical prophylaxis - cefazolin) Gram + cocci: - Pneumococci - Streptococci - Staphylocci - E coli - Klebsiella pneumonia - Poteus mirabilis Cephalexin oral - High urine concentration Treat: - UTI - Staphylococcal - Streptococcal - Should not be relied on in serious systemic infections Parenteral Cefazolin - Drug of choice for surgical prophylaxis - A choice in Penicillinase producing E coli and Klebsiella pneumonia - Alternative to patient allergic to penicillin |
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2. Generation |
Cefuroxime, Cefotetan, Cefoxitin B-lactamase producing H influenza and Moraxella catarrhalis Sinusitis Otitis Lower respiratory tract infections Cefuroxime treat - H influenza - K pneumonia - Cross BBB - less active than ceftriaxone on meningitis |
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Penicillin G |
IV Streptococcal Meningococcal Neurosyphilis |
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Penicillin V |
Oral Low systemic levels |
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Benzathine and procaine penicillin |
IM Long acting |
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Nafcillin and Oxacillin |
IV Stable to staphylococcal B lactamase |
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Ampicillin, Amoxicillin, ticarcillin, piperacillin |
Greater activity vs gram - bacteria Combo with B lactamase inhibitor --> restores activity against many B-lactamase producing Bacteria |
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Cefazoline |
IV First generation cephalosporins Skin and soft tissue infections UTI surgical prophylaxis |
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Cephalexin |
Oral First generation cephalosporin Skin and soft tissue infection UTI |
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Cefuroxime |
Oral and IV 2nd generation cephalosporin Improved activity vs pneumococcus and Hemophilus influenza |
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Cefotetan and cefoxitin |
IV 2nd generation cephalosporins Active vs Bacteroides fragilis - allows for use in abdominal and pelvic infections |
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Ceftriaxone |
IV 3rd generation cephalosporins Good CNS penetrations Pneumonia Meningitis Pyelonephritis Gonorrhea |
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Cefotaxime
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IV 3rd generation cephalosporins Similar to ceftriaxone |
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Ceftazidime |
IV 3rd generation cephalosporins Poor gram + activity Good activity vs Pseudomonas |
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Cefepime |
IV 4rd generation cephalosporins Broad activity with improved stability to chromosomal B lactamase |
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Ceftaroline |
IV Active against MRSA |
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Carbapenems |
Imipenem Meropenem Doripenem Ertapenem |
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Imipenem |
Cilastatin added to prevent hydrolysis by renal dehydropeptidase --> Imipenem-cilastatin Serious infections such as pneumonia and sepsis Seizures - renal failure |
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Meropenem and doripenem |
IV Similar activity to imipenem Stable to renal dehydropeptidase Lower incidence of seizures |
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Monobactams |
Aztreonam |
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Aztreonam |
IV No cross allergenicity with penicillins Infections caused by aerobic gram negative bacteria in patients with immediate hypersensitivity to penicillins |
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Glycopeptide |
Vancomycine |
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Vancomycin mechanism |
Inhibits cell wall synthesis by binding to D ala D ala terminus of peptidoglycan |
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Vancomycin |
IV Gram positive - sepsis, endocarditis and meningitis Oral Clostridium difficile colitis Toxicity Red man syndrome |
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Lipopeptide |
Daptomycin |
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Daptomycin mechanism |
Binds to cell membrane causing depolarization and rapid cell death |
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Daptomycin |
Gram positive Sepsis Endocarditis Vancomycin resistant strains of enterococci and staphylococci Toxicity Myopathy |
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Tetracycline mechanism |
Prevent bacterial protein synthesis by binding to the 30S ribosomal subunit |
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Tetracycline |
Bacteriostatic Infections caused by Mycoplasma Chlamydiae Rickettsiae Some spirochetes Malaria Gastric/duodenal ulcer by Helicobacter pylori Acne In combo with other antibiotics for plaque, tularemia, brucellosis Protozoal - Plasmodium falciparum Crosses placenta --> milk Avoid giving to baby |
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Tetracycline toxic |
Gastrointestinal Hepatoxicity Phototoxicity Deposition in bone and teeth Avoid giving to baby |
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Doxycycline |
Oral and IV Community acquired pneumonia Exacerbations of bronchitis |
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Tigecycline |
IV Active against tetracycline resistant bacteria |
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Macrolides member and mechanisms Toxicity |
Erythromycin Clarithromycin Azithromycin Telithromycin Prevent bacterial protein synthesis by binding to the 50 S Bacteriostatic Gastrointestinal Hepatoxicity QT prolongation |
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Erythromycin |
Oral and IV Inhibit cytochrome P450 inhibitor Community acquired pneumonia Pertussis Corynebacterial Chlamydial infections Useful as penicillin substitute in penicillin allergic patients with infections of staphylococci, streptococci or pneumococci |
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Clarithromycin |
Oral Added activity against M avium complex, toxoplasma and M leprae |
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Azithromycin |
Oral and IV 5 day course therapy Community acquired pneumonia Does not inhibit cytochrome P450 enzymes |
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Telithromycin |
Oral Not effected by effluex mediated resistance Active vs many eryhtomycin resistant pneumoocci |
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Lincosamide |
Clindamycine |
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Clindamycin mechanism and toxicity |
Prevents bacterial protein synthesis by binding to 50 S ribosomal subunit Bacteriostatic Nautropenia Risk factor for diarrhea and colitis due to Clostridium difficile |
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Clindamycin used against |
Skin and soft tissue infections Anaerobic infections |
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Streptogramins |
Quinupristin - dalfopristin |
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Quinupristin - dalfopristin |
Bactericidal Infections caused by staphylococci or vancomycin resistant E faecium |
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Quinupristin - dalfopristin mechanism and toxicity |
Prevent bacterial protein synthesis by binding to the 50 S Myalgias and arthralgias |
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Chloramphenicol mechanism and toxicity |
Prevent bacterial protein synthesis by binding to the 50 S Bacteriostatic Dose related anemia Gray baby syndrome |
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Oxazolidinones |
Linezolid |
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Linezolid mechanism and toxicity |
Prevents bacterial protein synthesis by binding to the 23 S ribosomal RNA of 50S subunit Bacteriostatic Duration dependent bone marrow suppression Optic neuritis neuropathy Thrombocytopenia |
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Linezolid active against |
Methicillin resistant staphylococci Vancomycine resistant enterococci |
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Chloramphenicol active against |
Alternative to B lactam for treatment of meningitis in patient with penicillin allergy |
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Aminoglycoside members |
Streptomycin Amikacin Gentamicin Tobramycin |
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Aminoglycoside mechanism and toxicity |
Prevent bacterial protein synthesis by binding to 30 s Bactericidal Nephrotoxicity - reversible Ototoxicity - irreversible Neuromuscular blockade Used most in combo with B lactam in serius infections like endocarditis - and with vancomycin and treatment of tuberculosis |
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Tobramycin |
IV More active than gentamycin vs Pseudomonas Less nephotoxicity |
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Gentamycin |
Aerobic gram - Synergistic activity in endocarditis caused by streptococci, staphylococci and enterococci |
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Streptomycin |
IM Widespread resistance - limit use to specific Tuberculosis and enterococcal endocarditis Combo with oral tetracycleine --> plague , tularemia, sometimes brucellosis Avoid in pregnancy --> can cause deafness in newborns Vestibular problems |
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Amikacin |
IV Active against enzymes that inactivate Gentamicin and tobramycin |
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Spectinomycin |
IM Treat antibiotic resistant gonococcal infections or gonococcal infections in penicillin allergic patients |
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Anti folate drugs |
Sulfonamides Trimethoprim-Sulfamethoxazole Trimethoprim Sulfadiazine Sulfisoxazole Pyrimethamine Pyrimethamine-sulfadoxine |
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Folate antagonist drugs mechanism |
Synergistic combination of folate antagonists blocks purine production and neucleic synthesis |
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Trimethoprim - sulfamethoxazole Effects Clinical Toxicity |
Bactericidal UTi P jiroveci pneumoa Toxoplasmosis - nocardiosis Rash Fever Bone marrow suppression Hyperkalemia |
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Sulfisoxazole |
Oral ONLY for lower UTI |
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Sulfadiazine |
Oral FIrst line therapy for toxoplasmosis when combined with pyrimethamine |
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Trimethoprim |
Oral Only lower UTI Made for patient allergy to sulfonamide |
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Pyrimethamine |
Oral First line therapy for toxoplasmosis when combined with sulfadiazine Coadminister with leucovorin to limit bone marrow toxicity |
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Pyrimethamine - sulfadoxine |
Oral Second line malaria treatment |
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Streptomycin |
1st line agent for tuberculosis Should be used only in combo to prevent resistance |
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Bacterial conjunctivitis - and trachoma |
Sodium sulfacetamide ophthalmic solution or ointment |
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Ciprofloxacin mechanism - class, effect and toxicity and clinical |
Fluoroquinolones Inhibits DNA replication by binding to DNA gyrase and topoisomerase IV Bactericidal Gastrointestinal Neurotoxicity tendonitis UTI Gastroenteritis Osteomyelitis Anthrax Tuberculosis and atypical mycobacteria |
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Drugs used in tuberculosis |
First lines: Isoniazid (INH) Rifampin Pyrazinamide Ethambutol Streptomycin |
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Isoniazid Mechanism Effects Clinical Toxicity |
Inhibits synthesis of mycolic acids, an essential component of mycobacterial cell walls Bactericidal vs M tuberculosis First line for tuberculosis Isoniazid induced hepatitis |
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Rifampin Mechanism Effects Clinical Toxicity |
Inhibits DNA dependent RNA polymerase - thereby blocking production of RNA Bactericidal vs susceptible bacteria and mycobacteria Resistance rapidly emerges when used as a single drug - therefore must be administered with isoniazid or other antituberculous drugs First line agent for tuberculosis Atypical mycobacterial infections Eradication of meningococcal colonization, staphylococcal infections Also active against Lepromatous leprosy Usually given in combo with dapsone or other antileprosy drug to prevent resistance Induce P450 Orange color to urine, sweat and tears Rash - thrombocytopenia Nephritis |
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Pyrazinamide Effects Clinical Toxicity |
Bacteriostatic vs M tuberculosis Front line drug used in conjucation with isoniazid and rifampin in short course (ie 6 months) as a "sterilizing" agent active against residual intracellular organisms that may cause relapse Hepatotoxic - hyperuricemia |
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Ethambutol Mechanism Effects Clinical Toxicity |
Inhibits mycobacterial arabinosyl transferases Bacteriostatic vs susceptible mycobacteria Always given in combination with isoniazid or rifampin vs tuberculosis and tuberculosis meningitis Retrobulbar neuritis --> loss of visual acuity and red-green color blindness |
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Streptomycin Mechanism Effects Clinical Toxicity |
Prevent bacterial synthesis by binding to the S12 ribosomal subunit Bactericidal vs susceptible mycobacteria Vs tuberculosis |
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Reason for second-line drugs for tuberculosis? |
1. In case of resistance to first line agents 2. In case of failure of clinical response to conventional therapy 3. In case of serious treatment-limiting adverse drug reactions |
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List all second line drugs for tuberculosis |
Ethionamide Capreomycin Cycloserine Aminosalicyclic acid (PAS) Kanamycin and Amikacin Fluoroquinolones Linezolid Rifabutin Rifapentine |
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Drugs against travelers' diarrhea caused by noninvasive strains of Escherichia coli |
Rifaximin |
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Drugs active against leprosy |
Dapsone and other sulfones Rifampin Clofazimine |
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Systemic antifungal drugs for systemic infections
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Amphotericin B |
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Amphotericin B Mechanism Effect Clinical Toxicity |
Formes pores in fungal membranes Fungicidal Localized and systemic: Candida albicans Cyrptococcus neoformans Histoplasma capsulatum Blastomyces dermatitidis Coccidioides immitis Aspergillus fumigatus Intrathecal for fungal meningitis Topical for ocular and bladder infection Infusion reaction Renal failure |
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Flucytosine Mechanism Effects Clinical Toxicity |
Antifungal Interferes with DNA and RNA synthesis in fungi Synergistic with amphotericin B for cyptococcal meningitis Synergistic with itraconazole for chromoblastomycosis Cryptococcus neoformans and chromoblastomycosis - infection Myelosuppression - bone marrow suppression - anemia, leukopenia, thrombocytopenia |
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Azoles Members Mechanism Toxicity |
Ketoconazole Itraconazole Fluconazole Voriconazole Blocks fungal P450 enzymes and interferes with ergosterol synthesis All azole drugs are prone to drug interactions because they affect the mammalial P450 system |
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Ketoconazole Clinical |
Broad spectrum but toxicity restricst use to topical therapy Broad spectrum: Candida Cyptococcus neoformans Blastomycosis Coccidioidomycosis Histoplasmosis |
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Itraconazole Clinical |
Same as ketoconazole + Sporothix |
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Fluconazole Clinical |
Excellent CSF penetration --> used in fungal meningitis (cryptococcal meningitis) Most commonly used for treatment of mucocutaneous candidiasis |
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Voriconazole Clinical |
Similar to itraconazole Excellent activity against Candida sp - including fluconazole resistant species such as Candida krusei Voriconazole is less toxic than amphotericin B Is therefore the treatment of choice for invasive aspergillosis |
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Posaconazole |
Broadest spectrum member of the azole Active against Candida and Aspergillus |
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Echinocandins Members Mechanism Effects Clinical |
Caspofungin Micafungin Anidulafungin Blocks B-glucan synthase Prevents synthesis of fungal cell wall Fungicidal vs mucocutaneous candidal infection Empiric antifungal therapy during febrile neutropenia Also Aspergillosis - used only if Amphotericin B doesnt work |
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Oral systemic antifungal drugs for mucocutaneous infections Members |
Griseofulvin Terbinafine |
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Griseofulvin |
Nail infections Often relapse Often replaced by newer antifungal medications such as itraconazole and terbinafine |
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Terbinafine Class Mechanism Effects Clinical |
Allylamine Inhibits epoxidation of squalene in fungi - increased toxic level to them Fungicidal Reduces ergosterol - prevent synthesis of fungal cell membrane Onychomycosis - nail Better than Griseofulvin because Griseofulvin induce P450 |
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Topical antifungal therapy Member |
Nystatin |
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Nystatin Forms Clinical |
Too toxic for parenteral administration - only used topically Craems, ointment VS Candida |
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Neuraminidase inhibitors |
Oseltamivir (orally) zanamivir - inhaled |
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Influenza type A and B What antiviral agents? |
Neuraminidase inhibitors: Oseltamivir Zanamivir |
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Inhibitors of viral uncoating |
Amamtadine Rimantadine Orally |
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Antiviral agent for influenza A And their toxicity |
Inhibitors of viral uncoating: Amantadine Rimantadine Amantadine - CNS - insomnia, dizziness, hallucination |
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ANtiviral agent for RSV? Respiratory syncytial virus |
Ribavirin - inhibitor of RNA polymerase Palivizumab - human monoclonal antibody |
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Ribavirin For what? Adverse effect? |
RSV Hepatitis C (In combination with interferon alfa 2b) Influenza A and B Parainfluenza HIV Dose dependent anemia |
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Hepatic viral infections HBV HCV What antiviral? |
Interferon |
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Interferon treats whatttt |
HBV HCV Cancer (such as leukemia and Kaposi's sarcoma) |
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HBV Goal of treatment What antivirals |
Primary goal - suppression of HBV DNA Interferon or... Lamivudine, Adefovir and so on |
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HCV Goal of treatment What drugs |
Primary goal - viral eradication Interferon Interferon + ribavirin Interferon + ribavirin + protease inhibitors (boceprevir...) or polymerase inhibitors (sofosbuvir) |
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Herpes infections |
Herpes simplex virus 1 (HSV 1) Herpes simplex virus 2 (HSV2) Varicella zoster virus VZV Cytomegalovirus CMV |
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CMV risk groups |
Unborn babies whose mothers become infected with CMV during the pregnancy Children with immune systems weakened by other disease or drug - or HIV |
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Acyclovir treats what?? |
HISV 1 HSV2 VZV |
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Valacyclovir |
Prevent CMV after organ transplantation Prevent VZV reactivation |
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Famciclovir |
HSV1 HSV2 VZV EBV HBV |
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Ganciclovir |
CMV HSV VZV EBV HHV-6 |
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Valgangciclovir |
CMV retinitis |
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Foscarnet |
Alternative drug for HSV and VZV (Acyclovir or ganciclovir resistant) |
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Cidofovir |
CMV retinitis in immunocompromised patients |
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HIV is what virus |
Retrovirus |
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What is HIV's target |
CD4+ receptor Helpter T cells - which are back bone of the immune system |
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HIV symptoms |
Retinitis Meningitis Encephalitis Pneumocystis Pneumonia Tuberculosis - multiple organs and so on |
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HIV transmitted by |
Unprotected SEX Mother to child Syrine sharing |
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WHat is HAART? |
Highly Active Antiretroviral Therapy U need at least 3 medications |
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Classes of antiretroviral drugs |
- NUcleosides and nucleotide reverse transcriptase inhibitors (NRTIs) - Non-nucleoside reverse transcriptase inhibitors (NNRTIs) - Protease inhibitors (PIs) - Integrase strand transfer inhibitors (INSTIs) HAART means - 2 drugs of NRTI and one from either PI / NNRTI / INSTIs |
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NNRTIs Member Mechanism |
Nonnucleoside reverse transcriptase inhibitors Nevirapine Delavirdine Efavirens Noncompetetive inhibitors of HIV reverse transcriptase |
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PIs Members Mechanism |
Protease inhibitors Saquinavir Ritonavir Indinavir..... |
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INSTIs Members Mechanism |
Integrase strand transfer inhibitors Dolutegravir Elvitegravir Raltegravir Inhibits integrase |
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HIV therapy |
Majority of drugs have serious adverse effects - monitor dose to limit the toxicity |
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Metronidazole treats (and Tindazole) |
Nitroimidazole - antiprotozoal drug Active against anaerobes like Bacteroides and Clostridium Vaginitis (trichomonas, bacterial vaginosis) Clostridium difficile colitis Brain abscess |
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Metronidazole mechanism effects and toxicity |
Disruption of electron transport chain Bactericidal vs anaerobic bacteria and protozoa Should avoid alcohol - it gives disulfiram like reaction with alcohol |
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Mupirocin |
Topical treatment of minor skin infections such as impetigo Staphylococcus aureus |
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Polymyxins B and E |
Attach to and disrupt bacterial cell membranes Bind and inactivate endotoxins Gram negative bacteria |
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Fidaxomicin |
Treat C difficile colitis |
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Urinary antiseptics members |
Nitrofurantoin Methenamine hippurate Methenamine mandelate |
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Nitrofurantoin Mechanism Effects Clinical Toxicity |
Disrupt protein synthesis and inhibits multiple bacterial enzyme systems Bactericidal Resistance to trimethoprim-sulfamethoxazole and fluoroquinolones has become more common in E coli - nitrofurantoin has become an important alternative oral agent for treatment of uncomplicated UTI Toxicity Anorexia Nausea Vomiting |
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Macrolide - Fidaxomicin |
Inhibits bacterial RNA polymerase Bactericidal in gram + bacteria C difficile colitis Oral |
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Alcohols |
Antisepsis and disinfection Ethanol and Isopropyl alcohol (isopropanol) |
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Chlorhexidine |
Sterilant /disinfection |
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Halogens |
Iodine Idophores Chlorine Sanitization Antiseptic Disinfectant |
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Phenolics - phenol |
Disinfectant |
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Aldehyldes |
Formaldehyde Glutaraldehyde Disinfection or sterilization of instruments |
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4 plasmodium typically cause human malaria |
Plasmodium falciparum P vivax P malariae P ovale |
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Chloroquine |
Prevents polymerization of hemoglobin breakdown MALARIA P falciparum is mostly resistant Is drug of choice for acute attack of nonfalciparum and sensitive falciparum malaria Also used as chemoprophylaxis - except in regions where P falciparum is resistant |
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Quine |
Mainly use in P falciparum resistant to chloroquine - in patients who can tolerate oral treatment MALARIA IV if complicated falciparum malaria Toxicity Cinchonism Black water fever Hemolysis in G6OD deficiency |
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Mefloquine |
First line drug for prophylaxis in areas with chloroquine resistance (falcoparum resistance) MALARIA |
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Primaquine |
MALARIA Is a tissue schizonticide Limit malaria transmission Eradicate liver stages of P vivax and P ovale Gi distress |
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Antifolate drugs |
Block folate synthesis Are blood schizonticides Mainly against P falciparum Chemoprophylaxis and treatment of chloroquine resistant species malaria Also Mefloquine resistant falciparum MALARIA Skin rashes GI distress Hemolysis ... |
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Other Antimalarial drugs |
Doxycyclines - chemoprophylactic for travelers with multi drug resistant P falciparum Amodiaquine - effective against P falciparum Atovaquone ... and so on so on lalalal |
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Drugs for amebiasis |
Diloxanide furoate Metronidazole and tinidazole Liminal agent |
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Asymptomatic amebiasis - which drug |
First choice is Diloxanide furoate (used in mild intestinal infection - amebiasis too) |
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Mild to severe intestinal infection - amebiasis |
Metronidazole or tinidazole with a luminal agent |
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Hepatic abcess and other extraintestinal disease - amebiasis |
Metronidazole or tinidazole with a luminal agent |
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Emetines |
Used as backup drug for treatment of severe intestinal or hepatic amebiasis |
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Iodoquinol |
Is orally active luminal amebicide Used as alternative to diloxanide for mild to severe intestinal infection |
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Metronidazole and Tinidazole toxicity |
Gastrintestinal irritation Paresthesias Dark coloration of urine |
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Paramomycin |
Used as luminal amebicide |
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Pentamidine |
Used in Trypanosomiasis and Pneumocystis jiroveci infections Toxicity PArenteral use Respiratory stimulation --> deppression - hypotension ..... |
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Trimethoprim - sulfamethoxazole (TMP - SMZ) |
First choice in prophylaxis and treatment of pneumocystis pneumonia (PCP) Prophylaxis in AIDS patients when CD4 is below 200 cell per micro liter |
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Pentamidine for trypanosomiasis caused by |
Typanosomiasis caused by T gambiense and Rhodesiense |
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Melarsopol - used for |
Trypanosomiasis ENters CNS African Sleeping sickness |
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Nifurtimox |
Trypanosomiasis caused by T cruzi |
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Suramin |
Trypanosomiasis in hemolymphatic stages of African trypanosomiasis T brucei gambiense and rhodesiense |
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Drugs for leishmaniasis |
Sodium stibogluconate |
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Metronidazole Tinidazole USES |
Amebiasis Giardiasis Trichomoniasis |
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Albendazole treats |
Nematodes: Ascaris lumbricoides (round worm) Hook worms: Necator americanus and Ancylostoma duodenale Trichuris trichiura (Whipworm) Cutaneous larva migrans Except: Enterobius vermicularis (pinworm) - Mebendazole Trichinella spiralis (trichinosis) - Mebendazole Strongyloides stercoralis (threadworm) - Ivermectin Onchocerca volvulus (onchocerciasis) - Ivermectin Wuchereria bancrofti and Brugia malayi (filariasis) - Diethylcarbamazine Cestodes (tapeworms) Cysticercosis (Porm tapeworm larval stage) Echinococcus granulosus (hydatid disease) |
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Mebendazole treats |
Nematodes: - Ascaris lumbricoides (round worm) - Hookworms: Necator americanus and Ancylostoma duodenale -Trichuris trichiura (whipworm) - Enterobius vermicularis (pinworm) - Trichinella spiralis (Trichinosis) |
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Praziquantel Treats |
Trematodes: (All trematodes except Fasciola hepatica (sheep liver fluke) Schistosoma haematobium Schistosoma mansoni Schistoma japonicum Paragonimus westermani Fasciolopsis buski (large intestinal fluke) Except Fasciola hepatica - Bithional or triclabendazole Cestodoes (3 of cestotodes) - Taenia saginata (beef tapeworm) - Taenia solium (pork tapeworm) - Diphylobothrium latum (fish tapeworm) Except: (These are treated with albendazole) Cysticercosis (pork tapeworm larval stage) Echinococcus granulosus (hydatid disease) |
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What treats Fasciola hepatica (Sheep liver fluke) |
Bithional or Triclabendazole |
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Niclosamide treats what |
Cestodes (same as praziquantel) - Taenia saginata (beef tapeworm) - Taenia solium (pork tapeworm) - Diphylobothrium latum (fish tapeworm) And 1 trematode: - Fasciolopsis buski |
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Miscellaneous anticancer drugs |
Imatinib Asparaginase Cetuximab Bevacizumab |
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CCS drugs (Cell cycle specific) |
- Antimetabolites (s-phase) -Taxanes (M phase) - Vinca alkaloids (M phase) - Antitumor antibiotic (G2 phase) - Bleomycin - Epipodophyllotoxins - Camptothecins |
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CCNS drugs (Cell cycle non specific) |
- Alkylating agents - Antibiotics |
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Camptothecins Class and member |
Natural product cancer chemotherapy drugs Topotecan and Irinotecan |
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Camptothecins Mechanism |
Inhibit topoisomerase I (Which is essential for the replication of DNA in human cells) |
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Topotecan and Irinotecan used as ? |
Topotecan - used in metastatic ovarian cancer when primary therapy has falled and also in treatment of small-cell lung cancer Irinotecan - used as first line drug (together with 5-FU and Leucovorin) for colon and rectal carcinoma |
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Etoposide Class and mechanism |
Podophyllotoxin Blocks the cells in the late S-G2 phase of the cell cycle Their major target is topoisomerase II |
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Etoposide used in
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Treatment of oat cell carcinoma of lung Combo with bleomycin and cisplatin for testicular carcinoma, germ cell cancer, small cell and non-small cell lung cancer, Hodkin's and non Hodkin's lymphomas, gastric cancer |
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Main side effects of Natural product anticancer |
- Myelosuppression - Peripheral neuropathy - Neurotoxicity - Allergic reactions |
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Taxanes Class and members |
Natural product cancer chemotherapy drugs Docetaxel Cabazitaxel Paclitaxel |
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Taxanes mechanism |
Acts as mitotic spindle poison Interfere with mitotic spindle |
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Docetaxel Carbazitaxel Paclitaxel Used in? |
Docetaxel: - 2nd line therapy of breast cancer , non-small cell lung cancer - major activity in head and neck cancer, small cell lung cancer, gastric or bladder cancer Cabazitaxel: - Useful in treatment of multidrug -resistant tumors Paclitaxel: - Ovarian, breast, non-small cell and small cell lung, head and neck, esophageal, prostate and bladder cancer |
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Vinca alkaloids Main side effects |
Myelosuppression Neurotoxicity Gastrointestinal disturbances Excessive sweating Depression Muscle cramps Vertigo and headaches |
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Vinca alkaloids members |
Vinorelbine Vincristine Vinblastine |
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Vinorelbine action |
Used in advances non-small cell lung cancer - either as single agent or with cisplatin |
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Vincrstine action |
Used in acute lymphoblastic leukemia in children, Wilms tumor, Hodgkin and non-Hodgkin lymphomas Same mechanism as Vinblastine |
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Vinblastine mechanism and used in.. |
Microtubule inhibitor Treat : Metastatic testicular carcinoma (together with bleomycin and cisplatin), non-Hodgkin lymphomas |
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All classes of natural product cancer chemotherapy And members of classes |
Vinca alkaloids (Vinblastine, Vincristine, Vinorelbine) Taxanes and related drugs (Paclitaxel, Docetaxel, Cabazitaxel) Epipodophyllotoxins (Etoposide) Camptothecins (Topotecan, Irinotecan) |
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Natural product cancer chemotherapy drug classes with mechanism |
Vinca alkaloids --> inhibit mitosis Taxanes and related drugs --> inhibit mitosis Epipodophyllotoxins --> inhibit topoisomerase II Camptothecins --> inhibit topoisomerase I |
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Antitumor antibiotics |
Anthracyclines Mitomycin Bleomycin |
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Anticancer antibiotic Mitomycin mechanism and use |
Acts as an alkylating agent and forms cross links with DNA ; forms oxygen free radicals, which target DNA Best available drug to use in combo with radiation therapy to attack hypoxic tumor cells Main clinical use in the treatment of squamous cell cancer of anus in combo with 5-FU and radiation therapy |
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Bleomycin mechanism and use and toxicity |
Active in G2 phase of tumor cell cycle Forms oxygen free radicals which bind to DNA causing single and double strand DNA breaks Treat Hodgkin's and non Hodgkin's lymphomas, germ cell tumor, head and neck cancer, squamous cell cancer of skin, cervix and vulva Main dose limiting is pulmonary toxicity |
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Anthracyclines members |
Doxorubicin Daunorubicin Idarubicin Epirubicin Mitoxantrone |
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Anthracyclines mechanism and toxicity |
Inhibit topoisomerase II Disrupt synthesis of DNA and RNA Generate free radicals that damage DNA Main dose limiting toxicity of all anthracycline sis myelosuppression with neutropenia; 2 forms of cardiotoxicity - acute and chronic form |
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Antitumor antibiotics classes with mechanisms |
Anthracyclines - - Oxygen free radicals bind to DNA causing single and double strand DNA breaks - Inhibit topoisomerase II Mitomycin: - Forms cross links with DNA - Acts like an alkylating agent - Form oxygen free radicals - target DNA Bleomycin: - Oxygen free radicals bind to DNA causing single and double strand DNA breaks |
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Alkylating agent mechanisms |
Main efect on DNA synthesis - alkylation of DNA (they are used in combo with other agents to treat variety of lymphatic and solid cancers) Resistant: - Increased capability to repair DNA lesions - Decreased transport of alkylating drug into cells |
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Alkylating agents - adverse effect: |
Nausea, vomiting (severe) All are mutagenic and carcinogenic Myelosuppression Alopecia Haemorrhagic cystitis Nephrotoxicity Neurotoxicity |
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Alkylating agents |
Classical Alkylating agents: NITROGEN MUSTARD: - Mechlorethamine - Chlorambucil - Cyclophosphamide - Melphalan Nitrosoureas - Carmustine - Lomustine - Streptozocin Non Classic Alkylating agents - Procarbazine - Dacarbazine - Bendamustine Platinum analogs - Cisplatin - Carboplatin - Oxaliplatin |
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Mechlorethamine mechanismAlkalating agents |
Alkalating agent Bind to DNa - prevent cell duplication Cause Lymphocytopenia |
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Nitrosoureas Members and action |
Carmustine , Lomustine Inhibit replication of DNA and RNA Good penetration oTO CNS |
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Platinum analogs Members and their actions |
Cisplatin, Carboplatin, Oxaliplatin Cisplatin - Has major activity in broad range of solid tumors Carboplatin - similar to cisplatin Oxaliplatin ... |
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Chemotherapy - composed of?
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Antimetabolites Alkylating agents Antitumor antibiotics Natural products ( Vinca alkaloids, Taxanes, Epipodophyllotoxins, Camptothecins) |
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Antimetabolites - |
Interfere with the availaability of normal purine or pyrimidine neucleotide precursors Cell cycle specific S phase |
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Antimetabolites Clases and their members |
FOLIC ACID ANTAGONISTS: - Methotrexate - Pemetrexed - Pralatrexat PURINE ANTAGONISTS - 6-Mercaptopurine - 6-Tioguanine - Fludarabine - Cladribine PYRIMIDYNE ANTAGONISTS - 5 - Fluorouracil - Capecitabine - Cytarabine - Gemcitabine |
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Folic acid antagonists - mechanisms and adverse effects |
Inhibit synthesis of folic acid Myelosuppression Mucositis Conjunctivitis Fatique Hand - Foot syndrome (reducing toxicity - supplementation with folic acid and vitamin B12) |
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Methotrexate Class Action Toxicity |
Folic acid antagonist Inhibits dihydrofolate reductase , inhibit thymidine synthase , inhibits de novo purine nucleotide synthesis Form intracellular polyglutamate metabolites Low dose MTX is effective as a single agent against certain inflammatory diseases ( severe psoriasis, rheumatoid arthritis) |
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Methotrexate resistance |
Decreased drug transport via reduced folate carrier or receptor protein Decreased formation of cytotoxic MTX polyglutamates and so on |
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Purine antagonist Class Action Adverse effects |
Antimetabolites Inhibit synthesis of nucleic acids and prevent cell division Myelosuppression Gastrointestinal disturbances Hepatotoxicity Immunosuppression |
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Pyrimidyne antagonists Class Action Adverse effects |
Antimetabolites Inhibit synthesis of DNA by inhibiting pyrimidine precursor thymidine Myelosuppression Gastrointestinal disturbances Alopecia Severe ulceration of the oral and GI mucosa Anorexia |
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Pyrimidyne antagonist members |
5 - Fluorouracil Capecitabine |
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5 - Fluorouracil mechanism
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Inhibits thymidine synthase Alters RNA and DNA synthesis and function |
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Capecitabine mechanism |
Inhibits thymidine synthase Alters RNA and DNA synthesis and function |
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Chemotherapy divided into 2 |
Cell cycle phase - specific - CCS
Cell cycle phase - nonspecific CCNS |
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CCS |
Agents with major activity in a particular phase of cell cycle Schedule dependent |
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CCNS |
Agent with significant activity in multiple phases Dose dependent |
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Resistance - how? |
Alterations in drug targets Alterations in intracellular retention of drug Alteration in drug detoxicification pathways Increased DNA repair Defective apoptosis Epigenetic changes |
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What is resistance and what kind of resistance do we have? |
Resistance is lack of response to drug-induced tumor growth inhibition Primary resistance No response from very first exposure Acquired resistance During continuation of therapy. Due to adaption of tumor cells or due to mutation in one or more gene |
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Why drug combination? |
Maximal cell kill within the range of toxicity tolerated Broader range of interaction Prevent or slow the drug resistance |
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Primary chemotherapy |
Chemotheramy is main modality of treatment Can be single drug or combination chemotherapy |
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Adjuvant chemotherapy |
Combined with radiation or surgery For advanced cancer Reduce the incidence of both local and systemic recurrence Improve overall survival of patients |
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Goals of chemotherapy |
To cure To control - decrease rate of relapse Palliation - relive symptoms |
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Management of chemotherapy |
Nausea and vomiting Bone marrow suppression - Anemia - Neutropenia (treat with Filgrastim) - Thrombocytopenia (treat with Molgramostim) |
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Gene therapy |
Alter the genes inside body's cell - to stop disease Replace a faulty gene or add a new gene - cure or improve body's ability to fight disease Hold promise for treating a wide range of disease : AIDS, diabetes, cancer, cystic fibrosis, heart disease |
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Hormone therapy |
Prednisone - anti-inflammatory corticosteroid - Treat acyte lymphocytic leukemia and Hodgkin and non Hodgkin lymphomas Tamoxifen - estrogen antagonist - First line therapy in treatment of estrogen receptor positive breast cancer Flutamide, Nilutamide, Bicalutamide - nonsteroidal antiandrogens |
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Why hormone therapy? |
Because cancer can depend on hormones to grow Sometimes - surgery to remove the organs that make the hormones Or drugs to stop hormone production |
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Interferons classes (Biological therapy) |
Alfa Beta Gamma |
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Interferons produced by |
Connective tissue Fibroblasts T lymphocytes |
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Interferon mechanism |
Suppress cell proliferation, activate macrophages, increased cytotoxicity of lymphocytes |
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Monoclonal antibodies Biological therapy |
Trastuzumab Rituximab Bevacizumab Cetuximab |
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Biological therapy - what is it |
Also called immunotherapy Use body's own immune system to fight infection and disease Monoclonal antibodies Interferon Interleukin 2 Colony stimulating factors |
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What is radiotherapy? |
Uses high-energy radiation to kill cancer Come from a machine outside the body - may come from radioactive material Can damage cancer cells and normal cells |
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What is surgery |
Removal of tumor and surrounding tissue Non hematological cancer can be cured |
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Cancer treatments: |
Surgery Hormone therapy Chemotherapy Immunotherapy Gene therapy Radiotherapy |
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Cancer staging |
Primary tumor T TX - cannot be evaluated T0 - no evidence of primary tumor T1 T2 T3 - size of tumor Regional lymph node (N) NX - cannot be evaluated N0 - No evidence N1 N2 N3 - degree of lymph node involved Distant metastasis (M) MX - cannot be evaluated M0 - no evidence M1 - Distant metastasis is present |
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Cancer causing factors |
Viral infection cancer: - Human papilloma virus - Epstein Barrvirus - Kaposis sarcoma herpes virus - Hepatitis B and C virus - Human T cell leukemia virus 1 Bacterial - Helicobacter pylori Parasitic: Clonorchis sinensis |
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What is carcinogen
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A factor in the environment that can cause cancer like: Tobacco smoking UV radiation Environmental pollution and so on |
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Benign vs Malignant tumor |
Benign: Slow growing Capsulated Non invasive Do not metastasize Well differentiated Malignant: Fast growing Non capsulated Invasive and infiltrate Metastasize Poorly differentiated |
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Major categories of cancer |
Carcinoma: Cancer derived from epithelial cells Sarcoma: Cancer arising from connective tissue Lymphoma and leukemia Cancers arising from blood-forming cells |
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Drugs that should be reconsidered or not used during pregnancy or child |
Aminoglycosides (eg gentamicin)
- Can cause neurologic damage Tetracyclines - Cause tooth enamel dysplasia and inhibit bone growth Sulfonamides - displace bilirubin from serum albumin - cause kernicterus in neonates Chloramphenicol - Gray baby syndrome Most antiviral and antifungal drugs Fluoroquinolones - can effect cartilage growth |
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Pharmacodynamics |
Action of drug on the body |
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Pharmacokinetics |
Action of the body on the drug including : Absorption Distribution Metabolism Elimination Elimination can be achieved by metabolism and excretion |
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Graded dose response |
Increase response to increase drug concentration |
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Efficacy |
Maximal effect that can be achieved with a drug - regardless of dose |
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Potency |
EC50 or ED 50 Amount of drug needed to produce a given effect |
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Agonist |
A drug that activate its receptor upon binding |
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Therapeutic index |
Range of safety of a drug Ratio of TD50 (or LD50) to ED50 For example ED50 is 3 mg LD50 is 150 mg Then therapeutic index is 150/3 --> 50 |
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Therapeutic window |
Dosage range between minimum effective therapeutic concentration or dose, and minimum toxic concentration or dose For example: Minimum therapeutic plasma concentration of theophylline is 8 mg/L and toxic effects are observed at 18 mg/L The the therapeutic window is 8-18 mg/L Example 2 The drug theophylline has a therapeutic concentation range of 8-20 mg/L - but may be toxic at concentration of more than 15 mg/L The therapeutic window for a patient might be 8-16 mg/L |
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First pass effect or presystemic elimination meaning |
Elimination of drug that occurs after administration but before it enters the systemic circulation |
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Bioavailability |
The fraction or percentage of administered dose of drug that reaches the systemic circulation |
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Volume of distribution |
Radio of amount of drug in the body to the drug concentration in the plasma or blood Vd= Amount of drug in the body / Plasma drug concentration |
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Clearance |
Rate of elimination to the plasma concentration Clearance (CL) = Rate of elimination / Plasma concentration |
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Half life |
The time required for the amount of drug in the body or blood to fall by 50% t 1/2 = (0.693 x Vd)/CL |
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Maintenance dosage |
Amount of drug /dose that needs to be taken to maintain a level of drug ? Dosing rate = (CL x Desired plasma concentration) / Bioavailability) - mg/h |
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Loading dose |
Is an initial higher dose of drug that may be given the in the beginning of treatment Loading dose = (Vd x Desired plasma concentration) / Bioavailability |
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Adjustment of dosage when elimination is altered by disease |
Renal disease or reduced cardiac output - might impair the clearance Then we have to adjust the dosage Corrected dosage = Average dosage x (Patients altered creatinine clearance CLcr / 100ml/min) Just read page 27-28 in Purple katzung |
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Penicillin + B-lactamase inhibitor |
Amoxicillin + Clavulanate = Augmentin Ampicillin + Sulbactam = Unasyn Piperacillin + Tazobactam = Zosyn Ticarcillin + Clavulanate = Timentin |
