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88 Cards in this Set
- Front
- Back
- 3rd side (hint)
What are Sulfonamides analogs of?
What is this term referred to as? |
PABA
Anti-metabolites |
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Sulfonamides are COMPETITIVE inhibitors of what enzyme and synthesis of what product?
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Dihyrdopteroate synthase
Dihydrofolate |
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Definition: A substance inhibiting cell growth by competing with, or substituting for, a natural substrate in an enzymatic process
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Anti-metabolite
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What is the Efficacy of Sulfonamides based on? (3)
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1. how tight they bind
2. how well it is recognized by the enzyme 3. Relative concentrations of PABA |
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Sulfonamides: Static or Cidal?
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Static
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How are Sulfonamides administered?
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Oral
Topical (burns) |
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Describe the distribution of Sulfonamides
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Good distribution including CNS
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What chemical modification (metabolism) yields inactive Sulfonamide?
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Acetylation
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How are Sulfonamides excreted?
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90% in urine by glomerular filtration
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Where in the body do Sulfonamides concentrate?
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Urine = 10-20X the blood concentration in the urine
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Sulfonamide used topically for burns
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Silver Sulfadiazine
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Sulfonamide used as Ophthalmic preparations (eye drops)
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Sodium Sulfacetamide
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What infection are Sulfonamides particularly used for?
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UTI's
*b/c they concentrate in the urine |
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Sulfonamide used for Ulcerative Colitis
-Explain the mechanism |
Sulfasalazine
-not absorbed by the gut but split by gut bacteria to release Aminosalicylate = anti-inflammatory |
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What drug are Sulfonamides commonly combined with?
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Trimethoprim
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Major adverse effect of Sulfonamides
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Allergic reactions
-fever -rash |
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What other drugs may Sulfonamides cross-react with?
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1. Carbonic anyhydrase inhibitors
2. Diuretics = Thiazide, Furosemide 3. Sulfonylurea hypoglycemics |
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Sulfonamides are the DOC for this infectious agent
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Nocardia
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Syndrome that can occur as an adverse effect of Sulfonamides
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Stevens-Johnson Syndrome
-erythema multiform that involves the skin and mucus membranes -hypersensitivity reaction |
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List the 4 Adverse effects of Sulfonamides
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1. Allergic reaction (SJS)
2. Crystalluria / Hematuria 3. Hematopoietic effects = depression in blood cell counts 4. Hemolytic anemias in G6PDH deficiency |
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List 3 ways in which microbes may become resistant to Sulfonamides
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1. overproducing PABA
2. loss of permeability 3. new form of Dihydropteroate synthetase which discriminates between PABA and sulfonamide |
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Drug that inhibits Bacterial Dihydrofolate Reductase?
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Trimethoprim
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Drug that inhibits Protozoan Dihydrofolate Reductase?
Name a specific microbe |
Pyrimethamine
Toxoplasma gondii |
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Drug that inhibits Mammalian Dihydrofolate Reductase
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Methotrexate
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Describe the distribution of Trimethoprim
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Wide distribution including CNS
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What enzyme does Trimethoprim inhibit?
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Dihydrofolate Reductase
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What is Trimethoprim usually combined with?
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Sulfamethoxazole
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What is the name of Trimethoprim-Sulfamethoxazole
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Co-trimoxazole (TMP-SMX) = synergistic
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What are 2 clinical uses of TMP-SMX?
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1. Pneumocystis pneumonia
2. complicated UTI |
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TMP-SMX: Static or Cidal?
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Cidal
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Name 3 adverse effects of Trimethoprim
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1. Megaloblastic anemia = causing cells to be Folate deficient
2. Leukopenia 3. Granulocytopenia **you're inhibiting THF synthesis so you kill cells with high proliferation rates **TMP = Treats Marrow Poorly |
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With what drug may the toxicity of Trimethoprim be alleviated?
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Folinic Acid
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What patients receiving Co-trimoxazole have a much higher incidence of adverse effects such as:
-fever, rashes, leukopenia, diarrhea |
AIDS patients with Pneumocystis
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What is the mechanism of action of Quinolones?
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Inhibits DNA gyrase (Topoisomerase II) = inhibit DNA replication
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Are Quinolones STATIC or CIDAL
What is the spectrum of Fluoroquinolones? |
CIDAL
Gram + & - |
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What was the protype Quinolone? Why was its use stopped? What was done to correct the drug?
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Nalidixic Acid
It was rapidly absorbed, metabolized, and EXCRETED = poor pharmacokinetics Added Fluorine to diminish metabolism |
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What ending do alot of Fluoroquinolones have?
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-floxacin
(Ciprofloxacin, Levofloxacin) |
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What can decrease the renal excretion of Fluoroquinolones?
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Probenicid
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List the adverse effects of Fluoroquinolones (-floxacins) (6)
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1. NVD syndrome
2. headaches, dizziness, insomnia 3. **Abnormal liver fxn tests** 4. **block Theophylline and Caffeine clearance** 5. **effects on collagen metabolism and cartilage development** 6. **Tendonitis and tendon rupture in adults** |
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What 2 things does Fluoroquinolones (-floxacins) block the clearance of?
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1. Theophylline
2. Caffeine |
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What group of people is Fluoroquinolone contraindicated in and why?
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Pregnant women and children b/c animal studies show damage to CARTILAGE
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How does resistance to Fluoroquinolones arise?
What specific species most often have resistance? |
Altered DNA gyrase
Pseudomonas, Staph, Serratia |
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What are 4 agents that are used for UTI's
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1. Penicillins
2. Aminoglycosides 3. Sulfas 4. Fluoroquinolones FAPS for UTI's |
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What is Nitrofurantoin's mechanism of action?
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unknown but may involve oxidative stress
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Is Nitrofurantoin STATIC or CIDAL?
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Either - depends on the bug
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Describe the pharmacokinetics of Nitrofurantoin
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rapidly absorbed, metabolized, and excreted in the urine -> 50% as an active drug
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What is Nitrofurantoin clinically used for?
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UTI's: Gram + and -
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This drug is most effective as a urine pH of < 5.5
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Nitrofurantoin
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What are the adverse effects of Nitrofurantoin?
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Anorexia, GI disturbances
Hemolytic anemia if G6PDH deficient |
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What patients do you never give Nitrofurantoin to and why?
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Those with Renal Insufficiency b/c will cause systemic toxicity
**rapidly absorbed, metabolized, and excreted in the urine -> 50% as an active drug |
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What bugs are resistance to Nitrofurantoin?
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ALL Pseudomonas
some Proteus |
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Describe Mycobacterial infections
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Chronic infections with long dormant periods separating intermittent active (symptomatic) periods
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What are the barriers in treating Mycobacterial infections?
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They are INTRACELLULAR pathogens = drug has to get into patient's cell and then into Mycobacteria
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How long is treatment for "uncomplicated" TB?
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6-9 months
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How long is chemoprophylaxis treatment for TB?
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1 year
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How long is treatment for Complicated TB (TB meningitis, Miliary TB)?
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2 years
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What is the general rule for treating TB?
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Combination chemotherapy due to rapidly developing resistance
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What is Isoniazid's mechanism of action?
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inhibits Mycolic Acid synthesis
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Isoniazid: STATIC or CIDAL?
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CIDAL in GROWING cells only
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Anti-TB with these pharmacokinetics:
-CNS levels ~20% of serum level -Intracellular = Extracellular |
Isoniazid
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What is the key factor in the pharmacokinetics of Isoniazid?
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Metabolism: acetylated in the liver
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Who are "Fast" acetylators of Isoniazid?
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1. 50% of US blacks and whites
2. most Eskimos, Asians, Native Americans |
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What is the half-life for Fast and Slow Acetylators of Isoniazid?
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Fast = < 1.5 hrs
Slow = > 3 hrs |
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In what patients may you have to alter doses when giving Isoniazid and why?
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Hepatic disease patients
- due to Acetylating ability **lower doses in Liver disease |
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What is excreted in the urine of Isoniazid?
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INH and Acetylated product
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What are the clinical uses of Isoniazid?
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Prophylaxis = used alone
Combo chemotherapy for TB **only agent used as solo prophylaxis against TB |
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What drugs is Isoniazid used with in Combination chemotherapy?
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RIPE
- Rifampin - Isoniazid - Pyrazinamide - Ethambutol |
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What are the adverse effects of Isoniazid dependent on?
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Dose and Duration
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What are the adverse effects of Isoniazid? (2) (hint)
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1. Hepatotoxicity that increases with age
-more common in alcoholics and pregnant women *induces CYP 2E1 along with alcohol to bioactivate Acetaminophen -> liver toxicity 2. Neurotoxicity |
INH = Injures Neurons & Hepatocytes
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How do you counter the neurotoxocity of Isoniazid?
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give Pyridoxine (vitamin B6)
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How do Mycobacteria become resistant to Isoniazid?
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deletion of katG gene = enzyme normally activates INH
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Where in the world is Isoniazid resistance higher? (2)
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Caribbean
Asia |
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What is Ethambutol's mechanism of action?
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inhibits synthesis of mycobacterial cell wall arabinogalactan
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What is the mnemonic for Anti-TB drugs
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INH-SPIRE
- Isoniazid - Streptomycin - Pyrazinamide - Isoniazid - Rifampin - Ethambutol |
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Anti-TB with these pharmakokinetics:
1. CNS level variable = 4-60% of serum 2. most excreted in urine = accumulates in renal failure |
Ethambutol
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Anti-TB that may cause dose-dependent Optic Neuritis
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Ethambutol
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Rifampin mechanism of action
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inhibits bacterial RNA synthesis
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Rifampin: STATIC or CIDAL
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CIDAL
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How is Rifampin excreted?
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Bile = can cause liver problems
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What are the adverse effects of Rifampin?
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1. Inducer of Microsomal enzymes
- alters half-life of Anticoagulants, oral contraceptives 2. Hepatotoxic 3. "Flu-like" syndrome 4. Gives orange color to body fluids |
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What are the 4 R's of Rifampin?
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1. RNA polymerase inhibitor
2. Revs up microsomal P-450 3. Red/orange body fluids 4. Rapid resistance if used alone |
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What are the clinical uses of Rifampin?
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1. Combo therapy for active TB
2. Single agent prophylaxis for INH-intolerant patients or INH-resistant bug |
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Pyrazinamide: Static or Cidal?
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STATIC
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What is this Anti-TB:
unknown but is activated by the Mycobacterium -strains lacking the activating enzyme are resistance |
Pyrazinamide
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What are the adverse effects of Pyrazinamide?
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1. Hyperuricemia
2. Gouty arthritis 3. Hepatotoxicity |
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Why was Streptomycin rarely used for TB? Why is it now used more often?
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Had bad pharmacokinetics and adverse side effects
Resistance to the other drugs |
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Why are second-line Anti-TB drugs usually not used?
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because the toxicity outweights the therapeutic effects EXCEPT for highly resistant strains
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List 5 2nd line Anti-TB drugs (hint)
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1. Cycloserine
2. Para-aminosalicylate 3. Ethionamide 4. Capreomycin 5. Dapsone *Others: Amikacin, -floxacin's |
ETHIOpian CYCList wearing CAPRis PAS's Da (p) zone but still takes 2nd place
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