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396 Cards in this Set
- Front
- Back
What is Selective Toxicity?
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Kills the invading organism w/o killing the host by taking advantage of differences between the invader and the host
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What is an antibiotic?
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A substance produced by microorganisms to kill of supress growth of other microorganisms
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What is an Antimicrobial?
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A substance that kills or suppresses the growth of microorganisms. Term includes antibiotics as well as synthetic substances made in the laboratory
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Is there a difference between Antibiotic and Antimicrobial?
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NOPE
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Name the different types of Anti-infectives?
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Antivirals, Antibioctics, Antimycobacterials, Antifungals, Antiprotozoals, Antihelmintics, and Urinary Anti-infectives
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Antimicrobial Agents can be either Bactericidal or Bacteriostatic. Describe these two terms?
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~Bactericidal: the organisms are killed INSTANTLY (like a bomb)
~Bacteriostatic: the organisms are PREVENTED from growing (like starvation) |
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What type of Antimicrobial Agents MUST be used in an Immunocompromised pt? Why?
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Bactericidal Agenst must be used b/c they lack proper immunity/antibody function
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Describe the Post-Antibiotic Effect (PAE)?
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Persistent suppression of organism growth after concentrations fall below the minimum Inhibitory Concentration (MIC)
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Describe Minimum Inhibitory Concentration (MIC)?
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Lowest concentration of an antimicrobial agent that prevents visible growth after an 18 – 24 hour incubation
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Describe Minimal Bacterial Concentration (MBC)?
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Minimal concentration that kills 99.9% of bacterial cells
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What are the different methods used for identification of the infecting organism? Which method is the simplest/fastest? Which provides conclusive identification?
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~Gram Stain (Fastest/Simplest)
~Culture and Sensitivity (most conclusive/Takes time!) ~Gene Amplification (newest) |
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When using Empiric Therapy, what factors should be considered before Tx?
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~Most LIKELY pathogen
~Host factors ~Drug factors |
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After initiating Tx, you should monitor the pt. If their Sx are not getting better by ____ days, you might need to think about increasing the dose or changing the Drug?
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By 3 days!
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How is a pts therapeutic response monitored?
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~Clinical Assessment
~Lab Test ~Assessment of Therapeutic failure (no improvement or worsening Sx's) |
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What considerations of the host should be taken into account before Antibiotic use?
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~Type of infection, immune status,
~Community-acquired ~Health care-associated vs nosocomial, ~Underlying co-morbidities |
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Different organsims of Community Acquired vs. Nosocomial?
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~Community Acquired: Strep Pneum (gram pos diplococci)
~Nosocomial: Gram Neg |
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Some pts (host) may have anaphylactic rxns to Abx you want to give, for this reason you should always have what?
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An Alternative drug that you can use
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Anaphylactic Rxns are Ig_ mediated?
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IgE Mediated
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For young children, they should not use either Tetracylines or Flouroquinolones for what reasons?
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~Tetracyclines cause Gray Teeth
~Fluoroquinolones cause Cartilage damage |
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Why does the anitomical site of infection need to be taken into account when Rx'ing an Abx?
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You need to make sure that the drug will reach the site of infection (i.e. DM Foot Infection- Abx will be appropriate for bacteria present, but the drug cant reach site due to poor perfusion secondary to swelling and co-morbid dz state)
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Which route of admin is the MOST reliable but LEAST convenient when giving Abx?
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IV route is the most reliable but least convenient (patient must usually be hospitalized)
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How can INFLAMMATION facilitate Abx distribution to site?
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Inflammation can facilitate antibiotic distribution because it increases blood flow to the area (and the inverse is true as healing occurs)
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What are the possible CNS SE's w/ prolonged use of PCN, Cephalosporins, Quinololones, and Imipenems?
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Seizures
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For pts taking Abx that can cause Hemotologic (blood) issues, their Abx use should always be monitored. Name the drug that causes the following issues:
~Neutropenia? ~Platelet Dysfunction? ~Hypoprothrombinemia? ~Bone-marrow suppression? ~Megaloblastic anemia? |
~Neutropenia – nafcillin
~Platelet Dysfunction – piperacillin ~Hypoprothrombinemia – cefotetan ~Bone-marrow suppression – chloramphenicol ~Megaloblastic anemia – trimethoprim |
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Name some common drugs that cause Nephrotoxicity, Photosensitivity and Diarrhea/Colitis?
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~Nephrotoxicity: Aminoglycosides and Vancomycin
~Photosensitivity: Quinolones, Tetracyclines and Sulfonamides ~Diarrhea/Colitis (Clostridium Difficile): Clindamycin |
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Will the Nephrotoxicity go away if the Aminoglycoside or Vancomycin is stopped?
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Yes
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Describe the effective uses of Abx Drugs that have a Narrow spectrum? (give an example)
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Effective against a SINGLE or LIMITED group of microorganisms (Metronidozole - Anaerobes)
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Describe the effective uses of Abx Drugs that have a Extended spectrum? (give an example)
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Effective against a LARGE number of Gram Pos and some Gram Neg bacteria (Amoxicillin)
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Describe the effective uses of Abx Drugs that have a Broad spectrum? (give an example)
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Effective against a WIDE variety of microbial species including Gram Pos, Gram Neg and Anaerobic bacteria (Fluoroquinolones [Moxifloxacin])
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Why do you want to minamize the use of Combo Abx when Tx'ing Empirically?
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~Reduces likelihood of development of resistant organisms
~Using multiple agents can disrupt the action of a single agent and increase the toxicity risk to the patient |
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What are some situations in which you would WANT to use Combination Abx therapy?
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~To provide broad spectrum therapy to Tx life threatening infections in seriously ill/immunocompromised pts
~To Tx Polymicronial Infections ~Empiric therapy when no one agent is active against potential pathogens ~To decrease toxicity (permit lwr dose of other agent) ~Synergism |
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What is Synergism? How is it beneficial in Combination Abx therapy?
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~The inhibitory or killing ability of two antimicrobials is greater than the expected antimicrobial ability based on their individual effects (1+1 = 2)
[i.e. β-lactams and Aminoglycosides --> 1+1 = 3 (or more!)] |
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What are the two types of Bacterial Resistance to Abx?
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~Innate Resistance
~Acquired Resistance |
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Describe Innate Resistance?
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Essentially you gave the wrong Drug for the wrong Bug!!!
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Describe Acquired Resistance?
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Adapted through spontaneous mutation or DNA transfer of drug use (Bug resistance to drug!)
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The use of Abx to PREVENT specific bacterial infections
should be used when efficacy has been proven and the benefits of prophylaxis therapy outweigh the risk of resistance. What are the two types of Abx prophylaxis? |
~Surgical Prophylaxis: i.e. upper GI, colon, prosthetics, C-section, dirty surgery, GSW
~Non-surgical Prophylaxis: i.e. prevention of urinary tract infections, bacterial endocarditis, ACNE |
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How long do Abx last for until resistance occurs?
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Antibiotics last for about 20 years until resistance
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Abx are classified based on effect of agent during cellular biochemistry. What are the Abx Classifications?
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1. Cell wall synthesis inhibitors (β- lactams)
2. Inhibition of synthesis or damage to cytoplasmic membrane (Polymyxins) 3. Inhibition or modification of protein synthesis - usually ribosomal (Tetracyclines, Macrolides, etc.) 4. Modification in energy metabolism - Folate Antagonists (Sulfonamides) 5. Modification in synthesis or metabolism of nucleic acids- DNA Gyrase Inhibitors (Fluoroquinolones) |
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****Name the SPACE bugs? What is their MAIN Tx option?
GRAM NEG BUGS |
~Must be Tx w/ 2 Abx: β-Lactams + Aminoglycoside
-Serratia (can be MDR) -Pseudomonas -Acinetobacter -Citrobacter -Enterobacter ~Cause of NOSOCOMIAL Infections |
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Name some main bacteria found in the NOSE?
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~Staphylococcus Aureus
~Staphylococcus Epidermidis |
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Name some main bacteria found in the THROAT?
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~Staphylococcus
~Haemophilus |
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Name some main bacteria found in the LARGE INTESTINE?
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~Bacteroides Fragilis
~E.Coli |
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Name some main bacteria found in the MOUTH?
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~Streptococcus
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Name some main bacteria found on the SKIN?
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~Staphylococcus Epidermidis
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Name some main bacteria found in the VAGINA?
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~Streptococcus
~Candida Albicans |
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Name some main bacteria found in the URETHRA?
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~E.Coli
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Name the Different Types Cell Wall Synthesis Inhibitors?
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~PCNs
~Cephalosporins ~Carbapenems ~Monobactams ~β-Lactamse Inhibitors ~Vancomycin ~Bacitracin |
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β-lactam drugs are named for their 4-membered ring and require actively proliferating bacteria to work effectively, this makes its MOA beneficial for SELECTIVITY why?
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This allows their MOA to be beneficial for SELECTIVITY because human cells do not have cell walls. This allows the drug to attack the organism, not the host!!!
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Bacteria often develop resistance to β-lactam Abx by synthesizing β-lactamase, an enzyme that attacks the β-lactam ring. To overcome this resistance, what is the course of action?
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β-lactam antibiotics are often given with β-lactamase inhibitors such as Clavulanic Acid
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Of the drug types that are Cell Wall Synthesis Inhibitors, which ones are β-lactam Agents?
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~Representative Agents
-Penicillins -Cephalosporins -Carbapenems -Monobactams -β-Lactamase Inhibitors |
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What are the diff types of Penicillins?
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~Penicillins (can be either drug or drug class…)
~Anti-Staphylococcal PCNs (Penicillinase or β-lactamase Resistant) ~Extended Spectrum PCNs -Aminopenicillins -Anti-pseudomonal PCNs (<-- used to tx pseudomonas) |
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What are the drugs of the PCNs drug class?
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~Penicillin G (inj)
~Pencillin VK (oral) <-- more acid stable |
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What are the drugs of the Anti-Staphylococcal PCNs (Penicillinase or β-lactamase Resistant)?
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~Dicloxacillin (Dynapen)
~Nafcillin (Unipen) ~Oxacillin (Prostaphlin) |
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Of the Extended-Spectrum PCNs drug class, what are the Aminopenicillins?
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~Amoxicillin (Amoxil)
~Amoxicillin / Clavulanic Acid (Augmentin) ~Ampicillin (Omnipen) ~Ampicillin / Sulbactam (Unasyn) |
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Amoxicillin is converted into what in the liver?
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Ampicillin
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Of the Extended-Spectrum PCNs drug class, what are the Anti-Pseudomonal PCNs?
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~Piperacillin (Pipracil)
~Piperacillin / Tazobactam (Zosyn) ~Ticarcillin (Ticar) ~Ticarcillin / Clavulanic Acid (Timentin) |
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What is the MOA of PCNs?
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Inhibit bacterial cell wall synthesis exposing the osmotically less stable membrane which can lead to cell lysis
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The Antibacteral Spectrum of PCNs depends on the ability to cross bacterial cell walls, explain?
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~Gram positive bacteria have cell wall that PCN can cross
~Gram negative bacteria have a lipopolysaccharide membrane that acts as a barrier to water soluble PCNs so entry must be gained by water filled channel |
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What are the Natural PCNs?
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~Penicillin G (inj)
~Pencillin VK (oral) <-- more acid stable |
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Why is Pen G only used as an injection?
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B/C it is unstable in stomach acid when it is given orally
-Use Pencillin VK (<-- more acid stable) |
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What is the Spectrum of use for the Natural PCNs?
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~Gram positive bacteria:
-Streptococci causes pharyngitis --> Tx with Pen VK -Viridans strep causes IE --> Tx'ed w/ Pen G ~Gram negative bacteria: -N. Meningitidis causes meningitis --> Tx'ed w/ Pen G ~Treponema Pallidum (spirochete) causes syphilis --> Tx'ed w/ Pen G |
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****What bacteria is resistant to Methicillin, a drug that used to be used as a Antistaphylococcal PCN, and is now Tx'ed w/ Vancomycin?
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~MRSA (Methicillin Resistant Staph Aureus)
~MRSE (Methicillin Resistant Staph Epidermidis) |
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What is the MOA of the Antistaphylococcal PCNs?
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Inhibits bacterial cell wall synthesis by binding to one or more of the PCNs Binding Proteins (PBPs)
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What are the uses for Antistaphylococcal PCNs?
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~Severe Infections: Osteomyelitis (Bone infections), Joint, Cellulitis and other tissue infections caused by Staph. aureus or group A strep
--> Tx w/ IV Nafcillin or Oxacillin ~Minor infections: Skin infections (Impetigo, Cellulitis) caused by Staphylococcal Aureus and Strep Group A --> Tx w/ Oral Dicloxacillin |
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What is the pregnancy catergory of Antistaphylococcal PCNs?
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Cat B
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What drug has a major interaction w/ Antistaphylococal PCNs?
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Warfarin
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What is the Spectrum of use for Extended Spectrum PCNs?
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Similar to Pen G, but has better activity against Gram Neg organisms due to ability to penetrate the outer membrane
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Extended Spectrum PCNs are inactivated by β-lactamases unless combined with what?
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β-Lactamase inhibitor such as **Clavulanic Acid, Tazobactam, or Sulbactam
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Describe the uses of β-Lactamase inhibitors again?
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~These substances look like a beta-lactam molecule but they have very little antibiotic activity
~Combined with other PCNs in order to extend their spectrum to include β-lactamase producing bacteria -Clavulanic acid (clavulanate) -Sulbactam -Tazobactam |
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What is the place in therapy of Amoxicillin (Amoxil)?
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~Otitis Media (caused by Strep Pneum or H. Influenzae)
~Endocarditis Prophylaxis |
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What is the place in therapy of Ampicillin (Omnipen)?
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~Meningitis (in conjunction w/ a gram neg agent --> Cefotaxime or Gentamicin)
~Neonatal Pneumonia (in conjunction w/ gram neg agent) |
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Are Ampicillin and Gentamicin used together on a routine basis?
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YES
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Why is this a good Synergistic relationship?
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PCN has the ability to destroy the cell wall and allows entry of the Aminoglycoside into the cell
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What is the place in therapy of the IV Combination agent Ampicillin / Sulbactam (Unasyn)?
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~Infected wounds w/ sepsis
~Peritoneum / Peritonitis 2nd to bowel perforation |
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What is the place in therapy of the Oral Tabs/Susp Combination agent Amoxicillin / Clavulanic Acid (Augmentin)?
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~TID dosing and BID dosing
~Otitis media resistant to amoxicillin ~Sinusitis ~Animal and Human bites ~Infected wounds |
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What is the Spectrum of Anti-Pseudomonal PCNs?
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Spectrum extends Ampicillin to include Pseudomonas Aeruginosa and several other gram neg bacteria (SPACE Bug Coverage)
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Why are two of the Anti-Pseudomonal PCNs (Piperacillin and Ticaracillin) not used alone?
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~B/C they are suseptable to β-Lactamase
~This is why they are combined w/ β-Lactamase Inhibitors such as: -Piperacillin / Tazobactam (Zosyn) -Ticarcillin / Clavulanic Acid (Timentin) |
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Regarding hypersensitivity, what percent of pts have PCN allergies?
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1-5% of pts (rash or anaphylaxis)
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PCNs can cause Diarrhea, is this an allergic rxn?
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No, it’s a SE
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****KNOW HOW TO CALCULATE CrCl...
What is the Crockroft-Gault Formula for CrCl? |
(140-age) x Body Weight (kg) [ X 0.85 for female ]
72 x SCr |
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What is the structure of The Cephalosporins?
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β-lactam ring attached to six sided ring
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What is the MOA of Cephalosporins?
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Same as the PCNs
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What are the different generations of Cephalosporins and what is the spectrum of each generation?
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~1st Gen: similar spectrum to Pen G; they are resistant to Penicillinases and β-lactamases (Gram Pos)
~2nd Gen: weaker Gram Pos, but some Gram Neg and Anaerobic activity (bacteroides) ~3rd Gen: enhanced Gram Neg activity but inferior to 1st Gen agents against Gram Pos ~4th Gen: Wide Spectrum (Gram Pos and Gram Neg) |
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What are some of the adverse rxns associated w/ Cephalosporins?
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~5-15% penicillin cross sensitivity (same rxn as they would w/ PCN)
~Superinfections are possible ~Cephalosporins are generally well tolerated and have few major side effects |
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What are the Cephalosporin 1st Gen Oral Agents?
[G+ AGENTS] |
~Cephalexin (Keflex)
~Cephradine (Velosef) ~Cefadroxil (Duricef) |
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What are the Cephalosporin 1st Gen Injectable Agents?
[G+ AGENTS] |
~Cefazolin (Ancef and Kefzol)
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What is the place in therapy for the 1st Gen Cephalosporin agents (oral, injectable)?
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~Oral: skin infections (Staph Aureus, Grp A Strep, UTIs
~Injection: pre/post surgery not involving the abdomin -Cefazolin is DOC for most surgical prophylaxis |
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What are the Cephalosporin 2nd Gen Oral Agents?
[G+, LITTLE G-, ADD ANAEROBIC AGENTS] |
~Cefuroxime (Ceftin)
~Cefaclor (Ceclor) ~Cefprozil (Cefzil) |
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What are the Cephalosporin 2nd Gen Injectable Agents?
[G+, LITTLE G-, ADD ANAEROBIC AGENTS] |
~Cefuroxime (Zinacef)
~Cefoxitin (Mefoxin) |
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What is the place in therapy for the 2nd Gen Cephalosporin agents (oral, injectable)?
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~Oral: option for resistant otitis media, alternate for community acquired pneumonia, pharyngitis and cat bites
~Injection: [Cefoxitin] used in pre/post surgery involving the abdomen |
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What are the Cephalosporin 3rd Gen Oral Agents?
[ENHANCED G-, lower G+ than 1st] |
~Cefpodoxime (Vantin)
~Ceftibutin (Cedax) ~Cefixime (Suprax) |
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What are the Cephalosporin 3rd Gen Injectable Agents?
[ENHANCED G-, lower G+ than 1st] |
Ceftriaxone (Rocephin) --> N. gonorrhea urethritis
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What are the Cephalosporin 3rd Gen IV Agents?
[ENHANCED G-, lower G+ than 1st] |
Cefotaxime (Claforan)
Cefatazidime (Fortaz) |
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What is the place in therapy for the 3rd Gen Cephalosporin agents (oral, injectable, IV)?
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~Oral: very similar to the 2nd gen orals, alternative in OM and resistant sinusitis
~Injection: Used to treat N. gonorrhea urethritis (Mix w/ Lidocaine- to be nice), Resistant OM, Tx of MENINGITIS, pharyngitis (gonococcus) ~IV: Used for severe gram negative infections including: MENINGITIS, endocarditis, joint infections and multiple other severe infections (good CNS penetration) |
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For Tx w/ Ceftriaxone (Rocephin) injection for Meningitis, what is the difference in dosing?
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Dosing will be twice daily, instead of the once daily dose for Gonorrhea
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What is the Cephalosporin 4th Gen Agent?
[GRAM + and GRAM - = WIDE SPECTRUM] |
Cefepime (Maxipime)
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What is the place in therapy for the 4th Gen Cephalosporin agent?
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Useful in Empiric therapy in Febrile Neutropenia (in Cancer pts)
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What is the Structure of Monobactam?
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B-Lactam ring is NOT fused to any other ring
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What is the Spectrum of Monobactams?
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~Pure Gram Neg agent (ALL Gram Neg)
-NO Gram Pos or Anaerobic activity ~Resistant to B-Lactamases |
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What is the ONLY Monobactam Agent?
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Aztreonam (Azactam)
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What is the place in therapy for Monobactam?
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Viewed as an alternative to Aminoglycosides in pts w/ diminshed renal function
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What are the available routes of admin for Monobactam?
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IV and IM routes -- NOT available orally!!
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What drug class has synthetic B-Lactams w/ MOA similar to the others?
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Carbapenems
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What is the Spectrum of the Carbapenems?
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Broadest Available Agents
-Gram Pos, Gram Neg and Anaerobic (similar to 4th Gen Cephalosporin) -Resistant to B-Lactamase -LAST LINE AGENT!!!!!!!!! |
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What are the Carbapenem Agents?
[Gram Pos, Gram Neg and Anaerobic agents] |
~Imipenem / Cilastatin (Primaxin)
~Meropenem ~Ertapenem |
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What are the Clinical Uses for Carbapenems?
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~Febrile Neutropenia
~Severe Resistance Infections |
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What are the adverse rxns associated w/ Carbapenems?
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~N/V, Rashes, and seziures
~Approx 50% cross reactivity w/ PCNs |
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What is the available route of admin for Carbapenems?
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ONLY available IV
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What is the MOA of Vancomycin?
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Inhibits bacterial cell wall synthesis at a site EARLIER than the B-lactams (PCNs, Cephalosporins, Carbapenems, Monobactams, β-Lactamase Inhibitors)
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What is the Spectrum of Vancomycin?
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~Effective against Gram Pos (narrow spectrum)
~Restrict use as directed: -B-Lactam resistant G+ bacteria (MRSA) -Pts who have allergies to B-Lactams -2nd line Tx for Life threatening Clostridium Difficile Colitis (prefer Metronidazole) |
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What are the routes of Admin for Vancomycin?
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~Oral dosages are not absorbed and only used for Clostridium difficile
~All other infections require slow IV infusion -Good penetration of infected CNS!!! |
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Vancomycin is Synergistic w/ ______ against Enterococcus Faecium and Faecalis?
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Aminoglycosides
|
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Vancomycin is not effectively removed by dialysis and renal adjustment required. Due to this possibility of Nephrotoxicity, what needs to be monitored?
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Creatinine Clearance (CrCl)
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What are the Adverse Rxns associated w/ Vancomycin?
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~Phlebitis, fever, chills, shock, flushing (red man syndrome), hearing loss (rare)
~Renal and ototoxicity risk is increased by concomitant aminoglycides |
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Describe Red Man (Red Neck) Syndrome?
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~Red man (Red Neck) Syndrome is a histamine rxn caused by infusing too fast!!!
~Avoid by infusing the dose over 1-2 hours ~THIS IS NOT AN ALLERGY |
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What is the MOA of Cyclic Lipopeptides?
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~Alternative to Vancomycin
~Binds to bacterial membranes and causes rapid depolarization leading to inhibition of protein, DNA and RNA synthesis (cell death) |
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What is the Cyclic Lipopeptide Agent?
|
Daptomycin (Cubicin)
|
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What are the Clinical Uses for Cyclic Lipopeptides?
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~For complicated Skin structure infections caused by Gram Pos bacteria
~Staph, Strep and Vanomycin susceptible E. Faecalis |
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What needs to be monitored weekly while on Cyclic Lipopetides?
|
Creatine Phosphokinase (CPK)
|
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What is the MOA, Spectrum and Uses of Bacitracin?
|
~MOA: Inhibits Cell Wall Synthesis
~Spectrum: Gram Pos Organisms ~Uses: Topical or Surgical irrigation soln only |
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Name the Drug that Inhibits the synthesis or damages the cytoplasmic membrane?
|
Polymixin B
|
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What is the MOA of Polymixin B? Spectrum?
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High molecular weight peptide that injures Gram Neg Bacteria plasma membranes
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What infection is Polymixin B used for?
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Acenitobacter Infections
|
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What is the route of admin for polymixin B?
|
Topical
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Many Topical Abx are in a combination w/ Polymixin B, Name two and the combinations?
|
~Neosporin
-Polymyxin B, Neomycin and Bacitracin ~Polysporin -Polymyxin B and Bacitracin |
|
What topical agent is effective against S. aureus, Group A strep infections (Impetigo), MSSA, and MRSA? This drug is more expensive than Bacitracin?
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Mupirocin (Bactroban)
|
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What is the MOA of Mupirocin (Bactroban)?
|
Inhibits bacterial protein synthesis (Note – It is NOT a Cell Wall Inhibitor)
|
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What are the drugs that Inhibit or Modify Bacterial Protein Synthesis?
|
~Chloramphenicol
~Tetracyclines ~Macrolides ~Clindamycin (its own drug class) ~Aminoglycosides & Spectinomycin ~Oxazolidinones ~Streptogramins ~Ketolides |
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This group of Abx will target what?
|
The Bacterial Ribosome which are smaller than Human Ribosomes
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What is the MOA of Chloramphenicol?
(DONT WORRY ABOUT!!!) |
Inhibits bacterial protein synthesis
-RARELY used due to toxicity!!! -Gray Baby Syndrome -Don’t worry about this drug!!! |
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What is the MOA of Tetracyclines?
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Inhibits bacterial protein synthesis
|
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What is the Spectrum of Tetracyclines?
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Broad spectrum Abx that is bacteriostatic (prevents organism from growing)
|
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What are Clinical uses of Tetracylines?
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Widespread use for mild illnesses; including acne
|
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What are the three Tetracycline Drugs?
|
~Tetracycline (Sumycin)
~Doxycycline (Vibramycin) ~Minocycline (Minocin) |
|
How are Tetracycline drugs eliminated from the body? Why can Doxy be used in pts w/ renal failure, but not the others?
|
~Tetracycline and Minocycline are eliminated renally
~Doxycycline is eliminated in feces and can therefore be used in renal failure |
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What are some Adverse rxns associated w/ Tetracyclines?
|
~GI (N/V/D)
-Reduced by taking med w/ food but absorption reduces. Tell patients to avoid dairy products / divalent cations / antacids 1 hr before and 2 hrs after dosing ~Deposition in calcified tissues (gray teeth) ~Phototoxicity ~Fatal hepatotoxicity |
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What pts are Tetracyclines Contraindicated in?
|
~Renal impairment (except Doxycycline)
~Pregnant or breast feeding women ~Children under 8 |
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What is the route of Admin and the Uses of Tetracycline (Sumycin)?
|
~Oral route
~Used in Helicobacter pylori protocols and for the Tx of Acne vulgaris |
|
What is the route of Admin and the Uses of Doxycycline (Vibramycin)?
|
~Oral and Injectable
~Uses: -Community Acquired Pneumonia -Chlamydia -Rickettsiae species: Rocky Mtn spotted fever -Bacillus anthracis, Y.pestis, & F. tularemia -Borrelia burgdorferi: Spirochete that causes Lyme Dz |
|
What are the Uses of Minocycline (Minocin)?
|
~All the Tetracyclines are alternative products for inflammatory
~This is the ONLY Tetracycline w/ possible MRSA coverage!!!!! |
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What are some SE's of Minocycline?
|
~Dizziness, N/V (due to concentration in the ear)
|
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What is the MOA of Macrolides?
|
Inhibits bacterial protein synthesis
|
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What is the Spectrum of Macrolides?
|
~Bacteriostatic or Bacteriocidal
-Helicobacter Pylori (PUD/DU) -Atypicals (mycoplasma, mycobacterium, legionella) |
|
What is the general rule about Macrolides in regards to PCN as a DOC?
|
As a general rule-- Macrolides are used in pts allergic to Penicillins in indications where penicillins are the first line agent
|
|
What are the Macrolide Drugs?
|
~Erythromycin
~Clarithromycin (Biaxin) ~Azithromycin (Zithromax) <--MC Macrolide!!!! |
|
Macrolides-- Take w/ or w/o food?
|
~Erythromycin: Take w/ food!!! (GI issues)
~Azithromycin: Take w/o regard to meals; avoid Antacids ~Clarithromycin: Take w/o regard to meals |
|
What are the Clinical Uses of Erythromycin?
|
~Used in Respiratory tract infections, Legionnaire’s disease, Alternate drug in Chlamydia
~Eye ointment is prophylaxis for Ophthalmia Neonatorum |
|
What are the Clinical Uses of Azithromycin? What is the Preg Cat?
|
~Urethritis (Chlamydia); respiratory & skin infection; community acquired pneumonia; Otitis media (5 day regimens)
~Pregnancy Cat B |
|
What are the Clinical Uses of Clarithromycin? What is the Preg Cat?
|
~Respiratory tract infections, Gastric H. pylori regimens and has some H. Influenza coverage
~Pregnancy Cat C |
|
What is the MOA of Clindamycin (Cleocin)?
(Its its own Class!!!!) |
Inhibits bacterial protein synthesis
|
|
What is the Spectrum of Clindamycin?
|
Infections caused by anaerobic bacteria possibly due to trauma and non-enterococcal gram positive cocci
|
|
What are some Adverve Rxns associated w/ Clindamycin?
|
~Diarrhea, nausea and skin rashes
~Overgrowth of Clostridium Difficile leading to potentially fatal Pseudomembranous Colitis |
|
What is the Tx for Pseudomembranous Colitis (overgrowth of Clostridium difficile)?
|
Metronidazole OR Vancomycin
|
|
What is Clindamycins Place in Therapy?
|
~Penetrating Wounds of the Abd
~Acne ~Bacterial Vaginosis ~Endocarditis Prophylaxis ~Sinus Surgery ~Mixed Polymicrobial Infections ~Alternative agent for Dog Bites |
|
What is the MOA of Aminoglycosides?
|
Inhibits bacterial protein synthesis
|
|
What other drug class is Aminoglycosides synergistic w/?
|
Synergistic effect w/ B-lactams; the B-lactams act on the cell wall which increases diffusion of Aminoglycosides into the bacterium (SPACE Bug Coverage)
|
|
What is the Spectrum of Aminoglycosides?
|
Aerobic Gram Neg Agent (SPACE Bug Coverage!!!)
|
|
Aminoglycosides are not generally Orally available due to highly polar structure, except in what drug?
|
Neomycin
|
|
How are Aminoglycosides distributed and what is the possible adverse rxns?
|
~High concentrations accumulate in the renal cortex and inner ear
-Tinnitis can occur leading to deafness or vertigo -Nephrotoxicity |
|
What are the Aminoglycoside Drugs?
|
~Gentamicin (Garamycin) <-- Most popular Inj
~Neomycin (Mycifradin) ~Tobramycin (Nebcin) ~Amikacin (Amikin) ~Streptomycin |
|
What is the Place in Therapy for Gentamicin?
|
~Tx of serious infections caused by susceptible organisms
~Complicated UTI DOC (Space Bugs) |
|
What other drug class is Gentamicin synergistic w/ in the Tx of Endocarditis or SPACE BUG Coverage?
|
B-Lactams or Vancomycin
|
|
Gentamicin Once A Day Dosing works b/c "Concentration Dependent Killing" is an important factor in its ability to destroy bacteria, what does this mean?
|
If you increased the dose (not frequency), you increase the rate of Killing bacteria
|
|
So how does this affect adverse rxns to Gentamicin in pts w/ burns, pregnancy, endocarditis, dialysis, etc?
|
Evidence now suggests that high-peak levels are not necessarily toxic, but rather it is the total dose that is important
|
|
****So how is Gentamicin dosed?
|
7mg/kg/day for 3 doses (days)
|
|
Example for Gentamicin dosage:
Calculate the dose: 200 lb pt w/ Gram Neg Sepsis |
91kg(7mg/kg) = 630 mg/day for 3 days!!!!
|
|
What are the uses for Tobramycin (Nebcin), Amikacin (Amikin), and Streptomycin?
|
~Tobramycin (Nebcin): Similar to Gentamicin
~Amikacin (Amikin): Effective against some bacteria that are resistant to Gentamicin ~Streptomycin: Currently used for the treatment of TB |
|
What is really the only use of Neomycin (Mycifradin), since the Topical ointment is largely ineffective?
|
Suppression of bowel intestinal bacteria (aerobic)-- used in conjunction w/ enteric coated E-mycin as a pre-op bowel preparation for decontamination
|
|
What is the MOA of Oxalodinones? What is the drug name? What is it used for?
|
~MOA: Inhibits Cell Wall Synthesis
~Drug: Linezolid (Zyvox) ~Use: for Vancomycin Resistant Enterococcus Faecalis (VREF) |
|
What is the MOA of Streptogramins? What is the drug name? What is it used for?
|
~MOA: Inhibits Cell Wall Synthesis in 2 phases
~Drug: Quinupristin / Dalfopristin (Synercid) ~Use: for Vancomycin Resistant Enterococcus Faecium (VREF) |
|
Why MUST Quinupristin / Dalfopristin (Synercid) be administered via central line?
|
Due to venous irritation
|
|
What are the different types of Antifolate (Folate Antagonist) Drugs?
|
~Sulfonamides
~Trimethoprim |
|
Describe the process of Antifolate Drugs?
|
~Folic acid is needed by all cells for growth and division
~Human cells absorb Folic Acid whereas bacteria cell walls are impermeable to folic acid and must synthesize folate ~Bacteria make folic acid from p-aminobenzoic acid (PABA) ~Sulfonamides are structural analogs of (PABA) and compete for the enzyme Dihydropteroate Synthetase |
|
What is the MOA of Sulfonamides?
|
Compete w/ PABA for the enzyme Dihydropteroate Synthetase
|
|
What is the Role of Sulfonamides?
|
~Bacteriostatic b/c they INHIBIT production of bacteria, not kill
~Selective b/c human cells and bacterial cells obtain folate in different ways |
|
What is the Spectrum of Sulfonamides?
|
Very Broad Spectrum:
-Some gram+ and gram- bacteria, enteric bacteria (E coli), Pneumocystis, Nocardia, Stenotrophomonas, S. hemolyticus |
|
What are the Clinical uses if Sulfonamides?
|
UTIs, Topical use for Burns, Prophylaxis for Otitis Media, Ulcerative Colitis and PCP
|
|
What are the three routes of admin, based of pharmacokinetics?
|
~Oral absorbable
~Oral nonabsorbable ~Topical |
|
What are some adverse rxns associated w/ Sulfonamides?
|
~Crystalluria (stone formation)-- DRINK WATER
~Hypersensitivity- rash, angioedema ~Stevens-Johnson Syndrome ~Sulfa Allergy ~Hemolytic Anemia (G6PD deficient pts) ~Photosensitivity |
|
What are the Contraindications of Sulfonamides?
|
Avoid use is children less than two months and pregnant women near end of term due to Kernicterus (bilrubin displacement)
|
|
Name the Sulfonamide Drug?
|
Sulfamethoxazole (Gantanol)
|
|
What is the MOA of Trimethoprim?
|
~Not a sulfonamide but it is an antifolate drug and it has a similar spectrum to the sulfa drugs
~Inhibits bacterial Dihydrofolate Reductase |
|
What the the Place in therapy for Trimethorpim?
|
Its biggest place in therapy is using it in conjunction with Sulfamethoxazole due to a synergistic effect
|
|
What are some adverse effects of Trimethorpim?
|
Folate deficiency causing --> megaloblastic anemia, leukopenia and granulocytopenia
|
|
What is the combination product between the Sulfonamide and the Trimethoprim?
|
Sulfamethoxazole and Trimethoprim (Septra or Bactrim)
|
|
What are the main uses for Sulfamethoxazole and Trimethoprim (Septra or Bactrim)?
|
~Prostatitis – DOC to fight Enterobacteriaceae
~Severe diarrhea from Shigella ~Uncomplicated urinary tract infections (DOC) -Alternative for adults and primary for children ~Respiratory tract infections -Pneumocystis Jiroveci pneumonia – DOC may require IV dosing - Most common opportunistic infection in AIDS |
|
What other Specific Folate Antagonists is the DOC for Otitis Media prophylaxis, but not effective for active Tx?
|
Sulfisoxazole (Gantrisin) Oral liquid
|
|
What Specific Folate Antagonists are used for Topical adjunctive Tx for 2nd and 3rd degree burns?
|
~Silver Sulfadiazine (Silvadene)
~Mafenide (Sulfamylon) |
|
Which one is the DOC for Non-Infected burns?
|
Silver Sulfadiazine (Silvadene)
|
|
What are the Specific Folate Antagonist agents used for the Tx of Inflammatory bowel Dz (Ulcerative Colitis and Crohns Dz), both being DOC for this indication?
|
~Sulfasalazine (Azufidine)
~Mesalamine (Asacol and Pentasa) |
|
Which Specific Folate Antagonist is used for conjunctivitis or other superficial ocular infections?
|
Sulfacetamide solution
|
|
Which Specific Folate Antagonist is used as the DOC in suppurative conjunctivitis in adults?
|
Polymixin B and Trimethoprim (Polytrim)
|
|
What are the Specific Folate Antagonist agents used for the Tx of Gardnerella Vaginalis?
|
~Sulfathiazole
~Sulfacetamide ~Sulfabenzamide (Sultrin Vaginal Cream) |
|
What drugs Modify Synthesis or Metabolism of Nucleic Acids- aka. DNA Gyrase Inhibitors?
|
Fluoroquinolones
|
|
How many Generations of Fluoroquinolones are there?
|
4 generations
|
|
Of the 4 generations, which drugs dow you need to know for the test???
|
~2nd Gen:
-Ciprofloxacin (Cipro) ~3rd Gen: -Levofloxacin (Levaquin) ~4th Gen: -Moxifloxacin (Avelox) -Trovafloxacin (Trovan) |
|
What is the MOA of Fluoroquinolones?
|
Inhibit the replication of bacterial DNA by interfering w/ DNA Gyrase (bacterial topoisomerase II) which is needed for bacteria to replicate, transcribe and repair DNA
|
|
What is the Spectrum of Fluoroquinolones?
|
Wide variety of Gram Neg organisms and some Gram Pos organisms (Pseudomonas species and Atypicals also)
|
|
What spectrum are the Fluoroquinolones most active?
|
Gram Neg, Pseudomonas species and Atypicals
|
|
Although they are overall well tolerated, what are the MC adverse rxns of Fluoroquinolones?
|
~GI SE's- N/V/D
~CNS- h/a, dizziness, agitation and sleep disturbances |
|
What are the Clinical uses of Fluoroquinolones?
|
~UTIs, Prostatitis, Gonorrhea, Infectious diarrhea, Community Acquired Pneumonia (CAP)
~Alternates for: -Bronchitis -Sinusitis -Skin |
|
Which Fluoroquinolone is used for MENINGITIS Prophylaxis?
|
Ciprofloxacin (Cipro)
|
|
What are some MAJOR Adverse Rxns associated w/ Fluoroquinolones?
|
~Exploding jt Syndrome (tendonitis and achilles rupture)
~Increased QT interval (Moxifloxacin) ~Nephrotoxicity (Ciprofloxacin) ~Phototoxicity ~Acute Hepatitis and Hepatic Failure (Trovafloxacin) |
|
What are the Contraindications of Fluoroquinolones?
|
Avoid in pregnancy and children under 18 due to articular cartilage erosion in animal studies
|
|
What is the #1 cause of UTIs at >90%?
|
Escherichia Coli
|
|
What is the #1 Tx of Uncomplicated UTIs?
|
Sulfamethoxazole and Trimethoprim (Septra or Bactrim)
|
|
What type of drugs do not cause systemic antibacterial effects b/c they concentrate in the urine?
|
Urinary Tract Antiseptics
|
|
What is the Urinary Tract Antiseptic drug?
|
Nitrofurantoin
|
|
What is the MOA of Nitrofurantoin?
|
Inhibits bacterial enzymes and damages bacterial DNA
|
|
What is the Spectrum of Nitrofurantoin?
|
~Includes both Gram +/- bacteria including E coli
~Resistance can be problematic (why this is the #2 drug for UTIs) |
|
Due to the Concentration of Nirtofurantoin in the urine, what might you want to tell your pt about the color of their urine?
|
It will discolor their urine BROWN
|
|
What are the adverse effects associated w/ Nitrourantoin?
|
~GI- N/V/D - symptoms reduced when taken with food
~Acute pneumonitis- RARE ~Hemolytic anemia- caution use in pts w/ G6PD |
|
For Tx'ing UTIs in pregnant women, what drug is considered by some to be the DOC, but is still not totally safe (possible mutagenic effect)? How long is the Tx?
|
~Nitrofurantoin (nothing else…gotta use it!!)
~Tx for 7 days |
|
What are the two forms of Nitrofurantoin? Whats the difference?
|
~Nitrofurantoin (Macrodantin)
-Active infections require QID dosing -Long term suppressive therapy is qd dosing ~Nitrofurantoin (Macrobid) -BID dosing for active infections |
|
What Miscellaneous UTI agent exerts local anesthetic/analgesic action of the urinary tract mucosa, which relieves pruritus and pain?
|
Phenazopyridine (Pyridium)
|
|
Can Phenazopyridine be used by itself? What color does it turn the urine?
|
~Must be used in conjunction w/ Abx
~Colors the urine orange-red |
|
What Miscellaneous Agent has ONLY Anaerobic bacteria and Protozoa spectrum and causes cell death by forming reduced cytotoxic compounds that bind to proteins and DNA?
|
Metronidazole (Flagyl)
|
|
What are the indicated uses of Metronidazole (Flagyl)?
|
~Anaerobic intra-abdominal infections including Abx associated enterocolitis including Clostridium Difficile
~Bacterial vaginosis- covers Trichomoniasis in F and M ~Helicobacter pylori ~Amebiasis – covers protozoal infections (E. histolytica; Giardia, Trichomonas) |
|
What are some possible adverse rxns of Flagyl?
|
~GI- N/V and cramps
~Might complain of metallic taste in their mouth |
|
What should be avoided by all pts taking Flagyl?
|
Avoid alcohol- Possible disulfiram reaction (N/V/D effects)
|
|
What are the two possible Tx's for Clostridium difficile?
|
Metronidazole OR Vancomycin
|
|
Why are fungal infections on the rise?
|
~Increased Broad-spectrum antibiotic usage
~Increasing number of immunodeficient patients |
|
What fungal infection is the MC? Where can it be cultured from?
|
~Candida Albicans is the MC
~Can be cultured from the mouth, vagina and feces |
|
What are some risk factors for invasive Candida?
|
~Prolonged Neutropenia (HIV)
~Recent Abd surgery ~Broad Spec Abx therapy ~Renal Failure ~Presence of IV catheters ~IV Drug users |
|
Antifungal Agents are divided into what 3 categories based on how and what the Tx?
|
1. Systemic Drugs (oral or IV)
2. Oral drugs for mucocutaneous infections 3. Topical drugs for mucocutaneous infections |
|
What are the different types of Antifungal drugs?
|
~Amphotericin B (Fungizone)
~Azoles ~Allylamines ~Griseofulvin (Gris-Peg) ~Anidulafungin (Eraxis) ~Nystatin ~Caspofungin (Cancidas) |
|
What is the MOA for Amphotericin B?
|
~Fungicidal that binds to Ergosterol more selectively than Cholesterol
~Disrupts fungal membrane function and allows lytes and macromolecules to leak from the cell |
|
When would resistance to Amphotericin B occur?
|
~Binding to ergosterol is impaired OR
~Ergosterol membrane concentration is decreased |
|
What is the Place in therapy for Amphotericin B?
|
Used in pts w/ Systemic Mycoses, meaning, pts who have a systemic fungal infection due to immune deficiencies who would otherwise not be infected (HIV)
|
|
What is Amphotericin B the DOC for?
|
The DOC for nearly all life threatening mycotic (fungal) infections
|
|
When is Amphotericin B used for Empiric Therapy?
|
For high risk untreated systemic infection patients
[e.g. neutropenic (HIV) pt on broad-spectrum antibiotic] |
|
Amphotericin B has a narrow therapeutic index, what are some adverse rxns to watch out for?
|
~Infusion Related Toxicity: Fever, chills, muscle spasm, vomiting, h/a, and HoTN
-reduced by slowing infusion rate and reducing dose -premedicate w/ antipyretics, antihistamines, meperadine and corticosteroid may be helpful |
|
What are some MAJOR Adverse Rxns associated w/ Amphotericin B?
|
~Renal Damage is the MOST significant toxic rxn (occurs in almost all pts)
~K+ and Mg++ wasting (K+ = arrhythmia, Mg++ = seizure) ~Anemia ~Intrathecal dosine (into spinal canal) can cause seizures |
|
How much total dose of Amphotericin B has a very HIGH incidence of Toxicity?
|
2g total dose of Amphotericin B
|
|
What needs to be monitored on this pt?
|
CrCl and Lytes (K and Mg)
|
|
What are the two alternative formulations of Amphotericin B that have fewer and less severe SE's?
|
~Amphotericin B (Lipid Complex) [ABLC] (Abelcet)
~Amphotericin B (Liposomal) [L-AmB] (AmBisome) -Better for long term therapy |
|
What are the subtypes of the Azole Antifungal drugs?
|
~Imidazoles (less specificity for erosterol, more drug-drug interactions)
-Ketoconazole (Nizoral) ~Triazoles (more specificity for ergosterol) -Fluconazole (Diflucan) -Itraconazole (Sporanox) -Voriconazole (Vfend) |
|
What is the MOA of Ketoconazole?
|
Inhibits fungal membrane function and increases permeability (by reducing fungal ergosterol synthesisby inhibiting fungal CYP 450 enzymes)
|
|
When taking Ketoconazole orally, the acidic environment helps w/ absorption. What can the pt drink to help w/ this?
|
Cola helps
|
|
What is Ketoconazole used to Tx?
|
~Tinea Versicolor
~Cushings Syndrome |
|
What are the Adverse effects of Ketoconazole?
|
~GI upset
~Endocrine effects- blocks androgen/steroid synthesis resulting in gynecomastia, decreased libido, impotence and menstrual irregularities (used in Cushing’s syndrome because of this) ~Monitor level in patients w/ hepatic dysfunction ~Drug interactions -Inhibits CYP450 system -Drugs that reduce stomach acid will reduce absorption of Ketoconazole |
|
Fluconazole (Diflucan) is essentially the same drug as Ketoconazole, what advantages does it have over Ketoconazole?
|
~Does not cause endocrine side effects
~Crosses BBB ~Fewer drug-drug interactions ~Avail in Oral and IV forms ~Acidic environment not required for absorption |
|
What are the Clinical uses for Fluconazole?
|
~Vaginal Candidiasis <--DOC!!!
~Oropharyngeal and Esophageal Candidiasis |
|
What is the MOA of Itraconazole (Sporanox)?
|
Same as other Azoles (inhibits CYP 450)
|
|
What helps absorption of Itraconazole?
|
Food and Low pH
|
|
What are the clinical uses of Itraconazole?
|
~Tinea
~Candidiasis ~Onychomycosis ~Poor CNS penetration |
|
What is the black box warning associated w/ Itraconazole?
|
Avoid use in congestive heart failure
|
|
What is the MOA of Voriconazole (Vfend)?
|
Works by inhibiting the fungal CYP450 enzyme system resulting in cell wall integrity problems
|
|
What are the clincal uses of Voriconazole?
|
Used for Aspergillus (mold) infections
|
|
Voriconazole is the alternate DOC for life threatening fungal infections behind what other drug?
|
Amphotericin B
(Voriconazole is as effective as Amphotericin B and it has LESS kidney problems) |
|
What should be monitored while the pt is on Voriconazole?
|
~Visual disturbances
~Liver and Renal Function |
|
Name the Allylamine antifungal drug?
|
Terbinafine (Lamisil)
|
|
What is the MOA of Terbinafine (Lamisil)?
|
Inhibiting squalene epoxidase resulting ina deficiency of egosterol and an accumulation of squalene within the fungal cell --> causing DEATH!!!!!
|
|
****What is the MAJOR advantage of Terbinafine over the Azoles?
|
It does NOT inhibit the fungal or human CYP450 system, so has very few drug interaction
|
|
Should Terbinafine be taken w/ or w/o food?
|
Should be taken w/ food --> Oral availablility is increased if taken w/ food
|
|
What are the Clinical uses of Terbinafine (Lamisil)? What is it the DOC in?
|
~Onychomycosis (<--DOC)
~Tinea |
|
What are the ADRs of Terbinafine? What needs to be monitored while on this drug?
|
~Liver Enzyme abnormalities (3.3%)
~Taste Disturbances (2.8%) ~Monitor AST/ALT for 3 months!!!! |
|
What is the MOA of Griseofulvin (Gris-Peg)?
|
~Fungistatic!!!
~Disrupts the mitotic spindle and inhibits mitosis |
|
Griseofulvin therapy will need to be continued until NEW tissue replaces the infected tissue, which is how long?
|
Weeks to months
|
|
What is the Place in Therapy for Griseofulvin?
|
Tinea Capitus (largely been replaced by newer antifungals)
|
|
What allows for better absorption of Griseofulvin?
|
Increased absorption w/ HIGH fat diet
|
|
What are the ADRs of Griseofulvin?
|
Induces CYP450 activity
|
|
What is the MOA of Anidulafungin (Eraxis)?
|
Inhibits glucan synthase blocking fungal production of D-glucan, an essential component of fungal cell walls
|
|
What are the clinical uses of Anidulafungin?
|
~Invasive Aspergillus in refractory cases
~Candidemia, Candida abscesses/peritonitis, esophagitis ~Empiric Tx of presumed fungal infections in Febrile neutropenia (HIV) |
|
ADRs of Anidulafungin?
|
Diarrhea and Hypokalemia (monitor K+ levels)
|
|
What is the Drug that has exactly the same MOA and Usage as Anidulafungin, but has different ADRs?
|
Caspofungin (Cancidas)
|
|
What are the ADRs of Caspofungin?
|
Heahache, fever, chills, phlebitis (monitor LFTs)
|
|
What is the MOA of Nystatin?
|
~Similar to Amphotericin B (Disrupts fungal membrane function and allows lytes and macromolecules to leak from the cell)
|
|
What is the Clinic Use of Nystatin?
|
Used for topical tx (swish and spit) of Oral Candida (Thrush)
|
|
According to the Sanford recommendation, what are the Primary and Secondary Tx's for Vaginal Candidiasis?
|
~Primary (DOC): Fluconazole OR Itraconazole
~Secondary: Intravaginal Imidazoles -Clotrimazole (Gyne-Lotrimin or Mycelex) -Miconazole (Monistat) -Terconazole (Terazol) -Butoconazole (Femstat, Gynazole 1, and Mycelex-3) -Tioconazole (Vagistat 1 and Monistat 1) |
|
What is the biggest reason for Fluconazole being the DOC over the Imidazoles?
|
Fluconazole requires a 1 day Tx, as opposed to the 3-7 day schedule for the Imidazoles
|
|
The medications for Malaria can be divided into what two major categories?
|
~Chemoprophylaxis- Medications used to prevent malaria
~Treatment- Medications used to treat active infections |
|
What are the Vectors and what actually causes Malaria?
|
~Vector: Anopheles Mosquito
~Cause: Plasmodium Protozoa |
|
What are the four species of Plasmodium Protozoa?
|
~P. Falciparum (MOST DANGEROUS)
~P. Vivax (most common) ~P. Malariae ~P. Ovale |
|
What are some of the S/Sx's of Malaria?
|
HIGH fever, HoTN, and swollen red limbs
|
|
What is the DOC used after the infected mosquito injects sporozoites into human hosts and sporozoites move to liver and develop into merozoites?
|
Primaquine
|
|
What are the Drugs used after merozoites leave liver, infect and destroy RBCs (where they use Hgb as a nutrient), and move to other RBCs?
|
Drugs that work here Chloroquine, Quinine, Mefloquine, and Pyrimethamine
|
|
When Rx'ing Malaria Chemoprophylaxis, what factors need to be considered before Rx?
|
~Location of Travel
~Time before travel ~Traveler specific factors (occupation, pregnancy status, underlying medical conditions) |
|
What are the different drugs used for Malaria Chemoprophylaxis?
|
~Atovaquone & Proquanil (Malarone) (<-- DOC)
~Doxycycline (Vibramycin) (<-- Military DOC) ~Mefloquine (Lariam) (<-- Alt #2) ~Chloroquine (Aralen) (<-- not used much/resistant) |
|
What is the Dosing Schedule for Chloroquine?
|
1-2 wks before travel, during, and 4 wks after travel
|
|
For areas of Chloroquine resistant P. Falciparum, what is the 1st line DOC, Alt #1 (Military DOC), and Alt #2?
|
~1st line (DOC): Atovaquone & Proquanil (Malarone)
~Alt #1 (Military DOC): Doxycycline (Vibramycin) ~Alt #2: Mefloquine (Lariam) |
|
Which Malaria Prophylactic drug is the BEST option in Kids and Pregnancy?
|
Mefloquine (Lariam)
|
|
What are some of the ADRs of Mefloquine?
|
~May produce some CNS SE's:
-Dizziness, not recommended for persons w/ epilepsy or seizure DOs, Severe psychiatric DOs, Cardiac conduction abnormalities. ~Vomiting – 3% |
|
What is the dosing Schedule for Mefloquine? Advantage?
|
~1 wk before travel, during, and 4 wks after travel
~Requires ONCE A WEEK DOSING |
|
What is the dosing Schedule for Doxy? Advantage?
|
~1-2 days before travel and 4 wks after
~Requires daily dosing |
|
Who is Doxy contraindicated in?
|
~Children <8 yrs
~Pregnant Women |
|
What is the dosing Schedule for Atovaquone & Proquanil (Malarone)? Advantage?
|
~1-2 days before travel and 7 days after
~Requires daily dosing |
|
What are the ADRs of Malarone?
|
Abdominal pain, N/V, and headache can occur
|
|
What Folate inhibitor is an alternate in the use of Malarial Prophylaxis?
|
~Pyrimethamine (Daraprim)
-Similar to trimethoprim |
|
What Antimalarial Agent is used as the DOC for eradication of DORMANT P. Vivax and P. Ovale?
|
Primaquine
|
|
When is Primaquine dosed?
|
14 days post travel
|
|
What travelers should NOT receive Primaquine? Why?
|
Can cause Hemolytic anemia in G6PD pts
|
|
What are the aspects of the DoD Insect Repellant System?
|
~Permethrin Impregnation Kit (IDA)
~Skin repellent (DEET 33% controlled-release lotion) ~Wear uniform properly ~DoD policy – required use |
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Describe the use of Permethrin Impregnation Kit (IDA)?
|
Used to treat the uniform; lasts approximately 50 washes
(make sure to wash 3-4 time before use) |
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How long does DEET last on the skin?
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12 hrs
|
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What is the general characteristic of Helminthic Nematodes?
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Elongated Roundworms
|
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What is the MC Helminthic infection in the US?
|
Enterobiasis (pinworms)
|
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What are the S/Sx's of Pinworm infections?
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Perianal Pruritus, restlessness, and insomnia
|
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What are the TWO main Antihelminthic Drugs?
|
~Mebendazole (Vermox)
~Pyrantel Pamoate (Antiminth) |
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What is the MOA of Mebendazole (Vermox)?
|
Irreversibly blocks uptake of glucose, thus depleting energy level
|
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What is the spectrum of use for Mebendazole?
|
Covers Pinworm (Enterobius vermicularis) and Round/Hook worm (Necator americanus)
|
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What is the dosing of Mebendazole?
|
~Single dose; repeat in 2 weeks if needed
~Take with high fat meal |
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What are the SE's and CI's of Mebendazole?
|
~SE's: abdominal pain and Diarrhea
~CI: Children <2 yrs and Pregnancy |
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What is the name of the OTC Drug used for the Tx of PINWORM?
|
Pyrantel Pamoate (Antiminth)
|
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What is the MOA of Antiminth?
|
Depolarizing neuromuscular blocker works to cause paralysis in worm
|
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What are the SE's and CI's of Antiminth?
|
~SE's: N/V/D
~CI: Children <2 yrs and Pregnancy |
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What are some other possible parasitic infections and the associated Tx's?
|
~Entamoeba Histolytica (amebiasis)
-Luminal agent (iodoquinol or paromomycin) + metronidazole (or tinidazole) ~Giardia Lamblia -Metronidazole or Tinidazole ~Pneumocystis Jiroveci Pneumonia (PCP) -Sulfamethoxazole-Trimethoprim (Septra) ~Toxoplasmosis Gondii (catbox) -Tx: Pyrimethamine + Sulfadiazine -Proph: Sulfamethoxazole-Trimethoprim (Septra) ~Trichomonas Vaginalis -Metronidazole |
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Why are Mycobacteria Infections so difficult to Tx w/ Abx?
|
~Slow growing bacteria (many Abx need fast growing cells to be effective)
~Cells have ability to go dormant ~Cells have lipid rich cell wall impermeable to many Abx ~Mycobacteria can live in human cells (macrophages) which protect them ~Mycobacterial infections have ability to develop resistance to single agents quickly |
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What is the causitive organism of Tuberculosis (TB)?
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Mycobacterium Tuberculosis
|
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What Dz is the leading cause of infectious death in the world?
|
TB
|
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What pts in the US are more lilely to develop TB?
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AIDS and Homeless pts
|
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Multi-Drug therapy for TB is standard, why?
|
Due to resistance!!!
|
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What are considered to be the 1st Line Antitubercular Agents?
|
~Isoniazid
~Rifampin ~Pyrazinamide ~Ethambutol ~Streptomycin |
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Tx of ACTIVE TB infection almost always requires how many of the 1st Line Anti-TB Agents?
|
4 of the 5 above drugs!!!!
-The choice is between Ethambutol OR Streptomycin |
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When is TB contageous?
|
When the pt has Active TB (coughing- spreads by inhaled airborne viable organism)
|
|
Name and describe the different phases of TB infection?
|
~Primary TB: usually clinically and radiographically silent because T cells and macrophages contain organisms
~Latent TB: individual does not have active disease and can’t transmit the organism but 10% will develop TB in their life time if not treated with medication ~Progressive Primary TB (Active TB): presents with the classic symptoms of TB (usually has immunity compromise) |
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What are the general S/Sx's of Active TB?
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Malaise, anorexia, weight loss, fever, night sweats, chronic cough, blood streaked sputum
|
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What are some additional complications of TB?
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Lungs collapse, pus in lungs, emphysema, pulmonary fibrosis
|
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PPD identifies infected individuals, but does not distinguish between what?
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Active and Latent infections
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PPD-- 0.1ml placed intradermally (ID) on forearm and is interpreted in 48-72hrs. What indicates a positive rxn? What does a pos rxn indicate?
|
~Positive Rxn = Raised area >5-15mm in diameter
~A Pos skin test only indicates EXPOSURE |
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What TB vaccine will cause a pt to have a Pos PPD?
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Bacillus Calmette-Guerin (BCG) vaccine
|
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What are the GOALS of TB Therapy?
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Eliminate all bacilli from infected individual without incurring drug-resistance
|
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For Tx of TB, administer multiple drugs for which the organism is susceptible! If Tx fails, ADD at least how many new anti-tubercular agents?
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Add at least TWO new Anti-Tubercular agents if Tx fails
|
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What is the major cause of Tx failure fo TB and developing drug resistance?
|
Non-Compliance!!!!
|
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What is the Tx Regimen for the Latent Infection?
|
~Isoniazid (INH) (susceptible) --> 300mg dose
~Continue therapy for 9 months ~Pyridoxine (B6)- possibly ~Routine LFTs (AST/ALT) q month |
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For pts who you foresee Noncompliance, what can be done?
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Direct Observed Therapy (DOT)
|
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How does the Tx for TB change in pts WITH HIV?
|
~Basic approach is similar to Tx for Non-HIV Pts
~General Considerations: -Longer Duration of Therapy -More drug-drug interactions (esp between anti-retroviral drugs and rifamycin derivatives (Rifampin & Rifabutin) -Pyridoxine (B6): should be added to INH regimen to reduce central & peripheral nervous system effects |
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What is the MOA of Isoniazid (INH)?
|
~Synthetic Analog of Pyridoxine (B6)
~Interferes w/ enzymes responsible for assembly of mycotic acids into the outer layer of the bacteria |
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What are the Uses of INH?
|
~Active TB (but not as a single agent)
~Use as a single agent for latent infections and exposure |
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Should you take INH w/ or w/o food?
|
Absorption is IMPAIRED w/ food
|
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What are the ADRs of INH?
|
~Peripheral neuritis- due to pyridoxine deficiency
-Give Pyridoxine (B6) daily with INH ~Hepatitis and idiosyncratic hepatotoxicity- Higher incidence with age, Rifampin use and alcohol use. Monitor liver transaminases |
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What pts are most at risk for developing Peripheral Neuritis?
|
Diabetic, uremic, malnourished, alcoholics, HIV, pregnancy and seizure disorder
|
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What is the MOA of Rifampin (Rifadin or Rimactane)?
|
Inhibts RNA synthesis by supressing the initiating step
|
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What are the Uses of Rifampin?
|
TB, Leprosy, Meningitis, amd other bacterial infections
|
|
What are some important facts that your pt might want to know while on Rifampin?
|
~Crosses BBB
~Stains urine, feces and other secretions red/orange |
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What are some ADRs associated w/ Rifampin?
|
~Nausea, vomiting, rash and fever
~Caution - hepatic failure because of jaundice, watch the elderly and alcoholics |
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Where else in therapy does Rifampin get used?
|
MRSA
|
|
Why does Rifampin cause so many drug interactions?
|
~Potent CYP450 Inducer w/ multi-drug rxns, including:
-HIV, OCPs, and Azole Antifungals |
|
What drug is very similar to Rifampin w/ the same activity and cross-resistance, but its advantage is less induction of the cytochrome P450 enzyme system?
|
Rifabutin
|
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Why is Rifabutin of significant value to HIV infected patients who are receiving antiretroviral therapy?
|
LESS multi-drug rxns!!!!
|
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What is the MOA of Pyrazinamide (PZA)?
|
UNK
|
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What are the Uses of Pyrazinamide?
|
~Use w/ INH and Rifampin in Active TB
~Use w/ Rifampin in pts w/ Latent TB who can’t tolerate INH/resistance to INH |
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What are the ADRs of Pyrazinamide?
|
~Hepatotoxicity (1 to 5%)
~May precipitate gouty attack due to hyperuricemia |
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When is the ONLY time you would use Pyrazinamide in a pregnant pt?
|
Should not be used unless documented resistance to other drugs and susceptibility to drug is shown
|
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What are the Uses of Ethambutol (Myambutol)?
|
~Use in combination w/ other agents for Active TB
(either this agent or Streptomycin is used as the 4th agent in Active TB infections when indicated) |
|
What are the ADRs of Ethambutol?
|
~Optic Neuritis- diminished VA and color discrimination (red-green color blindness)
|
|
Will the pts Optic probs ever reverse?
|
YES-- Stop the Med
|
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What is the MOA of Streptomycin?
|
It is an aminoglycoside so it inhibits bacterial protein synthesis
(Not used much for the Tx of TB) |
|
What are the Uses of Streptomycin?
|
May be alternative first line agent (vs. Ethambutol) added to a regimen for Tx of Active TB when INH resistance rate is >4% or patient is non-compliant
|
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What is the Standard route of Admin for Streptomycin?
|
Not orally available - IM is standard route
|
|
What are the ADRs of Streptomycin?
|
~Ototoxic and nephrotoxic
~Neonatal deafness (Do not use in pregnancy) |
|
Give a brief characteristic description of a Virus?
|
~Obligate Intracellular Parasite
~No Cell wall or cell membrane ~Uses host cells for metabolic processes for reproduction |
|
So, why is it hard to selectively target drugs against viral processes?
|
B/C the host wll be affected!!
|
|
For the prevention and Tx of Influenza Type A and B, the vaccine is the best approach. What are the two vaccine types that contain both Type A and B Influenza?
|
~Live, Attenuated Influenza Vaccine (FluMist)
~Inactivated Influenza Vaccine (Flu Shot) |
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Does the Respiratory Syncytial Virus (RSV) have a vaccine?
|
NO
|
|
Describe the two types of Influenza and the associated Sx's?
|
~Type A: Subject to mutation due to antigen drift
~Type B: Less likely to mutate ~Sx's: abrupt onset of fever, myalgia, HA, severe malaise, cough, sore throat and rhinitis |
|
Who is the Inactivated Influenza Vaccine (Flu Shot) recommended for (priority pts)?
|
~Children aged 6–23 MONTHS
~Adults aged >65 yrs ~Pregnant women in their second or third trimester (during influenza season) ~Persons aged >2 yrs w/ chronic conditions (cardiovascular, pulmonary, renal dysfunction, diabetes, immunosuppressed, etc) |
|
What pts are the next priority for the Inactivated Influenza Vaccine (Flu Shot)?
|
Those persons at greatest risk for transmission of disease to persons at high risk, including:
-Household Contacts and Health-Care workers |
|
What pts are approved for the use of the Live, Attenuated Influenza Vaccine (FluMist)?
|
~Healthy children and adolescents ages 5-17 yrs
~Adults age 18-49 yrs |
|
The FluMist must be stored frozen, once thawed how long do you have to use it?
|
Within 60 hrs
|
|
Which is more expensive, the Flu Shot or FluMist?
|
~FluMist $35.00/dose
~Flu Shot $3.00/dose |
|
When should Chemoprophylaxis be used instead of the vaccine for Influenza?
|
~High risk persons who have not been vaccinated
~2 weeks for vaccine to produce antibodies ~Allergies (eggs) ~Immunocompromised persons ~Control outbreaks in institution housing |
|
What are the Two drugs used for Influenza Chemoprophylaxis that cover Type A ONLY?
|
~Amantadine (BCF)
~Rimantadine |
|
What is the MOA of Amantadine and Rimantadine?
|
Blockade of the viral membrane matrix protein (M2) which acts as an ion channel required for viral/cell membrane fusion
|
|
Can Amantadine and Rimantadine be used in conjunction w/ the vaccine?
|
YES
|
|
What are some of the differences between Amantadine and Rimantadine?
|
~Amantadine crosses BBB; Rimantadine does NOT
~Amantadine is NOT metabolized by liver; Rimantadine is metabolized in the liver |
|
Between Amantadine and Rimantadine, which one could be used in a pt w/ Renal failure?
|
Rimantadine
|
|
Since Amantadine crosses the BBB, what other uses does it have?
|
Amantadine is used to Tx Parkinson’s Dz because it will cross the CNS and increase dopamine levels in neurons
|
|
What are the adverse SE's Associated w/ Amantadine and Rimantadine?
|
~Amantadine- CNS --> insomnia, dizziness and ataxia
~Rimantadine- Fewer CNS problems --> does not readily cross BBB |
|
What are the Two drugs used for Influenza Chemoprophylaxis/Tx that cover Type A and B?
|
~Oseltamivir (Tamiflu)
~Zanamivir (Relenza) |
|
What is the MOA of Oseltamivir (Tamiflu) and Zanamivir (Relenza)?
|
Inhibition of viral neuraminidase and virus replication
|
|
What are the Positive effects that Tamiflu and Relenza have on the duration of the Influenza illness?
|
Reduces duration by 1-3 days if started within 12hrs to 2 days of onset
|
|
What is recommended dosing duration for prevention vs. treatment for Tamiflu and Relenza?
|
~QD for 7 days for prevention (Tamiflu ONLY!!!!!, Relenza is NOT approved for prevention)
~BID for 5 days for treatment (both) |
|
What is needed to have before either of these Meds is Rx'ed?
|
Documented labs stating the pts has Type A and B Flu
|
|
What are the routes of admin for both Tamiflu and Relenza?
|
~Tamiflu
-Oral Capsule --> Take w/ food to prevent nausea -Suspension for kids ~Relenza -Dry powder inhaler (Not recommended for asthma/COPD) |
|
****How is RSV spread? Who is it most fatal in?
(Just know this about RSV!!!) |
~Spread person to person
~Can be fatal in premature babies <6 mo old, immune deficient babies and infants with chronic lung disease |
|
Describe the different types of Herpes Virus?
|
~HSV-1- gingivostomatitis in infants and children, irritability, anorexia, fever, gingival inflammation w/ painful ulcers in mouth
~HSV-2- transmitted primarily by direct contact ~Herpes Zoster- caused by varicella-zoster virus(chcknpox) |
|
Of these different types of Herpes, which has a vaccine? Name the vaccines?
|
~Vaccine for Herpes Zoster
~Varicella (Varivax) --> recommended after first birthday ~Zostavax patients 60 years and older |
|
What sre the Drugs used for the Tx of the Herpes Virus?
|
~Acyclovir (Zovirax) (<-- DOC)
~Valacyclovir (Valtrex) (<-- DOC) |
|
What is the MOA of Acyclovir (Zovirax)?
|
~Causes viral DNA chain termination by competing w/ Deoxyguanosine Triphosphate (dGTP) as a substrate for viral DNA polymerase
~Requires conversion by thymidine kinase first (inhibits viral DNA synthesis & viral replication) |
|
What are the Indicated uses of Acyclovir?
|
Genital herpes, cold sores (herpes labialis), herpes zoster (shingles, chickenpox)
|
|
What is the Organism Spectrum of Acyclovir?
|
Organisms include HSV-1 and 2, varicella-zoster and Epstein-Barr
|
|
What are some of the ADRs associated w/ Acyclovir?
|
~Not significant --> h/a, N/V/D have been reported
~IV --> renal/neuro toxicity (crosses BBB) |
|
What is the MOA of Valacyclovir (Valtrex)?
|
Prodrug of Acyclovir therefore same MOA but better bioavailability and LONGER DURATION
|
|
What are the Indicated uses of Valacyclovir (Valtrex)?
|
Genital herpes, Herpes zoster (shingles)
|
|
What Dz is responsible for a variety of infections ranging in severity (retinitis, esophagitis, hepatitis and GI) and is a major cause of morbidity and mortality in immunosuppressed pts?
|
Cytomegalovirus (CMV)
|
|
How is CMV transmitted and what is acquired?
|
CMV is transmitted through blood or bodily fluid and results in an acquired Acute Febrile illness
|
|
What can occur as a result of contracting CMV during pregnancy?
|
May result in abortion, stillbirth, post natal death due to hemorrhage, anemia, hepatic or CNS damage
|
|
What are the drugs used for the Tx of CMV?
|
~Ganciclovir (Cytovene and Vitrasert optic insert) (DOC)
~Foscarnet (Foscavir) (ALTERNATE) |
|
What is the MOA of Ganciclovir? (<-- DOC)
|
Guanine analog that competes for deoxyguanosine as a substrate for DNA (virostatic)
|
|
What are the indicated uses for Ganciclovir? (IV vs. Oral)
|
~IV product: only for CMV retinitis in immunocompromised pts and transplants
~Oral product: only for preventing CMV in HIV pts and maintenance for IV indications |
|
What are the Black Box Warnings of Ganciclovir?
|
Granulocytopenia, anemia, and thrombocytopenia
|
|
What is the MOA of Foscarnet?
|
Reversibly ihibits DNA and RNA polymerase thereby terminating chain elongation (virostatic)
|
|
What are the indicated uses of Foscarnet?
|
CMV retinitis and Acyclovir resistant HSV
|
|
Foscarnet can be used by itself or in conjunction w/ what other CMV Drug?
|
Ganciclovir
|
|
What are the ADRs/BBW of Foscarnet?
|
Nephrotoxicity, anemia, nausea and fever (Black Box warning)
|