Pharm Antimicrobials
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| Colonization | presence of an organism on or within the tissue, NOT resulting in an immune response or destruction of tissue (ex MRSA in nose)
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| Infection | presence of an organism on or within the tissue resulting in an immune response and/or destruction of the tissue
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| synergy | any combination of antimicrobials that when used together, increases the killing of an organism beyond that of either used alone (1+1=3)
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| antagonism | : any combination of antimicrobials that decreases killing of an organism beyond that obtained from either used alone (1+1=0)
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| potentiation | a drug which has no effect enhances the effect of a second drug (0+1=2)
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| What does a bacteriostatic antibiotic require for effective killing of organisms? | ability to inhibit growth and replication of bacteria. Body’s immune system required to immobilize and kill the organism.
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| Selective Toxicity | Ability of drug to injure a target cell or target organism without injuring other cells or organisms that are in intimate contact with the target (disrupt cell wall, inhibit enzyme unique to bacteria, disrupt bacterial protein synthesis)
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| List two methods by which antimicrobial agents may be classified. | By Organism and by mechanism of action
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| Narrow spectrum | active only against few bugs
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| Broad Spectrum | active against a variety of bugs
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| List four methods by which pathogens may be classified | - Gram Stain
- Shape (Cocci/bacilli)
- Need for Oxygen (aerobic/anaerobic)
- Site of residence in host cells (intra/extracellular)
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| Gram Positive | retain initial hematoxylin blue/purple- cell wall relatively simple
- thick layers of peptidoglycan on top of cytoplasmic membrane, favors antibiotic entry, especially charged compounds
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| Gram positive cocci | staph, strep pneumonia, strep pyogenes
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| gram positive rods | bacillus, listeria, clostridium (anaerobic)
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| Gram Negative | resist hematoxylin; take on red-pink eosin counterstain): cell wall more complex:
- periplasmic space (enzymes) and outer membrane with lipopolysaccharides (endotoxins) and porin channels on top of cytoplasmic membrane
- challenge to drug entry
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| gram negative cocci | H. influenza, neisseria, h. pylori
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| gram negative rods | escherichia, shigella, salmonella, klebsielle, enterobacter, proteus, psuedomonas
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| Empiric Therapy | need culture and sensitivity results but may treat before test results are available. Drug selection must be based on clinical evaluation and knowledge of which microbes are likely to cause an infection at a particular site
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| Discuss three factors to consider when making choices about an agent for empiric therapy. | 1) Identify Infecting Organism
2) Determine Drug Susceptibility
3) Determine Host factors, such as site of infection and status of defenses that may modify drug choice, route, or dosage
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| List three drugs that provide particularly good coverage for anaerobes | - 2nd generation cephalosporins
- carbapenems
- tetracyclines
- flagyl**
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| What drug classes make up the β-lactam family? | - Penicillins
- Cephalosporins
- Carbapenems
- Monobactams
- B-Lactamases
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| List three ways in which bacteria acquire resistance to β-lactam antimicrobials | 1) Inactivation of antibiotic by B- lactamase (Penicillinases) (most common)
2) Modification of target PBP’s (so penicillins/b lactams cant bind)
3) Presence of Efflux pump
4) Impaired penetration of drug to target PBP’s
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| Describe why β-lactam antibiotics are ineffective if the microorganism has β-lactamase enzymes. | a. Beta lactamases are enzymes that cleave the beta-lactam ring, rendering PCN inactive
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| Narrow Spectrum Penicillins: | penicillin G, Penicillin V, antistaphylococcal penicillins
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| Broad Spectrum Penicillins | ampicillin, amoxicillin
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| extended spectrum penicillins | piperacillin, ticarcillin, aziocillin (antipsuedomonal)
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| What is the main adverse effect seen with penicillins? | - most serious adverse reactions due to hypersensitivity
o rashes most common reaction
o ampicillin rash- in 50-100% patients with EBV
- Anaphylaxis: 1/10,000 patients
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| Which generation cephalosporin is most effective against gram positive? | 1st generation
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| Which generation is most effective against gram negative? | 5th generation
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| Cephalosporins should be avoided for which subgroup of patients who describe themselves as penicillin allergic? | patients with severe anaphylaxis to penicillins
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| Are penicillins or cephalosporins more stable to β-lactamases? | cephalosporins
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| Name the classes that inhibit cell wall synthesis. | BETA LACTAMS (Penicillin, Cephalosporins, Cabapenems, monobactams), GLYCOPEPTIDES (vancomycin)
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| 1 generation cephalosporins - spectrum | best activity against gram positive organisms, no ability to reach CSF.
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| 2nd generation cephalosporins- spectrum | enhanced activity against gram negative bacteria, does not reach CSF. Less active against gram positive. Used against H influenzae
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| Cephamycins | not true 2d generation cephalosporins, activity against anaerobes -- cefoxitin, cefotetan
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| 3rd generation cephalosporins- spectrum | less activity against gram positives, but greater activity against gram negatives, can cross BBB (First line for meningitis)
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| 4th generation cephalosporins- spectrum | extended spectrum, good gram positive an dnegative
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| 5th generation cephalosporins- spectrum | multidrug resistant staph aureus, VRSA, strep pneumonia, respiratory gram negatives, COMMUNITY ACQUIRED BACTERIAL PNEUMONIA and acute kin infections
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| Carbapenems | broadest spectrum of all beta lactams
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| Monobactams | gram negative rods
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| Beta lactamase inhibitors | Augmentin, Timentin, Unasyn, Zosyn
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| Glycopeptides: drug | Vancomycin
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| Vancomycin: MOA | cell wall synthesis inhibitor
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| Vancomycin- spectrum | gram positive bacteria, MRSA
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| Vancomycin: uses | sepsis, endocarditis caused by MRSA, meningitis with highly penicillin resistant pneumococcus
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| Red Man's Syndrome | AE of vancomycin, infusion related flushing (slow infusion or increase dosin interval)
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| - What newer drug(s) is/are available to treat vancomycin resistant enterococci (VRE)? | Linezolid (zyvox)
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| Protein synthesis Inhibitors (bacteriostatic) | Tetracyclines, macrolides, "other.misc."
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| Protein synthesis inhibitors (bactericidal) | aminoglycosides
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| Tetracylcines- spectrum | bacteriostatic protein synthesis inhibitors, broad spectrum
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| Tetracyclines- use | mycoplasma pneumonia, chlamydiae, rickettsiae.
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| Tetracyclines- adverse effects | tooth discoloration/deformation of bones, photosensitivity
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| Macrolides- drugs | Erythromycin, Azithromycin
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| Macrolides- spectrum | bacteriostatic protein synthesis inhibitors, gram positives
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| Macrolides- uses | diphtheria, chlamydia, CAP
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| Adverse effects of erythromycin | GI, acute hepatitis
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| drug interacitons of erythromycin | CYP inhibitors, can prolong QT interval, increase risk for sudden cardiac death
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| Other/Newer Bacteriostatic Protein synthesis inhibitors | Clindamycin, Streptogramins, Linezolid
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| Clindamycin- clinical use | head and neck infections
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| Streptogramins- clinical use | gram positive, drug resistant staph and strep, VRE
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| Linezolid- use | VRE
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| Aminoglycosides | bactericidal protein synthesis inhibitors, block protein synthesis at 3 points in pathway
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| Are aminoglycosides well absorbed orally? | polar- NO
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| Aminoglycosides- drugs | gentamycin, neomycin, tobramycin, kanamycin, amikacin
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| Aminoglycosides-spectrum | gram negative enteric bacteria (aerobic)
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| Aminoglycosides-clinical use | bacteremia and sepsis
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| Aminoglycosides-adverse effects | ototoxicity and nephrotoxicty
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| Antimetabolites- MOA | inhibit folic acid synthesis (folic acid needed for DNA synthesis)
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| Antimetabolites- drugs | Bactrim and Septra
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| Antimetabolites- Bactrim® and Septra® contain what two antimicrobial agents? What advantages result from giving these two agents in combination? | Trimethoprim- Sulfamethoxazole, synergistic
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| Antimetabolites- adverse effects | photosensitivity, Stevens johnson Syndrome
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| What is Stevens Johnson Syndrome? | serious and potentially fatal skin and mucous membrane eruption
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| DNA Gyrase Inhibitors | Fluoroquinolones - bactericidal
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| Fluoroquinolones - drugs | ciprofloxacin, levofloxacin
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| Ciprofloxacin- spectrum | more active against gram negatives
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| Levofloxacin- spectrum | superior activity against gram positives
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| Describe two key pharmacokinetic advantages possessed by Fluoroquinolones | high oral availability and wide distribution to tissues
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| Fluoroquinolones-uses | UTI!!!, resp. infections
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| Fluoroquinolones- Adverse effects | may prolong QT, tendonitis, arthritis, arthropathy
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| Metronidazole | antiprotozoal with potent activity against anaerobes- used in GI tract infections
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| Amphotericin B | broad spectrum antifungal, used for life threatening mycotic infections because of toxicity
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| azole antifungals | less toxic than amphotericin B, topical and systemic use
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| 4 drugs used for TB tx | Isoniazid, Rifampin, Pyrazinamine, Ethambutol
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| Isoniazid- MOA | inhibits synthesis of myco bacterium wall.
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| Isoniazid- AE | peripheral neuropathy (tx with Pyridoxine)
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| Rifampin - MOA | inhibits TB RNA synthesis/protein synthesis
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| Rifampin- AE | hepatotoxicity, red-orange body fluids
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| 4 methods of antimicrobial resistance | produce drug metabolizing enzymes (penicillinase), cease uptake of drugs, change in receptors, synthesize compounds that antagonize drug actions
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| How do microbes gain resistance? | Genetic Alterations (spontaneous mutation), DNA transfer (conjugation from other microbes), altered expression of proteins in drug resistant organisms (modified targets)
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| Suprainfection (superinfection) | new infection that appears during course of treatment for a primary infection. - develops when abx eliminate the inhibitory influence of normal flora, allowing a second infectious agent to flourish
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| Which antimicrobials are most often associated with superinfections? | braod spectrum!, 3rd generation cephalosporins, clindamycin
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| What is first line to treat C. Diff? | Metronidazole (flagyl)
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| Alternative to Flagyl for C. Diff tx | vancomycin
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| List two antimicrobial classes that should not be given during pregnancy | - fluoroquinolones
- tetracyclines
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| Safe in pregnancy | - Penicillins
- Cephalosporins (category B)
- Clarithromycin (category C)
- Erythromycin (not estolate)
- Azithromycin
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| List the 3 most common pathogens responsible for community acquired pneumonia (CAP), | o Strep pneumoniae (gm +)
o Mycoplasma pneumoniae (atypical)
o H. influenzae (gm -)
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| What is the first- choice drug for empiric treatment of pneumonia in a hospitalized patient? Which class can be used for single agent therapy for this indication? | Macrolide + Beta Lactam.
Respiratory fluoroquinolone
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| List the two most common pathogens responsible for pharyngitis | streptococcus pyogenes (group A beta hemolytic), viral
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| Tx of pharyngitis | Penicillin, amoxicillin
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| First line therapy for Otitis media | Amoxicillin or augmentin
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| Alternative therapy for Otitis media | 2nd and 3rd generation cephalosporins
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| List the two most common pathogens responsible for Urinary tract infections | E coli and pseudomonas
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| What is the first choice for complicated UTI treatment in women? a. How long should it be given (duration)? | o 7-21 days
Ciprofloxacin
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| What is the first choice therapy for uncomplicated urinary tract infection (UTI) in women? a. How long should it be given (duration)? | o 3 days (lower rate of recurrent infection than single dose)
o trimethoprim-sulfamethoxazole
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| First Choice drug for impetigo | mupirocin, alternative azithromycin, clarithromycin, 2nd generation cephalosporins
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| MRSA- tx | septra, bactrim, clindamycin, tatracylcines, rifampin, vancomycin, linezolid, daptomycin
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| First Line for E. Coli | cephalosporins
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| First Line for Pseudomonas aeruginosa | • Ciprofloxacin
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| First Line for Staphylococcus aureus | Penicillinase Producing: penicillinase resistant penicillin
Methicillin resistant: vancomycin with or without gentamycin/rifampin
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| first line for Haemophilus influenzae | Meningitis: cephalosporin (3rd generation).
Upper RTI/bronchitis: septra/bactrim
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