Pharmacology Atb Basic Principles And Cell Wall Inhibitors Spring 2011

Front 1

Antibiotics definition
Antimicrobial definition

Back 1

ATB = natural compound produced by bacteria or fungi to suppress growth of other microorganisms
Antimicrobial = synthetic agents to suppress growth of other microorganisms

Front 2

Drugs that work by inhibiting cell wall synthesis:

Back 2

- Bacitracin
- Beta Lectams
- Vancomycin
- Cycloserine
- Cephalosporins

Front 3

Drugs that work by inhibiting DNA replication:

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- Quinolones
- Nitroimidazoles

Front 4

Drugs that inhibit DNA-Dependant RNA polymerase:

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- Rifampin
- Rifabutin

Front 5

Drugs that inhibit Folic Acid Synthesis:

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- Trimethoprim
- Sulfonamides
- Sulfones

Front 6

Drugs that inhibit Cell membranes:

Back 6

- Polymyxins
- Daptomycin

Front 7

Drugs that inhibit Protein Synthesis:

Back 7

- Aminoglycosides
- Macrolides
- Ketolides
- Lincosamides
- Streptogramins
- Tetracyclines
- Glycyclines
- Chloramphenicol
- Oxazolidinones

Front 8

What factors influence selection of antimicrobial agent?

Back 8

1. Identification of Organism
2. Microbial susceptibility
3. Bactericidal vs Bacteriostatic
4. Bug-Drug Specificity
5. Knowledge of patient

Front 9

What factors are increasing the resistance to ATBs?

Back 9

- Indiscriminany use (against viruses, or because of environmental factors)

Front 10

What tests can you do for sensitivity testing?

Back 10

- disk diffusion
- microdilution
- E-test

Front 11

Explain disk diffusion

Back 11

Bacteria is placed on a dish, different spots of either diefferent ATBs or different strengths are placed on the dish and you look to see how far the ring goes out from each

Front 12

What is MIC? MBC?

Back 12

MIC - the minimum concentration that is needed to stop any growth
MBC - the minimum concentration needed to kill the bacteria

Front 13

What would be a reason to use a bactericidal ATB instead of a bacteriostatic ATB?

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Host immune's system; it needs to be working to be able to clear the body of the bacteria that is stopped from growing

Front 14

Common side effect of tetrayclines:

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can bind to calcium and discolor teeth and bones (don't use in children)

Front 15

What causes grey baby syndrome?

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Chloramphenicol
infants can't conjugate it, so they turn grey

Front 16

Explain time dependent killing

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You need to maximize time spent above the MIC; the conecntration above that doesn't matter, as long as it is above MIC for as long as possible

Front 17

Explain concentration dependent killing

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You can give one dose once a day because the ATB will get into th ebacteria anc continue to kill, even if levels drop
*Do not need to monitor levels!

Front 18

Appropriate uses of Combination ATB therapy

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- TX of life threatening infection (with unknown organism)
- polymicrobial infections
- enhanced antimicrobial activity (AGs + penicillins for P. Aerug)
- Tx resistant strains
- Lower doses of agents (less toxicity)
- may reduce resistant strains emerging (not proven)

Front 19

Mechanisms of Resistance

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1. Selection - strongest bacteria survive
2. Enzymes to destroy active drug
3. Change in permeability to drug
4. Change in efflux pathway
5. Change in affinity of site of active drug
6. Altered metabolic pathways
7. Altered enzymes with less affinity

Front 20

Examples of bacteria that produce enzymes to destroy drug

Back 20

Penicillinases
Carbepenemases
Cephalosporinases

Front 21

Examples of bacteria that change permeability

Back 21

Beta lactamases with porins

Front 22

Drugs affected by efflux changes

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Tetracyclines
Chloramphenicol
Macrolides

Front 23

Drugs affected by changes in affinity of site of drug or with altered enzymes with less affinity

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protein synthesis inhibitors

Front 24

Drugs that are affected by changes in altered metaolic pathways

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Sulfonamides

Front 25

Origins of resistance

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- Spores in a dormant stage
- A change in target structure after repliations
- Genetic changes

Front 26

What genetic changes can lead to resistance?

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- Mutational resistance (chromosomal change)
- Conjugation (passed on through plasmids)
- Transduction (phages can transfer DNA)
- Transformation (free DNA is absorbed)

Front 27

What bacteria commonly shows resistance by conjugation?

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gram negative bacteria

thwarts Vancomycin

Front 28

What bacteria commonly shows resistance by transduction?

Back 28

S. aureus

Front 29

What is the main difference between gram negative and positve bacteria?

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Gram negative have THIN cell walls, but two cell membranes
Gram positive have THICK cell walls and only one membrane

Front 30

Gram + stains ___
Gram - stains ___

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- pink
+ purple

Front 31

Cell wall is made of ____strands of ___ and ___

Back 31

Peptidoglucan strand of N-acetylglucosamine and N-acetylmuramic acid

Front 32

Transpeptidases do what?

Back 32

cross link adjacent strands to give lattice structure

Front 33

What are PBP's?

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Penicillin Binding Proteins
enzymes (transpeptidase, carboxypeptidase, trransglycosylase) responsible for maintenance and regularion of wall

Front 34

Beta lactams general MOA

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form covalent bonds with PBP transpeptidases to inhibit activity

Front 35

Vancomycin general MOA

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binds end of polypeptide chain to prevent elongation

Front 36

Bacitracin general MOA

Back 36

Inhibits lipid carrier bringing strand out of cell

Front 37

Beta Lactam agents:

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- Penicillines
- Cephalosporins
- Monobactams
- Carbapenems
- Beta Lactamase inhibitors

Front 38

Agents that work on cell wall synthesis:

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- Beta lactams
- Vancomycin
- Daptomycin
- Fosfomycin
- Bacitracin

Front 39

Beta Lactam general notes

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- ring is essential for activity
- bactericidal
inhibit both gram + and -

Front 40

Natural Penicillins (2)
work against?

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Pen G (IV) and Pen V (oral) against streptococcal and pneumococcal

Front 41

Penicillinase Resistant Penicillins (4) work against?

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- Methacillin
- Dicloxacillin
- Nafcillin
- Oxacillin
against penicillinase producting staphylococcal

Front 42

Broad Spectrum Penicillins (5) work against?

Back 42

- Ampicillin
- Amoxicillin
- Bacampicillin
- Amoxicillin + Clavulanic acid
- Ampicillin + Sulbactam
against S. pyrogenes, S. penuemoniae, H. influenzae

Front 43

Antipseudomonal Penicillins (4) against?

Back 43

- Piperacillin
- Ticarcillin
- Ticarcillin + Clavulanic acid
- Piperacillin + Tazobactam
against P. aeruginosa, Proteus Enterobacter

Front 44

PKinetics of Penicillins

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oral availability (except Pen G), acid stability
Absorption DECREASED by food
limited lipid solubility - distributes well into tissues
Eliminated by active tubular secretion

Front 45

A/E of Penicillins

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- Allergies (environmental exposure)
- CNS irritation (seizures)
- GI irritation (diarrhea)

Front 46

What mechanisms of resistance inhibit Penicillins?

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- Production of beta lactamases
- Add/Lack of specific binding to PBPs
- Cell membrane doesnt lyse after binding
- Organisms without cell wall aren't affected by Penicillins (mycoplasma)

Front 47

Misuse of Penicillins can lead to?

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- selection of resistant strains
- super infections - fungal or C. Difficile
- Transfer of beta lactamase to other organisms

Front 48

Cephalosporin general notes:

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- structurally similar to penicillins
- usually not 1st line
- each generation increases gram NEG activity
- cross sensitivity with penicillins
- poor oral absorption

Front 49

1st generation Cephalosporins:(4) against?

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- Cefazolin
- Cephalexin
- Cephradine
- Cefadroxil
against streptococci, S. Aureus

Front 50

2nd gen Cephalosporins (4) against?

Back 50

- Cefuroxime
- Cefprozil
-Cefmetazole
- Loracarbef
against E Coli, Klebsiella, proteus, H. influenzae, moraxella

Front 51

3rd gen Cephalosporins (9) against?

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- Cefotaxime
- Cefpodoxime
- Cefibuten
- Cefdinir
- Cefditoren
- Ceftizoxime
- Ceftriaxone
- Cefoperazone
- Ceftazidime
against Enterobacteriacae, p aeruginosa, serratia, nisseria gonorrhea, pseudomonas

Front 52

4th gen Cephalosporins (1) against?

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- Cefepine
**Is lactamase resistant

against Enterobacteriacae, p aeruginosa, serratia, nisseria gonorrhea, pseudomonas (same as 3rd)

Front 53

5th gen Cephalosporins (1) against?

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- Ceftobiprole
against MRSA, enterococcus pseudomonas

Front 54

A/E of Cephs

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- allergy (CI in penicillin allergy)
- Nephrotoxic
- Bleeding disorders b/c methothiotetrazole ring interferes with Vit K

Front 55

Carbapenems (4)

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Imipenem
Meropenem
Ertapenem
Dorapenem

Front 56

Carba general notes

Back 56

- Broadest spectrum beta lactams
- gram neg, pos, anaerobes, P. aeruginose (not erta)
- IV
- excreted by kidney

Front 57

Inidications of carbas

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- mixed anaerobic/aerobic abdominal infections
- multi-drug resistant org
- serious nocosomal infections (imip, mero)
- community infection (erta)
- abdominal + complicated UTI (dora)

Front 58

A/E Carbas

Back 58

- sensitivty with other beta lactams
- seizures at high doses
- anemia, altered bleeding time

Front 59

Monobactam (1) and general notes

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Aztreonam
- against gram NEG, p. aeruginosa
- ***NO GRAM POS activity!
- Multi-drug resistant org
- IV or IM
- Renal excretion

Front 60

A/E Monobactams

Back 60

- N/V
- Diarrhea
- Seizures
- bone marrow suppression with long term use
- NO cross reactivity with other beta lactams

Front 61

Vancomycin notes

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- For gram POS, MRSA, penicillin-resistant enterococci and streptococci
- IV
- reserved for severe infections
- Pseudomembranous colitis due to C. Difficile (use Metronidazole)
- renal excretion

Front 62

Vacnco A/E:

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- fever, chills, shock
- Redman Syndrome
- nephrotoxicity
- ototoxicity (with other agents, like AGs or furosemide)

Front 63

Telavancin notes

Back 63

- Vanco derivative
- Skin and skin structure probs, MRSA, gram POS and nocosomial pneumonia
- MOA: disrupts membranes to depolarize bacteria, AND inhibits cell wall synthesis

Front 64

A/E Telavancin

Back 64

- N/V, foamy urine
- decreased renal function
- redman syndrome
- taste disturbances
- may interfere with clotting tests
- teratogenic - do preg test before treating
- QT prolongation

Front 65

Daptomycin notes

Back 65

Cyclic lipopetide
MOA: binds to cell membrane resulting in depolarization and loss of membrane potential and cell death
- Broad spectrum gram POS, vanco resistant bacteria, staphylococci, streptococci
- IV, adjust for renal def
- Infactived by pulmonary surfactant so NOT FOR PNEUMONIA

Front 66

Fosfomycin notes

Back 66

MOA: Blocks first step of peptidoglycan synthesis
- single dose tx for uncomp UTI due to E.Coli or enterococci faecalis
- concentrated and excreted unchanged in urine
A/E: N/V, diarrhea, vaginitis, asthenia

Front 67

Bacitracin notes

Back 67

MOA: cyclic polypeptide that blocks lipid carrier molecule to move peptidoglycan to cell wall
- gram POS
- use Topically OTC
- Nephrotoxicity if systemic use