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Flashcards in Drugs Deck (78):
1

Concentration dependent killing
Vs.
Time dependent killing

Kill based on peak concentration (optimal above 10x MIC)

Kill based on amount of time concentration above MIC

2

Inhibitors of cell wall synthesis

Penicillins
Carbapenems
Cephalosporins
Aztreonam
Vancomycin
Bacitracin
Cycloserine

3

Inhibitors of protein synthesis/structure

Aminoglycosides
Chloramphenicol
Erythromycin, clindamycin, lincomycin
Tetracyclines
Streptogramins/linezolid

4

Interference with cell membrane function

Polymixin B, colistin

Azole and polyene (antifungals)

5

Interference with DNA/RNA synthesis

Rifampin
Fluoroquinones

6

Inhibitors of metabolism

Isoniazid, ethambutol

Sulfonamides, trimethoprim

7

Guidelines for selecting and using antimicrobial agents

Confirm presence of infection

Determine site of infection
Determine causative organism(s)
Select drug
Follow response and alter therapy as necessary

8

Select a drug based on

Sensitivity of the microorganism
Physiochemical properties
Toxicities of the drug
Patient characteristics

9

Reasons to start empiric abx coverage

Site of infection difficult to culture
Serious or life threatening infections

Notes: culture site before starting
Gram stains - quick and very informative for selecting

10

Penicillins/cephalosporins
Mechanism of resistance

Beta-lactamases
PBP changes
Porin channel changes

11

Aminoglycosides
Mechanism of resistance

Enzyme inactivating

12

Macrolides
Mechanism of resistance

Methyltransferases that alter drug binding sites on 50s ribosomal subunit

13

Tetracyclines
mechanism of resistance

Transport systems that pump drugs out of the cell

14

Sulfonamides
Mechanism of resistance

Increased PABA formation
Target enzyme sensitivity

15

Fluoroquinones
Mechanism of resistance

Target enzyme changes
Drug efflux

16

Gram positive class

Staphylococcus
Streptococcus
Enterococcus

17

Gram negative
Piddly

Haemophilus
Morexella
Morganella
Shigella
Salmonella
(Providencia, neisseria)

18

Gram negative
Fence

Proteus
Eschericia coli
Klebsiella

19

Gram negative
SPACE

Serratia
Pseudomonas
Acinetobacter
Citrobactor
Enterobactrer

20

Atypical class

Chlamydia
Mycoplasma
Legionella

21

Anaerobes class

Peptostreptococcus
Bacteroides
Clostridium

22

Post Antibiotic Effect (PAE)

Persistent effect on bacterial growth following brief exposure of organisms to a drug

Aminoglycosides & fluoroquinones

23

Penicillin G

Binds PBP & blocks crosslink peptidoglycan

Strep, some enterococcus

Acid labile

Rheumatic fever prophylaxis

24

Penicillin VK

Binds PBP

Strep, some enterococcus

Acid stabile

Absorption not slowed by food

25

Anti penicillinase penicillin (anti staph)

Methicillin, nafcillin, oxacillin (IV drugs)

cloxacillin, dicloxacillin (PO drugs)

Nafcillin - hepatic elimination

Strep and beta lactamase staph

26

Ampicillin

Bind PBP

Strep, ENTEROCOCCUS, and PEK gram neg

Diarrhea is major side effect

27

Amoxicillin

Bind PBP

Strep, enterococcus, PEK gram neg

Absorb not slowed by food

Diarrhea less so than amp

28

Carbenicillin

Bind PBP

Strep, PEK and SPACE gram neg (pseudomonas requires high concentrations)

Absorption not delayed by food

High urine but low systemic concentration

29

Ticarcillin

Bind PBP

Strep, PEK and SPACE gram neg (pseudomonas req. high concentration)

High sodium load!! (CHF, renal fail, hypernat.)

30

Pipercillin

Bind PBP

Strep, enterococcus, PEK and SPACE gram neg

Sodium load but much lower than ticarcillin

31

Adding beta lactamase inhibitor to penicillin

Augmentin- amox/clavulanic acid
Unasyn- amp/sulbactam
Zosyn- pipercillin/ tazobactam

Adds staph and anaerobes

32

Cephalosporins (general)

Bind PBP inhibit peptidoglycan crosslink

Oral admin - rapid, thorough absorption
Most renal excretion

Probenecid interaction: prolonged excretion if tubular secreted
Warfarin: potentiates bleeding

33

Cephalosporins (General)

Binds PBP and inhibits peptidoglycan crosslink

Oral admin - rapid, thorough absorption

Probenicid: prolong excretion of tubular secreted drugs
Warfarin: potentiation of anticoagulant effects

34

1st Gen. Cephalosporins
Cephalexin, Cefazolin

Coverage: strep, staph, piddly

cefazolin - surgical prophylaxis, long 1/2 life
minor skin and soft tissue infections

35

2nd Gen. Cephalosporins
Cefaclor, Cefuroxime

Coverage: strep, staph, H. Flu., M. Cat., PEK

Cefaclor - serum-like sickness in kids

36

2nd Gen. Cephalosporins (Cephalomycins)
Cefotan, Cefoxitin

Coverage: strep, staph, H. Flu., M. Cat., PEK, Anaerobes

Cefotan has NMTT group (alcohol & bleeding)

Used for abdominal/GI surgery, more severe skin and sot tissue infections

37

3rd Gen. Cephalosporins
Ceftriaxone

Coverage: strep, H Flu, M Cat, PEK, SACE

Good choice for meningitis but need high concentrations

Ceftriaxone hepatic excretion (diarrhea)

38

3rd Gen. Cephalospporins (Anti-pseudomonals)
Ceftazidime, Cefoperazone

Coverage: strep, poor staph, H Flu, M Cat, PEK, SPACE

Cefoperazone has NMTT group (alcohol & bleeding)
Cefoperazone is hepatc excretion (diarrhea)

Community acquired Pneumonia

39

4th Gen. Cephalosporins
Cefapime

Coverage: strep, staph, H Flu, M Cat, PEK, SPACE

nosocomial acquired pneumonia

40

5th Gen. Cephalosporins
Ceftaroline

Coverage: strep, staph (including MRSA), H Flu, M Cat, PEK, SCE

41

Carbapenems (General)

Binds PBP induces cidal effect

Covers most of our general classes

Save for life threatening or multiple organism infections and/or ESBL producing organisms

42

Imipenem

extensive renal metabolism by dehydropeptidase-1 (cilistatin inhibits this enzyme)

seizures - increased risk especially if history; must adjust for renal function

43

Meropenem

Does not cause seizures s can be used for meningitis

44

Ertapenem

No enterococcus or SPACE coverage

Once a day dosing (higher compliance?)

45

Doripenem

Newest carbapenem

46

Aztreonam

Coverage: Gram negs including SPACE

Used when anaphalaxis to penicillin

adverse hematological effects

Save for extreme situations

47

Aminoglycosides

Binds outer membrane of gram - and rearranges LPS and crosses into cell binding 30s and 50s ribosomal subunit decreasing protein synthesis and causing misread RNA

Coverage: Gram- including SPACE

poorly absorbed in GI, excreted in urine almost unchanged

Ototoxicity, Nephrotoxicity, Neuromuscular blockade (rare)
Gent & Tobra want trough under 2

Neomycin - gut decontamination for surgery
Streptomycin - reserved for TB

Hartford Nomogram

48

Vancomycin

inhibits synthesis peptidoglycan polymers by binding D-alanyl-D-alanine precursor

Coverage: gram+ (MRSA & penicillin allergy)

poorly absorbed in GI, renal excretion, usually IV except in C Diff

Red Man Syndrome, ototoxic, nephrotoxic

Can be used for endocarditis prophylaxis

49

Quinupristin/Dalfopristin

Irreversibly binds 50s subunit
Quinupristin - inhibit chain formation (early termination)
Dalfopristin - interferes with peptidyl transferase
individual = static Combo = cidal

MRSA, VRE (faecium), PCN resistant strep pneumo, anaerobes, and some gram-

IV (PICC or central line) because toxic to veins

50

Linezolid

Bind 23s of 50s ribosomal subunit inhibiting protein synthesis

MSRA, PCN resistant strep pneumo, VRE, Vanc intermedia staph aureus

100% bioavailable by IV and PO

thrombocytopenia, superinfection, mitochondrial toxic over long courses

MAO inhibition (SSRIs and cytokine storm)

51

mupirocin

Topical ointment that eliminates MRSA in nares (bactroban)

52

Colistin - Polymixin E

Coverage: Pan-resistant gram negs, such as carbapenem resistant enterobactericae, SPACE and resistant PEK

nephrotoxic and neurotoxic

reserved for last ditch effort

53

Fosfomycin

single dose for MDR UTIs

54

Tigecycline

Coverage: resistant gram- and gram+ and anaerobes, but not pseudomonas or bacteremias

Higher mortality rate, low serum because goes to tissue

Bacteriostatic

55

Daptomycin

Coverage: Gram+ including MRSA and VRE
skin and soft tissue infections, staph aureus bactermia, and endocarditis right side

Rhabdomylysis, requires CPK monitoring
Eosinophilic pneumonia (rare)

56

Televancin

Skin and soft tissue gram+

Red Man Syndrome, QT prolongation, nephrotoxicity

57

Sulfonamides

Structure similar to PABA, compete for Dihydropteroate synthetase depriving cell of folic acid for DNA synthesis; does not affect host cell

Coverage: Gram+, Gram- piddly and PEK and CE

excreted via glomerular filtration (used for UTI)

Steven Johnson's Syndrome,
Nephrotoxicity - increased with IV make sure pt. is hydrated, crystalluria
Kernicterus - elevated levels of unconjugated bilirubin in fetal blood if given to female in third trimester

Treats acute uncomplicated UTIs, Toxoplasmosis, Pneumocystis carinii, nocardosis, malaria if chloroquine resistant

58

Trimethoprim

Inhibits Dihydrofolate reductase, prevents formation of tetrahydrofolic acid, does affect human enzyme

Coverage: Gram+, Gram- piddly, PEK, and CE; Pneumocystis carinii if used with Dapsone

Renal excretion: most glomerular filtration some secretion

Caution in patients with folate deficiency (pregnant or alcoholic)

Treats acute uncomplicated UTIs or recurrent UTI prophylaxis

59

Bactram
Sulfamethoxazole/trimethoprim

Synergy combined mechanisms - cidal -reduce resistance

UTIs, respiratory tract infections, GI, STDs, travellers diarrhea

combined adverse effects

Drug of choice for strenotrophomonas maltophilia
Warfarin interaction: one of the worst potentiators
Methotrexate interaction: increase free concentraion

60

Nitrofurantoin

May interfere with early bacterial carb metabolism, inhibiting acetyl CoA

Gram positive resistant (MRSA), some Gram- but not Pseudomonas

Excretion is linear and related to creatinine clearance, impaired GFR = increased toxicity

Pulmonary reactions (sually reversible)

Used almost exclusivley for UTIs, do not use in males because of prostate tissue

61

Methenamine

hydrolyzed to formaldehyde at urine pH, denatures proteins

avoid in hepatic insufficiency (ammonia byproduct) and renal insufficiency (acidosis)

Only used as UTI prophylaxis, increased urine output decreases effects by voiding formaldehyde decreasing exposure time

62

Macrolides (General)

Binds reversibly to 50s ribosomal subunit decreasing protein synthesis - Bacteriostatic

Gram positives and atypicals

Distributes to tissues longer than blood
Very high concentration in alveolar macrophages and leukocytes

Use in Penicillin allergy, Mycoplasma pneumonia, C. trachomatis (no estolate form if pregnant), Legionnaires disease

63

Erythromycin

Estolate form not effected by hepatic metabolism

More severe GI symptoms (cramps),
Large IV dose may cause QT prolongation, ototoxicity, and thrombophlebitis
Cholestatic Hepatitis (rare) - DO NOT USE ESTOLATE in PREGNANT WOMEN

Motilin stimulation, P-450 enzymes: decreased metabolism of Theophylline, Warfarin, Carbemazepine, cyclosporine

64

Clarithromycin

Picks up H Flu, M Cat, and H Pylori

GI symptoms less severe, Headache, Dizziness, Allergy

P-450 enzymes: decreased metabolism of Theophylline, Warfarin, Carbemazepine, cyclosporine

65

Azithromycin

Picks up H Flu, M Cat, and H Pylori (possibly)

Slow release allows 5 day therapy, but lasts 10 days

GI symptoms less severe, Headache, Dizziness, Allergy

Does not inactivate P-450 enzymes, less worry of drug interactions

66

Clindamycin

Binds 50s ribosomal subunit leading to decrease in protein synthesis

Gram+, anaerobes

90% bioavailability, liver metabolism

Principally associated with diarrhea and C. Diff

67

Chloramphenicol

Binds 50s ribosomal subunit reversibly

Gram+ and -, anaerobes, chlamydia, rickettsia

aplastic anemia (idiosyncratic),
grey baby syndrome (babies lack conjugation system so drug builds up)

great for meningitis but not first line

68

Quinolones (General)

Inhibit DNA gyrase reducing supercoiling leading to DNA cleavage

Oral dose excellent bioavailability, do not take with Mg, Al, Ca beacuse chelation,

Musculoskeletal tendon rupture, no use

69

Ciprofloxacin

SPACE, atypicals (watch Chlamydia resistance)

most potent against Gram- (pseudomonas)

70

Levofloxacin

SPACE, atypicals, Gram+

71

Moxifloxacin

SACE, atypicals, Gram+, anaerobes, (no UTIs)

Complicated intrabdominal infections

72

Gemifloxicin

Gram+

73

Tetracyclines (General)

Binds 30s reversibly to decrease protein synthesis - static

Gram+ (staph/strep), Gram- (H Flu, Neisseria), atypicals, rickettsia

Photosensitivity
Can replace bone and dentin (don't use in children under 8)
Fanconi-Like Syndrome (if drug outdated) - lethargy, polydipsia, polyuria, proteinuria, acidosis

Di/trivalent cations decrease absorption
Warfarin - enhances anticoag

74

Doxycycline

hepatobiliary secretion

75

Minocycline

hepatobiliary secretion

Dizziness, ataxia, vertigo

76

Tetracycline

renal excretion

77

Oxytetracycline

renal excretion

78

Demeclocycline

renal excretion

used to treat SIADH