Pharmacology - T3 E. Antimicrobial Therapy

Front 1

define: antibiotic
p139

Back 1

old: substances produced by microorganisms that supress growth of other organisms. new: now include purely synthetic agents
antimicrobial = antibiotic (and antifungal)

Front 2

how are antibiotics selective in their toxicity?
p139

Back 2

they expoloit bichem differences b/w humans and microorganisms. ie "magic bullet" (paul ulrich) drug - cell walls, microsomal subunits, DNA gyrase, membrane sterols

Front 3

what are some things that could be targeted by antibiotics?

Back 3

cell walls
different microsomal subunits
DNA gyrase
membrane sterols

Front 4

what drugs inhibit cell wall synthesis?
p139

Back 4

Penicillins and Cephalosporins - b/c they resemble D-alanyl-D-alanine (cross linking PGcans). compete for transpeptidase = lysis

Front 5

what drugs inhibit bacterial protein synthesis?
p140

Back 5

Erythromycins and Clindamycin, bind the 50s ribosomal subunit. no translocation, no elongation. leads to bacteriostatic actions

Front 6

what drugs disrupt cytoplasmic membrane?
p140

Back 6

NYSTATIN (and other antifungals) bind sterols in memB. Form Pores. more side effects b/c subtle differences b/w mammalian and bacterial cell memB's

Front 7

What drugs discrupt DNA synthesis?
p141

Back 7

FLUOROQUINONES and METRONIDAZOLE. F's inhibit DNA gyrase combating "supercoiling" of DNA
host cells do not have DNA gyrase

Front 8

difference b/w narrow and broad (extended) spectrum antibiotics?
p141

Back 8

no specific definitions. when choosing antibiotic it's always to use one that is effective against the organisms causing the infection and has Narrowest spectrum possible

Front 9

get effective antibiotic concentration a site of action. (dose administered, route of administration, distribution of the drug, frequency of administration)
p141

Back 9

dose - aim 4-8X the MIC (loading dose good dentally) Route - serious infections, IV used (IM also bypasses stomach acid) Distribution - b/c solubility some antibiotics distribute more readily to bone, abscesses, brain, etc

Front 10

how frequent administer antibiotics?
p142

Back 10

controlled by biotransformation and excretion rates. determines the maintenance levels in blood, should be above MIC's.

Front 11

time dependent antibiotics
vs
concentration dependent antibiotics
p142

Back 11

timing big b/c thie concentrations fall below MIC and effectiveness curtailed, inhibitors of cell wall, zb.
Conc. dependent posess postantibiotic effects, inhibit bacteria after below MICs ie. erytrhomycin / clindamycin

Front 12

age/size of bacterial infection. most antibiotics work best on actively dividing cells. when is best time to administer?
p142

Back 12

soon for max benefits. or it gets established and lotta cells, more beta-lactamase activity and bacteria become less susceptible to antibiotics (inoculum effect). especially in abscess

Front 13

T/F antibiotics, when used correctly can cure us.
p142

Back 13

actually its our host defense mechanisms. antibiotics jus limit # of pathological organisms. [our defense down w/ pathological conditions and drugs]

Front 14

what drugs hinder cell growth, weakening host defense?
p142

Back 14

drugs that hinder cell grown include corticosterioids, antineoplastic agents, etc

Front 15

what are the 2 types of bacterial resistance?

Back 15

Natural - existed before discovery of antibiotic. ie. gm - bacteria are not effected by pennicillin
acquired - occurs as consequence of antibiotic use and is result of selection for resistance organism. horizontal (transduction, transformation) vertical (duplications)

Front 16

direct toxicities in antibiotics are seen why?
p143

Back 16

adverse effects that are the result of innate ability of antibiotic directly modify cellular processes of the host. (often more for those that interfere with protein synthesis)
orally - local, but allergies exist, look at pennicillin, zb. skin rash to anaphylaxis

Front 17

indirect toxicities in antibiotics are seen why?
p144

Back 17

distrubance of hosts microflora that allows overgrowth of less susceptible bacteria or fungal leading to various problems . SUPERINFECTIONS ! broader spectrum = higher risk

Front 18

what is the most serious superinfection caused by dental antibiotics?
p144

Back 18

pseudomemranous colitis. caused by toxins produced by overgrowin Clostridium difficile. destroy intestinal mucosa. bloody diarrhea = talk to dr.

Front 19

Pennicillin
- pharmacokinetics
- indications
p145

Back 19

absorbed well orally, resists stomach acid. distributes poorly in brain. doesn't undergo metabolism, peed out.
1st choice in acute orofacial infections. >90% effective + narrowest spectrum (not recommended for IE chemoprophylaxis)

Front 20

why not pennicillin?
p145

Back 20

allergy, toxic, resistance
allergy -> 5-15% population. skin rxn, cross allergenicity w/ other penicillins (and beta lactam agents), misdagnosed often (if someone has flu, zb) get tested

Front 21

toxic/resistant pennicillin?
p145

Back 21

low incidence of superinfection (diarrhea), little direct toxicity,
Resistant - subject to cleavage by beta lacamase (via staph, zb), conferred via plamids. can make fat PBPs with low penn affinity.

Front 22

amoxicillin AMOXIL
pharmacokinetics
p146

Back 22

orally well absorbed (better than ampicillin), acid stable, same distribution as pen VK, 60% less prtoein binding than pen VK, longer half life, tid (good compliance), enerohepatic cycling (some)

Front 23

when use amoxicillin?
p146

Back 23

First choice for oral IE chemoprophylaxis, longer duration. possible substitute for pen VK if compliance is an issue

Front 24

adverse effects of Amoxicillin?
p146
Amox - developed as an extended spectrum penicillin, dental advantage questionable

Back 24

similar pattern of allergnicity as pen VK. greater incidence of superinfection than pen VK (b/c broader spectrum)
Note: suseptible to penicillinase

Front 25

Amoxicillin + Clavulanate (Augmentin) wtc?
p147

Back 25

clavulanate inhibits the action of penicillinase, this combination expands effectiveness of amoxicillin. use if penicillinase-producers suspected (if pen VK failed) use for medically compromised pt.

Front 26

Cephalexin (KEFLEX) cephalosporin antibiotic, first generation agent.
What's its pharmacokinetics?
p147

Back 26

absorbed well orally
like pen VK, little is metabolized, excreted via urine
suseptible to beta-lactamase (cephalosprinase)

Front 27

indications for Cephalenxin?
p147

Back 27

3rd choice for acute orofacial infections. 3rd in IE chemoprophylaxis regimen in pen-allergic pts

Front 28

adverse effects of cephalexin?
p147

Back 28

much less allergenic than pen VK
8% cross allergenicty with penn's. those immeiately sesnitive to penn, contraindicated! 1st dose in Office ( if penn allergic) superinfection possible
broad spectrum - GI problems

Front 29

ERYTHROMYCIN (E-Mycin) - microlide antibiotics.
what's the pharmacokinetics?
p148

Back 29

orally well absorbed. base susceptible to stomach acid, often enteric coating. well distributed. take on empty stomach (except sterate form). undergoes enterohepatic cycling (pood out)

Front 30

indications for Erythromycin?
p148

Back 30

2nd choice for penn-allergic pt's, if tolerable. not routinely used in IE chemoprophylaxis

Front 31

Adverse effects of erythromycin?
p148
resistance develops rapidly to erythromycin (all routes) and bactriostatic for most common oral pathogens

Back 31

allergenicity much less than pen VK, BUT cholesostatic hepatitis can occur.
SPASMOGENIC - cramp and diarrhea. low superinfections (narrow spectrum). will inhibit p450 in liver (esp CYP3A4) basis for many drug interactions

Front 32

Azithromycin & Clarithromycin - 2nd generation macrolides. why's this any better than erythromycin?
p149

Back 32

less spasmogenicity, tollerated better and longer duration, qd, or bid dosing, better dosing

Front 33

Azithromycin VS. clarithromycin

Back 33

clarithromycin has broader spectrum, including anaerobic oral pathogens
clarithromycin cna be taken With meals
Azithro mycin is associated with fewer drug interactions

Front 34

CLINDAMYCIN (CLEOCIN): lincosamides
pharmacodynamics?
p149

Back 34

well absorbed orally
noted for ability to penetrate bone
undergoes considerable enterhepatic cycling.

Front 35

indications for CLINDAMYCIN?
p149

Back 35

penn allergic pts with acute orofacial infections, especially bone infections
adjuct to penn whin unsuccessful, anaerobes or P-ase producers
FIRST choice for IE chemoprophylaxis in penn allergic pts

Front 36

adverse effects of Clindamycin?
p149

Back 36

low allergenicity and resitance development. Superinfections posssible. mostly pseudomembranous colitis (Bad rap)

Front 37

METRONIDAZOLE (Flagyl)
mechanism
p150

Back 37

reduced in cytoplasm by iron compounds, etc. generates nitro radical anion that attacks DNA
active only against obligate anaerobes

Front 38

indicaions for METRONIDAZOLE

Back 38

adjunct with Pen VK when pen VK alone is not successful
refractory periodontal disease

Front 39

TETRACYCLINE (Achromycin)
pharmacokinetics
p150

Back 39

absorption down by cations (Ca+, Fe, Mg, Al+) will precipitate
differential distribution to bone, skin fetus, teeth, enterohepatic cycling, inhibits GI organism

Front 40

tetracycline indications
p150

Back 40

refractory periodontal disease - after scaling and root planing, rarely used today.

Front 41

adverse effects of teteracycline
p150

Back 41

discolors teeth causing enamel hypoplasia, contraindicated (prego). expiration date, b/c toxic breakdown, resistance fast, superinfection common (Broad specctrum, bacteriostatic)

Front 42

Doxycycline (Atridox, periostat), a tetracycline
indications?
p151

Back 42

refractory periodontal disease, adjunct to scaling and root planing.
limited clinical significance with extra expense and time required

Front 43

Rationales for doxycycline ?

p151

Back 43

ARIDOX - antibacterial activity directed to discrete area, limits systemic side effects.
PerioSTAT - systemic delivery of subantibiotic doses, inhibit inflammatory activity of PMNs w/in sulcus, limits toxicity, limits resistance development

Front 44

Macrolide antibiotics have the ability to block cytochrome p450 nzymes (CYP3A4 zb) see high drug levels so contraindications with what drugs?
p151

Back 44

"satin" anticholesterol agents (ZOCOR)
felodipine (PLENDIL)
ergot alkaloids (CAFERGOT)
sildenafil (VIAGRA)
warfarin (COUMADIN)

Front 45

why should someone be careful when drugs Digoxin (Lanoxin) and erythromcin are taken together?
p152

Back 45

GI bacteria help regulate blood levels of digoxin by feeding off the drug when it enters intestines, lowers conc grad of digoxin.
erythromycin decreases these bacteria, increaseblood digoxin, a NTI drug

Front 46

Methotrexate (RHEUMATREX) and penicillins: penn's are CONTRAINDICATED, why?
p152

Back 46

penicillins interfere with the methotrexate metabolism which increase risk of renal toxicity of MTX

Front 47

contraceptives and antibiotics. break through pregnancy. 75% of all incidents involve what?
p152

Back 47

rifampin, causes inducction of liver CYP450 system. no problem with other antibiotics. warn patients.

Front 48

t/f administration of an antibiotic prior to dental procedure can decrease risk of a posttreamtnet infection

Back 48

true

Front 49

Macrolide antibiotics have the ability to block cytochrome p450 nzymes (CYP3A4 zb) see high drug levels so contraindications with what drugs?
p151

Back 49

"satin" anticholesterol agents (ZOCOR)
felodipine (PLENDIL)
ergot alkaloids (CAFERGOT)
sildenafil (VIAGRA)
warfarin (COUMADIN)

Front 50

why should someone be careful when drugs Digoxin (Lanoxin) and erythromcin are taken together?
p152

Back 50

GI bacteria help regulate blood levels of digoxin by feeding off the drug when it enters intestines, lowers conc grad of digoxin.
erythromycin decreases these bacteria, increaseblood digoxin, a NTI drug

Front 51

Methotrexate (RHEUMATREX) and penicillins: penn's are CONTRAINDICATED, why?
p152

Back 51

penicillins interfere with the methotrexate metabolism which increase risk of renal toxicity of MTX

Front 52

contraceptives and antibiotics. break through pregnancy. 75% of all incidents involve what?
p152

Back 52

rifampin, causes inducction of liver CYP450 system. no problem with other antibiotics. warn patients.

Front 53

t/f administration of an antibiotic prior to dental procedure can decrease risk of a posttreamtnet infection

Back 53

true

Front 54

rationale for antibiotic chemoprophlaxis, 2
p153

Back 54

1. dental procedures cause transient bactermias, endocarditis is life threatening. aim is to us only when antibiotic risk will not exceed potential benefits.

Front 55

Cardiac conditions asoociated with IE include: prosthetic cardiac valve, previous infective endocarditis and what?

Back 55

CHD (congenital heart disease) 1. unrepaired cyanotic CHD (palliative shunts/ conduits), 2. completely repaired congenital heart defect with prosthetic material or device w/in 6 mo. 3. repaired CHD prosthetic, 4. cardiac transplantation who have valvulopathy

Front 56

when are procedures where endocarditis prophylaxis is recomended for high risk pts vs NOT recommended
p154

Back 56

Yes: procedure manipulates gingival tissue or periapical region of teeth or perforation of oral mucosa
no: local anesthetic in infected tissue, placing appliance, placing brackets, taking radiographs, adjusting appliances, shedding 1' teeth, or bleeding from trauma to the lips or oral mucosa

Front 57

specific regimens, see p 155

Back 57

see p 155, ties it together well

Front 58

what if pt is already taking antibiotics?
p 156

Back 58

us antibiotic that targets differnt mechanism of action, reducing cross-resistance
if on pen, then use clindamycin zb

Front 59

what if pt has unexpected bleeding?
p156

Back 59

stop treatment, go back to typical regiment

Front 60

what if pt has multiple day treatments?
p156

Back 60

use typical acute maintenance dose of antibiotic between treatments and use the typical prophylatic dose 30-60 min before the next days procedure

Front 61

what patients are at potential increased risk of hematogenous total joint infections, HIGH risk?
p156

Back 61

those with inflammatory arthropathies, rheumatoid arthritis, systemic lupus erythematosus, or disease/drug/radiation-induced immunosuppression

Front 62

what patients are at potential increased risk of hematogenous total joint infections, MODERATE risk?
p156

Back 62

insulin-dependent diabetic (type I), first 2 yrs following joint placement, previous prosthetic joint infection, malnourishment and hemophilia

Front 63

hematogenous prosthetic total joint infection.
prophylaxis (antibiotic) may be indicated because of risk of bacteremia when?
p157

Back 63

same as cadidates for endocarditis prophylaxis

Front 64

when is prosthetic joint antibiotic prophylaxis considered?
p157

Back 64

used to prefent infection of total knee and hip prosthesis SHOULD be considered if pt is a high risk pt, used if procedure = high incidence of bacteremia

Front 65

when may prosthetic joint antibiotic prophylaxis considered?
p157

Back 65

if pt is a moderate RISK pt and you are performing a procedure that is associated with High Incidence of Bacteremia

Front 66

consultation: pt presents w/ prophylaxis recommendationcontrary to JADA guidelins, a consultation with the physician is suggested. purpose of mtg?
p157

Back 66

determine if there are any unusual circumstances that would lead physician to suggest a regimen that deviates for the guidelines, if not, follow guidelines not ithe physicians recommendations

Front 67

p 158 specific drug regimens:

Back 67

see p 158

Front 68

pt has acute orofacial infection. day 1: incise and drain, collect specimen for testing later and Rx?
p159

Back 68

penicillin V (Pen-VEE K); 1000mg loading dose; 500mg Q6H "for 5 days"

Front 69

pt has acute orofacial infection. day 2: call pt, if not improved (fever, pain swelling, malaise) and Rx?
p159
p159

Back 69

metronidazole (FLAGYL) 250mg Q6H "for 5 days" to be taken along with the Pen-Vee K

Front 70

pt has acute orofacial infection. day 3: if not improved, switch antibiotics and Rx?
p159

Back 70

clindamycin (CLEOCIN) 300mg loading dose; 150 mg Q6H "for 5 days", send speciment o labe for sensitivty testing

Front 71

pt has acute orofacial infection. day 4: if not improved?
p159

Back 71

if not improved, send to hospital dental service

Front 72

__________ would be a rational subsitution for Pen VEE K for the initial antibiotic. broader spectrum makes it a bit more effective against orofacial pathogens, more help for the host defense mechanism. p159

Back 72

augmentin

Front 73

for penicillin-allergic patients, what would be the 1st drug of choice?
p159

Back 73

Clindamycin (cleocin), 150mg Q6H "for 5 days"

Front 74

what is the "backup drug" if Clindamycin doesn't work (and pt is penicillin allergic)
p159

Back 74

Clarithromycin (BIAXIN) 1000mg loading dose; 500mg Q12H "for 5 days"

Front 75

duration of antibiotic treatment, t/f should not be a ritual! rarely should exceed 5 days t/f not need to be taken for all 5 days, discourage what?

Back 75

t/t/t
discourage indiscriminat use of antibiotics ot decrease resistance development

Front 76

how long take antibiotics after systems subside?
p160

Back 76

2 days after

also, if source of infection is eliminated, an orofacial infection should not "rebound" once the systoms of infection have subsided