Dental Antibiotic Pharmacology Part 2 Flashcards
why not use augmentin for everything?
- cost
- 3x more side effects
- resistance
what is a narrow therapeutic spectrum ang give example
act on a single organism or type of organism
- ex: penicillin
what is an extended spectrum drug and give example
- works on gram positives and also some gram negatives
- amoxicillin-clavulanic acid
what is a broad spectrum antibiotic and give example
- affect a wide variety of organisms
- cindamycin
- may cause superinfections of unaffected microbes or fungi
enough antibiotics are prescribed every year for ______ americans to receive an antibiotic prescription
5 of every 6 americans
________ of antibiotic courses prescribed in the US outpatient setting are deemed unnecessary
more than 30%
total inappropriate antibiotic use (unnecessary antibiotic use plus inappropriate antibiotic selection, dosing, and duration) is near_______ of outpatient antibiotics
50%
what is the most prescribed antibiotic by dentists
amoxicillin
most beta lactamases ________- the activity of cepahlosporins
do not
cephalosporins are active against:
gram negatives producing b-lactamase
each successive generations of cephalosporins include more:
gram-negative activity
cephalosporins are ____against anaerobes
poor
describe the side effects of cephalosporins
limited
cephalosporins are ______ in penicillin intolerance history
safely tolerated
describe 1st generation cephalosporins
- excellent against gram positive coverage- step spps. and staph aureus
- some gram negative activity:
- proteus, e.coli and klebsiella
- limited oral gram negatives- No P. gingivalis
what are the orals for 1st generation cephalosporins
- cephalexin (Keflex)
- cefadroxil (Duricef)
describe the 2nd generation cephalosporins
- still excellent gram positive coverage- strep spps
- some additional gram negatives:
- morexella, haemophilus, enterobacter, neisseria
- still overall limited oral gram negatives- YES P. gingivalis
what are the orals for 2nd generation cephalosporins
-cefaclor
- cefuroxime
- cefprozil
are there perio indications for 1st and 2nd generation cephalosporins
no
how can 1st and 2nd generation cephalosporins be used in dentistry
for early odontogenic infections
individuals allergic to amoxicillin may receive cephalexin as long as:
the reaction was not anaphylactic like
what are the cell wall active antibiotics
- beta lactams: penicillin and cephalosporins
what are the non cell wall active antibiotics
- macrolides
- clindamycin
- doxycyline
- metronidazole
- trimethoprim-sulfamethoxazole
what antibiotics do ribosome, protein synthesis inhibition
- macrolides
- clindamycin
- doxycyline
what antibiotics do DNA inhibition
- metronidazole
- trimethoprim- sulfamethoxazole
what is another name for metronidazole and what does it do
- flagyl
- bactericidal against all obligate anaerobes: bacteroides spps and fusobacterium
- breaks DNA structure directly through production of free radicals
- antiprotozoal: amoeba, trichomonas, giardia
what are the adverse reactions to metronidazole
- metallic taste, dry mouth
- dark urine
- skin rashes
- disulfiram reaction (headache, flushing)
- avoidance of alcohol no longer required
what is the mechanism of action of metronidazole
CYP2C9 inhibitor
what are the drug interactions with metronidazole
- warfarin
- lithium
- phenytoin
consistent INR elevations observed with warfarin and:
- bactrim
- metronidazole (flagyl)
- fluconazole
what are the general medical uses for metronidazole
- deep space abscesses
- gastrointestinal infections
is resistance a problem with metronidazole and is it given IV or oral
not a problem. given IV and oral
what are the dental uses for metronidazole
- combined with beta lactams - 1st line for serious orofacial infections
- management of refractory or progressive periodontitis
what is the dental prescription for metronidazole
- 500mg po Q8h x 5 days
what are the protein synthesis inhibitors
- clindamycin - static
- macrolides - static
- tetracycline- static
how is clindamycin given
IV or PO
what is the activity of clindamycin
- strep and staph including MRSA
- anaerobic gram negatives: actinomyces, bacillis, bacteroides (increases resistance)
- no aerobic gram negatives
what are the clinical advantages of clindamcyin
PVL toxin inhibition
what are the disadvantages of clindamycin
- c. difficile infection
- clindamycin oral suspension unpleasant taste
- high doses of oral clindamycin (>450mg Q6h) may cause esophagitis
what are the dental advantages of clindamycin
- high penetration into saliva, gingival tissues, and bone
- ## minimal renal concerns
what is clindamycin prescribed for in dentistry
late or severe endo infections and abscesses with severe PCN allergy
what is the prescription for clindamycin in dentistry
150mg PO TID x 5 days
- may use 300mg but more likely to have GI side effects, reserve for severe infections
single dose clindamycin associated with:
significant rates of fatal and nonfatal ADRs
is clindamycin recommended for antibiotic prophylaxis for a dental procedure
no
what are the tetracylcines
- tetracyclin
- doxycyline
- minocycline
what is the MOA of tetracyclines
bind to 30S subunit of ribosome
describe the MOA of tetracyclines
- bacteriostatic
- broad spectrum activity but mostly for gram positives
- requires active transport into cells source of resistance
- chelate/bind divalent cations: binds with Ca2+ and Mg2+, antacids, iron or multivitamins
- no renal or hepatic adjustment: cleared totally unchanged in fecal excretion
will tooth discoloration occur with doxycycline
no but recommended to only give for less than 21 days for children of all ages
what are the doxycycline considerations
- avoid during pregnancy
- gi upset: more common with hyclate salt, monohydrate less acidic, better tolerated
- erosive esophagitis- avoid taking at bedtime, drink full glass of water
- peak plasma concentration may be reduced ~20% by high fat meal or milk
- phototoxicity may occur
- renal/hepatic disease patients can use doxy
what are the dental uses of tetracyclines
periodontal only
tetracyclines are no longer used for odontogenic infections due to:
resistance
what periodontal uses are tetracyclines used for
- management of localized juvenile periodontitis - aggregatibacter actinomycecomitans - make beta lactamase
- AA sensitive to tetracyclines, fluoroquinolones, bactrim, augmentin
- low dose systmeic doxy for refractory agg perioodntitis (periostat 100mg PO daily)
- local appilcation in adjunctive tx for resistant periodontitis: atridox gel , arestin
what are the additive effects of tetracyclines
- concentrates in the gingival crevice extremely well, 7-20 times more than any other drug
- anticollagenase
- anti inflammatory
- inhibition of bone resorption
- promotes reattachment
what are the macrolides
- azithromycin
- clarithromycin
- erythromycin
what is the MOA of macrolides
binds to 50S ribosome (Static), prevents transpeptidation
- time dependent killing effect
describe clarithromycin
- avoid use
- liver metabolism: moderate CYP3A inhibitor
- prodrug: metabolized to active compounds
- less drug-drug interactions than erythromycin but more than azithromycin
what is clarithromycin prescribed for
- h.pylori- chronic dyspepsia, peptic ulcer development, and gastric cancer
what are the side effects of clarithromycin
metallic taste
describe erythromycin, adverse effects, MOA
- not used as antibiotic
- narrow spectrum: LOTS of resistance
- adverse effects: prokinetic, GI disturbances, diarrhea, cramping
- strong inhibitor of CYP3A, many drug interactions
- highest QTc prolongation risk among antimicrobials
what do erythromycin and clarithromycin do to CYP3A4 metabolism
slow it
erythromycin and clarithromycin can cause accumulation of what other drugs
- benzodiazepines
- transplant drugs
- HIV drugs
0 CCBs
azithromycin has a _____ effect on CYP3A4
limited
describe azithromycin, MOA, and side effects
- given IV and PO
- improved infected tissue penetration and half life
- concentrates in tissues, phagocytes, and fibroblasts giving it a long half life
- no phase I metabolism
- eliminated unmetabolized- no drug interactions
- long half life (60 hours)qday dosing
- must use loading dose 2x
- side effects: possible reversible tinnitus with large doses
- liver reports- jaundice, necrosis, failure
what are the dental uses for macrolides
- used in odontogenic and periodontal infections in early, non-abscess infections as 2nd alternative or in severe penicillin allergies
describe macrolides activity
no activity against bacteroides, common in dental abscesses
why is macrolides alternative antibiotic in odontogenic infections
- less effective than beta lactams (2nd choice)
- overall limit use due to already high resistance rates
- 50% of viridans group streptococci resistant
what are the drug selection factors
- common pathogens- empiric therapy targets
- site of infection - ability to penetrate infection site
- patient allergies and drug adverse reactions
- renal and hepatic function , patients age: clearance and metabolism of antibiotics
- concomitant medications and past medical histroy
- pregnancy or breastfeeding
what is a teratogen and what are the types
- agent that can potentially cause a birth defect or negatively alter cognitive and behavioral outcomes
- physical, cognitive, behavioral
what are the determinants of teratogenicity
- dose of toxicant
- half life of toxicant
- placental permeability
-stage of development
exposure during weeks ______ may cause death of child
3-7
at 20 weeks during the _____ period, exposure may result in:
organogenesis; developmental or functional changes
what are good safety in pregnancy and lactation
- cephalosporins, penicillins, clindamycin, azithromycin
what should you avoid in pregnancy and breastfeeding and why
- doxycyclines: Ca2+ chelation
- fluoroquinolones; kidneys/cartilage
- sulfamethoxazole/trimethoprim- various/kernicterus
- metronidazole in 1st trimester- limited data
what are the 3 indications for antibiotics and describe each
- prophylactic therapy: to prevent an infection
- empiric therapy: to cover most likely pathogens
- directed therapy: target toward specific pathogen
when are antibiotics recommended in dentistry
- NUG- systemic symptoms or immunocompromised
- aggressive periodontitis
- fascial space infection
- endo/perio with systemic symptoms
when are antibiotics not recommended in dentistry
- endodontic conditions
- chronic periodontitis or gingivitis
- periodontal abscess
- NUG- no systemic symptoms
when should you consider systemic antibiotics in dentistry
- signs/symptoms of systemic spread- pyrexia, malaise, worsening of general condition
- rapid onset and progress
- infection in immunocompromised patients
- swelling involving submental/submandibular or parapharyngeal spaces
- presence of trismus indicates involvement of per mandibular spaces
when are antimicrobial agents indicated
if fever and regional lymphadenopathy are present or when infection has perforated the bony cortex and spread into surrounding soft tissue
what should be prescribed in early infection (less than 3 days)
- penicillin VK or amoxicillin: if recent mild/mod intolerance- ceftin. if severe allergy - clindamycin
- no improvement after 48 hours: d/c penicillin and switch to augmentin or amoxicillin + metronidazole
what should be prescribed for late infections (abscess or greater than 3 days)
- think anaerobes and gram negative
- augmentin
- amoxicillin + metronidazole
- cephalosporin + metronidazole
- severe allergy - clindamycin
pathogenesis involves following sequence of events:
- formation of a small thrombus on an abnormal endothelial surface: surgical intervention
- turbulent blood flow produced by congenital or acquired heart disease
- bacteria access blood circulation (bacteremia)
- secondary infection of thrombus with bacteria circulating in bloodstream
- proliferation of bacteria resulting in cardiac vegetation on endothelial surface
when is prophylaxis against IE reasonable
if it involves manipulation of gingival tissue, manipulation of periapical region of teeth, or perforation of the oral mucosa in patients with the following:
- non native cardiac valves
- cardiac valves repaired with prosthetic material
- previous IE
- cardiac transplant with valvular regurgitation
- pediatric: unrepaired cyanotic congenital heart disease or repaired congenital heart disease with residual shunts or valvular regurgitation
what is the benefit of IE prophylaxis
70% reduction in risk
when do you avoid antibiotic prophylaxis
- routine anesthetic injections through noninfected tissue
- dental radiographs
- placement of removable prosthodontic appliances
- placement or adjustment of orthodontic appliances
- placement of ortho brackets
- shedding of deciduous teeth
- bleeding from trauma to the lips or oral mucosa
what are the normal oral flora of the mouth
- viridans group streptococci
- strep spps.
- lactobacillus
- actinomyces spps.
- prevotella spps
cephalosporins should not be used in:
an individual with a history of anaphylaxis, angioedema or urticarial with penicillin or ampicillin
what are the choices of prophylactic antibiotic
- clindamycin 600mg
- cephalexin 2g
- amoxicillin 2g
- clarithromycin 500mg
- azithromycin 500mg
what are the resistance considerations with AB prophylaxis
azithromycin and penicillin
amoxicillin for:
- non-allergic ADR Hx
- vomiting
- nausea
- runny nose
- cough
- family hx of allergy
cephalexin for:
- low risk ADRs hx
- diarrhea
- non hive rash
- itching
azithromycin for:
- high risk ADRs
- lip/facial swelling
- breathing difficulty/wheezing
- skin peeling
- mouth blisters
- drop in BP
- hive rash
describe the AB prophylaxis considerations
- AB should be prescribed and administered before procedure
- single dose only
- if pt forgets to take AB before procedure instruct to take within 2 hours following procedure
- if procedure spans multiple days, a separate preventative dose is recommended for each procedure
who is at highest risk for IE
patients with prosthetic heart valves, previous IE, and some types of congenital heart disease
who is at highest risk for bacteremia
pts undergoing procedures that involve manipulation of gingival tissue, manipulation of the PA region of teeth, or perforation of the oral mucosa
AB prophylaxis reduces _____ but no high level studies confirm that it reduces_______
bacteremia; IE
what is the preferred AB prophylaxis
amoxicillin 2g x1 dose 30-60 mins prior
are prophylactic ABs recommended for prosthetic joints
no
why do we not need to give AB prophylaxis for joint replacement
- there is evidence that dental procedures are not associated with prosthetic joint implant infections
- there is evidence that antibiotics provided before oral care do not prevent prosthetic joint implant infections
- there are potential harms of ABs including risk for anaphylaxis, AB resistance, and opportunistic infections like C difficile
- the benefits of antibiotic prophylaxis may not exceed the harms for most patients
- the individual patients circumstances and preferences should be considered when deciding whether to prescribe prophylactic antibiotics prior to the dental procedure
