Pharmacology

• for the treatment of infection not resolved after removing the causative factors with primary dental care
• for antibiotic prophylaxis

• treatments such as debridement, endodontics, or extractions
• used to treat infection and remove causative factors of it

• organisms become permanantly established, and colonization begins
• adult body harbors inigenous flora including; bacteria, viruses, fungi, and protozoa
• interaction between these microbial ecosystems determines the normal flora: representing the population of microorganisms inhabiting healthy individuals

• Autogenous: infection caused by body's normal flora, normal flora has become pathogenic (i.e. candidiasis
• environmental/cross: infection related to the proliferation of transient microorganisms obtained from other humans, animals, or the environment

• Prokaryotic: bacterial cells
• Eukaryotic: host, or body cells

• Selective toxicity by: attacking targets unique to bacteria and not present in host cells
• attacking targets in bacteria similar, but not identical to those in host cells
• attacking targets in bacteria that are shared by the host, but vary in importance

• Remove infectious debris and allow the host's immune response to be initiated
• select the agent to which the infecting organism is susceptible
• select the agent with the narrowest spectrum and least toxicity that is active against the infecting organism

• Bactericidal: can kill bacteria, and depend less on the hosts immune system
• Bacteriostatic: do not kill, but slow the growth of microorganisms, and depend more on hosts immune system

• Suprainfection: opportunistic infection caused by the overgrowth of microorganisms that are not susceptible to antibacterial chemotherapy
• occurs often when broader spectrum antibacterial agents are used, and harmless bacteria in normal flora are killed, which increases the risk for overgrowth of unaffected microorganisms in the normal flora

• fever
• spreading infection
• lymphadenopathy
• antibiotic prophylaxis

a higher than normal dose, given to achieve adequate blood levels of the antibiotic quickly

• Narrow: limited bacterial species (some gram-+, some gram--, some aerobic, facultative, or anaerobic)
• Extended: greater number of microorganisms (most gram-+, many gram--, including some aerobic, facultative, or anaerobic)
• Broad: kill or suppress growth of a wide variety of both gram-+ and gram-- aerobic, facultative, or anaerobic organisms

?Narrow spectrum?

• Acute: poorly localized, they are spreading infections
• Chronic: are more localized

Individual antibacterial agents cannot destroy all bacteria; so the immune system must remove necrotic cells

• Inhibitors of Cell Wall synthesis: penicillins, cephalosporins, bacitracin, vancomycin
• Inhibitors of protein synthesis (translation): macrolides, clindamycin, tetracylcine (doxycycline, minocycline), neomycin
• Inhibitors of DNA synthesis and integrity: metronidazole, fluoroquinolones

• Bactericidal: traget metabolic pathways essential for bacterial survival. They act by inhibiting cell wall synthesis leading to cell death associated with cell division, or DNA inhibition leading to cell death not related to cell division
• Bacteriostatic: target metabolic pathways that are necessary for bacterial cell growth but not for survival. LEading to inhibition of multiplication and cell division (reversible once treatment is terminated). they act on protein synthesis (translation)

• penicillin and cephalosporin
• Prototype: penicillin G
• Doseforms: pencillin V, procaine penicillin G, benzathine penicillin G, penicillin VK, methicillin, oxacillin, cloxacillin, dicloxacillin, nafcillin, ampicillin, amoxicillin, amoxicillin with clavulanic acid, carbenicillin, ticarcillin, ticarcillin w/clavulanic acid, piperacillin, mezlocillin, cephalexin, cephradine, cefadroxil, cefaclor, cefixime

• Fluoroquinolons (Cipro, Levaquin): inhibits DNA gyrase function, results in a break in DNA strands, leading to cell death
• Metronidazole: used for periodontal infection, effective against obligate anaerobes
• Metronidazole combined with amoxicillin or penicillin VK for effective therapeutic effect in mixed infections

• Macrolides: erythromycin, clarithromcin, azithromycin
• lincosamides
• chloramphenicol
• tetracyclines
• aminoglycosides: gentamicin, neomycin, streptomycin

• Macrolides: 50S
• Tetracyclines: 30S

• gentamicin
• neomycin
• streptomycin

• Genetic, acquired, and biofilm-related drug resistance
• A factor thought to significantly influence the development of antibiotic resistance is the indiscriminate use of antibacterial agents, such as taking antibiotics for viral infections where they are not effective

Take the agent 30 minutes before, or 2 hours after a meal

• pt presents with: malaise, fever, chills, trismus, rapid respiration, swelling, lymphadenopathey, or hypotension
• Signs and symptoms of infection escalate rapidly
• oral soft tissue swelling spreads to adjacent anatomical spaces affecting breathing and swallowing
• systemic considerations: heart disease, neutropenia,splenectomy, diabetes, end-stage renal disease, organ transplant, HIV, TJR, hepatic dysfunction, pregnancy

• Penicillin VK (unless they are allergic to it)
• it is effective against most causative microorganisms and is a narrow-spectrum antibacterial

• Secondary Advantages: Metronidazole kills anaerobic components of infection and is beta-lactamase resistant it is useful in periodontal infections; Erythromycin drug of choice for tx of infections for pts with allergy to beta-lactam antibiotics
• Secondary Disadvantages: many oral gram-- anaerobes have resistance to erythromycin, and they may be resistant to clindamycin. Large number of drugs interact with erythromycin, it is less safe, it has adverse GI affects, it is very expensive, and can cause death from cardiac causes following the administration of macrolides

• Tertiary advantages: clyndamycin is the drug of choice for the tx of a complicated or long standing odontogenic infection; it is beta-lactamase resistant, and has excellent activity against gram-+ cocci and most oral gram-- anaerobes
• Tertiary disadvantages: Gastric side effects, including pseudomembranous colitis, high cost, drug-resistance

• 2 locally applied tetracycline formulations: doxycycline and minocycline
• very little systemic absorption which reduces side effects
• highly concentrated combined with a bioabsorbable polymer to be maintained within the sulcus
• most efficacious in depper pockets (more than 7 mm)

• It is said that the dose is too low to affect microorganisms, and it is prescribed for 3 months, then reevaluatede and can be continued for up to a year
• it uses the matrix metalloproteinase inhibitory effect as primary mechanism to slow the progression of periodontal inflammation
• available in a 20-mg tablet taken twice daily

Indications for prophylaxis for TJR pts: all pts during first 2 years following joint replacement; immunocompromised/immunosuppressed pts with rheumatoid arthritis, systemic lupus erythematosus, or drug or radiation induced immunosuppresion, or pts with comorbitidites, previous prosthetic joint infections, malnourishment, hemophilia, HIV infection, insulin-dependant diabetes, malignancy

• pts not allergic to penicillin: cephalexin, cephradine, or amoxicillin; 2 g orally 1 hr prior
• pts unable to take oral med and not allergic to pen: cefazolin or ampicillin, cef 1g, or amp 2 g or IV 1 hr prior
• pts allergic to pen, and pts who cant take oral med and are allergic to pen: clindamycin; 600 mg orally or IV 1 hr prior

High incidence: tooth extraction, perio procedures (surgery subging placement, scaling, probing, recall maint.), implant placement and replantation of avulsed teeth, endodontic instrumentation, initial placement of ortho bands (not brackets), intraligamentary and intraosseous local anesthetic injection, oral prophylaxis where bleeding is anticipated

Indicators: prosthetic cardiac valves, previous endocarditis, congenital heart disease with; unrepaired dyanotic CHD including SHUNTS, and conduits, completely repaired CHD with prosthetic material or device, repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or device, or cardiac transplant recipients who develop cardiac valvulopathy

• Oral: amoxicillin, A-2g, C-50mg/kg
• unable to take oral: ampicillin, A 2g or IV, C-50mg or IV, or cefazolin or ceftriaxone, A-1 g or IV, C-50 mg or IV
• allergic to penicillin or ampicillin: cephalexin, A-2 g, C 50mg; clindamycin, A-600 mg, C-20 mg; or azithromycin or clarithromycin; A - 500 mg, C-15 mg
• Allergic to Pen and unable to take oral meds: cefazolin or ceftriaxone; A 1 g IM or IV, C - 50 mg IM or IV; or clindamycin; A 600 mg IM or IV, C 20 mg IM or IV

• ORAL HEALTH IS MORE IMPORTANT THAN ANTIBIOTICS TO PREVENT IE
• pts must be advised of the importance of maintaining meticulous oral hygiene and receive regular dental care to avoid formation of transient bacteremias

• all dental procedures that involve:
• manipulation of gingival tissue
• manipulation of perioapeical region of teeth
• perforation of oral mucosa

• The selected antibacterial agent is to be taken 30 minutes to 1 hour prior to the dental procedure
• when client doesn't take antibiotic, recommendations say that animal studies suggest that protection may be gained if it is taken within 2 hours of the procedure

It is recommended that a drug from a different class be used for chemoprophylaxis to counter the possibility of antibiotic resistant microorganism formation

• Pts taking anticoagulants: NOT IM INJECTIONS
• Removal of Spleen: contact physician
• Uncontrolled diabetes mellitus
• end-stage renal disease: consult with physician
• organ transplant: consult with physician
• HIV infection: only after consultation with physician

• Drug-Drug interactions: metronidazole interacts with alcohol to cause antabuse effect of mausea, abdominal cramps, and vomiting
• Antibacterial agents and oral contraceptives: they reduce the efficacy of oral contraceptives, especially rifampin, women should be warned of these interactions, and should used alternative nonhormone contraception methods
• GI disturbances: acute onset of nausea, retching, and vomiting, diarrhea; if pt complains of bloody diarrhea with lower abdominal cramping, C. difficile may be possible which is potentially FATAL
• Oral side effects: unpleasant taste or red urine with metronidazole, staining of teeth or mucosa, or Oral candidiasis
• Allergic reactions

recommends that women be advised of the potential risk of an interaction between the antibacterial agent and the oral contraceptive, and an alternative nonhormonal contraception should be used during periods of antibacterial chemotherapy

Penicillin