dh206: pharmacology chapter 7: antiinfective agents lisa mayo, rdh, bsdh copyright © 2011, 2007...

DH206: PharmacologyChapter 7:Antiinfective Agents

Lisa Mayo, RDH, BSDH

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.


Chapter 7 Antiinfective Agents

1. Definitions2. ABX & dentistry3. Adverse Effects4. Bactericidal Antibiotics5. Bacteriostatic Antibiotics6. Misc Antibiotics7. Infective Endocarditis8. TB


1. Definition


1. Definitions Antibiotics: substances produced by living

organisms which are harmful to other organisms◦Natural or semisynthetic◦BacteriCIDAL or bacterioSTATIC ◦Narrow-Spectrum or Broad-Spectrum Narrow = Gram (+) only PEN/MACROLIDE Broad = Gram (+) & (-) CLINDAMYCIN


1. Definitions Synergism

◦Combination produces more than an additive effect (1 + 1 > 2)

◦Bactericidal combs are generally synergistic ◦Bacteriostatic combs usually additive

Antagonism◦Occurs when a combination produces less

effect than either agent alone◦(1 + 1 < 2)◦Bactericidal + bacteriostatic


2. ABX & Dentistry


2. ABX & Dentistry Perio Therapy

◦ Aggressive perio = systemic abx useful (bacteria invade soft tissues & cannot be removed through SCRP)

◦ Chronic perio = systemic abx NOT used (Arestin) Endo Therapy

◦ Uncomplicated = no abx◦ Lesion spread into soft tissue & is not draining, systemic

involvement = yes abx (PEN VK) Implants

◦ Pen VK + oral rinse if post-op infection occurs◦ Peri-implantitis = yes abx◦ Perio-mucositis = no abx DO NOT MEMORIZE

TABLE 7-1, TOO MUCH!


3. Adverse Effects

1. Bacterial Resistance2. Superinfections & GI Effects (nausea,

vomiting, diarrhea)3. Allergic Reactions4. Photosensitivity5. Drug Interactions6. Pregnancy


3. Adverse Effects1. Bacterial Resistance

Abx use promotes development of ABX-resistant bacteria

Increasing problem: culture & sensitivity tests should be performed before Rx given for an abx

Natural & acquired resistance Acquired: abx kills some but not all bacteria or

bact mutate Natural: bact always been resistant


3. Adverse Effects

2. Superinfections & GI EffectsBroad-spectrum abx can eradicate organisms that

are a part of normal flora of GI, mouth, respiratory tract, vagina This can allow for growth of other organisms (fungi,

bacteria)Pseodomembranous colitis causes inflammation of

bowel (common with CLINDY)Tx for p.colitis: Vancomycin, Metronidazole

ERYTHROMYCIN most common for GI issues


3. Adverse Effects

3. Allergic Reactions

4. Photosensitivity: Sensitivity to UV lightSunburn easilyCIPRO & DOXYCYCLINE most common

ABX ALLERGIC POTENTIAL

PenicillinCephalosporin

High

ErythromycinClindy

Low


3. Adverse Effects

5. Drug InteractionsAll abx can interact with other drugs &

food consumption (can ↑ or ↓ effects)1) Oral Contraceptives: abx interfere with

metabolism of contraceptives2) Oral anticoagulants: Abx ↓ bacterial

flora that produce vitamin K (↑ anticoagulant effects) (EXCEPTION TO RULE: PEN & TETRACYCLINE)


3. Adverse Effects

6. Pregnancy

ABX PREGNANCY USEPenicillin Erythromycin

Yes (no teratogenicity)

Metronidazole NoTetracycline No


NBQ

A primary concern for using antibiotics for infections that are not bacterial in nature is that:

a. Drug-resistant microorganisms could developb. Drug-drug interactions increasec. Drug dependence will developd. Significant diseases could occur


NBQ

Which of the following defines antimicrobial activity of an antibiotic that kills sensitive bacteria?

a. Narrow-spectrumb. Broad-spectrumc. Bactericidald. Bacteriostatic


NBQ

All of the following are adverse reactions to antibiotics EXCEPT which one?

a. Superinfectionsb. GI issuesc. Allergic reactionsd. Inhibits bacterial growthe. Photosensitivity


4. Bactericidal ABX

1. Penicillins2. Cephlosporins3. Nitroimadazoles4. Quinolones(Fluoroquinolones)5. Vancomycin6. Aminoglycosides

I USE DIFFERENT ORGANIZATION THAN BOOK – DIVIDED INTO CIDAL vs STATIC CATEGORIES


4. Bactericidal ABX

1. Penicillin Discovered by Alexander Fleming Most all produced from a strain of penicillium

chrysogenumi Some produced semi-synthetically Protype: PEN G (most potent penicillin) Administration: oral, parental NEVER TOPICAL (allergic rxns)

P.75-77


1. Penicillin: CHEMISTRYPenicillins structureoCan alter the structure by adding various

saltsoHow there are different pen drugsoMain differences in penicillins

1. Acid stability in the stomach2. Resistance to enzymatic destruction by

penicillinase & antibacterial spectrum

4. Bactericidal ABX


1. Penicillin: CHEMISTRY◦β-lactam ring fused to a five-member, S-

containing thiazolidine ring Neither ring has antimicrobial action

◦Term beta-lactam used to classify penicillin, cephalosporin, carbapenem, monobactam antibiotics

◦Active pen made by adding different functions grps to position 6 (see next slide)

4. Bactericidal ABX


1. Penicillin: CHEMISTRY: Beta-Lactam Ring◦Responsible for the antibacterial activity◦When the β-lactam ring broken = antimicrobial

action is lost◦Action

β-lactam ring inhibits bacterial enzymes (called pen-binding proteins=PBPs) located on bacterial cell walls= leads to cell death

Resistant bacteria to penicillin’s are able to produce enzymes (beta-lactamases) that break open the ring

4. Bactericidal ABX


1. Penicillin: Spectrum of Activity◦ Gram (+) primarily (narrow-spectrum)◦ Some gram (-) (broad-spectrum)

4. Bactericidal ABX

Type of PEN Examples Notation

Narrow spectrum Pen GPen V

PROTYPEDental infections

Broad spectrum AmoxicillinAmpicillin

Premed Dental infections

Beta-lactamase inhibitors

Augmentin Refractory perio

Penicillinase-resistance penicillin

Not used in dentistry

Extended spectrum Not used in dentistry

KNOW THIS, NOT TABLE

7-2


1. Penicillin: USESPen VK & AmoxoMild-Moderate dental infections (endo,

perio, oral surgery)oSalt of PEN V is called PEN VK: more

soluble than the free acid and better absorbed when taken orally

oAmox: Premed

4. Bactericidal ABX

P.77


1. Penicillin: PEN RESISTANCECertain bacteria have the ability to produce

enzymes that inactivate penicillin’s (narrow & broad spectrum)

These enzymes are referred to as beta-lactamases

β-lactamases that inactivate penicillin's are referred to as penicillinases

Clavulanic acid can be added to AMOX to avoid destruction by β-lactamase enz = AugmentinClavulanic acid has NO antibacterial action, it

allows the β-lactamases to bind with it and this leave AMOX alone

4. Bactericidal ABX


AUGMENTIN

Clavulanic Acid

β-lactamase Bacteria

β-lactamase

+ =

AMOX

Bacteria


1. Penicillin: ADVERSE REACTIONS (have wide margin of safety)1) Allergic reactions: 10% population2) GI upset: can use lactobacillus acidophilus

4. Bactericidal ABX


1. Penicillin: DRUG INTERACTIONS1) PEN + Bacteriostatic ABX = PEN not as

effective2) Birth control3) Probencid (gout drug) = ↑levels PEN in blood

by ↓ renal elimination

4. Bactericidal ABX


4. Bactericidal ABX

1. Penicillin's2. Cephlosporins3. Nitroimadazoles4. Quinolones(Fluoroquinolones)5. Vancomycin6. Aminoglycosides


4. Bactericidal ABX

2. CephalosporinsStructurally similar to penicillinsHave a β–lactam ringBroad spectrumX-hypersensitivity possible w/PENUses

Skin, bone, GI, Respiratory, ear infectionsNOT indicated for endo/perio infections (PEN

used)

P.77-78


4. Bactericidal ABX2. Cephalosporins

Book correction: 4-generations, not 3Adverse rxns same as PENDrug interactions: same as PEN except add

WarfarinActions of Warfarin may be increased


4. Bactericidal ABX

2. Cephalosporins

First generation cefadroxil(Duricef)cephalexin(Keflex)

Second generation

cefaclor(Ceclor)cefuroxime-axetil(Ceftin, Veftin)

Third generation omnicef(Cefdinir)cefixime(Suprax)ceftibuten(Cedax)

Fourth generation Only injectable


NBQWhich of the following antibiotics is considered a broad-spectrum cephalosporin-type antibiotic?

a. Pen VKb. Cefaclor (Ceclor)c. Clindamycind. Erythromycin


4. Bactericidal ABX



4. Bactericidal ABX

3. Metronidazole(Flagyl)Effective against bacteria & protozoa

(NBQ)Can tx vaginal & resp infections

Antiinflammatory effectsUsed in tx of Pseudomembranous colitis

P.82-83


4. Bactericidal ABX

3. Metronidazole(Flagyl): USESNUGPeri-implantitisRefractory/aggressive perio: can be used

in combo w/AMOX or AUGMENTINoGood against Aa and Pg


4. Bactericidal ABX

3. Metronidazole(Flagyl): ADVERSE EFFECTS GI Metallic taste Dry mouth Darkened urine


4. Bactericidal ABX

3. Metronidazole(Flagyl): DRUG INTERCATIONSAlcohol oProduces a reaction similar to when a

recovering alcoholic drinks while taking disulfiram (Antabuse)

oNO ALCOHOL for 3 days after abx stoppedLithium (bipolar)Cimetidine (antiulcer drug)Warfarin: cause ↑ bleeding


NBQ

Which of the following drugs is contraindicated while a patient is taking metronidazole?

a. Penicillinb. Alcoholc. Aspirind. Mushrooms


4. Bactericidal ABX



4. Bactericidal ABX

4. Quinolones(Fluoroquinolones)Most common: CIPROFLOXACINInhibit bacterial DNA replicationFacultative gram (-) anaerobesUSESoSinusitis, acute bronchitisoSkin, eye infections, UTIoChronic perio

P.86


4. Bactericidal ABX

4. Quinolones(Fluoroquinolones)Calcium products taken 4 hours before or

2 hours after CIPRODrug InteractionsoWarfarinoTheophylline (asthma drug)oCaffeine


4. Bactericidal ABX

4. Quinolones(Fluoroquinolones)end in ~floxacin

Quinolones(Fluoroquinolones)ciprofloxacin(Cipro)

norfloxacin(Noroxin)

enoxacin(Pentrex)

lomefloxacin(Maxaquin)

ofloxacin(Floxin)

levofloxacin(Levaquin)

Moxifloxacin(Avelox)


NBQWhich of the following is the mode of action for Cephalosporins?

a. Interfere with bacterial protein synthesisb. Affect bacterial cell wallc. Interfere with normal biosynthetic

pathways in bacteriad. None of the above


NBQWhich antibiotic/antimicrobial is associated with the highest incidence of drug allergy?

a. Ciprofloxacin (Cipro)b. Pen VKc. Clindamycind. Metronidazole (Flagyl)


Levofloxacin (Levaquin) has which of the following modes of action?

a. Affects bacterial cell wallb. Affects bacterial DNAc. Interferes with bacterial protein synthesisd. Interferes with bacterial metabolic pathways

NBQ


4. Bactericidal ABX



4. Bactericidal ABX

5. Vancomycin(Vancocin)Use is increasingGram (+)Adverse Effect: red-man syndrome (NBQ)Uses: pseudomembranous colitis (NBQ)


4. Bactericidal ABX



4. Bactericidal ABX

6. AminoglycosidesBactericidal Gram (-) aerobicInhibits PRO-synthesis on 30S ribosomeUSES

Hospitalized patients with serious gram (-) infections


4. Bactericidal ABX6. Aminoglycosides

Aminoglycoside USES

streptomycin TB tx when other drugs have failed

neomycin Topical

gentamycin Topical

tobramycin Injection

amikacin Injection


Which of the following antibiotics are useful in treating odontogenic infections?

a. Azithromycin (Zithromax, Z-pak)b. Clindamycinc. Pen VKd. Cephalexin (Keflex)e. All the above

NBQ


5. Bacteriostatic ABX

1. Macrolides2. Lincomycins (Clindamycin)3. Tetracyclines4. Sulfanamides



1. MacrolidesInhibit multiplication of bacteria by reversibly

binding to the 50S ribosomal subunit of bacteriaoThis action inhibits PRO synthesis of the

bacterial cellExcreted by bile, not urineMost common adverse effect: GI upsetUSEoSinusitis, ear infectionsoGonorrhea, community-acquired pneumonia,

PID, chlamydia, diphtheria

P.78



1. Macrolides

Generation Macrolide Notations

First generation

Erythromycin • Gram (+) & (-)• Used when pt’s

allergic to PEN

Second generation

Clarithromycin(Biaxin)Azithromycin(Zithromax, Z-Pak)

• Broader spectrum than 1st generation

• Fewer adverse effects

• Azithro: useful in perio disease tx, antinflammatory



1. Macrolides: DRUG INTERACTIONSPotential to inhibit drug metabolism of other

drugs through inactivation of P-450 enzyme system

Antacids ↓ effectiveness of macrolides


5. Bacteriostatic ABX2. Lincomycins

Clindamycin(Cleocin)Inhibits PRO synthesis of 50S ribosome

like MacrolidesUSESoPerio abscess or perio diseaseoChronic bronchitis, community-acquired

pneumonia, sinusitisoPremed

P.82


5. Bacteriostatic ABX2. Lincomycins

Adverse effects: pseudomembranous colitisoMany dentists avoid Clindy as a 1st line

drug due to this side effectoDisease can be fatal (persistent diarrhea)

ContraindicationsoCrohn’s diseaseoUlcerative colitis


NBQ

An overgrowth of which of the following organisms is responsible for antibiotic-associated diarrhea?

a. Streptococci mutansb. Mucobacterium tuberculosisc. Clostridium difficiled. Staphylococci aureus


5. Bacteriostatic ABX3. Tetracyclines

Broad spectrumMechanism of Actiono Inhibit PRO synthesis at 30S ribosome (not

50S like macrolides, clindy)o Inhibit host production of collagenase in cells

such as PMNs Collagenase: enzyme that makes up

connective tissue of periodontiumoConcentrate in GCF & maintain high

substantivity on root surfaces oFound in saliva & breast milk



3. Tetracyclines



3. Tetracycline: ADVERSE EFFECTSoStain teethoMinocycline: blue/grayoTetracycline: yellow/brown

oSkin hyperpigmentationoMinocycline: dizziness



3. TetracyclinesCANNOT take with milk (next slide)Take with full glass water to prevent ulcersUSESoChronic, refractory & aggressive perio

diseaseoChlamydia, syphilis, traveler’s diarrheaoHelicobacter pylorioAcne



3. Tetracyclines: DRUG INTERACTIONSoDairy products: tetracycline binds with calcium

& this will inhibit absorption of drugoAntacids delay absorption tetracyclinesoWarfarinoOral sulfonylureas – can lead to hypoglycemiaoDO NOT use during pregnancyoShould NOT be use in last ½ of pregnancy or in

kids <9yrs (NBQ) Mosby’s says 7-12yrs


5. Bacteriostatic ABX4. Sulfonamides

Bacteria have an essential requirement for paraaminobenzoic acid (PABA) which is folic acid

Sulfonamides are competitive antagonists of PABA

Block synthesis of folic acid↓

Inhibits bacterial growth↓

Produces bacteriostatic effect



USESoOtis mediaoUTIoPneumocystis carinii in AIDS patients

(pneumonia)DRUG INTERCATIONS

oWarfarinADVERSE EFFECTS

oStomatitisoSkin rashoSulfa allergy rxn



Sulfonamides

sulfisoxazole+trimethoprim(Bactrim) Most common

sulfadiazine(Microsulfron)

sulfamethoxazole(Gantanol)

sulfisoxazole(Gantrisin)

trimethoprim(Proloprim)


Sulfonamides (also known as sulfa drugs) are structurally similar to:

a. Penicillinsb. Erythromycinsc. Salicylic acidd. Para-aminobenzoic acid (PABA)

NBQ


NBQ

All of the following antibiotics have been used in the treatment of aggressive periodontitis EXCEPT which one?

a. Clindamycinb. Ciprofloxacinc. Erythromycind. Doxycycline


NBQ

Which of the following is the mode of action of the Tetracyclines?

a. Bacterial cell wall destructionb. Prevent protein synthesis in the bacterial cellc. Interfere with nucleic acid syntheiss in the

bacterial celld. Cause mutations within bacterial DNA


NBQ

Which antibiotic below is associated with the adverse effect of pseudomembranous colitis?

a. Pen VKb. Erythromycinc. Tetracyclined. Cephalexin (Keflex)e. Clindamycin


NBQ

Which antimicrobial is associated with photosensitivity?

a. Tetracyclineb. Pen VKc. Metronidazole (Flagyl)d. Clindamycin


NBQWhich of the following rugs can be used in a pregnant patient?

a. Tetracyclineb. Pen VKc. Doxycyclined. Minocycline


7. Prevention of Infective Endocarditis



CONDITIONS REQUIRING PREMED PER AHA1. Artificial heart valves2. Hx IE3. Congenital heart conditions4. Cardiac transplant that develops a problem in

a heart valve



Premed drugs: taken 30-60min prior to dental appt

Alpha-hemolytic streptococci most common agent that causes IEo Reason why AMOX best drug to prevent IE

Recommended 7 days between dental appts for patients that need premed



SITUATION DRUG DOSE ADULTS

DOSE KIDS

Oral AMOX 2g 50mg

Unable to take oral meds

AmpicillinCephalosporins (cefazolin, ceftriaxone)

2g parental1g parental

50mg50mg

Allergic to pen/ampicillin

Cephalexin(Keflex)ClindamycinAzithromycin or clarithromycin

2g600mg500mg

50mg20mg15mg

Allergic to pen/ampicillin & unable to take oral meds

Cephalosporins (cefazolin, ceftriaxone)Clindamycin

1g600mg

50mg20mg

HAVE TO KNOW EVERYTHING ON THIS GRAPH!!


NBQ

Which of the following 2 penicillins are recommended by the AHA to prevent endocarditis in patients undergoing invasive dental procedures?

a. Penicillin VKb. Ampicillin (Polycillin)c. Cloxacillind. Amoxicillin (Amoxil)


NBQ

Your patient is taking erythromycin twice daily for 1 month for an upper respiratory tract infection. She has a history that requires antibiotic prophylaxis prior to probing/scaling. She is allergic to penicillin. Which of the following antibiotics could be used is you had to premedicate while taking erythromycin?

a. Ampicillinb. Cephalexin (Keflex)c. Azithromycin (Zithromax)d. Pen VK


NBQ

Which of the following antibiotics can be used for prophylaxis against IE if a patient is allergic to penicillin?

a. Ampicillinb. Erythromycinc. Azithromycin d. Doxycycline


8. Tuberculosis


8. Tuberculosis

TB is caused by the acid-fast bacterium Mycobacterium tuberculosis

Treatment is difficult for several reasons1. Patient inadequate defense mechanisms2. Tubercle bacilli resistant strains 3. Most of the drugs available are not

bactericidal 4. Drugs toxic so cannot be used in sufficient

doses5. Patient compliance: long-term tx, 3-4 drugs

for tx


8. Tuberculosis

Drugs 1. isoniazid(INH)2. rifampin(Rifadin)3. pyrazinamide(PZA)4. ethambutol(Myambutol) 5. Streptomycin


8. Tuberculosis isoniazid(INH)

Drug of choice1st drug used and taken for 9 months

rifampin(Rifadin) + pyrazinamide(PZA)Taken for 2 months in combo with each other &

INHrifampin used alone for 4 months ONLY (resistance

develops quicklyethambutol(Myambutol)

Use for 1st 2moResistance develops quicklyLast resort drug

Aminoglycoside: StreptomycinUsed when other ABX have failed


8. Tuberculosis

DRUG ADVERSE EFFECTS (NBQ) isoniazid(INH)

Hepatitis: ↑ risk with alcohol & acetaminophen use

AnemiaPyridoxine(B6) deficiency: causes peripheral

neuropathy (numbness fingers/toes)


All of the following drugs are useful for treating tuberculosis EXCEPT which one?

a. Isoniazidb. Streptomycinc. Rifampind. Erythromycine. Ethambutolf. Pyrazinamide

NBQ


Which of the following serum-level parameters should be monitored in the tuberculosis patient taking INH?

a. Liver enzymesb. Sodium chloridec. Calcium ionsd. Potassium

NBQ


Which of the following is also referred to as INH?a. Rifaminb. Isoniazidc. Ethambutold. Fluroquinolonee. Pyrazinamide

NBQ


Which of the following TB drugs cause red/orange saliva?

a. Rifaminb. Isoniazidc. Ethambutold. Fluroquinolonee. Pyrazinamide

NBQ


A MAJOR problem with anti-TB drugs is:a. Many drugs are toxic to normal cells in the bodyb. Many drugs are not specific enough to kill the bacteriac. Drug resistanced. Drug dependence

NBQ

dh206: pharmacology chapter 7: antiinfective agents lisa mayo, rdh, bsdh copyright © 2011, 2007...

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