DRUGS USED IN ENDODONTICS

By

Dr.Anoop.V.Nair

PG

Dept of Cons. Dentistry & Endodontics

KVG Dental College, Sullia

CONTENTS

• Introduction and classifications

• PART I

Pain and analgesics

• PART II

Corticosteroids

• PART III

Antibiotics and its usage

• PART IV

Local anaesthetics

• PART V

Antimicrobial agents

• PART VI

Drugs and pregnant patients

• PART VII

Anxiety and fear

• PART VIII

The medically complex endodontic patient

References

• A medicine or other substance which has a physiological effectwhen ingested or otherwise introduced into the body

-Oxford dictionary

• A pharmaceutical drug, also referred to as a medicine or (loosely)medication, officially called medicinal product, can be looselydefined as any chemical substance — or product comprising such —intended for use in the medical diagnosis, cure, treatment, orprevention of disease.

• The word pharmaceutical comes from the Greek word Pharmakeia.

• According to the Food, Drug, and Cosmetic Act,

(1) : a substance recognized in an official pharmacopoeia or formulary

(2) : a substance intended for use in the diagnosis, cure, mitigation,treatment, or prevention of disease

(3) : a substance other than food intended to affect the structure orfunction of the body

(4) : a substance intended for use as a component of a medicine butnot a device or a component, part, or accessory of a device

Definitions

CLASSIFICATIONSBased on when the drug is administered-

• Pre treatment- analgesics, antibiotics, anti-anxiety

• Treatment- corticosteroids, antibiotics, anti-microbials, local anaesthesia

• Post treatment- antibiotics, corticosteroids, analgesics

Based on route of administration-

• Local- topical antibiotics, anti-microbials, topical anaesthetics

• Systemic- oral- antibiotics, analgesics, anti anxiety

- injectable- im/iv- antibiotics, analgesics, sedatives

• Inhalation- sedatives, anaesthesia

PART IPAIN AND ANALGESICS

IN ENDODONTICS

• The skill of the clinician is often judged primarily by their success or failure of pain control.

-Cohen, Pathways of the Pulp

The

Trigeminal

Pain

System

ANALGESICS-NONNARCOTIC

Management of endodontic pain is multifactorial anddirected at reducing the peripheral and centralcomponents of hyperalgesia through combinedendodontic procedures and pharmacotherapy.

2 classes mainly-

NSAIDS

Acetaminophen

NSAIDS

• Very effective in managing pain of inflammatory origin- binds toplasma proteins- exhibit increased delivery to inflamed tissue viaextravasation of plasma proteins.

• Less studies done comparing NSAIDS on endodontic pain inparticular

• Ibuprofen- considered the prototype of contemporary NSAIDs andhas a well-documented efficacy and safety profile.

• Etodolac (i.e., Lodine) has minimal gastrointestinal (GI) irritation.

• Ketoprofen (i.e., Orudis) has been shown in some studies to besomewhat more analgesic than ibuprofen

• They act primarily through the inhibition of cyclooxygenase (COX)enzymes 1 and2.

• COX-1 is expressed throughout the body and has a role in protection ofstomach mucosa, kidney function and platelet action.

• COX-2 is induced by various endogenous compounds such ascytokines, mitogens and endotoxins in inflammatory cells and isresponsible for the elevated production of prostaglandins duringinflammation.

• Nakanishi et al demonstrated high levels of expression of COX-2 in samples of human dental pulps with a diagnosis of irreversible pulpitis.

• These two proteins share a 60% homology and catalyze the conversion of arachidonic acid into prostaglandin E2.

• PGE2 is subsequently metabolized by a variety of syntheses into PGH2, PFI2, PGD2, PGF2 and thromboxane A2.

• Inhibiting COX-2 blocks prostaglandin formation and ultimately prevents inflammation and sensitization of the peripheral nociceptors.

Pharmacological Strategies to Control Post-operative Endodontic PainZahed Mohammad, Alireza Farhad, Meisam KhalesiDent Res J 2007; 4(2): 61-68

• NSAIDS combined with other drugs (e.g., flurbiprofen with tramadol) or pretreatment and posttreatment application of NSAIDs provides effective pain control.

• The introduction of selective inhibitors of COX-2 offered thepotential for both analgesic and antiinflammatory benefits andreduced GI irritation.

• Oral surgery pain studies evaluating COX-2 inhibitors haveindicated that Rofecoxib (i.e.,Vioxx) has significant analgesicefficacy.

• COX-2 levels are increased in inflamed human dental pulp, anda COX-2 inhibitor (rofecoxib) is analgesic in patients withendodontic pain.

• Concern has been raised that the COX-2 inhibitors may alsodisplay at least some GI irritation in patients with preexisting GIdisease

• Increased risk for prothrombic events following long-term administration

of rofecoxib (VIOXX), which led to the withdrawal of this drug from the

market in 2004.

• Diclofenac (Voltaren) is a relatively COX-2-selective drug and seems

to have a similar degree of COX-2 selectivity as celecoxib.

• Diclofenac was associated with increased CV events.

• In the randomized trial analysis, there was an increase in CV risk with

high-dose ibuprofen.

Based on the available data, the FDA has requested that manufacturers of

all prescription products containing nonselective NSAIDs revise their

product labeling to include

(1) a boxed warning regarding the potential serious adverse CV events

and the serious, potentially life-threatening GI adverse events

associated with the use of this class of drugs

(2) a contraindication for use in patients who have recently undergone

coronary artery bypass surgery

(3) a medication guide for patients, regarding the potential for CV and GI

adverse events associated with the use of this class of drugs.

Given this situation and reasonable alternative NSAIDs, its recommended not

considering COX-2 inhibitors for treating routine endodontic pain patients.

Limitations and Drug Interactions

• NSAIDs exhibit an analgesic ceiling that limits the maximal level of

analgesia and induces side effects, including those affecting the GI

system (3% to 11% incidence) and the CNS (1% to 9% incidenc of

dizziness and headache).

• NSAIDs are contraindicated in patients with ulcers and aspirin

hypersensitivity.

• Also associated with severe GI complications

• Risk of adverse effects increases with increasing lifetime accumulated

dose of these drugs.

• Acetaminophen and opioid combination drugs represent alternatives

for those patients unable to take NSAIDs

Acetaminophen• one of the most commonly used drugs

• found in Combination products for the relief of pain and symptoms of

cold or flu.

• considered safe when taken at normal doses, but in higher doses

causes liver toxicity and has become the most common cause of acute

liver failure

• conjugated in the liver to form inactive metabolites.

• A small portion is metabolized by the cytochrome P450 system to form N-

acetyl-p-benzoquinone imine (NAPQI), which is very toxic but is

generally detoxified by glutathione and converted into nontoxic

compounds.

• Large doses of acetaminophen saturate the main route of metabolism,

causing more acetaminophen to be converted to NAPQI.

• Liver injury occurs once glutathione becomes depleted and NAPQI is

allowed to accumulate.

• Healthy adults should not take more than 4 g (4000 mg) of

acetaminophen in a 24-hour period.

Opioid Analgesics

• potent analgesics

• used in dentistry in combination with acetaminophen, aspirin, or

ibuprofen

• activate mu opioid receptors located at several important sites in the

brain

• Activation of these receptors inhibits the transmission of nociceptive

signals from the trigeminal nucleus to higher brain regions

• opioids also activate peripheral opioid receptors located in dental pulp

• Intraligamentary injection of morphine has been shown to significantly

reduce pain in endodontic patients and other inflammatory pain states

• Adverse side effects, which can include nausea, emesis, dizziness,

drowsiness, and the potential for respiratory depression and constipation.

A combination formulation is preferred because it permits a lower dose of

the opioid, thereby reducing side effects

• Codeine is often considered the prototype opioid for orally available

combination drugs.

• 60-mg dose of codeine produces less analgesia than either aspirin

650 mg or acetaminophen 600 mg

PART II

CORTICOSTEROIDS

• Corticosteroids contain 21 carbon atoms in a four memberedhydrocarbon ring system.

• They comprise glucocorticoids and mineral corticoids.

• Glucocorticoids have been used in endodontics for their potent anti-inflammatory effects.

• The anti-inflammatory properties of glucocorticoids were firstappreciated and utilized as an adjunct in endodontic therapy almosthalf a century ago.

• Glucocorticoids have been used as an intracanal medication eitheralone or in combination with antibiotics/ antihistamines, and systemicallyas a means to decrease pain and inflammation in endodontic patients

• Glucocorticoids have effects on carbohydrate, protein and fat metabolism, and other activities that are inseparably linked to these.

• Actions include-

• Carbohydrate & protein metabolism- promote glycogen deposition in liver, increase uric acid secretion, maintains blood glucose levels during starvation so that brain continues to get its nutrients.

• Fat metabolism- promote lipolysis, subcutaneous tissue over extremities loses fat- moon face, fish mouth, buffalo hump

• Calcium metabolism- inhibit intestinal absorption and enhance renal excretion of calcium

• Water excretion- maintain normal GFR

• CVS- restrict capillary permeability, maintain tone of arterioles and myocardial contractility.

• Skeletal muscles- optimum level needed for normal muscular activity-

Hypocorticism- diminished work capacity and weakness due tohypodynamic circulation

Hypercorticism- muscle wasting and myopathy weakness

• CNS- pharmacological doses- mild euphoria- insomnia, anxiety or depression

• Stomach- aggrevate peptic ulcer

• Inflammatory responses- irrespective of type of injury, inflammatory response suppressed.

• Action is non-specific, reduction of increased capillary permeability, local exudation, cellular infiltration, phagocytic activity and late responses like capillary proliferation, collagen deposition, fibroblastic activity and scar formation, limits recruitment of inflammatory cells at local site.

• Post treatment pain or flare-up after endodontic treatment

inflammation, infection, or both in the periradicular tissues.

• Establishing patency and subsequently debriding and shaping theroot canal system irritate the periradicular tissues introduce

bacteria, bacterial products, necrotic pulp tissue, or caustic irrigating

solution through apical foramina.

• In response to this irritation inflammatory mediators (e.g.,

prostaglandins, leukotrienes, bradykinin, platelet-activating factor,substance P, etc.) released into the tissues surrounding the apical

area of the tooth.

• Pain fibers are directly stimulated or sensitized, and an increase in

vascular dilation and permeability results in edema and increased

interstitial tissue pressure.

Glucocorticosteroids reduce the acute inflammatory response by

• suppressing vasodilation,

• migration of polymorphonuclear (PMN) leukocytes

• phagocytosis

• inhibiting formation of arachidonic acid from neutrophil andmacrophage cell membrane phospholipids, thus blocking the COXand lipoxygenase pathways and respective synthesis of PGs andleukotrienes.

• Wolfson and Blitzer stated that hydrocortisone as an intracanalmedication resulted in reduction and elimination of inflammatoryreactions in periapical tissues.

• Ehrmann reported that ledermix (triamcinolone dimethylchlorotetracycline in a water soluble cream) stopped the painassociated with pericementitis.

• Langeland et al demonstrated that Ledermix as an intracanalmedication eliminated post-endodontic treatment pain within minutesto a few hours after placement.

• Chance et al compared the effect of intracanal meticortelone(prednisolone acetate 2.5%) vs. saline on post-treatment pain in adouble-blind study.

• The results indicated that the corticosteroid was effective significantly inreducing the incidence of pain in vital teeth when compared to saline.

• However, there was no difference between the two solutions in necroticteeth.

Ledermix• Ledermix is a paste that combines 1% triamcinolone acitonide (a

corticosteroid) and demethylchlorotetracycline(demeclocycline, a tetracycline analog).

• Used as a pulp capping agent, and as a root canal medicamentfor both vital and necrotic cases because of its anti-inflammatoryand antimicrobial properties.

• Both components of Ledermix can diffuse into dentin andthrough the apical foramen.

• The concentration of demeclocycline in the root canal wasshown to be much higher than is required to inhibit bacteria;however, this activity tends to decrease considerably by 7days.

• It may be combined with calcium hydroxide at a 50:50 ratio toenhance its antimicrobial efficacy, but this tends to reduce thediffusion of its main ingredients.

• Efficacious against pulpal pain in some earlier studies, possiblybecause of its corticosteroid content; however, pulp capping forpainful cases with pulp exposures is not currently recommendedbecause of its low long-term prognosis.

• In a randomized clinical trial to compare Ledermix withformocresol and calcium hydroxide used as interappointmentmedicaments on postinstrumentation flare-ups, no differenceswere detected among the three medicaments.

Intracanal Administration

• In 50 consecutive patients requiring nonsurgical root canal treatment of

vital teeth, one investigator alternately placed a dexamethasone

solution or saline placebo as intracanal medicaments after the root

canals had been cleaned and shaped.

Pretreatment pain ratings were collected, and at 24, 48, and 72 hours after

treatment.

Results indicated a significant reduction in pain at 24 hours but no,

significant difference at 48 and 72 hours.

Intracanal steroids appear to have significant effects for reducing

postoperative pain.

Moskow A, et al: Intracanal use of a corticosteroid solution

as an endodontic anodyne. Oral Surg Oral Med Oral Pathol

58:600, 1984.

Systemic Administration

In one double-blind, randomized, placebo-controlled study,

dexamethasone (4 mg/ml) or saline was injected intramuscularly at the

conclusion of a single-visit endodontic appointment or at the first visit of

a multivisit procedure.

Results indicated that the steroid significantly reduced the incidence

and severity of pain at 4 hours when compared with the placebo.

Pain was reduced at 24 hours, but it was not statistically significant, and

no difference in incidence or severity was seen at 48 hours

106 patients with irreversible pulpitis and acute periradicular

periodontitis were given an intraoral intramuscular injection of

dexamethasone at different doses, either on completion of a single-visit

endodontic treatment or after the first visit of a multivisit procedure.

Systemic administration of dexamethasone was shown to significantly

reduce the severity of pain at 4 and 8 hours, with an optimum dose

between 0.07 and 0.09 mg/kg.

No significant reduction in the severity of pain was noted at 24, 48, and

72 hours, and no overall effect was seen on the incidence of pain.

Another study compared the effect on intraligamentary injection of

methylprednisolone, mepivacaine, or placebo in preventing

posttreatment endodontic pain.

The results showed methylprednisolone significantly reduced

postoperative pain within a 24-hour follow-up period

In a double-blind placebo controlled study, patients with irreversible

pulpitis were given 4 mg of dexamethasone or placebo by means of a

supraperiosteal injection at the apex of the treated tooth following

pulpectomy.

This is an injection technique that most clinicians would be familiar with (as

opposed to intramuscular injection).

Posttreatment pain was significantly reduced in the steroid group during

the first 24 hours. There was no difference at 48 hours.

Collectively, these studies on systemic steroid administration indicate that

corticosteroids reduce the severity of posttreatment endodontic pain

compared with placebo treatment.

‘However, given the relative safety/efficacy relationship between steroids

and NSAIDs, most investigators choose an NSAID as the drug of first choice

for postoperative pain control.’

PART III

ANTIBIOTICS

Endodontics in the adult patient: the role of antibioticsL.P. Longmana, A.J. Preston, M.V. Martin, N.H.F. Wilson

Journal of Dentistry 28 (2000) 539–548

• The first reported local use of an antibiotic in endodontics was in1951 when Grossman used a polyantibiotic paste known as PBSC (amixture of penicillin, bacitracin, streptomycin, and caprylatesodium).

• PBSC contained penicillin to target Gram-positive organisms,bacitracin for penicillin resistant strains, streptomycin for Gram-negative organisms, and caprylate sodium to target yeasts - thesecomponents were suspended in a silicone vehicle.

• Later, Nystatin replaced caprylate sodium as an antifungal agent ina similar medicament, known as PBSN.

Bacteria are involved in endodontic cases with apical periodontitis, the

incidence of a posttreatment infection or flare-up is a concern to clinicians

providing endodontic treatment.

Use of antibiotics is controversial for several reasons.

1. overprescribing antibiotics, especially when these drugs are notindicated, has led to increased bacterial resistance and patient

sensitization.

2. antibiotics have been mistakenly prescribed for patients with

severe pain who have a vital tooth (i.e., when bacteria are

unlikely to be a causative factor in periradicular pain).

3. even when bacteria are likely to be present, data fromcontrolled clinical trials provide little or no support for the hypothesis

that antibiotics reduce pain.

• Antibiotic usage in endodontic therapy is almost totally empirical

driven by opinion and medico-legal concerns.

• The rational use of antibiotics is based upon three variables:

- a defined indication

- the appropriateness of the antibiotic, and - the adverse effects associated with the drug.

Antibiotics are prescribed in endodontic practice for either therapeutic

or prophylactic purposes.

Penicillins

• Penicillins have a short half-life, limited to about 1 hour.

• Amoxicillin is generally considered the penicillin of first choicebecause of its somewhat better absorption from the gut.

• Also used for periodontal abscesses, periapical abscesses,pericoronitis, acute suppurative pulpitis, necrotizing ulcerativegingivitis, oral cellulitis etc

• Less active against Shigella and H.influenza

• Majority of cases resolve with 250-500 mg TDS given for 5 days.

Cephalosporins

• Obtained from fungus Cephalosporium.

4 generations-

First generation- high activity against gram +ve, weak against gram –ve

• Cefazolin, cephalexin, cephradine, cefadroxil

Second generation- more active against gram -ve

• Cefaclor, cefuroxime

Third generation- highly augmented activity against gram –veenterobacteriaceae, some inhibit pseudomonas, less active on grampositive cocci and anaerobes

• Cefixime, cefdinir, cefotaxime, ceftizoxime, cefoperazone

Fourth generation- highly resistant to B-lactamases, active against manybacteria resistant to earlier drugs. P.aeruginosa and staph.aureus alsoinhibited.

• Cefepime, cefpirome

• All bactericidal, same mechanism of action as penicillin, i.e inhibition ofbacterial cell wall synthesis.

Metronidazole

• Metronidazole (Flagyl®) is also considered a bactericidal drugbecause of its fast killing time.

• It attacks the bacteria’s DNA and works against obligateanaerobes but not against facultative bacteria or aerobes.

• Metronidazole is often used in combination with anotherantibiotic, usually amoxicillin, to combat the stomach ulcer–causing Helicobacter pylori.

• Combination helps in severe dental infections

• Metronidazole shares properties with disulfiram (Antabuse®), adrug used to help alcoholics avoid alcohol by inducing violentvomiting.

Patients taking metronidazole should be cautioned about notusing alcohol for the time they are taking the drug plus 1 dayfollowing to allow the drug to be eliminated from their system.

• The half-life of metronidazole is in the 8- to 10-hour range. Sideeffects include an unpleasant, metallic taste and browndiscoloration of the urine, effects that are dose related.

Macrolides

• Erythromycins kill bacteria by slowing the manufacture of bacterialprotein but do not alter the rate of human protein synthesis.

• Alternative to penicillin

• Act by inhibiting bacterial protein synthesis

• Narrow spectrum, mostly gram +ve, few gram –ve, highly activeagainst Str.pyogens, Str.pneumonia, N.gonorrhoeae etc

• Acid labile, enteric coated tablets to protect it from gastric acid,crosses serous membranes and placenta but not blood brainbarrier.

• Plasma t1/2 is 1.5 hours

• Dose- 250-500 mg 6 hourly

• Adverse effects- GIT- diarrhoea, epigastric pain, high doses-hearing impairment, hypersensitivity

• Second choice drug to penicillins in dental infections, valuable topatients allergic to penicillins

Azithromycin- expanded spectrum, better tolerability, improvedpharmacokinetics.

• More active than other macrolides against H.influenza,Peptostreptococcus, Clostridia

• Less active against gram +ve cocci

• Acid stability, rapid oral absorption, marked tissue distribution andintracellular penetration.

• Absorption decreased by food

• Dose- azithral 500 mg once daily 1 hour before or 2 hours afterfood for 3 days is sufficient for most infections

• Mild gastric upset, abdominal pain, headache and dizziness

Clindamycin (Cleocin®)

often indicated in endodontic infections.

• It is rapidly and completely absorbed and has a good spectrum ofkilling oral pathogens, including many anaerobes.

• It was, however, the first antibiotic to be associated with causingpseudomembranous colitis, a life-threatening condition in whichlarge patches of gut slough epithelium because of toxins fromovergrowth of the nonsusceptible organism Clostridium difficile.

• The average half-life of clindamycin is about 3 hours.

Tetracyclines

• Tetracyclines, including tetracycline-HCl, minocycline,demeclocycline and doxycycline, are a group of broad-spectrumantibiotics that are effective against a wide range ofmicroorganisms.

• Bacteriostatic in nature.

• This property may be advantageous because, in the absence ofbacterial cell lysis, antigenic byproducts such as endotoxin are notreleased.

• Inhibition of mammalian collagenases, which prevent tissuebreakdown.

• Inhibition of clastic cells, which results in anti-resorptive activity

• In endodontics, tetracyclines have been used to remove the smear layer from instrumented root canal walls, for irrigation of retrograde cavities during periapical surgical procedures, and as anintracanal medicament.

• Barkhordar et al. evaluated the effect of doxycycline-HCl on thesmear layer of instrumented root canal walls. They showed thatdoxycycline-HCl eliminated smear layer in a concentrationdependent manner with 100 mg/ml doxycycline being moreeffective than lower concentrations.

• In another investigation, Haznedaroglu and Ersev used scanningelectron microscopy (SEM) to assess the effect of tetracycline-HCl asan endodontic irrigant in removing the smear layer. They reportedthat tetracycline was as effective as citric acid in removing thesmear layer.

• Barkhordar and Russell evaluated the effect of doxycycline on theapical penetration of dye through the margins of retrograde fillings.The teeth with retrograde IRM or amalgam fillings placedsubsequent to doxycycline irrigation had significantly less dyepenetration than those that were not irrigated with doxycycline.

• Carson et al. used an agar diffusion test to compare theantimicrobial activities of 6% and 3% sodium hypochlorite(NaOCl) solutions, 2% and 0.12% chlorhexidine gluconate (CHX),and 0.01% and 0.005% doxycycline (Doxy) on fourmicroorganisms associated with endodontic infections of teeththat had not been previously treated, namelyPeptostreptococcus micros, Prevotella intermedia,Streptococcus sanguis, and Lactobacillus acidophilus.

For the first three of these organisms, the general order ofantimicrobial effectiveness was

0.01% Doxy >0.005% Doxy >6% NaOCl >3% NaOCl >2% CHX > 0.12%CHX

However, for L. acidophilus, the order of effectiveness was

6% NaOCl >3% NaOCl >2% CHX > 0.01% Doxy >0.005% Doxy >0.12%CHX.

• Pinheiro et al. evaluated the antibiotic susceptibility ofEnterococcus faecalis isolates from canals of root-filledteeth with periapical lesions.

• The antibiotics were benzylpenicillin, amoxicillin, amoxicillinwith clavulanic acid, erythromycin, azithromycin,vancomycin, chloramphenicol, tetracycline, doxycycline,ciprofloxacin and moxifloxacin.

• The vast majority (85.7%) of the isolates were susceptible totetracycline and doxycycline.

• Chai et al. investigated the antimicrobial efficacy of six groups of

antibiotics (ampicillin co-trimoxazole, erythromycin,

oxytetracycline, vancomycin, and vancomycin followed b

gentamicin) and calcium hydroxide agains Enterococcus

faecalis biofilm in a membrane filter model.

• They concluded that erythromycin, oxytetracycline and Ca

(OH)2 were 100% effective in eliminating the E. faecalis biofilm,

whereas ampicillin, co-trimoxazole, vancomycin, and

vancomycin followed by gentamicin were ineffective.

Based on the hypotheses that microorganisms can reach the apicalarea of recently replanted teeth from the oral cavity (or fromcontaminated root surfaces during the extra-oral time), and thattetracyclines can potentially inhibit this route of bacterialcontamination, Cvek et al. developed a protocol for the topicaltreatment of exposed roots with doxycycline before replantation.

• Aim was to eliminate the microorganisms from the root surface ofan avulsed tooth via direct local application of the antibiotic inorder to decrease the frequency and severity of the inflammatoryresponse.

• Topical doxycycline significantly increased the chances ofsuccessful pulp revascularization and decreased the number ofmicroorganisms that could be isolated from the root canals.

• They also reported a decreased frequency of ankylosis, externalreplacement resorption and external inflammatory resorption.

• The beneficial effect of soaking a tooth in doxycycline has alsobeen confirmed by Yanpiset and Trope

Substantivity of tetracyclines

• Tetracyclines readily attach to dentine and are subsequentlyreleased without losing their antibacterial activity.

• This property creates a reservoir of active antibacterial agent, whichis then released from the dentine surface in a slow and sustainedmanner.

• Stabholz et al. compared the antibacterial substantivity of twoconcentrations of tetracyclineHCl (50 mg/ml, 10 mg/ml) and 0.12%chlorhexidine.

• Their findings showed that both concentrations of tetracyclinedemonstrated residual antibacterial activity and the antibacterialsubstantivity of the three solutions in descending order was: 50mg/ml tetracycline >10 mg/ml tetracycline > 0.12% CHX.

• Abbott et al. demonstrated that tetracyclines form a strong reversible bond with the dental hard tissues and that they exhibit slow release over an extended period of time up to at least 12 weeks.

BioPure (MTAD)

• Bio Pure (Dentsply, Tulsa Dental, Tulsa, OK, USA), otherwise known asMTAD (mixture of tetracycline, acid and detergent), is a relativelynew root canal irrigant which was introduced by Torabinejad andJohnson in 2003.

• This solution contains 3% doxycycline (at a concentration of 3%),citric acid (4.25%) and a detergent, Polysorbate 80 (0.5%).

• Several studies have evaluated the effectiveness of MTAD fordisinfection of root canals.

• Torabinejad et al have shown that MTAD is able to remove thesmear layer and is effective against E. faecalis.

• Shabahang et al. cleaned and shaped root canals of extractedhuman teeth and exposed them to human saliva. They thencompared the antibacterial efficacy of a combination of 1.3%NaOCl as a root canal irrigant and MTAD as a final rinse with that of5.25% NaOCl. Their findings showed that using MTAD in addition to1.3% NaOCl was more effective at disinfecting root canals thanusing 5.25% NaOCl alone.

• Tay et al. found that when MTAD was applied to 1.3% NaOCl-irrigated dentine, its antimicrobial substantivity was reduced. Theyattributed this to the oxidation of MTAD by NaOCl in a mannersimilar to the peroxidation of tetracycline by reactive oxygenspecies.

• Shabahang and Torabinejad compared the antibacterial effectsof MTAD with those of NaOCl and EDTA by using standard in vitromicrobiological techniques and they reported that MTAD wassignificantly more effective against E. faecalis.

• Kho and Baumgartner compared the antimicrobial efficacy of 1.3%NaOCl /MTAD against E faecalis with that of the combinedalternate use of 5.25% NaOCl and 15% EDTA for root canalirrigation.

• This investigation showed consistent disinfection of infected rootcanals when a combination of 5.25% NaOCl and 15% EDTA wasused.

• However, the combination of 1.3% NaOCl/ MTAD left nearly 50% ofthe canals contaminated with E. faecalis.

• Mohammadi and Yazdizadeh evaluated the substantivity of NaOCl,CHX and MTAD substantivity of MTAD was significantly greater thanCHX and NaOCl.

Tetraclean

• Tetraclean (Ogna Laboratori Farmaceutici, Muggiò(Mi),Italy), like MTAD, is a mixture of an antibiotic, an acid and adetergent. However, the concentration of the antibiotic,doxycycline (50 mg/ml), and the type of detergent(polypropylene glycol) differ from those of MTAD.

• Giardino et al.compared the surface tension of 17% EDTA,Cetrexidin, Smear Clear, 5.25% NaOCl, MTAD andTetraclean.

• The NaOCl and EDTA had the highest surface tension,whereas Cetrexedin and Tetraclean had the lowest values.

• In another study, they compared the antimicrobial efficacyof 5.25% NaOCl, MTAD, and Tetraclean against an E.faecalis biofilm generated on cellulose nitrate membranefilters.

• Only the NaOCl could disaggregate and remove the biofilmat every time interval tested although treatment withTetraclean caused a high degree of biofilm disaggregationat each time interval when compared with MTAD.

Combination of Ledermix and calcium hydroxide

• The combination of Ledermix paste with calcium hydroxide wasadvocated by Schroeder initially for the treatment of necroticteeth with incomplete root formation.

• A 50:50 mixture of Ledermix paste and calcium hydroxide has alsobeen advocated as an intracanal dressing in cases of infectedroot canals.

• It has been shown that the 50:50 mixture results in slower releaseand diffusion of the active components of Ledermix paste, whichmakes the medicament last longer in the canal.

• This in turn helps to maintain the sterility of the canal for longer andalso maintains a higher concentration of all components within thecanal.

• Seow showed that for Streptococcus sanguis and S. aureus, the

addition of only 25% by volume of Calyxl (a calcium hydroxide in

saline paste) (Otto and Co. Frankfurt, Germany) to Ledermix

converted the zone of complete inhibition originally seen in

Ledermix to one of only partial inhibition.

• Chu et al. compared the efficacy of disinfection of root canals

with periapical radiolucencies when treated with either

antibiotics/ steroid medicaments (Ledermix or Septomixine) or acalcium hydroxide paste (Calasept, Speiko, Darmstadt,

Germany).

• Their finding showed that in the Ledermix group, 38 strains of

bacteria were recovered. The Septomixine group had 25 strains,

and the Calasept group had 25 strains.

• Gram-positive facultative anaerobic cocci (includingstaphylococci and streptococci) were more prevalent than the

gram-negative obligate anaerobic rods after treatment in all

three groups.

Septomixine Forte• Septomixine Forte (Septodont, Saint- Maur, France) contains two

antibiotics: Neomycin and Polymixin B sulfate.

• Tang et al. who demonstrated that a routine one-week

application of Septomixine Forte was not effective in inhibiting

residual intracanal bacterial growth between appointments.

• In addition, although the anti-inflammatory (corticosteroid) agent,

dexamethasone (at a concentration of 0.05%), is clinically

effective, triamcinolone is considered to have less systemic side

effects.

Triple antibiotic paste• The infection of the root canal system is considered to be a

polymicrobial infection, consisting of both aerobic an anaerobic

bacteria.

• Because of the complexity of the root canal infection, it is unlikelythat any single antibiotic could result in effective sterilization of the

canal.

• More likely a combination would be needed to address the diverse

flora encountered.

• A combination of antibiotics would also decrease the likelihood of

the development of resistant bacterial strains.

• The combination that appears to be most effective consists of

metronidazole ciprofloxacin, and minocycline.

• Sato et al. evaluated the potential of a mixture of ciprofloxacin,metronidazole and minocycline to kill bacteria in the deep layers

of root canal dentine in situ.

• Results showed that no bacteria were recovered from the

infected dentine of the root canal wall 24 h after application of

the drug combination, except in one case in which a few

bacteria were recovered.

• Hoshino et al. investigated the antibacterial effect of a mixture of

ciprofloxacin, metronidazole, and minocycline with and without

the addition of rifampicin, on bacteria from infected dentine of

root canal walls.

• The efficacy was also determined against bacteria of carious

dentine and infected pulps, which may the precursory bacteria of

infected root dentine.

• They found that alone, none of the drugs resulted in complete

elimination of bacteria. However, in combination; these drugs

were able to consistently sterilize all samples.

• Iwaya et al. reported a necrotic immature mandibular second

premolar with periapical involvement and sinus tract.

• Instead of the standard root canal treatment protocol and

apexification, antimicrobial agents (metronidazole andciprofloxacin) were used in the canal, after which the canal was

left empty.

• Radiographic examination showed the start of apical closure five

months after the completion of the antimicrobial protocol.

• Thickening of the canal wall and complete apical closure was

confirmed 30 months after the treatment, indicating therevascularization potential of a young permanent tooth pulp into a

bacteria-free root canal space.

Takushige et al. evaluated the efficacy of polyantibiotic paste

consisted of metronidazole, ciprofloxacin, and minocycline, on the

clinical outcome of so-called “Lesion Sterilization and Tissue Repair,”

(LSTR) therapy in primary teeth with periradicular lesions.

Results showed that in all cases, clinical symptoms such as gingival

swelling, sinus tracts, induced dull pain, spontaneous dull pain, and

pain on biting disappeared after treatment, although in four cases

clinical signs and symptoms were finally resolved only after

retreatment using the same procedures.

Thus, gingival abscesses and fistulae, if present, disappeared after a

few days.

Endodontics and therapeutic antibiotics

a. Adjunct to operative treatment

In healthy patients endodontic infections can be treated solely by the

early establishment of drainage and removal of the cause of the

problem, for example, debridement of the infected root canal system or

surgical removal of extraradicular infection.

1. In acute dentoalveolar infections antibiotics may be indicated

because there is a diffuse spreading infection or evidence of systemic

involvement.

Antibiotics are not an alternative to dental intervention; they are an

adjunct to it

2. In medically compromised patients host-defence mechanisms may

be thought to be inadequate the operative treatment of acute

dentoalveolar infections may sometimes be supplemented with

therapeutic antibiotics.

3. A patient’s resistance to infection may be reduced by medication

(e.g. corticosteroids, antimetabolites), systemic disease such as

leukaemia, HIV or poorly controlled Type I diabetes

b. Contingency treatment

On rare occasions, it may not be possible to obtain drainage or remove the

cause of infection by operative treatment.

There is no evidence that the use of antibiotics in this situation is of any

benefit; definitive treatment is required.

The principle purposes of prescribing are to: limit the local spread of

infection, treat systemic infection and bring about symptomatic relief

Examples1. Patient has cellulitis associated with an acute periapical infection,originating from a tooth that has a well-retained intraradicular post

drainage of infection cannot be achieved by the incision of the soft tissues

and intracanal instrumentation.

2. Failure to achieve anaesthesia for the extraction of an abscessed tooth

can necessitate a prescription for antimicrobials in acute periapical

infection.

3. When an anxious or phobic patient presents with acute periapical

infection, and cannot accept treatment without the assistance of sedation.

4. Uncooperative patients with physical or learning disabilities may not be

amenable to immediate operative treatment.

c. Antibiotics at obturation

• Anecdotal evidence cites the use of systemic antibiotics at the time of

obturation, when pus remains in the root canal system, despite

repeated inter-appointment dressings.

• There is no scientific evidence that this practice is beneficial.

• Antibiotic therapy has also been suggested for one visit endodontics,

undertaken when there is infection present in the root canal.

• There is no evidence that antibiotics are efficacious in this situation,

the root canal is dressed rather than obturated.

d. Antibiotics for perio-endo lesions

• There are no authoritative studies to support the use of systemic

antibiotics in the management of “perio-endo” lesions.

• The treatment of combined lesions is based upon the basic principles of

endodontic and periodontal therapy, and is dependent upon the

aetiology of the condition.

• Endodontic treatment usually involves root canal treatment, or less

commonly root resection or repair of a perforation.

• Systemic antibiotics are not a substitute for effective mechanical

debridement of the root canal system and root surface.

Which antibiotic?

• At least 70 different bacterial species have been isolated from root

canals and synergistic relationships are thought to exist between them.

• Certain bacteria seem to occur in pairs and these include: Bacteroides

vulgaris and Fusobacterium necrophorum; Peptostreptococcus spp. and

Prevotella spp; P. micros and P. melaninogenica; Prevotella and

Eubacterium ssp.

• The majority of symptomatic, infected root canals contain anaerobes; it

has been proposed that the larger the number of bacterial species

present the more symptoms will be experienced.

• It has also been demonstrated that intracanal flora from teeth with failed

endodontic therapy differs markedly from the root canals of untreated

teeth.

• Empirical prescribing of anti-microbials as part of endodontic management

is problematic, given the diversity of potential pathogens and their differing

drug sensitivities.

• Culture and sensitivity testing is not routinely recommended for endodontic

procedures

The most commonly prescribed antibiotics are erythromycin,

amoxicillin, penicillin and metronidazole

Some anaerobes isolated from the endodontic lesions are resistant to

penicillin and therefore serious infections are treated empirically with a

combination of metronidazole and a penicillin

Duration of antibiotic therapy required for acute dentoalveolar

infections has never been defined precisely.

• Tendency in dental practice to use courses of antibiotics 3–5

days for the treatment of infection .

• There is increasing awareness of the value of the commensalflora in the host’s defence system both in the oral cavity and in

other body sites.

• Prolonged courses of antibiotics destroy the commensal flora

and abolish colonisation resistance.

• The prescribing of systemic antibiotics must therefore be

justifiable.

Few studies on the use of antimicrobials have supported the view that it is

not necessary to complete the course of antibiotics.

• One study has advocated that a two-dose administration of an anti-

microbial agent is as efficacious as a 5 day course in the management

of acute dentoalveolar infections; this was not a double blind placebo

controlled trial.

• Two separate investigations, compared three anti-microbial agents, and

showed that the majority of patients were asymptomatic after 2 days

therapy.

• Majority of patients 2 or 3 days of oral antibiotics, in doses

recommended by the BNF, will suffice for acute dentoalveolar

infections.

• Alternatively, a two-dose regime of 3 g amoxicillin can be used in

patients who are not allergic to penicillin.

• Fazakerley MW, McGowan P, Hardy P, et al.

A comparative study of cephradine, amoxycillin and phenoxymethylpenicillin in the

treatment of acute dentoalveolar infections. British Dental Journal1993;174:359–63.

• Martin MV, Longman LP, Hill JB, et al.

Acute alveolar infections: an investigation of the duration of antibiotic therapy.

British Dental Journal 1997;183:135–7.

Topical antibiotics and endodontics

The limited spectrum of activity of the antibiotic preparations available, the

potential for bacterial resistance, the risk of drug hypersensitivity and the

potential to mask certain aetiological factors limit their

usefulness.

PulpitisThere is no convincing evidence to justify the use of Ledermix (Lederle Lab

Gosport, Hants, UK) to sedate the pulp prior to definitive treatment.

There is no indication for the use of topical antibiotics in the treatment of

pulpitis

Pulp capping

Calcium hydroxide- most popular agent for both direct and indirect pulp

capping.

Anti-bacterial action, stimulates secondary dentine formation.

Ledermix is the most commonly used alternative to calcium hydroxide and

contains a steroid (triamcinolone) and an antibiotic

(demethylchlortetracycline).

Ledermix is a topical preparation, available as either a paste or a cement.

Root canal therapy

• The most important elements of root canal preparation are effective

access and aseptic biomechanical preparation.

• Early investigations evaluated two antibiotic-containing preparations:

Grossman’s polyantibiotic paste, which contains penicillin, bacitracin or

chloramphenicol and streptomycin

• A mixture of neomycin, polymixin and nystatin.

• Both of these had some efficacy as intracanal medicaments.

Perio-endo lesions

Topical antibiotics, such as the tetracyclines or metronidazole, may be

applied by some clinicians, to the periodontal defect as an adjunct to

root planing.

Flare-ups

• Topical antibiotics have been used to reduce post-operative pain and

swelling following root canal preparation; this is often referred to as a

flare- up.

• In the treatment of infected root canals where there is often a need to

carry out the treatment over more than one visit, with an antibacterial

intracanal medicament placed between visits; the intracanal

medicament that is commonly used is calcium hydroxide.

Tooth avulsion

Ledermix has been used as an intracanal medicament in the management

of tooth avulsion, but it is not clear whether the beneficial effect is due to

the action of the steroid or the antibiotic.

Antibiotic prophylaxis and endodontics

Healthy patient

There is no evidence that antibiotic prophylaxis, given to healthy patients

undergoing surgical endodontics is efficacious.

Despite this, antibiotics are sometimes prescribed prophylactically to

prevent infection at the site of surgery.

• Ideally, antibiotics should be given prior to reimplantation.

• Often not possible and could necessitate a delay in tooth replacement,

adversely affecting the prognosis.

• Re-implantation is therefore, one of the rare situations when

chemoprophylaxis may have to be given post-operatively, assuming

there are no medical contraindications

• The re-implantation of teeth should not be considered if the procedure

places the patient at risk from haematogenous spread of infection.

• An example would be a patient with acute leukaemia or HIV infection.

• Once the decision to re-implant has been made, the timing of antibiotic

prophylaxis is critical if serious sequelae are to be avoided.

• It would be logical to administer antibiotic prophylaxis prior to

implantation, to ensure adequate antibiotic serum levels at the time of

operation.

Prophylaxis for the medically compromised

• Patients who are susceptible to IE, or osteoradionecrosis, and those who

have endoprostheses

• Second category is patients with impaired host-defence mechanisms

• These patients are potentially at risk from opportunistic infections.

• Patients who are receiving renal dialysis or have had organ transplants

are included in this group.

Infective endocarditis

• Dental procedures that reliably cause a transient bacteraemia could

result in IE.

• The use of chemoprophylaxis is well established and necessary

medico-legally for surgical endodontics, in patients at risk from IE.

• It is unrealistic and undesirable to give systemic prophylaxis for every

endodontic procedure that may occasionally cause bleeding or a

bacteraemia, including the placement of rubber dam.

• Simple pre-operative mouthrinsing and disinfection of the gingival tissues

with chlorhexidine reduces the magnitude of a bacteraemia

• Elective endodontic procedures should be avoided wherever possible, in

patients who have a damaged endocardium and concomitant gingival

inflammation.

Radiotherapy

• After radiotherapy, there is a diminution of the vascular supply in the

irradiated area especially in the mandible.

• This is a progressive risk that does not reduce with time

• Risk of infection is much greater with exodontia than root canal therapy,

consequently non-surgical endodontics is the preferred treatment for a

necrotic pulp in irradiated patients.

Prosthetic implants• The prophylactic antibiotics should target the putative pathogens,

staphylococci and to a lesser extent oral streptococci

• Patients with cardiac pacemakers, intraocular lenses, breast implants,

penile implants and prosthetic vascular grafts are not considered to be

especially susceptible to infection from dental bacteraemias.

• The use of antibiotic prophylaxis in patients with intravascular access

devices and CSF shunts is contentious.

• Neurosurgeons are more likely to recommend prophylaxis for patients

with ventriculoatrial shunts, than for the more commonly used

ventriculoperitoneal shunts

Immunocompromised patients

• Patients who are immunocompromised, including patients who

have organ transplants or indwelling intraperitoneal catheters,

do not require antibiotic prophylaxis for dental treatment.

• It can be concluded, therefore, that endodontic treatment

does not require antibiotic prophylaxis.

Systemic antibiotics should normally only be prescribed to treat dental

infections on the basis of a defined need.

• The potential benefits of antibiotic administration should therefore

outweigh the possible disadvantages associated with their use.

• A dentist who prescribes an antibiotic for a questionable indication

may be seen as placing a patient at risk from potential adverse effects

of drugs.

PART IV

LOCAL ANESTHETICS

Local anesthetics (CLASSIFICATION): Injectable

a. Short duration (30 minutes of pulpal anesthesia)-

Procaine

b. Intermediate duration (60 minutes of pulpal anesthesia)-

Lignocaine, prilocaine

c. Long duration (over 90 minutes of pulpal anesthesia)-

Tetracaine, bupivacaine, ropivacaine, dibucaine

Surface anestheticSoluble

Cocaine

Lignocaine

Tetracaine

Benoxinate

Insoluble

Benzocaine

Butylaminobenzoate ( Butamben)

Lignocaine (lidocaine)

• Most widely used

• Surface application and injectable

• Blocks nerve conduction in 3 mins whereas procaine may takeupto 15 mins

• Overdose causes muscle twitching, convulsions, cardiacarrhythmias, fall in BP, coma, respiratory arrests

• Dental use- 2% with or without adrenaline 1:80,000

Mepivacaine

• Available in formulation containing levonordefrin, an adrenergic agonist, 1:20000 conc.

Articaine

• 4% solution containing 1:100,000 and 1:200,000 epinephrine

• Amide anesthetic that contains thiophene ring and ester linkage.

• Maximum dose is 7 catridges compared to 13 catridges of 2% lidocaine

• Potential to cause methemoglobinemia and neuropathies

Bupivacaine and etidocaine

• Prolonged pain control, long acting

• Etidocaine withdrawn from market recently

• Bupivacaine exhibits prolonged soft tissue numbness or lip sign

• Slower onset than lidocaine but twice the duration of action (around 4 hours) in mandible

Ropivacaine

• Structural homologue of bupivacaine that appears to have a lower potential for CNS and CV toxic effects.

• Cardiac patients (e.g., those with unstable angina pectoris, history of

myocardial infarction or stroke within the past 6 months, severe

hypertension, uncontrolled congestive heart failure, or heart transplant)

should not receive a local anesthetic containing a vasoconstrictor and

should consult their physicians before undergoing endodontic treatment.

• Local anesthetics may interact with a patient’s medications

• Thorough review of the medical history is an absolute requirement.

• Potential drug-drug interactions occur primarily with the vasoconstrictors

in local anesthetic formulations.

• Judicious use of local anesthetic solutions without vasoconstrictors (e.g.,

3% mepivacaine) is a reasonable alternative for adult patients.

PART V

ANTIMICROBIAL AGENTS

Antimicrobial agents may be disinfectants and antiseptics that

destroy or inhibit the growth of microorganisms and thereby prevent

infection by pathogenic or potentially pathogenic microorganisms.Disinfectants are used on inanimate objects or surfaces, whilst

antiseptics are used on living tissues.

McDonnell G, Russell AD. Antiseptics and disinfectants:

activity, action, and resistance. Clinical Microbiology

Reviews 1999;12:147–79.

Conventional antiseptics 1. Alcohols – Ethyl alcohol, Isopropylalcohol

2. Phenolic Compounds – Camphorated phenol,

Monochlorophenol, Thymol, Cresol, Creosote

3. Heavy Metal Salts

4. Cationic Detergents – Quarternary ammonium compounds

5. Halogens – Hypochlorite, Chloramine T, Iodine, Iodophores

ChemotherapeuticsAntibiotics

Classification of antimicrobial agents.

• The mechanism of action of antimicrobial agents is varied as theyhave multiple sites of action except for antibiotics, which havevery specific sites of action.

• The nature of the organism, antimicrobial agent and theconcentration determine the response of the microorganisms tothe antimicrobials.

• The cell wall, cytoplasmic membrane and ribosomes ofvegetative cells, the coat and cortex of bacterial spores,envelope and capsid of viruses and proteins (structural proteins,enzymes), nucleic acids and polysaccharides are some of thesites of action of antimicrobial agents.

• These antimicrobial actions eventually result in the loss ofimportant cell functions like protein synthesis and metabolism,replication, transcription and destruction of cell membranes withleakage of cell contents

Mechanism of action

• The two most important features which determine the efficacy ofantimicrobial agents are the killing and the cleaning potential ofthe agent.

• The antimicrobial activity may vary from inhibition of metabolismto destruction of the microorganisms.

• The specific target of action of antimicrobials is difficult toelucidate as antimicrobial agents act on multiple cellcomponents, resulting in both primary and secondary effects,which in turn is hard to distinguish.

Sodium hypochlorite

• Concentrations ranging from 0.5 % to 5.25 %.

• This is due to its antimicrobial and dissolving effects onnecrotic tissues (Sodium hypochlorite is a reducing agentwith 5 % of available chlorine

• lubricant, antiseptic agent, bleach and also dissolves tissue

• Antibactericidal ability of NaOCl results from the formationof hypochlorous acid (HOCl) when in contact with organicdebris.

• HOCl exerts its effect by the oxidation of sulphydryl groupswithin bacterial enzyme systems, thereby disrupting themetabolism of the microorganism.

• Cvek M et al. in his study reported that flushing with sterilesaline had poor antibacterial action (9 %) when comparedto sodium hypochlorite (25 %)

• The antibacterial action of NaOCl is time dependent.

• In an in vivo study, Ringel et al. noted that in root canals ofpermanent teeth 2.5 % NaOCl had a more powerfulantibacterial effect than 2 % chlorhexidine gluconate, asNaOCl was a powerful solvent for necrotic and organicmaterial.

• Naenni et al reported that only sodium hypochloriteshowed effective necrotic tissue dissolution among 10 %chlorhexidine, 3 % and 30 % hydrogen peroxide, 10 %peracetic acid, 5 % dichloroisocyanurate (NaDCC), and 10% citric acid.

Chlorhexidine gluconate

• Chlorhexidine (CHX) is widely used in periodontal andendodontic treatment as an irrigant.

• There are various mechanisms of antimicrobial action forchlorhexidine.

• It attaches electrostatically to negatively charged sites onbacteria and also to its cytoplasmic membrane.

• The leakage of intracellular material is due to the loss ofosmotic balance by CHX.

• The binding of CHX to hydroxyapatite and soft tissueschanges their electrical field to compete with the binding ofbacteria

Cetrexidin♦ (Vebas, San Giuliano, Milan, Italy)

Antiseptic agent that is being evaluated.

• It consists of 0.2 % chlorhexidine gluconate and 0.2 % cetrimide.

• Cetrimide (cetiltrimethyl ammonium bromide), is a quarterneryammonium compound and a cationic detergent that is effectiveagainst many Gram positive and Gram negative bacteria

• Study on the antimicrobial effectiveness and cytotoxicity of 4irrigant solutions, viz 5.25 % sodium hypochlorite (NaOCl), 0.2 %chlorhexidine gluconate plus 0.2 % cetrimide (CetrexidinR), 2 %chlorhexidine gluconate and 0.9 % sterile saline solutiondemonstrated that NaOCl should remain in the canal for asubstantial period so that it can act upon the bacterial cellslocated in the irregularities within the canal.

• In this study, 5 minutes following the irrigation process,chlorhexidine gluconate had a more rapid and stronger actionon E. faecalis than NaOCl.

Calcium hydroxide

• Calcium hydroxide is the most commonly used inter-appointment intracanal endodontic medicament.

• The publication of research data on the antibacterial action ofcalcium hydroxide in root canal treatment by De Moor & DeWitte led to increased use of calcium hydroxide in endodontictreatment.

• The antibacterial activity is a result of free hydroxyl radicalliberation and diffusion of hydroxyl radicals resulting in a highlyalkaline environment(pH 12.5).

• These hydroxyl ions penetrate the dentinal tubules and exerttheir effect.

• These hydroxyl radicals cause bacterial cell death by threepossible mechanisms.

• The first mechanism is by splitting DNA strands and therebypreventing DNA replication and disrupting cellular activity.

• Another method is by lipid peroxidation, which leads to thedestruction of both phospholipidand cell membrane, finallyresulting in loss of unsaturated fatty acids and massive destructionof membrane.

• The third mechanism is by protein denaturation and damage ofcell metabolism.

• Calcium hydroxide also shows increased activity againstanaerobes in comparison to paramonochlorophenol andformocresol.

Hydrogen peroxide

• The mechanism of action is by the reaction of superoxide ions,resulting in formation of hydroxyl radicals.

• Hydroxyl radicals are strong oxidants and they destroy membranelipids, DNA and other essential cell components.

• The oxidation of sulphydryl groups and double bonds in proteins,lipids, and surface membranes is responsible for the antimicrobialaction.

• In addition, the chloride in the bacteria may be oxidized tohypochlorite when myeloperoxidase enzyme is present.

• Hydrogen peroxide is an oxidizing solution and is usually used incombination with sodium hypochlorite for root canal irrigation.This results in two kinds of reactive oxygen species, the superoxideanion radical (O2 -) and the hydroxyl radical (OH-).

• Root canal irrigation with NaOCl and H2O2 induces both biologicaland mechanical effects.

• The biological effect of NaClO and H2O2 owes to tissue irritationdue to the chemical reactions of O2 - and OH-, while themechanical effect results from O2 bubbling.

• The effervescent action resulting in the release of nascent oxygenresults in the agitation of the root canal contents and the debris isflushed out.

• The tissue dissolution and antimicrobial effect are the main modeof action of the combined solutions.

• The final irrigation of the canal should be done with sodiumhypochlorite, as hydrogen peroxide can form gas in the presenceof necrotic debris and blood leading to pain.

Formocresol

• Formocresol consists of formalin and tricresol in a ratio of 1:1.

• Tricresol is a combination of o-, m-, and p-cresols.

• The application time and the concentration of formocresolinfluence the histologic reaction of vital pulp.

• Formocresol is a bactericidal agent and the mode of action is byfixation, which results in inhibition of bacteria.

• Formocresol causes zones of necrosis, fixation, and inflammation.

• It results in healing with inflammation and eventual replacementwith granulation tissue, bone or osteodentin in some cases.

Ferric sulphate

• 15.5 % used as a haemostatic agent in pulpotomy procedures.

• Landau and Johnsen in 1988

• The mode of action is by the formation of a ferric ion proteincomplex in the presence of blood resulting in the mechanicalsealing of cut vessels by the membrane of this complex.

• This ultimately leads to haemostasis

• Pulpal reaction of ferric sulfate and formocresol did not differfrom each other.

• Ferric sulphate is less toxic than formocresol and hence it may beconsidered as an alternative to formocresol for pulp therapy inprimary molars.

• As ferric sulphate causes only haemostasis, it is a moreappropriate pulpotomy agent and may be considered a goodreplacement for formocresol in pulpotomy.

Peracetic Acid• Peracetic acid has a wide spectrum of antimicrobial action at low

concentration, and within short duration.

• Aqueous solution of peracetic acid (PAA) has high microbicidalactivity against a broad range of microorganisms.

• Peracetic acid is an effective germicide against bacteria, yeast,and viruses at 0.03 % or lower concentration.

• Alasri et al. state that when peracetic acid and hydrogen peroxideare used together, they have a combined action on biofilms owingto the microbicidal activity of peracetic acid and detachment ofbiofilm by hydrogen peroxide.

• The sporicidal action decreased with storage due to hydrolysis ofperacetic acid, whereas it increased with high pH concentration.

• The drawback of high pH concentration is the carcinogenicpotential of 1 % peracetic acid, as it is a tumor promotor.

• The sporicidal action in a study by Jose-Luis and Aylin was asfollows: hypochlorite > peracetic acid > copper ascorbate >glutaraldehyde > peroxide > phenol > formaldehyde.

• Ageing, pH, and temperature were found to greatly influence theorder of the efficacy of these agents

• According to Naenni N et al., among the commonly usedendodontic irrigants like 10 % chlorhexidine, 3 % and 30 %hydrogen peroxide, 10 % peracetic acid, 5 %dichloroisocyanurate (NaDCC), and 10 % citric acid, all hadlower tissue dissolution capacity in comparison to 1 % (wt/vol)sodium hypochlorite (NaOCl).

Chloramine T

• Chloramine T is N-chloro-p-toluensulphonamidesodium.

• It is used as an effective oral antiseptic agent.

• The mode of action is by the conversion of amino acids intoaldehydes, carbon dioxide, ammonia and nitriles.

• Irrigation with a combination of hydrogen peroxide andchloramine, chloramine or glutaraldehyde were moreeffective irrigants than normal saline, 1% metronidazole or3% hydrogen peroxide

Hexetidine1,3-bis(2-ethylhexyl)-5-amino-5-methyl hexahydropyrimidine.

• Hexetidine is a good antibacterial and antifungal agent with awide spectrum of activity both in vivo and in vitro.

• Hexetidine rinse is widely used as an antiplaque andantigingivitis, as it decreases supragingival plaque and gingivalinflammation.

• In vitro and in vivo action against Gram-positive and Gram-negative bacteria as well as yeasts (Candida albicans) is wellknown.

• In addition, it is also used as an astringent, local anaestheticand deodorant.

• It has not been widely used in endodontic treatment.

• Studies on in vitro oral biofilm models demonstrate thatantimicrobials like chlorhexidine, hexetidine, delmopinol,amine fluoride/stannous fluoride, triclosan, and phenoliccompounds interfere with bacterial metabolism and mayinhibit biofilm development and maturation

Aminefluoride

• 38 % diamine silver fluoride, or Ag(NH3)2F, is used as aNd:YAG laser initiator.

• Yokoyama K and co-workers reported that pulsed Nd:YAGlaser or iontophoresis following Ag(NH3)2F increased thepermeability of the root canal wall and occlusion of dentinaltubules.

• Root canals treated using irradiation with an Nd:YAG laserthat has been coated with Ag(NH3)2F solution showedimproved results compared to either iontophoresis aftercoating with Ag(NH3)2F solution, or coating alone.

Cetylpyridinium chloride

• Cetylpyridinium chloride (CPC) is a quaternary ammoniumsalt (C21H38ClN; molecular weight, 358.07) having acombination of hydrophilic and lipophilic affinities.

• CPC is commonly used as a broad-spectrum antimicrobialagainst oral bacteria and with properties and uses typical ofcationic surfactants.

• The primary mechanism of action of CPC is by cellmembrane penetration, which results in leakage of cellcontents, disturbance of bacterial metabolism and inhibitionof cell growth.

• These eventually cause cell death.

• It exhibits surface-active properties.

• Thus the long duration of action is by virtue of the binding ofCPC to the glycoproteins covering the teeth and oralmucosa.

• Cetylpyridinium chloride (CPC) is recognied as an effectiveantiplaque agent and commonly found in oral hygiene aids.

• It is less commonly used in root canal treatment.

• Several animal studies on the cytotoxicity of CPC haveshown it to be a highly safe and effective antimicrobialagent.

• CPC has the distinction of being recognized by the FDAPlaque Subcommittee after a six year review of over 40active ingredients as being one of the only three (stannousfluoride and essential oils – the remaining two safe agents)antimicrobial agents which is safe and effective(concentration range of 0.05 and 0.10 %) for the treatmentof plaque-induced gingivitis.

PART VIIANXIETY AND FEAR IN THE

ENDODONTIC PATIENT

Most common fears of man-

• Fear of height

• Fear of flying

• Fear of mice

• Fear of public speaking

• Fear of dentists

‘Our most common fears.’

Dental health advisor, Spring 1987

• Incidence of dental phobia or ODONTOPHOBIA- 10-30 % of adults,moderate to severe odontophobia

• Fear and pain are a potent combination capable of provokingsome of the most catastrophic situations imaginable in the dentaloffice, such as cardiac arrest.

• Sedation occurs as a result of CNS depression, from minimalsedation to general anesthesia.

• Minimal sedation- ‘anxiolysis’, a minimally depressed level ofconsciousness that retains the persons ability to independentlyand continuously maintain an airway and respond appropriatelyto physical stimulation or verbal command and that is producedby pharmacologic or nonpharmacologic method or acombination thereof.

• Nitrous oxide/oxygen (N2O-O2)

• Moderate sedation- ‘conscious sedation’, drug induceddepression of consciousness during which pateints respondpurposefully to verbal commands, either alone or accompaniedby light tactile stimulation.

• Deep sedation- drug induced depression of consciousness duringwhich patients cannot be easily aroused but respondpurposefully following repeated or painful stimulation.

• Sedation- Iatrosedation- ‘no drugs’ sedation, relaxation of the patient by the dentists behaviour.

• Drug sedation/ techniques-

• Inhalation sedation-

• N20-O2, rapid onset of action, level of CNS depression that can be rapidly increased if necessary, level of CNS depression that can be rapidly decreased if necessary, complete recovery following the delivery of 100% O2 at the completion of procedure- permits the patient to leave the clinic unescorted, no other route of drug administration offers this advantage.

• Because of rapid onset, it can be titrated, which increases both the safety and success of the technique.

• Only disadvantage for endodontists is the nasal hood on the way which is not a problem once experienced.

Oral conscious sedation-

• Least controllable route

• Slow onset of action usually

• Erratic absorption of the drug from the GIT

• Only advantage is easy for dentist and patient

• CNS depressants given night prior to planned appointment, in the morning 1 hr prior to the scheduled dental visit, to assist them in overcoming any last minute increase in their anxiety.

Generic name Proprietary name Dosage

Benzodiazepines

Alprazolam Niravam, Xanax 0.25-0.5 (max 4mg/day)

Diazepam Valium 2-10 mg BID-QID

Flurazepam Dalmane 15-30mg at bedtime

Lorazepam Ativan 2-3mg/day BID-TID

Midazolam Versed 0.25-1mg/kg pediatric

Oxazepam Serax 15-30 tid-qid severe

Triazolam Halcion 0.25 qhs

Non-benzodiazepine

anxiolytics

Eszopiclone Lunesta 2mg qhs

Zaleplon Sonata 10qhs insomnia

Zolpidem Ambien 10 mg qhs

Hypnotics

Chloral hydrate 500 mg- 1 gm, max 2

gm/day

Hydroxyzine Atarax 50-100 mg

Intravenous conscious sedation

• Rapid onset, titration possible to desired level, more safer than oral

• Requires fasting prior to procedure

• Inability to quickly lessen the level of CNS depression

• Inability to reverse the action of some drugs (barbiturates)

• Prolonged clinical recovery

• Benzodiazepines, midazolam, diazepam

• Venipuncture skill required

Intramuscular

• Drug by passes the GI tract, being absorbed directly into the system

• Hepatic first pass effect neglected, leading to more reliableabsorption and more rapid onset of action

• Titration not possible

• Doses decided by weight (mg/kg)

• Reversal done with iv flumazenil or naloxone

• Im not controllable like iv so sedation limited to moderate level,doctor should be trained to recognize and manage the patiententering deep sedation

Intranasal

• Newer technique in dentistry

• More rapid absorption since nasal mucosa is highly vascular

• No injection needed

• Cannot be titrated

• Dosage based on weight

• Sedation limited to moderate, not controllable

• IN midazolam commonly used

General anesthesia

Provided to dentist by an anesthetologist

PART VIIITHE MEDICALLY COMPLEX

ENDODONTIC PATIENT

‘Never treat a stranger.’

- Sir William Osler

• The value of a thorough medical and dental history of a patient

cannot be overemphasized.

• Recognition of a medical condition that requires treatment

modification prior to treatment can avert significant treatment

complications.

ASA Physical Status Classification System & therapy

modifications• ASA Physical Status 1 - A normal healthy patient

No therapy modifications, stress reduction as indicated

• ASA Physical Status 2 - A patient with mild systemic disease

Possible stress reduction and other modifications as needed

• ASA Physical Status 3 - A patient with severe systemic disease

Possible stress modifications, stress reduction and medical consultation are

priorities

• ASA Physical Status 4 - A patient with severe systemic disease that is a

constant threat to life

Minimal emergency care in office, may consist of pharmacologic

management only, hospitalize for stressful elective treatment, medical

consultation urged

• ASA Physical Status 5 - A moribund patient who is not expected to

survive without the operation

Treatment in the hospital is limited to life support only, eg:- airway and

haemorrhage management

• ASA Physical Status 6 - A declared brain-dead patient whose organs are

being removed for donor purposes

Not applicable

Antibiotic prophylaxis recommended, based on risk

stratification for infective endocarditis Highest risk of adverse outcome from infective endocarditis• Prosthetic heart valve

• Previous infective endocarditis

• Congenital heart disease (CHD)

• Unrepaired cyanotic CHD, including palliative shunts and

conduits• Completely repaired congenital heart defect with prosthetic

material or device, whether placed by surgery or catheter,

during the first six months after the procedure

• Repaired CHD with residual defects at the site or adjacent to the

site of a prosthetic patch or prosthetic device

• Cardiac transplant recipients who develop cardiac valvulopathy

Risk of dental procedure-All dental procedures that involve manipulation of gingival tissue orthe periapical region of the teeth or perforation of the oral mucosa

Antibiotic prophylaxis for dental procedures- all regimens

are a single dose given 30-60 mins before the procedureStandard oral regimen

Adults- 2 gm amoxicillin

Children- 50 mg/kg

Alternative oral regimen for patients allergic to penicillin or patients who are

currently taking a penicillin class antibiotic

Adults-

2 gm cephalexin or 600 mg clindamycin or 500 mg azithromycin

Children-

50 mg/kg cephalexin or 20 mg/kg clindamycin or 15 mg/kg azithromycin

Patients unable to take oral medication

Adults-

2 gm iv / im ampicillin or 1 gm im / iv cefazolin or ceftriaxone

Children-

50 mg/kg im or iv ampicillin or 50 mg/kg im or iv cefazolin or ceftriaxone

Alternative im/iv regimen for patients allergic to penicillin and unable to take

oral medications

Adults-

1 gm im/iv cefazolin or ceftriaxone or 600 mg im/iv clindamycin

Children

50 mg/kg im/iv cephazolin or ceftriaxone

20 mg/kg im/iv clindamycin within 30 mins before the procedure

ReferencesBOOKS• Cohen’s Pathways of the pulp- 10th edition

• Ingles Endodontics- 6th edition

• Essentials of pharmacology- KD Tripathi, 2006

• Endodontics- Arnaldo Castellucci- Vol 1 and 2

• Endodontics- principles and practise- M.Torabinejad, 4th edition

• Harty’s Endodontics in clinical practise, 6th edition

ARTICLES

• Pharmacological Strategies to Control Post-operative Endodontic Pain Zahed Mohammad, Alireza Farhad, Meisam Khalesi Dent Res J 2007; 4(2): 61-68

• Endodontics in the adult patient: the role of antibiotics L.P. Longman, A.J. Preston, M.V. Martin, N.H.F. Wilson Journal of Dentistry 28 (2000) 539–548

• Fazakerley MW, McGowan P, Hardy P, et al. A comparative study of cephradine, amoxycillin and phenoxymethylpenicillin in the treatment of acute dentoalveolar infections. British Dental Journal1993;174:359–63.

• Martin MV, Longman LP, Hill JB, et al. Acute alveolar infections: an investigation of the duration of antibiotic therapy. British Dental Journal 1997;183:135–7.

• McDonnell G, Russell AD. Antiseptics and disinfectants: activity, action, and resistance. Clinical Microbiology Reviews 1999;12:147–79.

• Anaesthetising Painful Pulp in Endodontics-A Review. Rakesh Mittal, Jamal M El- Swiah, Vandana Dahiya; JOHCD, September 2011;5(3)

• Pharmacological Strategies to Control Post-operative Endodontic PainZahed Mohammadi, Alireza Farhad, Meisam Khalesi, Dent Res J 2007; 4(2): 61-68

• An update on the antibiotic-based root canal irrigation solutions. ZahedMohammadi, IEJ Vol 3, No 2 Spring 2008

• Endodontic Consideration for the Usage of Drugs in Pregnant and Lactating Mothers AGGARWAL R, SINGLA M, MITTAL N, Journal of Clinical and Diagnostic Research. 2010 August ;(4):2974-2978

• Antimicrobial agents used in endodontic treatment. Marina George Kudiyirickal, Romana Ivančaková, ACTA MEDICA (Hradec Kralove) 2008;51(1):3–12

• Antibiotics as an intracanal medicament in endodontics: A review NeelamMittal, Jyoti Jain, indian journal of dentistry 4(2013) 29-34

• Are antibiotics effective for endodontic pain? Ashraf f. Fouad, Endodontic Topics 2002, 3, 52–66

THANK

YOU