drugs used in endodontics

1. DRUGS USED IN
ENDODONTICS
By
Dr.Anoop.V.Nair
PG
Dept of Cons. Dentistry & Endodontics
KVG Dental College, Sullia

2. 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

3. • A medicine or other substance which has a physiological effect
when 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 loosely
defined as any chemical substance — or product comprising such —
intended for use in the medical diagnosis, cure, treatment, or
prevention 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 or
function of the body
(4) : a substance intended for use as a component of a medicine but
not a device or a component, part, or accessory of a device
Definitions

4. CLASSIFICATIONS
Based 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

5. PART I
PAIN AND ANALGESICS
IN ENDODONTICS

6. • The skill of the clinician is often judged primarily by
their success or failure of pain control.
-Cohen, Pathways of the Pulp

7. The
Trigeminal
Pain
System

8. ANALGESICS-
NONNARCOTIC
Management of endodontic pain is multifactorial and
directed at reducing the peripheral and central
components of hyperalgesia through combined
endodontic procedures and pharmacotherapy.
2 classes mainly-
NSAIDS
Acetaminophen

9. NSAIDS
• Very effective in managing pain of inflammatory origin- binds to
plasma proteins- exhibit increased delivery to inflamed tissue via
extravasation of plasma proteins.
• Less studies done comparing NSAIDS on endodontic pain in
particular
• Ibuprofen- considered the prototype of contemporary NSAIDs and
has 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 be
somewhat more analgesic than ibuprofen

10. • 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 of
stomach mucosa, kidney function and platelet action.
• COX-2 is induced by various endogenous compounds such as
cytokines, mitogens and endotoxins in inflammatory cells and is
responsible for the elevated production of prostaglandins during
inflammation.
• 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 Pain
Zahed Mohammad, Alireza Farhad, Meisam Khalesi
Dent Res J 2007; 4(2): 61-68

11. • 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 the
potential for both analgesic and antiinflammatory benefits and
reduced GI irritation.
• Oral surgery pain studies evaluating COX-2 inhibitors have
indicated that Rofecoxib (i.e.,Vioxx) has significant analgesic
efficacy.
• COX-2 levels are increased in inflamed human dental pulp, and
a COX-2 inhibitor (rofecoxib) is analgesic in patients with
endodontic pain.
• Concern has been raised that the COX-2 inhibitors may also
display at least some GI irritation in patients with preexisting GI
disease

12. • 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.

13. 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.

14. 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

15. 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.

16. • 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.

18. 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.

19. A combination formulation is preferred because it permits a lower dose of
the opioid, thereby reducing side effects

20. • 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

21. PART II
CORTICOSTEROIDS

22. • Corticosteroids contain 21 carbon atoms in a four membered
hydrocarbon 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 first
appreciated and utilized as an adjunct in endodontic therapy almost
half a century ago.
• Glucocorticoids have been used as an intracanal medication either
alone or in combination with antibiotics/ antihistamines, and systemically
as a means to decrease pain and inflammation in endodontic patients

23. • 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.

24. • 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.

25. • Post treatment pain or flare-up after endodontic treatment 
inflammation, infection, or both in the periradicular tissues.
• Establishing patency and subsequently debriding and shaping the
root 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.

26. Glucocorticosteroids reduce the acute inflammatory response by
• suppressing vasodilation,
• migration of polymorphonuclear (PMN) leukocytes
• phagocytosis
• inhibiting formation of arachidonic acid from neutrophil and
macrophage cell membrane phospholipids, thus blocking the COX
and lipoxygenase pathways and respective synthesis of PGs and
leukotrienes.

27. • Wolfson and Blitzer stated that hydrocortisone as an intracanal
medication resulted in reduction and elimination of inflammatory
reactions in periapical tissues.
• Ehrmann reported that ledermix (triamcinolone dimethyl
chlorotetracycline in a water soluble cream) stopped the pain
associated with pericementitis.
• Langeland et al demonstrated that Ledermix as an intracanal
medication eliminated post-endodontic treatment pain within minutes
to 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 a
double-blind study.
• The results indicated that the corticosteroid was effective significantly in
reducing the incidence of pain in vital teeth when compared to saline.
• However, there was no difference between the two solutions in necrotic
teeth.

28. 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 medicament
for both vital and necrotic cases because of its anti-inflammatory
and antimicrobial properties.
• Both components of Ledermix can diffuse into dentin and
through the apical foramen.
• The concentration of demeclocycline in the root canal was
shown to be much higher than is required to inhibit bacteria;
however, this activity tends to decrease considerably by 7days.

29. • It may be combined with calcium hydroxide at a 50:50 ratio to
enhance its antimicrobial efficacy, but this tends to reduce the
diffusion of its main ingredients.
• Efficacious against pulpal pain in some earlier studies, possibly
because of its corticosteroid content; however, pulp capping for
painful cases with pulp exposures is not currently recommended
because of its low long-term prognosis.
• In a randomized clinical trial to compare Ledermix with
formocresol and calcium hydroxide used as interappointment
medicaments on postinstrumentation flare-ups, no differences
were detected among the three medicaments.

30. 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.

31. 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.

32. 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.

33. 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.’

34. PART III
ANTIBIOTICS

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

36. • The first reported local use of an antibiotic in endodontics was in
1951 when Grossman used a polyantibiotic paste known as PBSC (a
mixture of penicillin, bacitracin, streptomycin, and caprylate
sodium).
• PBSC contained penicillin to target Gram-positive organisms,
bacitracin for penicillin resistant strains, streptomycin for Gram-
negative organisms, and caprylate sodium to target yeasts - these
components were suspended in a silicone vehicle.
• Later, Nystatin replaced caprylate sodium as an antifungal agent in
a similar medicament, known as PBSN.

37. 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 not
indicated, 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 from
controlled clinical trials provide little or no support for the hypothesis
that antibiotics reduce pain.

38. • 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.

39. Penicillins
• Penicillins have a short half-life, limited to about 1 hour.
• Amoxicillin is generally considered the penicillin of first choice
because of its somewhat better absorption from the gut.
• Also used for periodontal abscesses, periapical abscesses,
pericoronitis, acute suppurative pulpitis, necrotizing ulcerative
gingivitis, oral cellulitis etc
• Less active against Shigella and H.influenza
• Majority of cases resolve with 250-500 mg TDS given for 5 days.

40. 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 –ve
enterobacteriaceae, some inhibit pseudomonas, less active on gram
positive cocci and anaerobes
• Cefixime, cefdinir, cefotaxime, ceftizoxime, cefoperazone
Fourth generation- highly resistant to B-lactamases, active against many
bacteria resistant to earlier drugs. P.aeruginosa and staph.aureus also
inhibited.
• Cefepime, cefpirome
• All bactericidal, same mechanism of action as penicillin, i.e inhibition of
bacterial cell wall synthesis.

41. Metronidazole
• Metronidazole (Flagyl®) is also considered a bactericidal drug
because of its fast killing time.
• It attacks the bacteria’s DNA and works against obligate
anaerobes but not against facultative bacteria or aerobes.
• Metronidazole is often used in combination with another
antibiotic, usually amoxicillin, to combat the stomach ulcer–
causing Helicobacter pylori.
• Combination helps in severe dental infections
• Metronidazole shares properties with disulfiram (Antabuse®), a
drug used to help alcoholics avoid alcohol by inducing violent
vomiting.
Patients taking metronidazole should be cautioned about not
using alcohol for the time they are taking the drug plus 1 day
following to allow the drug to be eliminated from their system.
• The half-life of metronidazole is in the 8- to 10-hour range. Side
effects include an unpleasant, metallic taste and brown
discoloration of the urine, effects that are dose related.

42. Macrolides
• Erythromycins kill bacteria by slowing the manufacture of bacterial
protein 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 active
against 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 brain
barrier.
• 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 to
patients allergic to penicillins

43. Azithromycin- expanded spectrum, better tolerability, improved
pharmacokinetics.
• More active than other macrolides against H.influenza,
Peptostreptococcus, Clostridia
• Less active against gram +ve cocci
• Acid stability, rapid oral absorption, marked tissue distribution and
intracellular penetration.
• Absorption decreased by food
• Dose- azithral 500 mg once daily 1 hour before or 2 hours after
food for 3 days is sufficient for most infections
• Mild gastric upset, abdominal pain, headache and dizziness

44. Clindamycin (Cleocin®)
often indicated in endodontic infections.
• It is rapidly and completely absorbed and has a good spectrum of
killing oral pathogens, including many anaerobes.
• It was, however, the first antibiotic to be associated with causing
pseudomembranous colitis, a life-threatening condition in which
large patches of gut slough epithelium because of toxins from
overgrowth of the nonsusceptible organism Clostridium difficile.
• The average half-life of clindamycin is about 3 hours.

45. Tetracyclines
• Tetracyclines, including tetracycline-HCl, minocycline,
demeclocycline and doxycycline, are a group of broad-spectrum
antibiotics that are effective against a wide range of
microorganisms.
• Bacteriostatic in nature.
• This property may be advantageous because, in the absence of
bacterial cell lysis, antigenic byproducts such as endotoxin are not
released.
• Inhibition of mammalian collagenases, which prevent tissue
breakdown.
• 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.

46. • Barkhordar et al. evaluated the effect of doxycycline-HCl on the
smear layer of instrumented root canal walls. They showed that
doxycycline-HCl eliminated smear layer in a concentration
dependent manner with 100 mg/ml doxycycline being more
effective than lower concentrations.
• In another investigation, Haznedaroglu and Ersev used scanning
electron microscopy (SEM) to assess the effect of tetracycline-HCl as
an endodontic irrigant in removing the smear layer. They reported
that tetracycline was as effective as citric acid in removing the
smear layer.
• Barkhordar and Russell evaluated the effect of doxycycline on the
apical penetration of dye through the margins of retrograde fillings.
The teeth with retrograde IRM or amalgam fillings placed
subsequent to doxycycline irrigation had significantly less dye
penetration than those that were not irrigated with doxycycline.

47. • Carson et al. used an agar diffusion test to compare the
antimicrobial 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 four
microorganisms associated with endodontic infections of teeth
that had not been previously treated, namely
Peptostreptococcus micros, Prevotella intermedia,
Streptococcus sanguis, and Lactobacillus acidophilus.
For the first three of these organisms, the general order of
antimicrobial 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.

48. • Pinheiro et al. evaluated the antibiotic susceptibility of
Enterococcus faecalis isolates from canals of root-filled
teeth with periapical lesions.
• The antibiotics were benzylpenicillin, amoxicillin, amoxicillin
with clavulanic acid, erythromycin, azithromycin,
vancomycin, chloramphenicol, tetracycline, doxycycline,
ciprofloxacin and moxifloxacin.
• The vast majority (85.7%) of the isolates were susceptible to
tetracycline 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.

49. Based on the hypotheses that microorganisms can reach the apical
area of recently replanted teeth from the oral cavity (or from
contaminated root surfaces during the extra-oral time), and that
tetracyclines can potentially inhibit this route of bacterial
contamination, Cvek et al. developed a protocol for the topical
treatment of exposed roots with doxycycline before replantation.
• Aim was to eliminate the microorganisms from the root surface of
an avulsed tooth via direct local application of the antibiotic in
order to decrease the frequency and severity of the inflammatory
response.
• Topical doxycycline significantly increased the chances of
successful pulp revascularization and decreased the number of
microorganisms that could be isolated from the root canals.
• They also reported a decreased frequency of ankylosis, external
replacement resorption and external inflammatory resorption.
• The beneficial effect of soaking a tooth in doxycycline has also
been confirmed by Yanpiset and Trope

50. Substantivity of tetracyclines
• Tetracyclines readily attach to dentine and are subsequently
released without losing their antibacterial activity.
• This property creates a reservoir of active antibacterial agent, which
is then released from the dentine surface in a slow and sustained
manner.
• Stabholz et al. compared the antibacterial substantivity of two
concentrations of tetracyclineHCl (50 mg/ml, 10 mg/ml) and 0.12%
chlorhexidine.
• Their findings showed that both concentrations of tetracycline
demonstrated residual antibacterial activity and the antibacterial
substantivity of the three solutions in descending order was: 50
mg/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.

51. BioPure (MTAD)
• Bio Pure (Dentsply, Tulsa Dental, Tulsa, OK, USA), otherwise known as
MTAD (mixture of tetracycline, acid and detergent), is a relatively
new root canal irrigant which was introduced by Torabinejad and
Johnson 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 for
disinfection of root canals.
• Torabinejad et al have shown that MTAD is able to remove the
smear layer and is effective against E. faecalis.
• Shabahang et al. cleaned and shaped root canals of extracted
human teeth and exposed them to human saliva. They then
compared the antibacterial efficacy of a combination of 1.3%
NaOCl as a root canal irrigant and MTAD as a final rinse with that of
5.25% NaOCl. Their findings showed that using MTAD in addition to
1.3% NaOCl was more effective at disinfecting root canals than
using 5.25% NaOCl alone.

52. • Tay et al. found that when MTAD was applied to 1.3% NaOCl-
irrigated dentine, its antimicrobial substantivity was reduced. They
attributed this to the oxidation of MTAD by NaOCl in a manner
similar to the peroxidation of tetracycline by reactive oxygen
species.
• Shabahang and Torabinejad compared the antibacterial effects
of MTAD with those of NaOCl and EDTA by using standard in vitro
microbiological techniques and they reported that MTAD was
significantly more effective against E. faecalis.

53. • Kho and Baumgartner compared the antimicrobial efficacy of 1.3%
NaOCl /MTAD against E faecalis with that of the combined
alternate use of 5.25% NaOCl and 15% EDTA for root canal
irrigation.
• This investigation showed consistent disinfection of infected root
canals when a combination of 5.25% NaOCl and 15% EDTA was
used.
• However, the combination of 1.3% NaOCl/ MTAD left nearly 50% of
the canals contaminated with E. faecalis.
• Mohammadi and Yazdizadeh evaluated the substantivity of NaOCl,
CHX and MTAD substantivity of MTAD was significantly greater than
CHX and NaOCl.

54. Tetraclean
• Tetraclean (Ogna Laboratori Farmaceutici, Muggiò(Mi),
Italy), like MTAD, is a mixture of an antibiotic, an acid and a
detergent. 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 and
Tetraclean.
• The NaOCl and EDTA had the highest surface tension,
whereas Cetrexedin and Tetraclean had the lowest values.
• In another study, they compared the antimicrobial efficacy
of 5.25% NaOCl, MTAD, and Tetraclean against an E.
faecalis biofilm generated on cellulose nitrate membrane
filters.
• Only the NaOCl could disaggregate and remove the biofilm
at every time interval tested although treatment with
Tetraclean caused a high degree of biofilm disaggregation
at each time interval when compared with MTAD.

55. Combination of Ledermix and calcium hydroxide
• The combination of Ledermix paste with calcium hydroxide was
advocated by Schroeder initially for the treatment of necrotic
teeth with incomplete root formation.
• A 50:50 mixture of Ledermix paste and calcium hydroxide has also
been advocated as an intracanal dressing in cases of infected
root canals.
• It has been shown that the 50:50 mixture results in slower release
and diffusion of the active components of Ledermix paste, which
makes the medicament last longer in the canal.
• This in turn helps to maintain the sterility of the canal for longer and
also maintains a higher concentration of all components within the
canal.

56. • 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 a
calcium 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 (including
staphylococci and streptococci) were more prevalent than the
gram-negative obligate anaerobic rods after treatment in all
three groups.

57. 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.

58. 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 unlikely
that 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.

59. • 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.

60. • 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 and
ciprofloxacin) 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 the
revascularization potential of a young permanent tooth pulp into a
bacteria-free root canal space.

61. 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.

62. 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

63. 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
Examples
1. 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.

64. 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.

65. 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.

66. 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.

67. • 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

68. 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 commensal
flora 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.

69. 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.

70. 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.
Pulpitis
There 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.

71. 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.

72. 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.

73. 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

74. • 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.

75. 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.

76. • 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.

77. 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

78. 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.

79. PART IV
LOCAL ANESTHETICS

80. 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 anesthetic
Soluble
Cocaine
Lignocaine
Tetracaine
Benoxinate
Insoluble
Benzocaine
Butylaminobenzoate ( Butamben)

81. Lignocaine (lidocaine)
• Most widely used
• Surface application and injectable
• Blocks nerve conduction in 3 mins whereas procaine may take
upto 15 mins
• Overdose causes muscle twitching, convulsions, cardiac
arrhythmias, fall in BP, coma, respiratory arrests
• Dental use- 2% with or without adrenaline 1:80,000

82. 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

83. 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.

84. • 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.

87. PART V
ANTIMICROBIAL AGENTS

88. 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.

89. 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
Chemotherapeutics
Antibiotics
Classification of antimicrobial agents.

90. • The mechanism of action of antimicrobial agents is varied as they
have multiple sites of action except for antibiotics, which have
very specific sites of action.
• The nature of the organism, antimicrobial agent and the
concentration determine the response of the microorganisms to
the antimicrobials.
• The cell wall, cytoplasmic membrane and ribosomes of
vegetative 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 the
sites of action of antimicrobial agents.
• These antimicrobial actions eventually result in the loss of
important cell functions like protein synthesis and metabolism,
replication, transcription and destruction of cell membranes with
leakage of cell contents
Mechanism of action

91. • The two most important features which determine the efficacy of
antimicrobial agents are the killing and the cleaning potential of
the agent.
• The antimicrobial activity may vary from inhibition of metabolism
to destruction of the microorganisms.
• The specific target of action of antimicrobials is difficult to
elucidate as antimicrobial agents act on multiple cell
components, resulting in both primary and secondary effects,
which in turn is hard to distinguish.

92. Sodium hypochlorite
• Concentrations ranging from 0.5 % to 5.25 %.
• This is due to its antimicrobial and dissolving effects on
necrotic tissues (Sodium hypochlorite is a reducing agent
with 5 % of available chlorine
• lubricant, antiseptic agent, bleach and also dissolves tissue
• Antibactericidal ability of NaOCl results from the formation
of hypochlorous acid (HOCl) when in contact with organic
debris.
• HOCl exerts its effect by the oxidation of sulphydryl groups
within bacterial enzyme systems, thereby disrupting the
metabolism of the microorganism.
• Cvek M et al. in his study reported that flushing with sterile
saline had poor antibacterial action (9 %) when compared
to sodium hypochlorite (25 %)

93. • The antibacterial action of NaOCl is time dependent.
• In an in vivo study, Ringel et al. noted that in root canals of
permanent teeth 2.5 % NaOCl had a more powerful
antibacterial effect than 2 % chlorhexidine gluconate, as
NaOCl was a powerful solvent for necrotic and organic
material.
• Naenni et al reported that only sodium hypochlorite
showed effective necrotic tissue dissolution among 10 %
chlorhexidine, 3 % and 30 % hydrogen peroxide, 10 %
peracetic acid, 5 % dichloroisocyanurate (NaDCC), and 10
% citric acid.

94. Chlorhexidine gluconate
• Chlorhexidine (CHX) is widely used in periodontal and
endodontic treatment as an irrigant.
• There are various mechanisms of antimicrobial action for
chlorhexidine.
• It attaches electrostatically to negatively charged sites on
bacteria and also to its cytoplasmic membrane.
• The leakage of intracellular material is due to the loss of
osmotic balance by CHX.
• The binding of CHX to hydroxyapatite and soft tissues
changes their electrical field to compete with the binding of
bacteria

95. 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 quarternery
ammonium compound and a cationic detergent that is effective
against many Gram positive and Gram negative bacteria

96. • Study on the antimicrobial effectiveness and cytotoxicity of 4
irrigant solutions, viz 5.25 % sodium hypochlorite (NaOCl), 0.2 %
chlorhexidine gluconate plus 0.2 % cetrimide (CetrexidinR), 2 %
chlorhexidine gluconate and 0.9 % sterile saline solution
demonstrated that NaOCl should remain in the canal for a
substantial period so that it can act upon the bacterial cells
located in the irregularities within the canal.
• In this study, 5 minutes following the irrigation process,
chlorhexidine gluconate had a more rapid and stronger action
on E. faecalis than NaOCl.

97. Calcium hydroxide
• Calcium hydroxide is the most commonly used inter-
appointment intracanal endodontic medicament.
• The publication of research data on the antibacterial action of
calcium hydroxide in root canal treatment by De Moor & De
Witte led to increased use of calcium hydroxide in endodontic
treatment.
• The antibacterial activity is a result of free hydroxyl radical
liberation and diffusion of hydroxyl radicals resulting in a highly
alkaline environment(pH 12.5).
• These hydroxyl ions penetrate the dentinal tubules and exert
their effect.

98. • These hydroxyl radicals cause bacterial cell death by three
possible mechanisms.
• The first mechanism is by splitting DNA strands and thereby
preventing DNA replication and disrupting cellular activity.
• Another method is by lipid peroxidation, which leads to the
destruction of both phospholipidand cell membrane, finally
resulting in loss of unsaturated fatty acids and massive destruction
of membrane.
• The third mechanism is by protein denaturation and damage of
cell metabolism.
• Calcium hydroxide also shows increased activity against
anaerobes in comparison to paramonochlorophenol and
formocresol.

99. 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 membrane
lipids, DNA and other essential cell components.
• The oxidation of sulphydryl groups and double bonds in proteins,
lipids, and surface membranes is responsible for the antimicrobial
action.
• In addition, the chloride in the bacteria may be oxidized to
hypochlorite when myeloperoxidase enzyme is present.
• Hydrogen peroxide is an oxidizing solution and is usually used in
combination with sodium hypochlorite for root canal irrigation.
This results in two kinds of reactive oxygen species, the superoxide
anion radical (O2 -) and the hydroxyl radical (OH-).

100. • Root canal irrigation with NaOCl and H2O2 induces both biological
and mechanical effects.
• The biological effect of NaClO and H2O2 owes to tissue irritation
due to the chemical reactions of O2 - and OH-, while the
mechanical effect results from O2 bubbling.
• The effervescent action resulting in the release of nascent oxygen
results in the agitation of the root canal contents and the debris is
flushed out.
• The tissue dissolution and antimicrobial effect are the main mode
of action of the combined solutions.
• The final irrigation of the canal should be done with sodium
hypochlorite, as hydrogen peroxide can form gas in the presence
of necrotic debris and blood leading to pain.

101. 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 formocresol
influence the histologic reaction of vital pulp.
• Formocresol is a bactericidal agent and the mode of action is by
fixation, which results in inhibition of bacteria.
• Formocresol causes zones of necrosis, fixation, and inflammation.
• It results in healing with inflammation and eventual replacement
with granulation tissue, bone or osteodentin in some cases.

102. 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 protein
complex in the presence of blood resulting in the mechanical
sealing of cut vessels by the membrane of this complex.
• This ultimately leads to haemostasis
• Pulpal reaction of ferric sulfate and formocresol did not differ
from each other.
• Ferric sulphate is less toxic than formocresol and hence it may be
considered as an alternative to formocresol for pulp therapy in
primary molars.
• As ferric sulphate causes only haemostasis, it is a more
appropriate pulpotomy agent and may be considered a good
replacement for formocresol in pulpotomy.

103. 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 microbicidal
activity 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 peroxide
are used together, they have a combined action on biofilms owing
to the microbicidal activity of peracetic acid and detachment of
biofilm by hydrogen peroxide.

104. • The sporicidal action decreased with storage due to hydrolysis of
peracetic acid, whereas it increased with high pH concentration.
• The drawback of high pH concentration is the carcinogenic
potential of 1 % peracetic acid, as it is a tumor promotor.
• The sporicidal action in a study by Jose-Luis and Aylin was as
follows: hypochlorite > peracetic acid > copper ascorbate >
glutaraldehyde > peroxide > phenol > formaldehyde.
• Ageing, pH, and temperature were found to greatly influence the
order of the efficacy of these agents
• According to Naenni N et al., among the commonly used
endodontic irrigants like 10 % chlorhexidine, 3 % and 30 %
hydrogen peroxide, 10 % peracetic acid, 5 %
dichloroisocyanurate (NaDCC), and 10 % citric acid, all had
lower tissue dissolution capacity in comparison to 1 % (wt/vol)
sodium hypochlorite (NaOCl).

105. 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 into
aldehydes, carbon dioxide, ammonia and nitriles.
• Irrigation with a combination of hydrogen peroxide and
chloramine, chloramine or glutaraldehyde were more
effective irrigants than normal saline, 1% metronidazole or
3% hydrogen peroxide

106. Hexetidine
1,3-bis(2-ethylhexyl)-5-amino-5-methyl hexahydropyrimidine.
• Hexetidine is a good antibacterial and antifungal agent with a
wide spectrum of activity both in vivo and in vitro.
• Hexetidine rinse is widely used as an antiplaque and
antigingivitis, as it decreases supragingival plaque and gingival
inflammation.
• In vitro and in vivo action against Gram-positive and Gram-
negative bacteria as well as yeasts (Candida albicans) is well
known.
• In addition, it is also used as an astringent, local anaesthetic
and deodorant.
• It has not been widely used in endodontic treatment.
• Studies on in vitro oral biofilm models demonstrate that
antimicrobials like chlorhexidine, hexetidine, delmopinol,
amine fluoride/stannous fluoride, triclosan, and phenolic
compounds interfere with bacterial metabolism and may
inhibit biofilm development and maturation

107. Aminefluoride
• 38 % diamine silver fluoride, or Ag(NH3)2F, is used as a
Nd:YAG laser initiator.
• Yokoyama K and co-workers reported that pulsed Nd:YAG
laser or iontophoresis following Ag(NH3)2F increased the
permeability of the root canal wall and occlusion of dentinal
tubules.
• Root canals treated using irradiation with an Nd:YAG laser
that has been coated with Ag(NH3)2F solution showed
improved results compared to either iontophoresis after
coating with Ag(NH3)2F solution, or coating alone.

108. Cetylpyridinium chloride
• Cetylpyridinium chloride (CPC) is a quaternary ammonium
salt (C21H38ClN; molecular weight, 358.07) having a
combination of hydrophilic and lipophilic affinities.
• CPC is commonly used as a broad-spectrum antimicrobial
against oral bacteria and with properties and uses typical of
cationic surfactants.
• The primary mechanism of action of CPC is by cell
membrane penetration, which results in leakage of cell
contents, disturbance of bacterial metabolism and inhibition
of cell growth.
• These eventually cause cell death.
• It exhibits surface-active properties.
• Thus the long duration of action is by virtue of the binding of
CPC to the glycoproteins covering the teeth and oral
mucosa.

109. • Cetylpyridinium chloride (CPC) is recognied as an effective
antiplaque 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 have
shown it to be a highly safe and effective antimicrobial
agent.
• CPC has the distinction of being recognized by the FDA
Plaque Subcommittee after a six year review of over 40
active ingredients as being one of the only three (stannous
fluoride 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 treatment
of plaque-induced gingivitis.

110. PART VII
ANXIETY AND FEAR IN THE
ENDODONTIC PATIENT

111. 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

112. • Incidence of dental phobia or ODONTOPHOBIA- 10-30 % of adults,
moderate to severe odontophobia
• Fear and pain are a potent combination capable of provoking
some of the most catastrophic situations imaginable in the dental
office, such as cardiac arrest.
• Sedation occurs as a result of CNS depression, from minimal
sedation to general anesthesia.

113. • Minimal sedation- ‘anxiolysis’, a minimally depressed level of
consciousness that retains the persons ability to independently
and continuously maintain an airway and respond appropriately
to physical stimulation or verbal command and that is produced
by pharmacologic or nonpharmacologic method or a
combination thereof.
• Nitrous oxide/oxygen (N2O-O2)
• Moderate sedation- ‘conscious sedation’, drug induced
depression of consciousness during which pateints respond
purposefully to verbal commands, either alone or accompanied
by light tactile stimulation.
• Deep sedation- drug induced depression of consciousness during
which patients cannot be easily aroused but respond
purposefully following repeated or painful stimulation.

114. • 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.

115. 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.

116. 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

117. 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

118. Intramuscular
• Drug by passes the GI tract, being absorbed directly into the system
• Hepatic first pass effect neglected, leading to more reliable
absorption 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 patient
entering deep sedation

119. 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

120. PART VIII
THE MEDICALLY COMPLEX
ENDODONTIC PATIENT

121. ‘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.

122. 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

123. 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 or
the periapical region of the teeth or perforation of the oral mucosa

124. Antibiotic prophylaxis for dental procedures- all regimens
are a single dose given 30-60 mins before the procedure
Standard 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

125. References
BOOKS
• 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.

126. • 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. Zahed
Mohammadi, 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 Neelam
Mittal, 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

127. THANK
YOU