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Drugs in Endo
Drugs in Endo
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
Definitions
• 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
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
2 classes mainly-
NSAIDS
Acetaminophen
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
• 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.
(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).
• potent analgesics
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.
c. Antibiotics at obturation
• Antibiotic therapy has also been suggested for one visit endodontics,
undertaken when there is infection present in the root canal.
• 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
Perio-endo lesions
• 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
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.
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.
Surface anesthetic
Soluble
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 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
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.
Conventional antiseptics
1. Alcohols – Ethyl alcohol, Isopropylalcohol
Chemotherapeutics
Antibiotics
Mechanism of action
• 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
• 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.
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 %)
• 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.
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
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
• 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.
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.
• 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.
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-).
• 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.
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.
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.
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.
• 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