Beruflich Dokumente
Kultur Dokumente
in Pediatric Dentistry
Steven Schwartz, DDS
Continuing Education Units: 2 hours
Disclaimer: Participants must always be aware of the hazards of using limited knowledge in integrating new techniques or
procedures into their practice. Only sound evidence-based dentistry should be used in patient therapy.
Medication prescription is more complicated than in the past with an increasing number of issues, such as
microbial resistance to prescribed antibiotics, drug interactions, and increased number of medications used
by both adult and pediatric patients. In this course the reader will learn the characteristics, warnings and
precautions, and proper dosages for adult and pediatric patients for the following categories of medications:
Antimicrobials (antibiotics, antifungals, and antivirals), analgesics, and fluorides.
ADA CERP
The Procter & Gamble Company is an ADA CERP Recognized Provider.
ADA CERP is a service of the American Dental Association to assist dental professionals in identifying
quality providers of continuing dental education. ADA CERP does not approve or endorse individual courses
or instructors, nor does it imply acceptance of credit hours by boards of dentistry.
1
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
Approved PACE Program Provider
The Procter & Gamble Company is designated as an Approved PACE Program Provider
by the Academy of General Dentistry. The formal continuing education programs of this
program provider are accepted by AGD for Fellowship, Mastership, and Membership
Maintenance Credit. Approval does not imply acceptance by a state or provincial board
of dentistry or AGD endorsement. The current term of approval extends from 8/1/2013 to
7/31/2017. Provider ID# 211886
Overview
Medication prescription is more complicated than in the past with an increasing number of issues, such as
microbial resistance to prescribed antibiotics, drug interactions and increased number of medications used
by both adult and pediatric patients. The widespread use of antibiotics has allowed common bacteria to
develop resistance to the drugs that were once effective in controlling the infection. Adults and children
are prescribed drugs to manage an increasing number of medical, physical and psychologic conditions,
many which interact with each other or produce side effects that require additional medications. The
administration of drugs to pediatric patients is further complicated by the necessity to adjust the dosages
of medications to accommodate their lower weight and body size. Dentists prescribe several categories of
medications to manage a variety of diseases and conditions associated with the oral cavity. Among these
conditions are bacterial, fungal and viral infections, pain, and caries prevention.
Learning Objectives
Upon completion of this course, the dental professional should be able to:
• Recognize the characteristics of antimicrobials, analgesics, and fluoride medications.
• Recognize the warnings and precautions for antimicrobials, analgesics, and fluoride medications.
• Recommend the proper dosages for antimicrobials, analgesics, and fluoride medications for adult and
pediatric patients.
2
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
patients is further complicated by the necessity to parasites. Antimicrobial activity is maximized when
adjust the dosages of medications to accommodate the specific microbe causing the infection is identified
their lower weight and body size. In this course by culture or serologic testing and the antimicrobial
the reader will find descriptions of the most most active against that microbe is administered in
commonly used medications used in dental care appropriate doses. The most common antimicrobials
with emphasis on the pediatric patient. As you used in dentistry are antibiotic agents, antifungal
review the medications you will see that the dose agents and antiviral agents.
and instructions on how to take them will vary from
patient to patient, depending on the patient’s age, Antibiotic Agents
weight and other considerations. The categories Antibiotics are drugs that are produced by microbes
of medications covered by this course are or by chemical methods to produce an antibacterial
antimicrobials, which include antibiotics, antifungals, action. Antibiotics are the second most prescribed
and antivirals, analgesics, and fluorides. group of drugs in dentistry, after local anesthetics.
The widespread use of antibiotics has resulted in
Adjustment of Dosages in Pediatric Patients common bacteria developing resistance to drugs
In general, pediatric patients cannot be given adult that once controlled them. To reduce the resistance
dosages of drug. The primary reason for this is the rate, health care providers must prescribe
difference in body size. While the drugs discussed antibiotics judiciously. Antibiotics should be
in this course provide the drug dosage for pediatric prescribed as soon as possible for optimal healing.
patients, the clinician may be faced with the need If the infection does not respond to the initially
to prescribe a drug not listed that does not provide prescribed drug, a culture from the infected site
that information. Several rules exist to compute is indicated. The duration of drug therapy should
the dosage of a drug for a child, the most common extend at least 5 days past the point of substantial
Clark’s Rule. Clark’s Rule determines the dose improvement or resolution of symptoms. The
suitable for a child based on the typical adult importance of completing a full course of antibiotic
weight of 150 lb (or 70 kg). Clarks Rule: therapy must be emphasized to the patient. Should
the antibiotic be discontinued prematurely, the
surviving bacteria can restart an infection that may
be resistant to the original antibiotic.
3
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
surrounding tissue and the patient does not bacteria. The efficacy of an antibiotic against
exhibit systemic signs of infection (fever and a particular bacteria is determined by culturing
facial swelling). the pathogen and testing its susceptibility to a
particular antibiotic. Unfortunately, culturing
Patients presenting with facial swelling secondary and susceptibility testing may take 24 hours to
to a dental infection receive dental treatment several days resulting in a delay in initiation of
accompanied by antibiotic therapy. If the clinician antimicrobial therapy. Thus, until culturing and
is able to achieve adequate local anesthesia, the susceptibility results are available a best guess is
dentist may render immediate treatment followed made for determining the most effective antibiotic
by a regimen of antibiotics. If the infection is of for a specific clinical situation.2
such severity that achievement of adequate local
anesthesia is questionable, then prescription of Causes and Treatment of Odontogenic
antibiotics for a period of 5‑10 days should be Infections
considered before rendering treatment. While Most orofacial infections are of odontogenic
oral antibiotics may be the simplest route of origin. Dental pulp infection, as a result of
administration, in cases of severe infection caries, is the leading cause of odontogenic
hospitalization and intravenous administration may infection. The major pathogens identified
be necessary. in dental caries are members of the viridens
(alpha-hemolytic) streptococci family including
Pediatric Periodontal Diseases Streptococcus mutans, Streptococcus sobrinis
Prolonged antibiotic therapy may be prescribed for and Streptococcus milleri. Once bacteria invade
the management of chronic periodontal disease, the dental pulp, an inflammatory reaction
especially in patients with an immunodeficiency results in necrosis and a lower tissue oxidation-
disease. In pediatric periodontal diseases reduction potential. At this stage, the bacterial
(neutropenias, Papillon-Fevere syndrome, leukocyte flora change from predominantly aerobic to more
adhesion deficiency) the immune system is unable anaerobic flora. Anaerobic gram-positive cocci
to control the growth of periodontal microbes. As (Peptostreptococcus) and anaerobic gram-negative
this is a chronic rather than an acute condition, rods (Bacteroides, Prevotella, Porphromonas
effective drug selection may be accomplished by and Fusobacterium) predominate. The infection
culture and susceptibility testing. progresses, forming an abscess at the apex of the
root, resulting in bone destruction. Depending on
Viral Diseases host resistance and bacteria virulence, the infection
Antibiotics should not be prescribed for may spread into the marrow, perforate the cortical
viral conditions (acute primary herpetic plate and spread to the surrounding tissues.
gingivostomatitis) unless there is strong evidence to
suggest that a secondary infection exists. Additionally, the anaerobic bacteria inhabiting
the periodontal tissues may provide an
Oral Contraceptive Use additional source of odontogenic infection. The
It is not uncommon for oral contraceptives to most common anaerobes are Actinobacillus
be prescribed for adolescent females to prevent actinomycetemcomitans, Prevotella intermediud,
pregnancy. When antibiotics are prescribed in Porphyrommonas gingivalis, Fusobacterium
concurrence with oral contraceptives, the patient nucleatum, and Eikenella corrodens.
must be advised to use additional birth control
techniques as antibiotics may render the oral Most odontogenic infections (70%) contain mixed
contraceptive ineffective for at least 1 week beyond aerobic and anaerobic bacteria. Pure aerobic
the last dose. infections have less than a 5% incidence. Pure
anaerobic infections have a 25% incidence.
Antibiotics can be categorized by the bacteria The consensus by researchers is that in early
they target. They are either narrow or wide odontogenic infections, bacteria are aerobic
spectrum. Narrow spectrum antibiotics are with gram-positive, alpha-hemolytic streptococci
effective specifically against either gram-positive (S. viridens) predominating. As the infection
or gram-negative antibiotics. Broad spectrum matures and increases in severity the microbial
antibiotics are effective against a wider range of flora become a mix of aerobes and anaerobes.
4
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
Table 1. Empiric Antibiotics of Choice for Odontogenic Infections.
The anaerobes found are determined by the and the major pathogens of mixed anaerobic
site of origin; pulpal or periodontal. As the host infections. It would cause minimal adverse effects
defenses begin to control the infection process, and allergic reactions and be relatively low in cost.
the flora become predominantly anaerobic.3,4
In the absence of an allergic reaction, penicillin VK
Thus, the choice of antibiotic is influenced is the drug of choice in treating dental infections
by a number of factors: Stage of infection as it fits most of these criteria. If a patient
development and the ability of the patient to take with an early stage odontogenic infection does
the antibiotic – medical conditions or allergy. not respond to penicillin VK, there is a strong
probability of the presence of resistant bacteria.
Antibiotics may also be categorized by their Bacterial resistance to the penicillins is a result
method of attack. Bactericidal antibiotics of the production of beta-lactamase by the
actually kill microorganisms, while bacteriostatic bacteria. In these cases, beta-lactamase-stable
antibiotics slow bacterial growth and depend antibiotics should be prescribed to the patient.
on the host immune system to eliminate These include either clindamycin or amoxicillin/
the microorganism. An antibiotic may be clavulanic acid (Augmentin®). Another alternative
bactericidal for one microorganism and is to add a second drug to the penicillin (e.g.,
bacteriostatic for another. Bactericidals are metronidazole Flagyl®). If the penicillin antibiotics
preferable over bacteristatics in most situations. prove to be ineffective in management of the
Bacteriostatics should not be administered infection, culture and susceptibility testing would
to immunocompromised patients whose be indicated to identify the specific bacteria
compromised immune system may be unable responsible for the infection. The doses for the
to assist in clearance of the microorganism. above drugs may be found in Table 2.
Common bactericidals used in dentistry are
the penicillins and cephalosporins. Common Selected Antibiotics
bacteristatics are the macrolides, tetracyclines
and sulfonamides. Penicillin VK
Penicillin VK is a beta-lactam antibiotic and is
The ideal antibiotic for treating dental infections bactericidal against gram-positive cocci and the
would be bactericidal against gram-positive cocci major microbes of mixed anaerobic infections.
5
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
Table 2. Empiric Antibiotics of Choice for Odontogenic Infections.
Adverse drug reactions include mild diarrhea, Warnings/Precautions: Use with caution in
nausea and oral candidiasis. There is a 0.7 patients with severe renal impairment (modify
to 10% allergy rate among patients. About dosage), history of seizures, hypersensitivity to
85% of allergic reactions are delayed and take cephalosporins.
greater than 2 days to develop. The usual
allergic responses exhibited are skin rashes The usual daily dose of penicillin VK for treating
that usually respond to antihistamine therapy odontogenic infections is:
(diphenhydramine, Benadryl®). Severe reactions Children ≤ 12 years of age: 25-50 mg/kg of body
of angioedema have occurred, characterized weight in divided does every 6-8 hours.
by severe swelling of the lips, tongue, face, and Children > 12 years of age and adults: 250-500
periorbital tissues. Patients reporting a history of mg every 6 hours for at least 10 days.
penicillin allergy should never be given Penicillin Penicillin VK is supplied as 125 or 250 mg/5 ml
VK. The alternative antibiotic is clindamycin. If solution or 250 and 500 mg tablets.
the allergy reaction is of the delayed type and not
anaphylactoid, a first-generation cephalosporin Sample penicillin VK prescription for a 3-year-old
may used as an alternative. patient weighing 12 kg (25 lb) with facial swelling:
Rx: Penicillin VK 125 mg/5 ml
Penicillin VK may be given with meals, however Disp: 200 ml
blood concentrations are slightly higher when Sig: Take 1 teaspoon every 6 hours for 10 days
given on an empty stomach. The preferred dosing
is one hour before meals or two hours after meals. Clindamycin
In the event of penicillin allergy, clindamycin is
Contraindications: Hypersensitivity to penicillin or an alternative choice in treating mild or early
any component of the formulation. odontogenic infection. Clindamycin, because
6
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
of its broad spectrum of activity and resistance Contraindications: Hypersensitivity to amoxicillin,
to beta-lactamase degradation is an excellent penicillin or any component of the formulation.
substitute for penicillin resistant bacteria. It is
highly effective against almost all oral pathogens. Warnings/Precautions: Use with caution in
It is not effective against mycoplasma or gram- patients with severe renal impairment (modify
negative aerobes. Administration with food does dosage); low incidence of cross-allergy with other
not significantly impair absorption. Adverse beta-lactams and cephalosporins exists.
effects of clindamycin include abdominal pain,
nausea, vomiting, and diarrhea. The usual daily oral dose for treating odontogenic
infections in children is:
Contraindications: Hypersensitivity to clindamycin Children under 12 years: 20-40 mg/kg divided in
or any component of the formulation; previous 2-3 doses daily for 10 days.
pseudomembranous colitis, regional enteritis, Children over 12 years and adults: 250-500 mg 3
ulcerative colitis. times/day, maximum 2-3 gm/day for 10 days.
Amoxicillin is supplied as a 125, 200, 250, 400 mg/
Warnings/Precautions: Use with caution in 5 ml solution or chewable tablets; 250 or 500 mg
patients with liver dysfunction (modify dosage); capsules.
can cause severe and fatal colitis; discontinue
drug if significant diarrhea, abdominal cramps or Sample amoxicillin prescription for a 3-year-old
blood and mucus passage occurs. patient weighing 12 kg (25 lb) with facial swelling:
Rx: Amoxicillin 125 mg/5 ml
The usual daily oral dose for treating Disp: 150 ml
odontogenic infections in children is: Sig: Take 1 teaspoon every 8 hours for 10 days
Children under 12 years: 10-25 mg/kg/day in 3
equally divided doses for 10 days. In situations when amoxicillin is ineffective due to
Children over 12 years and adults 600-1800 mg/ possible bacterial resistance to the drug and the
day in 3 divided doses for 10 days. The patient cannot tolerate the adverse gastrointestinal
maximum dose is 2-3 gms/day. side effects of clindamycin, clavulanate potassium
Clindamycin is supplied as a 75 mg/5 ml solution can be administered in conjunction with amoxicillin
or 150, 300, 450, 600, 750, 900 mg tablets. (Augmentin®). Clavulonic acid binds and inhibits
beta-lactamases that inactivate amoxicillin. It is
Sample clindamycin prescription for a 3-year-old recommended to be taken with food to increase
patient weighing 12 kg (25 lb) with facial swelling: absorption and decrease GI intolerance.
Rx: Clindamycin 75 mg/5 ml
Disp: 150 ml Contraindications: Hypersensitivity to amoxicillin,
Sig: Take 1 teaspoon every 8 hours for 10 days clavulanic acid, penicillin or any component of the
formulation; history of hepatic dysfunction.
Amoxicillin
Some clinicians select amoxicillin over penicillin Warnings/Precautions: Prolonged use may result
VK to treat odontogenic infection because of in superinfection. Use with caution in patients with
a more convenient dosing regimen e.g., 2-3 severe renal impairment (modify dosage). Incidence
doses daily for amoxicillin versus 4 doses of diarrhea is higher than with amoxicillin alone.
daily for penicillin VK. Except for coverage of
Haemophilus influenzae in acute sinus and otitis The usual daily oral dose of Augmentin® for
media infections, amoxicillin is not any more treating odontogenic infections in children is:
effective than penicillin VK for the treatment of Children ≥ 3 months and < 40 kg: 20-40 mg/kg/day
odontogenic infections. It is less effective than in 3 divided doses.
penicillin VK against aerobic gram-positive cocci Children > 40 kg and adults: 250-500 mg every 8
and similar in efficacy against anaerobes. Thus hours or 875 mg every 12 hours.
penicillin VK is the drug of choice for treating Augmentin® is supplied as 125, 200, 250, 400 mg/
odontogenic infections. 5ml solution, chewable tablets and tablets.
7
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
Sample amoxicillin/clavulanate (Augmentin®) Sample cephalexin prescription for a 3-year-old
prescription for a 3-year-old patient weighing patient weighing 12 kg (25 lb) with facial swelling:
12 kg (25 lb) with facial swelling: Rx: Cephalexin 125 mg/5 ml
Rx: Augmentin® 125 mg/5 ml solution (or Disp: 200 ml
chewable tablets) Sig: 1 tsp every 6 hours for 10 days
Disp: 150 ml (or 30 chewable tablets)
Sig: 1 tsp (or tablet) every 8 hours for 10 days Second-generation Cephalosporins
The advantage of the second-generation
First-generation Cephalosporins cephalosporins over the first-generation
The first-generation cephalosporins are cephalosporins is that they are more effective
alternatives to penicillin VK for the treatment of against some of the anaerobes, however, they are
odontogenic infections. The oral dosage forms more effective in treating early infections rather
of this class are cefadroxil (Duracef®), cephalexin than late infections.
(Keflex®), and cephradine (Velosef®). They are
indicated as alternatives to penicillin VK in early Contraindications: Hypersensitivity to cefaclor,
infection because they are bacterially effective any component of the formulation, or other
against aerobes but not anaerobes. They are cephalosporins.
active against gram-positive staphylococci
and streptococci, but ineffective against Warnings/Precautions: Modify dosage in patients
enterococci. The rate of cross reactivity between with severe renal impairment; prolonged use
cephalosporins and penicillins is 1% when the may result in superinfection. Use with caution
allergic reaction to penicillin is delayed. It should in patients with a history of penicillin allergy.
be used with caution in those patients exhibiting Extended release tablets are not approved for use
anaphylactoid reactions. in children < 16 years of age.
Contraindications: Hypersensitivity to cephalexin, The oral dosage forms of these drugs, cefaclor
any component of the formulation, or other (Ceclor®) and cefuroxine (Ceftin®), have the
cephalosporins. advantage of twice-a-day dosing
Warnings/Precautions: Modify dosage in patients The usual daily oral dose for treating
with severe renal impairment; prolonged use odontogenic infections is:
may result in superinfection. Use with caution in Children under 12 years: 20-40 mg/kg/day divided
patients with a history of penicillin allergy. May every 8-12 hours with a maximum dose of 2 g/day.
cause antibiotic associated colitis. Children over 12 years and adults: 250-500 mg
divided every 8-12 hours.
Cephalexin (Keflex®) is the first-generation Cefaclor and cefuroxine are supplied as 125, 187,
cephalosporin most often used to treat 250, 375 mg/5 ml suspensions and 250 and 500 mg
odontogenic infections. capsules.
The usual daily oral dose for treating Sample cefaclor/cefuroxine prescription for a
odontogenic infections in children is: 3-year-old patient weighing 12 kg (25 lb) with
Children under 12 years: 25-50 mg/kg/day facial swelling:
in divided doses every 6 hours. For severe Rx: Ceflacor 125 mg/5 ml
infections the dosage is 50-100 mg/kg/day in Disp: 150 cc
divided doses every 6 hours with a maximum Sig: 1 teaspoon every 8 hours for 10 days
does of 3 g/day for 10 days.
Children over 12 and adults: 250-1000 mg every 6 Macrolides (Erythromycin, Clarithromycin,
hours with a maximum of 4 g/day. Azithromycin)
Supplied as a 125, 250 mg/5 ml suspension and The macrolides are antibiotics with a spectrum
250 and 500 mg capsules. of coverage similar to penicillin, with the addition
8
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
of some penicillanase-producing staphylococci, doses; do not exceed 3.2 g/day
chlamydiae, Legionella, mycoplasma and others. Stearate: 30-50 mg/kg/day in 2-4 divided doses;
Erythromycin is the most popular macrolide. In its do not exceed 2 g/day
free base form it is unstable at gastric pH so it is
administered as a salt form (stearate or estolate) or Adults and children > 12 years
with an enteric coating. (Note: Due to differences in Base: 250-500 mg every 6-12 hours
absorption the three forms have different dosages). Ethylsuccinate: 400-800 mg every 6-12 hours
Its most common side effect is gastrointestinal
upset. Clarithromycin and azithromycin are Supplied as:
structural derivates of erythromycin with a broader Capsules, delayed release enteric coated tablets
spectrum of activity and increased bioavailability. as base (Eryc®) 250 mg
Both agents exhibit less gastrointestinal upset than Suspension, oral, as estolate: 125 mg/5 ml, 250
erythromycin. Macrolides are bacteriostatic rather mg/
than bacteriocidal and thus are not recommended in 5 ml
immuno-compromised patients. Suspension, oral, as ethylsuccinate: 200 mg/5 ml,
400 mg/5 ml
In the past, macrolides were considered highly Tablet, chewable, ethylsuccinate: 200 mg
effective antibiotics for treating dental infections Tablet, as base: 250 mg, 500 mg
and frequently substituted in penicillin allergy. Tablet, as ethylsuccinate: 400 mg
Currently, however, the high resistance rates Tablet as stearate: 250 mg, 500 mg
of oral streptococci and oral anaerobes to the
macrolides has reduced their use in dental Sample erythromycin estolate prescription for
infections. For patients with a penicillin allergy a 3-year-old patient weighing 12 kg (25 lb) with
clindamycin is the preferred alternative antibiotic facial swelling:
for treating dental infections. Rx: Erythromycin estolate 125 mg/5 ml
Disp: 200 ml
Contraindications: Hypersensitivity to erythromycin Sig: 5 ml every 6 hours for 10 days
or any component of the formulation.
Clarithromycin (Biaxin®)
Warnings/Precautions: Use with caution in Children ≥ 1 month: 15 mg/kg/day divided every
patients with hepatic impairment. Administration 12 hours for 7 days; maximum 1 gm/day
may be accompanied by malaise, nausea, Adults: 250-500 mg every 12 hours or 1000 mg
vomiting, abdominal colic and fever. Discontinue (Two 500 mg extended release tablets) once daily
use if these occur. Avoid using erythromycin for 7-14 days
lactobionate in neonates since formulations may
contain benzyl alcohol which is associated with Supplied as:
toxicity in neonates. Use in infants has been Granules for oral suspension: 125 mg/5 ml, 250
associated with infantile hypertrophic pyloric mg/
stenosis. Interacts with numerous other drugs 5 ml (50 ml, 100 ml)
increasing the serum levels of the drugs. Confirm Tablet: 250 mg, 500 mg
patient’s medical history before prescribing. Tablet, extended release: 500 mg
The oral dosages and dosage forms of the Sample clarithromycin prescription for a 3-year-
macrolides are: old patient weighing 12 kg (25 lb) with facial
swelling:
Erythromycin Rx: Clarithromycin 125 mg/5 ml
Infants and children < 12 years Disp: 100 ml
Base: 30-50 mg/kg/day in 2-4 divided does; do not Sig: 5 ml every 12 hours for 7 days
exceed 2 g/day.
Estolate: 30-50 mg/kg/day in 2-4 divided doses; Azithromycin (Zithromax®)
do not exceed 2 g/day Children > 6months: 10 mg/kg - day 1, followed
Ethylsuccinate: 30-50 mg/kg/day in 2-4 divided by 5 mg/kg/day for 4 days. Dose should be given
9
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
1 hour before a meal or 2 hours after. Maximum individuals who undergo dental, GI tract or GU
250 mg/day tract procedures.
Adolescents ≥ 16 years or adult: 500 mg – day 1 • The risk of antibiotic associated adverse events
then 250 mg days 2-5 exceeds the benefit from prophylactic antibiotic
therapy.
Supplied as: • Maintenance of optimal oral health and hygiene
Powder for oral suspension: 100 mg/5 ml, (15 ml) may reduce the incidence of bacteremia from
200 mg/5 ml (15 ml, 22.5 ml, 30 ml) daily activities and is more effective than
Tablets: Zithromax®, Z-Pak® 250 mg (6 tablets) prophylactic antibiotics for a dental procedure
for reducing the risk of bacterial endocarditis.
Sample azithromycin prescription for a 3-year-old
patient weighing 12 kg (25 lb) with facial swelling: The revised guidelines clarified when antibiotic
Rx:Azithromycin 100 mg/5 ml prophylaxis is/is not recommended, i.e.,
Disp: 30 ml
1. Only an extremely small number of cases might
Antibiotic Prophylaxis for Bacterial be prevented by antibiotic prophylaxis.
Endocarditis 2. Antibiotic prophylaxis for dental procedures is
Bacterial endocarditis is a microbial infection recommended only for patients with underlying
of the inner layer of the cardiac muscle cardiac conditions associated with the highest
(endocardium). Patients with congenital or risk of adverse outcomes from bacterial
acquired cardiac defects are believed to be at endocarditis.
high risk for developing bacterial endocarditis if a 3. For patients with these underlying cardiac
(dental) procedure causes a transient bacteremia. conditions, prophylaxis is recommended for all
Blood-bourne bacteria may lodge on the dental procedures that involve manipulation of
abnormal endocardium or heart valves, causing gingival tissues or the periapical region of teeth
endocardial infection. In 2007 the American or perforation of the oral mucosa.
Heart Association revised its 1997 guidelines on 4. Prophylaxis is not recommended based solely
prevention of bacterial endocarditis. The primary on an increased lifetime risk of acquiring
reasons for the revision include: bacterial endocarditis
• Bacterial endocarditis is much more likely
to result from frequent exposure to random Specific recommendations from the 2007 AHA
bacteremias associated with daily activities guidelines on prevention of bacterial endocarditis
than form bacteremia caused by dental, GI are included in the following tables. Consultation
tract, or GU tract procedures. with the patient’s physician is recommended to
• Prophylaxis may prevent an exceedingly small determine the patient’s susceptibility to bacterial
number of cases bacterial endocarditis, in endocarditis.
10
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
Table 4. Dental Procedures for Which Endocarditis Prophylaxis is/is not
Recommended for Patients in Table 3.
11
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
The drugs are administered until 2 days after fungal infections. The reason is due to the difficulty
symptoms disappear. in attaining adequate degrees of selective toxicity.
Since virus replication uses the same metabolic
Sample perscriptions: mechanisms essential for the function of normal
cells, it was difficult to find drugs that would inhibit
Topical Antifungals viral growth without killing the host. However
Rx: Nystatin ointment recent advances in the research of viral replication
Disp: 45 gm tube have lead to discovery of agents useful in antiviral
Sig: Apply locally as directed with a thin coat to activity in the oral cavity. The agents are not highly
the affected area 4-5 times/day effective and are best used as soon as symptoms
first appear. Systemic supportive therapy should
Rx: Nystatin 100,000 units/ml oral suspension be administered in conjunction with antivirals which
Disp: 300 ml includes forced fluids, high concentration protein,
Sig: Rinse with 1 teaspoon (5 ml) for 2 minutes vitamin and mineral food supplements and rest.
4-5 times/day and expectorate. Viral infections may become secondarily infected
with bacteria requiring antibiotics.
Rx: Clotrimazole (Mycelex®) 10 mg troches
Disp: 70 troches Oral viral infections are most commonly caused
Sig: Dissolve 1 troche in mouth 5 times/day until by the herpes simplex virus. The herpes zoster
gone or herpes varicella–zoster virus can cause similar
viral eruptions involving the oral mucosa.
Rx: Ketoconazole (Nizoral®) 2% cream
Disp: 45 gm tube Diagnosis of oral viral infections begins by
Sig: Apply locally as directed with a thin coat to evaluation of presenting signs and symptoms.
the affected area 4-5 times/day. A distinction must be made between lesions
associated with herpes and aphthous ulcers
Systemic Antifungals – The decision to use which do not have a viral etiology.
systemic antifungals are based on diagnostic
culture results. Viral lesions (Herpetic gingivostomatitis) are
Rx: Ketoconazole (Nizoral®) 200 mg tablets characterized by an initial acute onset of vesicular
Disp: 20 tablets eruptions on the soft tissues that quickly rupture
Sig: Take 1 tablet daily into small ulcerations that are covered by a
yellowish gray pseudomembrane surrounded by an
Rx: Fluconazole (Diflucan®) 100 mg tablets erythematous halo. The ulcers may coalesce to
Disp: 22 tablets form larger irregular ulcerations. The lesions are
Sig: Take 2 tablets day 1, then 1 tablets/day until found on the gingival, tongue, palate lips (labialis),
finished buccal mucosa, tonsils and posterior pharynx.
The ulcers gradually heal over 7-10 days without
Angular Cheilitis Treatment scarring. The disease is accompanied by high
Rx: Iodoquinol and hydrocortisone cream fever, malaise, irritability, headache and pain in
Disp: 45 gm tube the mouth during the first three days of onset. It
Sig: Apply locally as directed 3-4 times/day for 10 usually appears in children between the ages of
days to 2 weeks and re-evaluate six months and four years. Treatment consists of
administration of acyclovir and supportive therapy.
Rx: Nystatin and triamcinolone acetonide ointment
Disp: 45 g tube Contraindications: Hypersensitivity to acyclovir,
Sig: Apply locally as directed to affected area 4 valacyclovir, or any component of the formulation.
times/day for 10 days to 2 weeks and re-evaluate.
Warnings/Precautions: Use with caution in
Antivirals and Ulcerative Lesions immunocompromised patients. Safety and
Advances in the pharmacological treatment of viral efficacy of oral formulations have not been
infections lag behind the treatment of bacterial or established in pediatric patients < 2years of age.
12
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
The ointment is for external use only to the lips Rx: Docosanol (Abreva®) OTC ≥ 12 years and adults
and face. Do not apply to the eye or inside the Disp: 2 gm tube
nose or mouth. Treatment should begin at the Sig: Apply to lesion 5 times/day during waking hours
first sign of symptoms. for 4 days (begin when symptoms first appear)
The oral systemic dose of acyclovir (only given Recurrent Aphthous Stomatitis
in severe cases of HSV) is: Liquid volumes are prescribed for a 2 week course
Children ≥ 2 years and ≤ 40 kg: 20 mg /kg/dose
(up to 800 mg /dose) 4 times/day for 5 days Rx: Orabase® Protective Barrier (OTC)
Children > 40 kg and adults: 800 mg/dose 4 Disp: 1 package
times/day for 5 days Sig: Apply locally as needed every 6 hours.
13
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
levels (mild, moderate, severe) may be assigned Dosage:
for specific situations and procedures and Children < 12 years: 10-15 mg/kg dose every 4 to
the dentist should judiciously use his or her 6 hours as needed. Do not exceed 5 doses (2.6 g)
knowledge of analgesics to prescribe the most in 24 hours.
effective drug and appropriate dose to alleviate Adults: 325-650 mg every 4 to 6 hours or 1000 mg
pain while avoiding overmedication. 3-4 times/day. Do not exceed 4 grams/day.
14
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
a potential association with Reyes syndrome. events. NSAIDS can compromise renal function
Should not be prescribed during pregnancy. and hepatic function. They may increase risk
of gastrointestinal irritation, ulceration, bleeding
Warnings/Precautions: Use with caution in and perforation. Use caution with a history of GI
patients with platelet and bleeding disorders, bleeding or ulcers, concurrent therapy with aspirin,
renal dysfunction, dehydration, erosive gastritis, anticoagulants, corticosteroids, smoking and
or peptic ulcer disease. Avoid use in severe renal use of alcohol. Patients should be instructed to
failure or severe hepatic failure. Surgical patients contact healthcare provider if used for fever lasting
should avoid aspirin if possible, for 1-2 weeks prior >3 days or pain lasting >5 days in children and 10
to surgery to reduce the risk of excessive bleeding. days in adults.
Dosage: Ibuprofen
Children: Analgesic and antipyretic: Oral, rectal:
10-15 mg/kg dose every 4-6 hours up to a total of Dosage:
4 g/day Children < 12years: 4-10 mg/kg/dose every 6-8
Adult: Analgesic and antipyretic: Oral, rectal: 325- hours (maximum daily dose 40 mg/kg/day)
650 mg every 4-6 hours up to 4g/day Children > 12 years and adults: 200 mg–400 mg
every 4-6 hours (maximum daily dose: 1,200 mg/day)
Supplied as:
Tablets: 81 mg chewable, 325 mg, 500 mg Supplied as:
tablets, caplets Suspension, oral drops: 40 mg/ml
Suppository, Rectal: 300 mg, 600 mg Suspension, oral: 100 mg/5 ml
Tablet, chewable: 50 mg, 100 mg Contains
Nonsteroidal Anti-inflammatory Drugs – phenylalanine
NSAIDS (ibuprofen, naproxen) Tablet, capsules: 200 mg, 400 mg, 600 mg, 800 mg
The nonsteroidal anti-inflammatory agents
are derivatives of phenylalkanoic acid. They Naproxen
are divided into two categories; ibuprofen and
naproxen. They are similar in their actions and Dosage:
side effects but differ in their molecular structure Children ≤ 12 years: 5-7 mg/kg 2-3 times/day
with naproxen exhibiting greater anti-inflammatory Children > 12 years and adults < 65 years: Initial
action. They produce their analgesic effects 500 mg, then 250 mg every 6-8 hours, maximum
peripherally by inhibiting prostaglandin synthetase. 1250 mg/day.
They are superior to aspirin in their analgesic
(for moderate pain) and anti-inflammatory Supplied as:
properties. NSAIDs produce fewer bleeding Suspension: 125 mg/5 ml
problems than aspirin because their inhibition Caplet, gelcaps: 220 mg (equivalent to naproxen
of platelet aggregation is reversed as soon as 200 mg and sodium 20 mg)
they are fully excreted. Reported side effects Caplets, gelcaps, tablets 220 mg, 250 mg, 275 mg,
include gastrointestinal upset, rash headache, 375 mg, 500 mg, 550 mg
dizziness, eye problems, hepatic dysfunction and
renal dysfunction. Allergic reactions are very rare. Narcotic Analgesics
Chewable tablets may contain phenylalanine and Narcotic analgesics interact with opioid receptors
thus should be prescribed with caution in patients in the CNS. The interactions result in the narcotic
exhibiting phenylketonuria. pharmacologic effects of analgesia, sedation
and cough suppression. While significantly more
Contraindications: Hypersensitivity to ibuprofen, effective against severe and acute pain than
aspirin, other NSAIDS, or any component of the nonnarcotic analgesics they have the disadvantage
formulation, pregnancy (3rd trimester) and history of adverse effects such as sedation, respiratory
of asthma. depression and dependence.
Warnings/Precautions: NSAIDS are associated Codeine is the most commonly prescribed narcotic
with an increased risk of adverse cardiovascular for moderate to severe pain. It is absorbed well
15
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
when taken orally and may be used for severe medication. For the vast majority, recommended
pain that is not responsive to acetaminophen, doses of acetaminophen or NSAIDs will control
aspirin, and NSAIDS. Codeine is usually given in the pain. In the few cases that narcotics are
combination with non-narcotic analgesics, because prescribed the duration should be short and the
the narcotic acts at a central site and the non- dosage of codeine determined by weight to avoid
narcotic analgesic at a peripheral site providing respiratory depression.
enhanced analgesic activity. Codeine products
are recommended only for acute dosing (3 days Topical Anesthetics
or less) as they can cause nausea, sedation, Topical anesthetics are used in dentistry to reduce
constipation and dependency with prolonged use. the initial soft tissue pain associated with local
anesthetic administration and in management of
Contraindications: Same as for acetaminophen gum pain associated in teething and other soft
plus hypersensitivity to codeine or any component tissue irritation. Topical anesthetics are available
of the formulation, significant respiratory in gel, liquid, ointment, patch and pressurized spray
depression, acute or severe bronchial asthma, forms. When applying topical anesthetics to the
hypercapnia, and paralytic ileus. soft tissue, especially in young children, use the
smallest effective amount to avoid anesthetizing
Warnings/Precautions: Same as acetaminophen the pharyngeal tissues.
plus use with caution in patients with
hypersensitivity to other opioid agents. Use The most common topical anesthetics used in
with caution in patients with hypotension, dentistry are those with benzocaine or lidocaine.
adrenocortical insufficiency, thyroid disorders,
prostatic hyperplasia, urethral stricture, seizure Ethyl aminobenzoate (benzocaine) is an ester
disorder, CNS depression, head injury or increased local anesthetic. It is available in up to 20%
intracranial pressure. Safety and efficacy in concentrations. It is poorly absorbed into
pediatric patients has not been established. cardiovascular system. It remains at the site of
application longer, providing a prolonged duration
Dosage: of action. Localized allergic reactions may occur
Children ≤ 44 kg: Oral following prolonged or repeated use and it is reported
Codeine: 0.5-1 mg codeine/kg/dose every 4-6 hours to inhibit the antibacterial action of sulfonamides.
Acetaminophen: 10-15 mg/kg/dose every 4-6 hours
up to 2.6 gm/day Not known to produce systemic toxicity in adults, it
can produce local allergic reactions. In April 2011
Children > 44 kg and adults: Oral the Food and Drug Administration announced that
Codeine: 30-60 mg/dose every 4-6 hours. “Topical benzocaine sprays, gels and liquids used
Acetaminophen: 325-650 mg/dose every 4-6 hours, as anesthesia during medical procedures and for
up to 4g/day analgesia from tooth and gum pain may cause
methemoglobinenmia, a rare but serious and
Supplied as: potentially fatal condition. Children younger than
Elixir, suspension: Acetaminophen 120 mg and 2 years appear to be at particular risk. In the most
codeine phosphate 12 mg per 5 ml severe cases, methemoglobinemia can result in
Tablets: death. Patients who develop methemoglobinemia
#2 = 300 mg acetaminophen and codeine may experience signs and symptoms such as
phosphate 15 mg pale, gray or blue colored skin, lips and nail beds;
#3 = 300 mg acetaminophen and codeine headache; lightheadedness; shortness of breath;
phosphate 30 mg fatigue; and rapid heart rate.”6
#4 = 300 mg acetaminophen and codeine
phosphate 60 mg Most of the cases reported were in children
younger than 2 years who were treated with topical
Analgesics Commonly Prescribed for Children benzocaine gels for the relief of teeth pain. The
It has been reported that more than 20% of signs and symptoms can occur after a single
pediatric patients undergoing restorative treatment application or multiple applications and can begin
and extractions require post-operative pain within minutes and hours of application.
16
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
Table 6. Analgesics Commonly Prescribed for Children.5
17
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
Topical anesthetic manufacturers, i.e., Orajel, has amounts of fluoride, when prescribing systemic
removed benzocaine as its active ingredient and fluorides it is important the dental professional
substituted oil of cloves. take into account all the possible sources of
fluoride that the patient ingests, to determine
Lidocaine is absorbed by the soft tissue and the correct level of supplementation. In areas
can enter the cardiovascular system. Therefore, where the community water supply is fluoridated,
when using topical lidocaine in conjunction with children may be exposed to amounts of fluoride
injectable lidocaine, the clinician must calculate in excess of the recommended levels because of
the additive amount administered, especially in a ingestion of fluoride from swallowed toothpaste
small child, to avoid anesthetic toxicity. and concentrated fluoride reconstituted with
fluoridated water. Conversely, in areas with
Caries Prevention optimal fluoridation, some families avoid the use
Among the reasons for the significant reduction community fluoridated water supplies for drinking
in dental caries in children over the past several and cooking because of fear of chemical and
decades has been the increased availability of bacterial contamination. The bottled water the
fluoride. When administered in the appropriate family uses may not contain optimal levels of
dosage, fluoride is a highly safe and effective fluoride and thus fluoride supplementation should
method for the prevention and control of caries. be considered.
Although the precise mechanisms by which
fluorides act is not fully understood, three After investigation of the patient’s dietary intake
mechanisms are generally accepted: of fluoride and a risk assessment for the patient’s
proclivity for caries, the clinician can refer to
1. increasing the resistance of tooth structure to the Dietary Fluoride Supplementation Schedule
demineralization; as recommended by the American Academy of
2. enhancing the process of remineralization; and Pediatric Dentistry and the American Academy of
3. reducing the cariogenic potential of dental plaque. Pediatrics (Table 7).
The effects of fluoride are classified as either Practitioners should consider the following when
systemic or topical. Sources of systemic fluoride discussing fluoride intact with patients and
include drinking water from home and school, parents:
beverages such as soda, juice, and infant formula, • The preventive effects of fluoride are topical,
prepared food, professionally prescribed fluoride not systemic
products and ingestion of toothpaste. The • Fluoride intake for infants in concentrated or
sources of topical effects are available from powdered formula must be monitored
previously mentioned systemic sources contacting • Tooth brushing in children under three should
the teeth during ingestion, toothpastes containing be supervised
fluoride and professionally applied or self applied • Use only a smear or pea sized amount of
concentrated forms of fluoride. fluoridated toothpaste
• Encourage the child to spit out excess
Systemic Fluorides toothpaste
As fluorosis of the teeth has been associated with • Do not let the child eat toothpaste
chronic ingestion of greater than recommended
18
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
Contraindications: Hypersensitivity to fluoride, therapy), concentrated topical fluorides may be
tartizine or any component of the formulation; prescribed for home use. Topical concentrated
when fluoride content of water exceeds 0.7 ppm. agents for home use include 0.5% acidulated
phosphate fluoride, 1.1% sodium fluoride gel and
Warnings/Precautions: Prolonged ingestion of 0.4% stannous fluoride gel. Stannous fluoride gels
excessive doses may result in dental fluorosis and are preferable for younger children because a 0.4%
osseous changes. stannous fluoride preparation is approximately
one-fourth as concentrated as 0.5% acidulated
Systemic fluoride supplements are available as phosphate fluoride. The gel is available without
liquid or chewable tablets. The fluoride in most a prescription. The patient is instructed to brush
dietary fluoride supplements is incorporated as a small amount of gel on the child’s teeth before
sodium fluoride (NaF). One milligram of fluoride bedtime. Expectoration is encouraged however no
is equivalent to approximately 2.2 mg of sodium eating or drinking for 30 minutes. Depending on
fluoride. When prescribing fluoride the clinician the formulation and concentration of the product,
should specify the dose to be dispensed in terms application is daily or weekly.
of fluoride ion, sodium fluoride, or both. Fluoride
drops and tablets are available as sodium Safety and Toxicity
fluoride 0.5mg (0.25 mg fluoride), 1.1 mg (0.5 When used as directed, fluoride can improve
mg fluoride, and 2.2 mg (1mg fluoride). When the oral health of children. However, when used
prescribing chewable tablets it is recommended improperly it can produce chronic (fluorosis) and
that the child suck on the tablets before chewing acute problems. Therefore, it is imperative that the
and swallowing to maximize the contact time of practitioner instruct parents and patients about the
the fluoride with the tooth enamel. Samples of proper storage and use of fluoride products.
supplemental fluoride prescriptions are:
Accidental ingestion of excessive amounts of
12-month-old whose drinking water contains less fluoride can result in acute toxicity. Acute fluoride
than 0.2 ppm fluoride: toxicity usually manifests itself as nausea and
Rx: Sodium fluoride solution 0.5 mg/ml (0.25 mg vomiting but death has been reported. The amount
fluoride) of ingested fluoride necessary to produce acute
Disp: 50 ml toxicity is in proportion to the child’s weight. For
Sig: Dispense 0.5 ml of liquid in mouth before example, the lethal dose of fluoride for a 25 pound
bedtime three year old is approximately 500mg but would be
proportionately less for a child of lesser weight.
Four-year-old whose drinking water contains less
than 0.2 ppm fluoride: To reduce the possibility of ingestion of large
Rx: Sodium fluoride tablets 0.25 mg fluoride/tablet amounts of fluoride, it is recommended that
(0.55 mg NaF/tablet) no more than 120 mg of supplemental fluoride
Disp: 180 tablets be prescribed at any one time. Preparations of
Sig: Chew one (1) tablet, swish, and swallow after concentrated topical fluoride preparations (0.5%
brushing at bedtime. Nothing to eat or drink for 30 fluoride gels containing 5mg fluoride/ml) should
minutes. be limited to 30 to 40 ml. The recommended
treatment if a child ingests excessive amounts
Concentrated Topical Fluorides for Home Use of fluoride is to call local poison control for
For patients with a high caries rate or high-risk verification, induce vomiting as quickly as possible
assessment for caries (undergoing orthodontic and give milk every four hours to slow absorption.
19
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
Course Test Preview
To receive Continuing Education credit for this course, you must complete the online test. Please go to:
www.dentalcare.com/en-US/dental-education/continuing-education/ce336/ce336-test.aspx
6. A 3-year-old, 30 pound patient presents with large carious lesion on a maxillary primary molar
tooth accompanied with facial swelling. The clinician attempts to perform a pulpectomy on
the tooth, however the patient complains of severe pain during excavation of decay after
administration of 1.5 carpules of lidocaine 2% with 1:100,000 epinephrine. The clinician should
____________.
a. forego the pulpectomy and extract the tooth
b. administer one additional carpule of the lidocaine and continue treatment
c. administer one carpule of articaine 4% with 1:100,00 epinephrine and continue treatment
d. suspend treatment, prescribe an antibiotic for seven days, and have the patient return for treatment
20
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
8. In an early stage of infection the predominate bacteria are _______________.
a. aerobic bacteria
b. a mix of aerobic and anaerobic bacteria
c. anaerobic bacteria
d. nonspecific bacteria
10. The ideal antibiotic for treating dental infections would _______________.
a. be bactericidal against gram positive cocci
b. be bactericidal against major pathogens of mixed anaerobic infection
c. cause minimal adverse reactions
d. All of the above.
13. In the event of penicillin allergy, the alternative choice in treating mild or early odontogenic
infections is ____________.
a. Clindamycin
b. Amoxicillin
c. Erythromycin
d. a second-generation cephalosporin
21
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
16. An example of a topical antifungal ointment is ____________.
a. Nystatin
b. Ketoconazole
c. Fluconazole
d. A and B
20. The maximum daily dose of acetaminophen in children under 12 years of age is ____________.
a. 1.3 grams
b. 2.6 grams
c. 4 grams
d. 5 grams
22
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
24. When prescribing systemic fluoride supplementation the following should be considered
____________.
a. the patient’s age
b. the fluoride content of the community water supply
c. the patients dietary habits
d. All of the above.
25. The recommended treatment if a child ingests excessive amounts of fluoride is to _______________.
a. call local poison control for verification
b. induce vomiting as soon as possible
c. give milk every four hours to slow absorption
d. All of the above.
23
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016
References
1. Yagiela JA, Dowd FJ, Neidle EA. Pharmacology and therapeutics for dentistry, 5th ed. St. Louis, MO.
Mosby. 2004.
2. American Academy of Pediatric Dentistry reference manual 2014-2015. Pediatr Dent. 2014-2015;36
(6 Suppl):284-286.
3. Pinkham JR. Pediatric dentistry: infancy through adolescence, 4th ed. St. Louis, Mo. Elsevier
Saunders. 2005.
4. Robertson D, Smith AJ. The microbiology of the acute dental abscess. J Med Microbiol. 2009 Feb;
58(Pt 2):155-62. doi: 10.1099/jmm.0.003517-0.
5. Wynn RL, Meiller TF, Crossle HL. Drug information handbook for dentistry: including oral medicine for
medically-compromised patients & specific oral conditions, 12th ed. Hudson, OH. Lexi-Comp. 2006.
6. FDA. U.S. Food and Drug Administration. FDA Drug Safety Communication: Reports of a rare, but
serious and potentially fatal adverse effect with the use of over-the-counter (OTC) benzocaine gels
and liquids applied to the gums or mouth. 2011. Accessed December 22, 2015.
Email: sschwartz11@nshs.edu
24
Crest® Oral-B® at dentalcare.com Continuing Education Course, Revised January 8, 2016