Drugs, Disease, and Dentistry Elizabeth A. VandeWaa, Ph.D. University of South Alabama

Drugs, Disease, and
Elizabeth A. VandeWaa, Ph.D.
University of South Alabama
Drugs and Dentistry
 Local Anesthetics
 Pain Medications
 Bisphosphonates
 Drugs of Abuse
Sedatives: Just Relax…
 Sometimes used as preanesthetic
 When used with nitrous oxide, typically
less NO is needed (especially in children!!)
 Watch for oversedation and respiratory
To Ease the “Stress”…
 Benzodiazepines (Alprazolam, Oxazepam,
Midazolam, Diazepam) plus
antihistamines (Benedryl) and/or
Barbiturates (Secobarbital)
 Alprazolam
one of the top 20 drugs
prescribed in the US
 Loss of consciousness, respiratory
depression, death. Antidote to BZD overdose
is Flumazenil (Romazicon)
Pros and Cons of Sedative Use
 Reversing
agent; they work!; addictive;
amnesia; patient needs care in getting to/from
 No
reversing agent; respiratory depression;
patient care; sedating
 Long
duration of sedation in the elderly;
Potentially Problematic Drug
Chloral Hydrate plus Warfarin
 Prolongs
bleeding time
Chloral Hydrate plus Lasix
 Increases
Barbiturates plus Valproic acid
 Prolonged
HR, BP, diaphoresis
Barbiturates plus Warfarin
 Prolongs
bleeding time
Potentially Problematic Drug
Benzodiazepines plus….
 Decreased sedation
 Decreased sedation
Calcium Channel Blockers
 Increased sedation
 Increased sedation
 Increased sedation
Protease Inhibitors
 Increased sedation
Local Anesthetics—
Comfortably Numb
 Fairly
safe and superior to conventional
anesthetics in controlling procedural pain
when delivered via block injection or by
 Adverse effects of articaine (few) include
mandibular nerve injury, hypoesthesia, pain,
and tinnitus
Local Anesthetic Use
Safety Issues with these drugs
Never underestimate the importance of the
medical history. Always obtain complete
information at the preoperative appointment
and update it at the beginning of each
 Before the local anesthetic is administered,
address any fears or nervousness the patient
may have.
Local Anesthetics
Safety issues with these drugs
Make sure the patient is in a supine position
for the injections.
 Watch patients throughout the administration
of anesthetics. Do not leave them alone
following the injection.
Problematic Patients and LA
Cardiac Patient
 When
vasoconstrictors are used
Patient on Tricyclic antidepressants
 Recreational drug user—stimulants
 Allergic patient
Considerations with LA
Recreational use of cocaine by patients can
increase the risk of elevated blood pressure and
cardiac arrhythmias with injectable anesthetics
 Paresthesia has been reported occasionally
after local anesthesia with many of the amide
Considerations with LA
Levonordefrin should not be used with
tricyclic antidepressants, and reduced
dosages of epinephrine are recommended.
 May want to avoid this vasoconstrictor
altogether in patients with cardiovascular
disease (or discuss with their cardiologist)
LA Allergic Reactions
Allergic reactions to amide linkage
anesthetics are relatively rare and mostly
attributed to the preservatives or
antioxidants found in the anesthetic. Ester
linkage anesthetics (such as Novocain) had
a higher rate of reported allergy due to the
para-aminobenzoic acid (PABA)
LA and Allergic Reactions
Most reported allergic reactions are caused by
the preservatives methylparaben and
metabisulfite. Metabisulfite is added as an
antioxidant when vasoconstrictors are used in
 For
patients reporting a documented allergy to sulfites,
avoid anesthetics containing vasoconstrictors. For these
patients, plain anesthetics such as mepivacaine 3% or
prilocaine 4% are available without the preservative.
LA Allergic Reactions
For documented allergy to both ester and
amide groups, diphenhydramine can be
used for procedures of short duration. One
study found diphenhydramine efficacy
similar to that of prilocaine.
 Larger
studies needed to confirm this….but
Potentially Problematic Drug
Local anesthetic toxicity is additive in
combination. Combination therapy is
acceptable, but total dose should not exceed
maximum recommended doses.
Watch this especially in pediatrics!
child may be 1/3 to1/4 the size of an adult, but the
mouth is not. Thus, the drug need is about the
same….but metabolic and excretory rates are usually
reduced in children.
Potentially Problematic Drug
Amide local anesthetics (Lidocaine, Articaine,
Mepivacaine, etc.) plus inhibitors of drug
 Cimetidine,
The combination may prolong the effect of the
local or may enhance toxicity of local
Local Anesthetic Toxicity: CNS excitation,
seizures, respiratory depression, cardiac
Potentially Problematic Drug
Local anesthetic-induced
 Seen
with very high doses of Prilocaine or
Benzocaine, when patient is also taking
Dapsone, or is either very old or very young, a
COPD’er, anemic, or has G-6-PD deficiency.
Will present with cyanosis, dyspnea, and
increased heart rate. Methylene blue is the
Local Anesthetics
Safety issues with these drugs
 In
an emergency, ensure that someone
remains with the patient at all times,
monitoring breathing and heart rate until the
emergency is past or emergency medical
personnel arrive.
 Be prepared to assist with CPR
 Know where emergency equipment is located
Hair Color and Local Anesthesia?
A pharmacogenomic phenomenon
 Redheads are more resistant to local (and
general) anesthetics due to a mutation in
the MC1R gene
 They may require a clinically significant
higher dose of local anesthetics to numb
 Average
is 20-25% more!
Pregnancy and Locals
Data indicate that lidocaine and prilocaine may be safest
for use among pregnant and lactating women
Pregnancy Category B
 No harm to animals, but adequate and well-controlled
human studies have not been conducted….OR
studies conducted have not shown adverse effects
Pregnancy Category C
 No adequate trials in humans
Problematic Drugs
and Dentistry
Drugs that cause gingival hyperplasia:
Phenytoin (Dilantin)
Cyclosporin A (Gengraf)
Diltiazem (Cardizem)
Verapamil (Isopten, Calan)
Nifedipine (Procardia)
Aggressive oral hygiene (especially flossing)
seems to be helpful for this patient
Gingival Hyperplasia
Pain in Dentistry
Pain Medications in Dentistry
Two Types of Pain
 Two Types of Pain Medication
 Two Types of Patient!
“Rate Your Pain”
Two Types of Pain
Acute Pain
 Related
to procedure
 Short duration
 Inflammation-related, trauma related
 WILL “get better”
 Responds well to intervention, NSAIDs, ice,
Two Types of Pain
Chronic Pain
 Hopefully
NOT procedure-related, unless
patient needs extensive work
 May be infection-related
 Pain will be described as dull, persistent,
interfering with sleep—non-distractable
Two Types of Pain Medication
 All
CS, require prescription
 Compounded or single substances
 Short or long-acting
 REMS for some…
 Some
prescription, some not
 New formulations that may be helpful
 Multi-modal therapies
Two Types of Patient…
Type 1
 Compliant
 Opiate-naïve
 Fairly
high pain tolerance, “good soldier”,
good patient…but also may be an “underreporter”
Type 2
 “Experienced”,
possibly opiate tolerant
 Possible low tolerance to pain, but don’t rule
out pharmacogenomics
Controlled Substances
Schedule I: No approved medical use.
 Schedule II: Written prescription, signed
by prescriber. Oral orders ONLY in
emergencies with a written Rx to follow
within 72 h. No refills.
 Schedules III and IV: Oral or written
prescriptions. May be refilled up to 5
times, but refills must be made within 6
months of original order.
Pain Medications That May
Pose Problems
Opioids relieve dull, constant pain
 Can cause euphoria, sedation, reduction
of anxiety
 Can cause tolerance and physical
dependence…abuse liability
 And YOU may not be the only prescriber
The Doctor Shopper
Prescription Opiate Facts
US consumes 80 % of the world’s opioids and 99% of
the world’s hydrocodone
Accidental overdoses of Rx opiates kill more people in
17 states than do car accidents
Males are 1.5 times more likely to become addicted
AL is in the top 25% of states with 8.5-12.6 kg
prescription painkillers/10,000 people sold/year
 Drug overdose death rate about 13/100,000
 Highest in rural counties, females, middle-aged
Prescription Opiate Facts
Hydrocodone/APAP is the #1 prescribed
drug in the US!!!!
in 20 people in US take opiates for
nonmedical use
Enough Rx painkillers were prescribed in
2010 to medicate EVERY adult in the US
around –the-clock for one month
Opioid Related Deaths
Prescribing Opiates
Dentists prescribe 12% of all opiates in the US
 Accounting
for 1 billion doses per year
Opiates should be prescribed on a fixed schedule,
not as prn medications
Vicodin (Hydrocodone) and Percocet
(Oxycodone) are the most commonly prescribed
 Hydrocodone
is the most prescribed drug in the US
 There is a movement to ban Vicodin and Percocet
from commerce
Keeping Current With Drugs to
Manage Pain
Opiates are and will be mainstays of
chronic pain management
 Problems associated with use fall into 2
 Prescriber
education, liability, prescriptive
 User abuse, diversion
With Respect to Costs…
Prescription drug abuse accounts for 1
million ED visits/year
 Equal
to the number due to illegal drugs
60% of hospital costs related to opioid
overdoses are paid for with public funds
 What to do?
What To Do? Judicious
Approach to Prescribing
Institute clear policies and stick to those policies.
 If patients report that their medications have
been stolen, require that they report that to
the police and bring a police report to visit for
 Statewide databases that allow for tracking of
patient prescriptions, including prescriptions
for all schedule II drugs.
 REMS programs
 Fire the patient!
Opioid Sources in the Last 6 Months
Bought from a dealer
Someone gave them
Bought from a patient who sells their
Patients, %
Legitimate prescription for pain
Prescription from physician but no
legitimate reason
Prescription from multiple physicians
Prescription from physician who prescribes 3.4
Forged prescription
Other source
Risk Evaluation and Mitigation Strategies
REMS is being proffered as a way to
decrease the risks associated with longterm opiate use/abuse—long-acting drugs
included first
 Morphone,
morphine SR, hydromorphone ER,
methadone, oxycodone CR, oxymorphone
ER, transdermal fentanyl and transdermal
buprenorphine, morphine/naltrexone ER
Drug companies pay to educate
prescribers. IR drugs now being included
Will REMS Work?
FDA is asking that the training be
mandatory for anyone with a DEA#
 Advantages? OBVIOUS!
 Helpful
to the patient, prescriber
Disadvantages? OBVIOUS!
 Though
most prescribers are on board with
the idea….time, inconvenience
 The fear is that other drugs will be “switched
Making Opiates Safer--Latest
A bill introduced July 19, 2012 in the U.S.
House would require most painkillers to
have safeguards to prevent abuse
 If pain medications did not adopt the
safety features outlined in the bill, they
would be removed from the Food and
Drug Administration’s (FDA) approved list
of generic drugs
Opioids for Pain
Opioids used to treat chronic pain include
morphine sulfate (morphine, MSIR,
MSContin, Roxanol, Kadian, Avinza)
IR/ER, oxycodone (Oxycontin, OxyIR)
IR/ER, oxymorphone (Opana) IR/ER,
fentanyl (Duragesic) (IR/ER), methadone,
tramadol (Ultram, Ultracet) IR/ER,
hydromorphone (Dilaudid) IR,
hydrocodone/acetaminophen (Vicodin,
Lorset, Lortab, Norco) IR, and percocet
(oxycodone/acetaminophen) IR.
Tramadol (Ultram, Ryzolt)
Weak agonist at mu receptors, considered non-narcotic;
also blocks NE and serotonin reuptake
 Good PO for moderate to moderately severe ACUTE
 Not a CS, but….avoid prescribing to patients with a
history of drug abuse—diversion a problem
 Many drug interactions—watch for serotonin
syndrome, seizures!!
 Try limit use to about 5 days
 Requires metabolism, and 5-15% of the population
are slow metabolizers
Do NOT use ER tablets in patients with hepatic impairment!
Tapentadol (Nucynta)
A non-racemic molecule that is a moderate mu-opiate
agonist and only effects the uptake of norepinephrine
into nerve endings
No metabolic activation is required for analgesia and
there are no active metabolites
 This is an advantage over Tramadol
 It does not appear to cause the confusional states
sometimes associated with tramadol
 May be able to reduce morphine dose
 Useful for ACUTE pain
 C-II controlled substance
NSAIDs for Pain
Most widely used group of drugs for pain
 Side effects include GI bleeds/distress and
renal and hepatotoxicity
 No reduction of inflammation with
 Watch use in children, in alcohol use, high
BP, liver disease, renal disease
NSAIDs in Dental Practice
Lornoxicam (Xefo, Xafon, Lorcam, Acabel)
 Patients
receiving this drug in a single dose of
8 mg during dental procedures or immediately
after reported a “high level” of pain relief.
Relief was comparable to a 200-400 mg dose
of Ibuprofen.
Diclofenac Potassium (Cambio, Cataflam)
 50
mg tablets, IR preps gave patients good
pain relief, but are not recommended for use
beyond 48 h due to hepatotoxicity.
Newer Formulations of NSAIDs
 Sprix
nasal spray; Caldalor IV
 IV formulation (800 mg) reduces opiate need
by about 25% post-op
 No real worries about renal function since use
is short-term
 IV
for acute pain, or combined with an opiate
 Ofirmev; fast, penetrates CNS, anti-pyretic
 1000 mg in those weighing >50 kg every 6 h
For Chronic Pain…
Determine if infection is a possibility, then
 Consider other sources, such as
intracranial, vascular/myofascial,
neurogenic, TMJ, ear, eye, nasal,
paranasal sinus, lymph node, and salivary
gland pathology, as well conditions such
as untreated coronary vasospasm and
refractory angina.
For Chronic Pain…
Atypical facial pain or atypical odontalgia
of unknown etiology (termed persistent
facial pain of unknown etiology [PFPUE])
can be managed by multimodal drug
combination of opiates, NSAIDs, antiseizure agents, sedatives, antidepressants
may all be used
 Cognitive/behavior therapy may also be
Treatment of Pain—Multimodal
Opioids can help with ascending pain pathways
in chronic pain management.
 Plus
an antagonist to deal with opioid ADRs
NSAIDs can be used to decrease prostaglandin
formation centrally, and also to affect substance
P and serotonin pathways.
Membrane stabilizing drugs such as seizure
meds alter ion flux in nerve membranes, blunting
depolarization, affecting both pain transmission
and perception.
Anticonvulsants Used for Pain
Gabapentin (Neurontin), Pregabalin
(Lyrica), Tiagabine (Gabatril), Topiramate
 Good for neuropathic pain, pain due to
nerve injury, sensory neuropathy.
 May cause drowsiness, dizziness, report
any vision changes!!
Anticonvulsants Used for Pain
Carbamazepine (Tegretol)
Valproic acid (Depakote)
Phenytoin (Dilantin)
Clonazepam (Klonopin)
Lamotrigine (Lamictal)
Levetiracetam (Keppra)
Oxcarbazepine (Trileptal)
Zonisamide (Zonegran)
Antidepressants for Pain
Work best for neuritic or neuropathic pain,
less helpful for musculoskeletal pain
 Agitated or anxious patients do best with
antidepressants that are more sedating
 Most common SE are drowsiness,
constipation, dry mouth, blurred vision.
Watch for Serotonin Syndrome.
Antidepressants for Pain
 Not
as much GI upset as NSAIDs
 May help with sleep
 May reduce depression associated with
chronic pain
 May relieve anxiety associated with pain
 May increase effects of other pain meds
 Are non-addictive
 Safety is documented
Antidepressants Commonly
Prescribed for Pain
TCAs: Amitriptyline (Elavil), Desipramine
(Norpramin), Imipramine (Tofranil), and
Nortriptyline (Aventyl, Pamelor)
 Desipramine
has lowest SE profile
SSRIs: Duloxetine (Cymbalta),
Venlafaxine (Effexor), Mirtazepine
 Best
profile for pain. Other SSRIs not as
effective for chronic pain
New Uses of Old Drugs for
Muscle Relaxants
 Cyclobenzaprine
(Flexeril)—this is really a TCA, so it
has all the TCA side effects
 Carisoprodol (Soma)—now banned by European
Medicines Agency (our equivalent of the DEA) due to
abuse issues—watch for abuse potential!
 Methocarbamol (Robaxin) and Metaxolone
(Skelaxin)—older; sedation is main effect/SE
 Orphenadrine (Norflex)—this is actually Benedryl, so
sedation and inhibition of motor function will be seen
Older Drugs being Used in
Multimodal Strateiges
Tizanidine (Zanaflex)—an agent for spasticity that
shows some evidence for the treatment of chronic pain,
musculoskeletal pain, and neuropathic pain
 Alpha-agonist similar to clonidine; since it causes
significant sedation, should be reserved for night time
Lioresal (Baclofen)—antispasmodic that is being used
(off-label) for musculoskeletal pain. Sedation is side
effect of note.
Benefits of Multimodal Therapy
Using multi-modal analgesia (“balanced
 Benefit
the patient in that it can bring
sedation, pain relief while reducing
dependence/tolerance, and reduce tissue
 Benefit the prescriber in that it may mitigate
some of the adverse effects of opioids, may
reduce tolerance/dependence
Implications in
Dental Practice
Bone Disorders
Mainly seen in females, but males can be
afflicted, too
 More than 10 million women have osteoporosis
 Another 34 million have reduced bone mass
 Osteoporosis is the cause of 1.5 million fractures/year
 Of the 300,000 people who get hip fractures/year, 50,000 die
 Osteoporosis accounts for more than 432,000
hospital admits/year, 2.5 million office visits, and
180,000 nursing home admits
Price tag: $17 billion/year
Bone Resorption
Bone Disorders
After osteoporosis, Paget’s disease of the
bone is the most common bone disorder in
the US.
 3%
of people over age 40; 10% of those over
age 80
 Currently, about 8.2 million sufferers
Oral bisphosphonates include:
IV bisphosphonates include:
 Alendronate (Fosamax)
 Risedronate (Actonel)
 Ibandronate (Boniva)
 Tiludronate (Skelid)
 Etidronate (Didronel)
 Clodronate (Bonefos)
 Zoledronate (Zometa,
 Pamidronate (Aredia)
 Etidonrate (Didronel)
Bisphosphonate Use
Oral BPs are among the top 25 prescribed
drugs in the US
 Have
a high therapeutic index
Oral BPs decrease fractures in the hips
and vertebrae by 50%
 IV BPs increase compliance and decrease
fractures by 70%
Indications for Bisphosphonate Use
Postmenopausal osteoporosis
 Osteoporosis in men
 Glucocorticoid-induced osteoporosis
 Paget’s disease
 Hypercalcemia of malignancy
Mechanism of Action of BPs
BPs are incorporated into bone and inhibit
resorption by decreasing number and activity of
the osteoclasts.
 Since
these drugs are derivatives of pyrophosphate,
they “look” like a normal bone constituent. When they
are resorbed by osteoclasts, they inhibit their activity
 They decrease numbers of osteoclasts by reducing
osteoclast recruitment and by stimulating osteoblasts
So…if BPs Get Concentrated
in the Jaw…
They slow down the activity of osteoclasts
 This leads to areas of bone that do not get
resorbed, and instead die and become
avascular and necrotic
 If the mucosa happens to be damaged by
an invasive procedure at the same time,
the exposed bone cannot heal
Osteonecrosis of the Jaw
BP Use and the Oral
Health Professional
3 million take these meds orally
In 2003, iv bisphosphonates were linked to
osteonecrosis of the jaw
In 2004, some of the drugs on the market issued warning
statements in their prescribing information
This occurred when patients also had cancers,
significant osteoporosis or some other disease process
In 2005 a report came out that 7 of 63 oral
bisphosphonate users developed osteonecrosis of the
Legal cases began (for Fosamax) in August 2009
Bisphosphonates—Bad to the Bone?
Consider potential risks
 In
0.1-7% of patients—GI upset, pain,
esophageal pain or ulceration
 In <1% of patients—chest pain, angioedema,
and osteonecrosis of the jaw
 New warnings for atypical femur fractures
 IV infusion may induce renal failure, atrial
fibrillation (<0.1%)
ONJ in the Left Jaw
Drug Facts About BPs and ONJ
Doses for patients receiving chemotherapy
are up to 12-50 times higher than those for
 Half-life of these drugs is long—from
several days for Ibandronate (Boniva) to
up to 12 years for Alendronate (Fosamax)
 Elimination appears to be biphasic, with up
to 40% of the dose leaving after 90 days
Patients Most at Risk for ONJ
Take BPs by the IV route
 Are immunosuppressed
Secondary to GC use or
 Have
an invasive procedure plus
the above
Treatment of ONJ
Depends on the severity of the process
Stage I
 Disinfectant
Stage II
 Disinfectant
 Systemic antimicrobials
 Pain meds
Stage III
 As
above, plus surgical debridement or resection
Management of the Patient on
Oral BPs
Based on expert panel convened by ADA:
 Comprehensive
oral exam prior to beginning
BPs, if possible
 Thorough medical history
 Sterile technique
 Disinfectants and antibiotics as warranted
 Judicious use of invasive surgical techniques
In Patients Taking
Maintain good oral hygiene
 Do root canals rather than extractions
 Make sure not to injure soft tissue during
routine cleanings
 Do nonsurgical management of any dental
 Concomitant estrogen and/or GC use
MAY increase risk of a bad outcome
 If
the BP has been taken continuously more than 3
years, a drug holiday of 3 months before and 3
months after elective dental alveolar surgery is
recommended to prevent ONJ
 If the drug holiday is not authorized or not agreed to,
explain risks of ONJ
 No drug holiday needed for root canals, root scaling,
or restorative procedures
In Orthodontia
No invasive procedures
 No invasive laser therapy
 No extractions
 No implants, miniscrews
 Tooth movement in these patients may be
 Relapse rates may be higher
Not with BPs on Board
Drugs of Abuse and
Effects on the Mouth
Meth Mouth
Meth Mouth
Methamphetamine and
Tooth Damage
Methamphetamine causes tooth and
mouth damage due to:
 Its vasoconstrictive effect on blood
Its effect to cause the user to crave
Its effect to cause the user to not make
dental hygiene a priority!
Inhalation Damage
Meth Mouth
ADA Position on Management of
Meth User
Emphasize good oral hygiene and risk of
meth use
 Assess and treat damage from drug and
xerostomia—topical fluorides,
remineralization products, etc.
 Encourage use of artificial sweeteners
 Use pain meds, anesthesia, adjunctive
meds with care
Smokeless Tobacco
Smokeless Tobacco
15% of high school senior boys are current
users (higher in rural areas)
2/3 of high school boys have tried it; 15% of high
school girls have
Of those who have tried it, 90% say they first
Smokeless tobacco is easier to become
addicted to than cigarettes due to the higher
nicotine content
Tobacco Risks—Snuff Users
Oral cancer is one of the “top ten” most common
cancers in the world—the risk is increased 4-fold
for the smokeless tobacco user.
Halitosis, tooth discoloration, gum recession,
and tooth decay are common outcomes
associated with smokeless tobacco use. High
amounts of sugar and nicotine in the products
account for these.
Cancer in Teeth from a Smokeless
Tobacco User
Early Lesion from
Smokeless Tobacco
Squamous Cell Carcinoma
Ulceration from
Smokeless Tobacco!!
WHO Recommendations for Dental
Exams in Tobacco Users
Extraoral Exam: Inspect face, head, and neck for
growths, asymmetry.
Perioral and Intraoral Exam: Inspect lips, labial
mucosa, sulcus, tongue, hard and soft palates
for lesions, ulcerations, etc.
Dental and Periodontal Exam: Look for color
changes on the root and coronal surface of the
teeth; look for gingival recession.
Tobacco Risks--Smokers
Smokers have 67% greater tooth loss than
Smokers have more gingival inflammation
and supragingival plaque
 Four
times more likely to have an oral lesion than
a non-smoker
Smokers have a higher incidence of
periodontitis—2.5-3 fold—but may not have
bleeding gums due to the nicotine in tobacco
Smoker’s Teeth—Coming Soon to
a Cigarette Pack Near You?
New “Marketing”--Thailand
But the Biggest Deterrent of
If We’ve Missed Anything….
Hole in Soft Palate Due to Cocaine
Consider the impact of patient medications—licit
or illicit—on the mouth and teeth
When prescribing CS, be aware of REMS
programs for the protection of yourself and your
patient; limit pill count!
Watch drug combinations
Watch susceptible populations—children,
elderly, patients with hepatic or renal
impairment; consider pharmacogenomics