R e vie w of Top 10

P re s c r i b e d D r u g s a n d Th e i r
I n t e r a c t i o n w i t h D e n t a l Tre a t m e n t
Robert J. Weinstock,

DDS

a,b,

*, Michael P. Johnson,

DMD

a,b

KEYWORDS
 Drug interactions with dental treatment  Hypothyroidism  Hypertension  Diabetes
 Hypercholesterolemia  Asthma  Pain management
KEY POINTS
 The top 10 prescribed drugs and their interactions with dental treatment are reviewed.
 This article demonstrates the different ways drugs may interact with dental treatment for
example, side effects, drugdrug interactions.
 This article facilitates analysis of any drug and what to seek out when considering relevant
drug interactions with dental treatment.

The global proportion of people over the age of 60 is growing faster than any other age
group.1 Chronic medical conditions such as cancer, cardiovascular disease, hypertension, and diabetes are prevalent in this age group and contribute to this groups
overall morbidity and mortality.2 Poor oral health in this cohort is also common and
presents in the form xerostomia, tooth loss, periodontal disease, and edentulism.3
Dental visits by patients over age 65 are also increasing.4
Owing to our aging population and their multiple comorbidities, 9 out of 10 patients
over age 65 are taking one or more medications (compared with 1 in 4 when compared
with children). Because dentists will be seeing an increasing number of patients taking
1 or more medications, it is important for the dentist to become familiar with the interactions between dental treatment and commonly prescribed medications. Elements
of dental treatment with potential for interactions with medications include:
1. Local anesthetics;
2. The dental treatment itself; and
3. Medications the dentist may prescribe.

The authors have nothing to disclose.

a
Private Practice, 87 State Street, Guilford, CT 06437, USA; b Oral and Maxillofacial Surgery,
Yale-New Haven Hospital, 20 York Street, New Haven, CT 06510, USA
* Corresponding author. 87 State Street, Guilford, CT 06437.
E-mail address: rjw2119@gmail.com
Dent Clin N Am 60 (2016) 421434
http://dx.doi.org/10.1016/j.cden.2015.11.005
dental.theclinics.com
0011-8532/16/$ see front matter 2016 Elsevier Inc. All rights reserved.

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In this article, we review the top 10 prescribed drugs and their interactions with
dental treatment. According to the IMS institute national prescriptions audit of January
2015, the following drugs were the top 10 most prescribed drugs in the United States,
by number of dispensed prescriptions:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.

Levothyroxine
Acetaminophen with hydrocodone
Lisinopril
Metoprolol
Atorvastatin
Amlodipine
Metformin
Omeprazole
Simvastatin
Albuterol

LEVOTHYROXINE
Background

Levothyroxine is marketed as Synthroid (Abbvie Inc, North Chicago, IL) and is the most
commonly prescribed drug in the United States, with 119.9 million prescriptions
dispensed in 2014. Levothyroxine is a thyroid hormone supplement.
Pharmacology

The thyroid gland is responsible for synthesizing and releasing the hormones triiodothyronine and tetraiodothyronine (T4). Triiodothyronine is 10 times more potent than
T4; however, 80% of triiodothyronine is actually formed by deiodination of T4 in peripheral tissues.5 Levothyroxine is a synthetic form of T4.
Thyroid hormones are believed to exert their physiologic effect by modulating DNA
transcription and promoting protein synthesis. These proteins then act on their target
organs to secrete hormones that regulate growth and metabolism.6
Supplementing deficient thyroid hormones requires delicate titration because the
therapeutic index of levothyroxine is narrow. Excessive thyroid hormone administration can precipitate symptoms of thyrotoxicosis that include adverse cardiac, respiratory, central nervous system, and gastrointestinal, hepatic, and musculoskeletal
sequela.
Interactions with Dental Treatment

For the well-controlled hypothyroid patient taking a longstanding stable dose of levothyroxine, there are no specific interactions between levothyroxine and dental treatment. For patients who are recently diagnosed with hypothyroidism and are not yet
euthyroid, elective treatment is best deferred and emergent treatment carried out
with caution.7 The concern in the uncontrolled patient is that if the thyroid levels are
too high then thyrotoxicosis can ensue. Hypothyroidism rarely results in an emergent
situation; however, these patients are at risk for arrhythmias, heart failure, and
myxedema coma if severely deficient.8
Levothyroxine has several important relevant drugs interactions. Specifically, there
are interactions with levothyroxine and warfarin, ketamine, and carbamazepine. Levothyroxine increase the International Normalized Ratio (INR) in patients taking
warfarin. It is therefore important, especially when initiating levothyroxine, to monitor
INR levels and adjust warfarin dosage until the INR is stable. Levothyroxine may increase the hypertension and tachycardia that occurs with administration of ketamine

Review of Top 10 Prescribed Drugs

during parenteral sedation. Carbamazepine may increase thyroid hormone metabolism; thus, patients initiating these medications may need an adjustment of their levothyroxine dose.7

ACETAMINOPHEN WITH HYDROCODONE

Background

Opioids are central for pain management of the dental patient, especially when other
medications such as nonsteroidal antiinflammatory drugs (NSAIDs) are inadequate.
Hydrocodone with acetaminophen (hydrocodone/APAP) is marketed as Vicodin (Abbvie Inc, North Chicago, IL) and Lortab (UCB Inc, Smyrna, GA) and is the second most
commonly prescribed drug in the United States, with 119.2 million prescriptions
dispensed in 2014.5 Vicodin is a schedule II semisynthetic narcotic analgesic. All
hydrocodone/APAP formulations contain 300 mg of acetaminophen; the hydrocodone
contained in the tablet can be prescribed at 5, 7.5, or 10 mg.
Hydrocodone/APAP is an excellent analgesic; however, it is also a drug of abuse
with approximately 97,000 drug-related emergency room visits in 2011.9 Owing to
its abuse potential, the US Drug Enforcement Administration in 2014 rescheduled
hydrocodone from a schedule III to a schedule II drug.10
Pharmacology

Hydrocodone exerts its clinical effects by acting at the central nervous system opiate
receptors and at smooth muscle. There are multiple subtypes of opioid receptors; the
most commonly referenced are the m-1, m-2, d, k, and ORL-1 (nociceptin receptor).
The clinically useful action of hydrocodone, that is, analgesia, occurs at the m-1 receptor; however, the other opioid receptors are also activated by hydrocodone with m-2
activation resulting in respiratory and cardiovascular depression, and constipation.11
The APAP component acts as an antipyretic by modulating hypothalamic heat regulating centers. The analgesic qualities of APAP are believed to be owing to prevention
of prostaglandin synthesis. APAP is also a weak inhibitor of cyclooxygenase (COX)-1,
COX-2, and possibly also COX-3.12 The combination of an opioid with acetaminophen
improves the quality of pain relief when compared with APAP or an opioid alone.13
Hydrocodone is metabolized by the liver and excreted in the urine. Hydrocodone
has not been shown to have adverse effects in patients with renal failure14; however,
some authors recommend using lower doses in moderate renal failure and longer time
intervals in cases of severe renal failure.15 Acetaminophen has a plasma half-life of
1.25 to 3 hours and is increased in patients with liver damage.16 There is no ceiling
dose with hydrocodone; however, owing to potentially dangerous side effects, particularly respiratory depression, the lowest functional dose should be used. The
maximum acetaminophen dose in healthy patients should not exceed 4000 mg
because of the risk of hepatotoxicity. Because one can approach toxic levels of
APAP by taking opioids in combination with APAP, the US Food and Drug Administration (FDA) recommends discontinuing prescribing and dispensing of combination
drugs containing more than 325 mg of APAP.17
Interactions with Dental Treatment

There are no specific interactions between hydrocodone/APAP with dental procedures or local anesthetics. Because dentists will be prescribing opioids for perioperative pain management, we will present several pertinent scenarios warranting
prudent prescribing of hydrocodone/APAP.

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Patients on chronic opioids

Patients visiting the dentist may be taking hydrocodone/APAP for acute or chronic
pain. Patients receiving chronic opioid therapy present a unique perioperative
dilemma because they experience more severe acute pain and opioid-related complications than the opioid naive patient.18 It is believed that chronic opioid receptor activity induces a hyperalgesia, thereby decreasing a patients pain tolerance.19 When
presenting for a procedure that may incur postoperative pain, patients should be
encouraged to take their basal opioid the morning of the procedure. Then, using multimodal analgesia, nonopioid analgesics such as NSAIDs, APAP, COX-2 inhibitors,
clonidine, and anticonvulsants such as gabapentin and pregabalin, may be added
to the perioperative regimen.20 The use of anticonvulsants preoperatively may help
to decrease the amount of postoperative opioid required without increasing the side
effects of the opioid.21
The dentist is cautioned against prescribing increased doses of opioids for patients
on chronic opioids because the incidence of sedation is higher in the chronic opioid
group22 and without frequent clinical monitoring it may be difficult to identify the
appropriate postoperative opioid dose. The dentist is encouraged to consider the
use of long acting local anesthetics, preemptive analgesia, and perioperative NSAIDs
to mitigate the postoperative analgesic requirement required by the patient.
Patients with hepatic impairment

In patients with compromised liver function, peak plasma concentrations of hydrocodone can increase rapidly. The use of APAP in patients with compromised hepatic
function is controversial. APAP toxicity has been reported to occur more easily with
compromised hepatic function because these patients are more sensitive to the toxic
metabolites of APAP and have compromised ability to eliminate the toxic metabolites.23 Contradictory reports suggest that the impaired liver maintains its capacity
to metabolize and clear the toxic metabolites effectively and that APAP remains a
safe drug when taken at recommended dosages.2426
It is recommended that patients with cirrhosis not exceed a daily limit of 2000 mg
APAP.20,25,27 Practitioners should exercise caution when prescribing hydrocodone/
APAPcontaining medications to chronic alcoholics. In chronic alcoholics, the risk
of hepatotoxicity actually increase if, owing to the APAP, the alcoholic stops their
ethanol consumption.28 If they maintain their ethanol consumption, the risk of toxicity
from APAP decreases but the central nervous systemdepressing effects of ethanol
and hydrocodone are additive.
Drugdrug interactions

Hydrocodone is metabolized to hydromorphone (active metabolite) by the hepatic cytochrome P450 system, specifically, the CYP2D6 enzyme. Therefore, other medications that a patient is taking that are inducers and inhibitors of CYP2D6 can alter
the metabolism of hydrocodone.29 Patients who are poor metabolizers via CYP2D6
experience no analgesia from hydrocodone.30 Patients who are concomitantly taking
other narcotics, antihistamines, anxiolytics, and other central nervous system depressants should use caution when taking hydrocodone, because the central nervous system depression is additive.17
LISINOPRIL
Background

Lisinopril is an antihypertensive drug marketed as Zestril (AstraZeneca, Wilmington,

DE) and Prinivil (Merck, Whitehouse Station, NJ). It is the third most commonly

Review of Top 10 Prescribed Drugs

prescribed drug with 103.7 million prescriptions dispensed in 2014.5 Lisinopril belongs
to the class of antihypertensive agents called angiotensin-converting enzyme inhibitors (ACEi) and has extensive applications in the management of cardiovascular
disease.31
Pharmacology

The ACEi reduce blood pressure by modulating the hormones of the reninangiotensinaldosterone system. Renin is a hormone released by the juxtaglomerular cells
of the kidney in response to decreased renal perfusion and increased sympathetic activity32; renin is also produced locally in tissues. Renin cleaves and activates angiotensin I. Angiotensin I is cleaved by the angiotensin-converting enzyme into
angiotensin II.33 Angiotensin II acts centrally and peripherally to increase vascular
tone thus elevating blood pressure.34 Angiotensin II also promotes sodium retention
through it effects on aldosterone,35 and volume expansion through its effects on antidiuretic hormone.36 In summary, ACEi exhibit their effect by reducing systemic
vascular resistance without increasing the heart rate effectively reducing blood
pressure.37
Interactions with Dental Treatment

Routine dental procedures under local anesthesia can proceed safely in patients taking ACEi. Perioperative modification of lisinopril in patients who are receiving general
anesthesia is controversial. Most antihypertensive drugs are continued throughout the
perioperative period; however, some data show that continuing ACEi perioperatively
can exacerbate the hypotensive effect of anesthetics,3840 whereas other data show
no relation between continuing ACEi and intraoperative hypotension.41 Cumulative evidence recommends discontinuation of the ACEi the morning of surgery; however,
modification of anesthetic induction technique may possibly ameliorate the hypotensive effects of concomitant ACEi use and anesthetics.39
The side effects of ACEi are pertinent to the general dentist potentially affecting the
process of care delivery. The specific side effects include postural hypotension,
coughing, and angioedema, with angioedema potentially being life threatening.
Postural hypotension is a decrease in blood pressure that occurs when one rises
from a supine position to an upright position; this can potentially lead to dizziness
and syncope. To prevent issues related to postural hypotension, the patient should
be uprighted from the supine position slowly.
Between 10% and 35% of patients taking ACEi develop a dry cough.4244 This
cough may impact the delivery of dental care. The cough is believed to arise from increase in bradykinin production that stimulates the release of prostaglandins.45 The
cough usually develops within the first month and disappears within 1 week of cessation of the drug.46
A rare and potentially life-threatening condition linked to ACEi is the development of
angioedema. Oral or perioral angioedema describes a process of rapid swelling of the
lips, tongue, mucosal, and submucosal surfaces.47 The incidence of ACEi induced
angioedema is 0.1% to 0.2%.48 Angioedema can occur in any organ system and at
anytime, but more commonly the head and neck are affected typically occurs within
the first month of treatment.49 Patients of African descent are 3 times more likely to
be affected.50 Patients with perioral swelling may present to their dentist thinking
they have a tooth infection; therefore, the dentist should recognize the link between
ACEi and angioedema, and refer the patient to emergency department for definitive
management.

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Drugdrug interactions

Patient on ACEi should not take NSAIDs for perioperative pain management for longer
than 5 days because NSAIDs may decrease the effectiveness of the antihypertensive
effects of the ACEi.51 It has also been shown that combining NSAIDs and ACEi in susceptible patients may precipitate renal failure and subsequent electrolyte abnormalities.52 Therefore, caution should be used when prescribing NSAIDs to patients
taking ACEi, particularly the elderly, those with congestive heart failure, and those
with preexisting renal disease.53,54
METOPROLOL
Background

Metoprolol is marketed as Lopressor (Novartis, East Hanover, NJ) and is an antihypertensive, antiarrhythmic drug. It is the fourth most commonly prescribed drug with 83.3
million prescription dispensed in the United States in 2014.5 The indications for metoprolol include management of hypertension, angina pectoris, and to reduce mortality
from myocardial infarction.55,56
Pharmacology

Metoprolol is a beta-1 selective (cardioselective) beta-blocker. The beta-1 adrenergic

receptor modulates heart rate; the beta-2 adrenergic receptor modulates smooth
muscle relaxation. Beta-blockers are used to treat tachycardia and hypertension by
blocking the activity of endogenous catecholamines at the cardiac beta-1 receptors
and by inhibiting renin secretion by the kidneys.57 Beta-blockers are also used to treat
angina pectoris. The mechanism of action is likely related to reductions in heart rate,
myocardial contractility, and cardiac oxygen demand.58 Beta-blockers have also been
shown to improve survival after myocardial infarction.
Beta-blockers may be nonselective and block both the beta-1 and beta-2 receptors
or they may be beta-1 selective blockers. Beta-2 antagonism is not well-tolerated in
asthmatics; therefore, selective beta-1 blockers are typically used when they are indicated in the asthmatic patient.
Interactions with Dental Treatment

Cardioselective beta-blockers have less dental-related interaction than nonselective

beta-blockers. Nonselective beta-blockers can exacerbate bronchoconstriction in
asthmatics, and cause hypertension and reflexive bradycardia (severe enough to
require atropine) with epinephrine containing local anesthetics.59 As with ACEi, metoprolol can cause orthostatic hypotension; therefore, patients should be moved slowly
from a supine to an upright position. Metoprolol may also cause xerostomia, dysgeusia, and oral lichenoid reactions. NSAIDs taken by those on metoprolol may reduce the
antihypertensive effects of metoprolol.42
ATORVASTATIN AND SIMVASTATIN
Background

Atorvastatin is the fifth most commonly prescribed drug in the United States with 80.7
million prescriptions dispensed in 2014. Simvastatin is the ninth most commonly prescribed drug in the United States with 72.8 million prescriptions dispensed in 2014.5
Owing to the many similarities between these 2 drugs of same class, they are discussed jointly herein.
Atorvastatin is marketed as Lipitor (Pfizer, New York, NY). Simvastatin is marketed
as Zocor (Merck, Whitehouse Statin, NJ). Atorvastatin and simvastatin belong to the

Review of Top 10 Prescribed Drugs

group of cholesterol-reducing drugs known as hydroxymethylglutaryl-coenzyme A

reductase inhibitors. Cholesterol reducing medications are designed to reduce the
morbidity and mortality of coronary heart disease by reducing total cholesterol, lowdensity lipoprotein cholesterol, triglycerides, and increasing the high-density lipoprotein cholesterol. By reducing cholesterol, the disease process of atherosclerosis is
mitigated, therefore reducing the risk of adverse cardiovascular events such as angina
and myocardial infarction.6062
Pharmacology

Atorvastatin and simvastatin reduce cholesterol levels by inhibiting hydroxymethylglutarylcoenzyme A reductase, an enzyme required for the biosynthesis of cholesterol.
Cholesterol is circulated bound to lipoprotein complexes. These complexes are classified by the amount of cholesterol they can carry. Low-density lipoprotein cholesterol
carries low quantities of cholesterol and is a major contributing factor to atherosclerosis and cardiovascular disease.63 Conversely, high-density lipoprotein cholesterol
carries large quantities of cholesterol and is associated with decreased cardiovascular
risk.64
The statins are dependent on the liver for metabolism. The hepatic CYP3A4 enzyme
metabolizes atorvastatin and simvastatin. These statins can significantly elevate transaminases therefore these patients require regular hepatic function monitoring. Owing
to metabolism by CYP3A4, inducers and inhibitors of this cytochrome P450 system
may interact with these statins.61,62
Interaction with Dental Treatment

There are no specific interactions between dental treatment and patients taking these
statins. Dentists should, however, be cognizant of certain drugdrug interactions with
these statins. Patients taking coumadin may have elongation of their INR when starting
simvastatin; this interaction is not seen with atorvastatin.61,62,65 The INR may increase
with simvastatin owing to decreased warfarin metabolism and displacement of
warfarin from proteins.66 Therefore, patients starting statins while on coumadin should
have their INR closely monitored until a stable coumadin dose and desired INR are
reached.
Drugs that alter the activity at the hepatic CYP3A4 site may cause specific welldocumented toxicities unique to these statins. Drugs that the dentist may prescribe
that interact with atorvastatin and simvastatin include itraconazole, ketoconazole,
erythromycin, and clarithromycin. The adverse effects of statins, especially when
taken with a CYP3A4 inhibitor, include myopathy and muscle weakness that, if severe,
can result in rhabdomyolysis and acute renal failure. Confirmation of statin induced
myopathy is confirmed by history and elevation of creatinine phosphokinase.67
AMLODIPINE
Background

Amlodipine is an antihypertensive and antianginal drug marketed as Norvasc (Pfizer,

New York, NY). It is the sixth most commonly prescribed drug in the United States
with 78.3 million prescriptions dispensed in 2014. Amlodipine belongs to the class
of antihypertensives referred to as calcium channel blockers (CCB) and is commonly
prescribed for the treatment of hypertension and angina without congestive heart failure. Patients with coronary artery disease may be taking amlodipine to treat chronic
stable angina and vasospastic angina in patients without heart failure or an ejection
fraction of greater than 40%.67

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Pharmacology

Amlodipine exhibits its effects by inhibiting influx of extracellular calcium across

myocardial and vascular smooth muscle cells without disturbing serum calcium concentrations; this inhibits cardiac and vascular smooth muscle contraction thereby
dilating coronary and systemic arteries. Amlodipine consequently increases myocardial oxygen delivery in patients with vasospastic angina. Amlodipine is metabolized
extensively in the liver by cytochrome p450 enzyme, CYP3A4. Inhibition of this enzyme
will increase bioavailability and duration of action.68
Interaction with Dental Treatment
Amlodipine-induced gingival enlargement

Drug-induced gingival enlargement has been extensively described in the literature.

Kimball,68 who noted gingival enlargement associated with the use of the antiepileptic
drug phenytoin, first reported it in 1939. Since then many drugs, primarily from the 3
classes of drugs (anticonvulsants, CCB, and cyclosporins) have been associated
with gingival enlargement.
Despite the association of CCB and gingival enlargement, Amlodipine-associated
gingival enlargement is rare.69,70 Reports of amlodipine associated gingival enlargement has been shown primarily at higher doses (in excess of 10 mg per dose) and
in patients with poor plaque control. However, gingival enlargement has also been reported to occur in otherwise healthy patients even at lower doses (ie, 5 mg per
dose).71,72
Treatment consists of confirmation that the enlargement is in fact drug-induced
gingival hyperplasia, and not inflammatory or neoplastic. A discussion with the prescribing physician should explore the possibility discontinuing or substituting the
offending medication. With plaque control and drug cessation, most cases respond
favorably. Severe cases may require gingivectomy.
Patients on amlodipine should be informed of the potential for gingival enlargement
as an unwanted side effect, but should also be advised that it is rare, especially at
lower doses.73 Educating the patient, appropriate recall for prophylaxis, and home
plaque control play a critical role in preventing drug-induced gingival enlargement.
Hypotension after coprescription of macrolide antibiotics

Patients taking amlodipine are at increased risk for hypotension after the use of clarithromycin or erythromycin, but not azithromycin.
CCB are extensively metabolized by cytochrome P450 isoenzyme 3A4. This enzyme
plays an important role in the metabolism of many medications. It is strongly inhibited
by clarithromycin and erythromycin but not by azithromycin.72 The use of clarithromycin and erythromycin will increase serum levels of amlodipine, resulting in an increase
of the hypotensive effect. Therefore, it would be prudent to avoid macrolide antibiotics
in patients on CCB, although if one is required, azithromycin is the preferred drug.74
METFORMIN
Background

Metformin is an oral antihyperglycemic drug marketed as Glumetza (Salix Inc, Raleigh,

NC), Fortamet (Watson, Ft. Lauderdale, FL) Glucophage (Bristol-Myers Squibb,
Princeton, NJ), and Riomet (Ranbaxy, Jacksonville, FL). It is the seventh most
commonly prescribed drug in the United States with 76.9 million prescriptions
dispensed in 2014. Metformin is a first-line drug of choice for the treatment of type
2 diabetes mellitus, in particular, in overweight and obese people and those with
normal kidney function.

Review of Top 10 Prescribed Drugs

Pharmacology

Metformin lowers blood glucose via several mechanisms. Metformin belongs to the
class of oral antihyperglycemic agents referred to as biguanides, which reduce blood
glucose synthesis by activating adenosine monophosphate kinase.75 Metformin acts
by countering insulin resistance, particularly in liver and skeletal muscle. It suppresses
hepatic gluconeogenesis, increases peripheral insulin sensitivity in insulin sensitive tissues such as muscle and adipose tissue, and enhances the peripheral use of
glucose.76
Interaction with Dental Treatment

Metallic taste is associated with the use of metformin. This is referred to as dysgeusia.
Dysgeusia can interfere with the enjoyment of food and intake of adequate nutrition.
This side effect typically will resolve with continued use of the medication.
Long-term use of metformin may result in vitamin B12 deficiency. Vitamin B12 deficiency may manifest as altered taste, burning, or sore tongue, and/or enlarged or
altered tongue appearance.
Patients on metformin can very rarely develop angioedema, which would present as
a facial or tongue swelling. The skin of the face, particularly the perioral region, the oral
and pharyngeal mucosa, and the tongue, may swell over the period of minutes to
hours. This is considered a medical emergency, and if a patient presents as such to
a dental office, where angioedema is suspected, the patient should be sent to the
emergency department.
OMEPRAZOLE
Background

Omeprazole an antacid marketed as Prilosec (AstraZeneca, Wilmington, DE) is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease, gastroesophageal reflux disease, laryngopharyngeal reflux, and ZollingerEllison
syndrome. Omeprazole recently became available over the counter owing to its
proven safety and efficacy, so patients may fail to report the use of this drug in their
medical history.
Pharmacology

Omeprazole is a selective and irreversible proton pump inhibitor. It suppresses stomach acid secretion by specific inhibition of the H1/K1 adenosine triphosphatase system found at the secretory surface of gastric parietal cells. Because this enzyme
system is regarded as the acid (proton, or H1) pump within the gastric mucosa, omeprazole inhibits the final step of acid production.77
Interaction with Dental Treatment

Coadministration of omeprazole with warfarin should be avoided. A recent systematic

overview of warfarin and its drug and food interactions advised against combining
omeprazole with warfarin because it may increase the effects of warfarin.78 Thus,
dental patients on warfarin who may be self-prescribing omeprazole should be monitored before treatment.
In 2012, the FDA informed the public that the use of proton pump inhibitors might be
associated with an increased risk of Clostridium difficileassociated diarrhea
(CDAD).79 FDA reviewed reports from the FDAs Adverse Event Reporting System
and the medical literature for cases of CDAD in patients undergoing treatment with
proton pump inhibitors. A diagnosis of CDAD should be considered for patients taking

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proton pump inhibitors who develop diarrhea that does not improve. Additionally, dentists who prescribe antibiotics known to cause CDAD should remind patients of this
risk.
Hypomagnesemia has been reported in patients on omeprazole.80 The dentist
should be aware of signs of hypomagnesemia in patients on omeprazole. Magnesium
deficiency may cause weakness, muscle cramps, arrhythmias, depression, tetany,
and mental status changes.
ALBUTEROL
Background

Albuterol is a bronchodilator marketed as AccuNeb (Mylan, Morgantown, WV), ProAir

HFA (Ivax, Waterford, Ireland), Proventil (Merck, Whitehouse Station, NJ), and Ventolin
(GlaxoSmithKline, Research Triangle Park, NC) and is the tenth most commonly prescribed drug in the United States with 67.1 million prescriptions dispensed in 2014. Albuterol is a short-acting b2-adrenergic receptor agonist used for the relief of
bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. Albuterol is also prescribed to prevent breathing difficultiessecondary to bronchoconstrictionduring exercise.81
Pharmacology

Bronchodilators work through their direct relaxation effect on airway smooth muscle
cells. There are 3 major classes of bronchodilators, b2-adrenoceptor agonists, muscarinic receptor antagonists, and xanthines. These medications may be used individually
or in combination. Albuterol is the only one of the bronchodilators that is, inhaled; this
minimizes systemic effects, such as tremor, headache, muscle cramps, palpitations,
and tachycardia. Albuterol is a fast-acting and short lasting bronchodilator for rescue
of symptoms, as opposed to maintenance.81
Interaction with Dental Treatment

A common side effect of albuterol is tremor, but patients can experience tachycardia
or palpitations after use. Chronic use of albuterol is known to cause xerostomia in patients, which can lead to an increased caries risk, gingivitis, increased periodontal disease risk, compromised enamel. Additionally, the risk for oral candidiasis increases
with the use of albuterol.
SUMMARY

Owing to an increasing number older patients seeing their dentist and presenting with
multiple comorbidities and taking multiple medications, it behooves the dentist to
familiarize themselves with the possible interactions between dental treatment and
these drugs. Medications may alter the perioral and oral environment resulting in a
disturbance in normal function or as in the case of ACEi and metformin, a potentially
life-threatening form of angioedema. Specific drugdrug interactions may result in
profound morbidity. This document reviewed the top 10 medications prescribed in
2014 and their interactions with dental treatment. In addition to understanding the
specific interaction of the top 10 prescribed medications, the dentist hopefully enlightened as how to evaluate any medication their patients may be taking, and how to logically consider the interactions that medication may have with the patients dental
treatment.

Review of Top 10 Prescribed Drugs

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