DentalPharmacology

Robin A Seymour

Drug Interactions in Dentistry

Abstract: An increasing number of our patients are on medication of various types. This increase in prescribed medicines also raises
the significant issue of potential drug interactions between those drugs used in dental practice and those taken by the patient. This
article addresses those interactions and, where appropriate, puts them into perspective and attempts to quantify the risk. Mechanisms of
relevant drug interactions are also discussed. Certain categories of drugs are more likely to be involved in interactions and again these are
highlighted. Drug interactions relevant to dentistry can for the most part be prevented. A careful drug history should be taken from each
patient and updated on a regular basis.
Clinical Relevance: This article highlights drug interactions that can arise in dental practice and how they can be avoided and managed.
Dent Update 2009; 36: 458470
Drug interactions are quite simply an
interaction between two or more medications
that the patient may be prescribed. In
the dental setting, such interactions may
occur between those drugs prescribed or
administered in dental practice and the
patients current medication.
It is now widely recognized
that our patients are living longer and
retaining their teeth into old age. One major
contribution to this increase in life expectancy
is improved medication and a greater choice
of drugs to treat the frequent age-related
illnesses. It has been estimated that 75% of
the population over the age of 55 are taking
medication in order to sustain various bodily
functions.1 As the number of patients taking
one or more drugs increases, the risk of drug
interactions between the patients medication
and those drugs commonly prescribed in
dental practice, will also increase. As new
drugs are developed and come into clinical
practice, the risk of drug interactions should
always be considered.

Broad principles of drug

interactions
Drug interactions can involve
Robin A Seymour, Professor of
Restorative Dentistry, School of
Dental Sciences, Newcastle University,
Framlington Place, Newcastle upon Tyne
NE2 4BW, UK.

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Figure 1. Interaction between tetracyclines and various metallic ions found in antacids.

a variety of mechanisms and their

significance can relate to certain
categories of drugs and/or their
pharmacological properties. For example,
a drug with a low therapeutic index,
that is also extensively protein bound,
is susceptible to drug interactions. The
therapeutic index of a drug is a measure
of the ratio of the median lethal dose
(LD50) to the median effective dose
(ED50). The lethal dose is the dose of drug
required to be lethal for 50% of a group
of animals. ED50 is the dose required to
produce a response in 50% of subjects

tested. The therapeutic index of a drug

gives some idea of its margin of safety.
A drug with a low (narrow) therapeutic
index is potentially less safe than a drug
with a high (wide) therapeutic index (eg
warfarin and digoxin).
Other principles of
drug interaction can be considered
in terms of pharmacokinetic and
pharmacodynamic properties.
Pharmacokinetic interactions can be
further categorized under the headings
of absorption, distribution, metabolism
and excretion.
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Pharmacokinetic interactions

of free or pharmacologically active drug.

This is illustrated by the anticoagulant drug
warfarin, which has a low therapeutic index
and is 9899% protein-bound. Aspirin and
other non-steroidal inflammatory drugs are
also extensively protein-bound. If aspirin is
given to a patient on warfarin, then more
of the anticoagulant will be displaced from
the binding site, causing an increase in the
free, pharmacologically active warfarin.
The result of such an interaction is an
increase in the patients INR and a serious
haematological risk (see later). This type of
drug interaction is illustrated in Figure 2.

Drug absorption

Most drugs are absorbed in the

upper part of the gastro-intestinal tract.
Absorption depends upon factors such as
a drugs ability to survive the low gastric
pH, the effect of food, and the formation
of irreversible complexes with other drugs
or constituents of food. Benzylpenicillin
is deactivated by gastric acid and so can
only be given by injection. The pH of the
stomach affects the absorption of the
antifungal agent ketoconazole, where the
acidic conditions aid dissolution prior to
absorption. Drugs which reduce the acidity
of the stomach, such as antacids, H2receptor
blockers (ranitidine) and proton-pump
inhibitors (omeprazole) will reduce the
absorption of ketoconazole.2
Tetracyclines form chelates with
divalent and trivalent cations (eg Al3+, Bi2+,
Ca2+, Fe2+, Mg2+, Zn2+) (Figure 1). Chelated
tetracyclines are poorly absorbed, resulting
in reduced antimicrobial activity. Salts of
aluminium, calcium and magnesium are
the main ingredients of antacids; also the
ACE-inhibitor quinapril contains magnesium
carbonate. These drugs should be avoided
if a patient is prescribed tetracyclines.
In addition, some food substances
contain calcium ions, especially dairy
products, and hence patients prescribed
tetracyclines should be advised not to take
milk, indigestion remedies or medicines
containing iron or zinc at the same time of
day. Incompatible preparations should be
taken 23 hours apart. Ideally, tetracyclines
should be taken on an empty stomach or 60
minutes before or after food.3

The problem with warfarin is

compounded by its low therapeutic index.
Warfarin is 99% protein-bound, with only
1% available to affect blood coagulation. If
a further drug is administered that reduces
warfarin binding from 9998%, then the
amount of free or active warfarin increases
from 12%. This is a 100% increase in
the amount of pharmacologically active
warfarin, which will raise the patients INR.
All drugs which exhibit
more than 90% protein binding are at
a significant risk from drug interactions.
Within this category are, in addition

Drug distribution

When a drug is absorbed

from the gastrointestinal tract it is often
distributed in the bloodstream bound
to plasma protein. The bound portion is
considered pharmacologically inert, whereas
the so-called free or unbound portion may
interact with the receptor binding site. The
number of binding sites is limited and other
drugs compete for the protein binding
site, resulting in an increase in the free
pharmacologically active portion.
Displacement of one drug
from its binding site by another drug that
competes for the same binding site will
have a significant effect on the amount
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Figure 2. (a) Aspirin and warfarin in terms of protein binding. (b) Diagram to show the interaction
between aspirin and warfarin in terms of competition for protein-binding sites.

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to warfarin, oral anti-diabetic drugs

(chlorpropamide and other sulphonylureas),
and the anti-epileptic drug, phenytoin.

Rifampicin
(enzyme inducer)

Erythromycin
(enzyme inhibitor)

Drug metabolism

Many drugs are metabolized

(biotransformed) in the liver, rendering
the drug inactive, or changing its physicochemical properties to make it easier to
excrete. The liver also biotransforms inert prodrugs to more active metabolites. This is the
case with codeine, the metabolite morphine
being more pharmacologically active than the
parent drug.
Drugs biotransformed in the liver
by enzymes are collectively known as drug
metabolizing enzymes (DME). Of the various
DMEs, the ones most frequently the target of
drug interactions are the cytochrome P450
isoenzyme system.4 The cytochrome P450
nomenclature is as follows: CYP stands for
cytochrome P. This is followed by a number
representing the subfamily and then another
number representing the individual gene.
The cytochrome enzymes most frequently
involved in drug interaction include CYP1A2,
CYP2C9, CYP2C19, CYP2D6, CYP2E1 and
CYP3A4.
These CYP45O enzymes can be
induced or inhibited by drugs. For example,
although not particularly relevant to dentistry,
the anti-tuberculosis drug rifampicin induces
the CYP450 enzyme that metabolizes the
oral contraceptive, leading to pill failure.5
By contrast, the antibiotic erythromycin
is an enzyme inhibitor for CYP3A4, which
includes the enzyme responsible for the
biotransformation of simvastatin and
atorvastatin.6 This interaction can potentially
increase the risk of statin-induced myopathy
(Figure 3).
It should also be recognized that
other substances, which may not be regarded
by patients as drugs, can also have an effect
on the cytochrome P450 group of enzymes.
Alcohol, smoking, various recreational drugs
and even char-grilled meats have been
identified as enzyme inducers. Grapefruit juice
has been shown to be an enzyme inhibitor.
Grapefruit juice consumption prior to oral
midazolam sedation could be problematic.
Taking 200 ml of grapefruit juice two hours
before oral midazolam can double the plasma
concentration of this benzodiazepine.7 Whilst
such high levels of midazolam should not
present a serious problem in an otherwise

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LIVER

DMEs

Simvastatin
Contraceptive pill

Increased risk of
simvastatin-induced
myopathy

Reduced plasma
concentration
of the
contraceptive
pill, increasing
the risk of pill
failure

Figure 3. Schematic diagram to illustrate the effect of drug interactions involving hepatic drug
metabolizing enzymes (DMEs).

healthy adult, this could be problematic in a

child or a medically compromised patient.
Drug excretion

The kidney is the main site of

drug excretion. Renal excretion of drugs
often involves an energy-dependent, multidrug efflux pump known as P-glycoprotein.
As with drug metabolizing enzymes, certain
drugs can induce or inhibit P-glycoprotein.
An inducer of P-glycoprotein will result in
more drug excretion, whilst the converse will
apply to an inhibitor. The latter will raise serum
concentration and increase the risk of toxic
effects.

Of dental relevance under this

category is the ability of non-steroidal antiinflammatory drugs, such as ibuprofen or
diclofenac, to inhibit the renal excretion of
lithium.8 Lithium has a narrow therapeutic
index and a raised serum concentration can
lead to severe renal and CNS toxicity.
Competitive inhibition is a
further process of drug interactions involving
excretion. Weak acids, such as the penicillins,
may compete with methotrexate in the renal
tubules for excretion, so that there is an
increase in serum methotrexate and increased
toxicity. NSAIDs inhibit the synthesis of
prostaglandins, which results in a fall in renal
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Antibiotic

Interacting drug

Mechanism

Outcomes and recommendations

Erythromycin

Theophylline, aminophyline
(systemic broncho-dilator)

Inhibition of CYP3A4

Increase in plasma concentrations of theophylline

leading to tachycardia, dysrythmias, tremorsseizure. Avoid prescribing erythromycin.

Erythromycin

Simvastatin

Inhibition of CYP3A4

Increase in plasma concentration of simvastatin

leading to increased risk of myalgias,
rhabdomyolysis and renal failure. Avoid prescribing
erythromycin or, if the antibiotic is essential , then
stop taking simvastatin.

Erythromycin

Ciclosporin and tacrolimus

Inhibition of CYP3A4

Increase in plasma levels of both

immunosuppressives leading to excessive
immunosuppression and increased risk of renal
toxicity. Avoid prescribing erythromycin if possible.

Erythromycin

Warfarin

Inhibition of CYP3A4

Increase in plasma concentrations of warfarin leading

to a raised INR and increased risk of bleeding.
Concurrent use need not be avoided as
erythromycin-induced inhibition of CY3PA4 is
somewhat unpredictable.

Erythromycin

Carbamazepine

Inhibition of CYP3A4

Increase in levels of carbamazepine leading to

increased risk of drowsiness, ataxia and confusion.
Avoid erythromycin.

Erythromycin

Midazolam

Inhibition of CYP3A4

Increase in plasma concentration of midazolam

leading to excessive and prolonged sedation. Avoid
erythromycin for some 12 hours before iv sedation
with midazolam.

Metronidazole

Alcohol

Blocks enzyme
acetaldehyde
dehydrogenase which
converts acetaldehyde
to acetic acid

Increase in levels of acetaldehyde which produces

flushing, headache, nausea and palpitations. Avoid
alcohol consumption during metronidazole therapy
and for at least 2-3 days after completing course.

Metronidazole

Warfarin

Inhibition of CYP3A4

Increase in plasma concentrations of warfarin

leading to a raised INR and increased risk of
bleeding. Avoid metronidazole.

Erythromycin

Calcium channel blocks,

eg nifedipine

Inhibition of CYP3A4

Increase in plasma concentration of nifedipine

resulting in severe risk of hypotension and oedema
formula. Avoid erythromycin.

Table 1. Possible drug interactions arising from antibiotic prescribing.

perfusion. This could lead to a rise in serum

methotrexate level and likewise increased
toxicity.

Pharmacodynamic drug
interactions
Pharmacodynamic interactions
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are those where the action of one drug is

enhanced by the action of another. These
actions may be additive or synergistic,
where the pharmacological effect is greater
than the simple sum of either drug alone.
Pharmacodynamic interactions occur at
the site of drug action, often at receptor
level. Examples of pharmacodynamic drug

interactions include the antiplatelet action

of aspirin and the anticoagulant effect of
warfarin, atropine and tricyclic antidepressants
(antimuscarinic effect), and opioid analgesics
and alcohol (sedative CNS effect). More recent
evidence has shown that non-steroidal antiinflammatory drugs, such as ibuprofen and
diclofenac, interact with selective serotonin
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reuptake inhibitors (eg Prozac). As both drugs

have an effect on platelet aggregation, this
interaction increases the risk of a NSAIDinduced gastrointestinal bleed.9

Drug interactions that are

significant in dental practice
Dental practitioners prescribe
relatively few categories of drugs and this
section will focus only on three widely used
categories:
Antibiotics;
Analgesics; and
Local anaesthetic solutions.

Drug interactions involving

antibiotics
A synopsis of possible drug
interactions relating to antibiotic prescription
is shown in Table 1.
Some of the drug interactions
involving antibiotics are worth highlighting.

Figure 4. Interaction between broad spectrum antibiotics and COC.

Metronidazole, erythromycin and warfarin

Both antimicrobials inhibit liver

enzymes CYP2C9 (metronidazole) and CYP3A4
(erythromycin). These enzymes are involved
in the metabolism of warfarin (especially
CYP2C9) and their inhibition will lead to
an increase in plasma concentrations of
warfarin, leading to an increased INR and risk
of bleeding.10 If either antibiotic is essential
in the management of a patients infection,
then control of the infection should take
precedent. It would be worthwhile informing
the patients physician before prescribing
metronidazole. An antibiotic-induced change
in hepatic metabolism of warfarin, and hence
an increase in INR, is likely to be of short
duration. Despite this, it is essential to check
the patients INR if he/she has recently (within
two to three days) completed a course of
either metronidazole or erythromycin.

Bacteriostatic
Tetracyclines
Erythromycin
Clindamycin

Bactericidal
Penicillins
Cephalosporins
Metronidazole

Table 2. Classification of antibiotics used in dentistry by their mode of action.

the efficacy of the bactericidal drug. For

example, tetracycline or erythromycin should
not be prescribed to a patient taking penicillin
or metronidazole. However, clinical evidence
to support this is not strong. There is no
rationale for using such a combination in
dentistry for the management of odontogenic
infections.

Antibiotics and oral contraceptives

Bactericidal and bacteriostatic antibiotics

Antibiotics have two modes of

action against bacteria; they either destroy
them (bactericidal) or stop them dividing
(bacteriostatic). Table 2 provides a list of
antibiotics used in dentistry categorized
according to their mode of action. Bactericidal
antibiotics are more effective if the bacteria
that they are targeting are dividing.
Theoretically, therefore, administration of a
bacteriostatic agent will reduce significantly

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An oral contraceptive pill

contains a combination of oestrogen and
progestogen (combined oral contraceptive,
COC) or progestogen alone (progestogen only
pill, POP). There are two ways in which oral
contraceptives can be affected by antibiotics:
first, their metabolism can be induced leading
to lower levels of the circulating hormones
and thus failure of effect. This can occur
with the antibiotic rifampicin; secondly, by
their effect on the gut flora, eg amoxicillin,

erythromycin and the tetracyclines. Antibiotics

used in dentistry will affect the gut flora.
Although numerous case reports
have appeared in the literature indicating
that systemic antibiotic therapy has resulted
in pill failure, evidence from controlled trials
are lacking. Following initial absorption
of the oestrogen component of a COC, it
undergoes conjugation with glucuronic
acid in the liver. Once conjugated, the
oestrogen is pharmacologically inactive and
is excreted via the bile into the gut. In normal
circumstances, the conjugate is hydrolysed by
colonic bacteria, which releases the oestrogen
to be reabsorbed for the suppression of
ovulation. This process is illustrated in Figure
4. Thus a viable gut flora is thought to be
necessary for oestrogen metabolism and pill
efficacy. As progestogen does not undergo
enterohepatic recycling, POPs are not affected
by antibiotics. Many antibiotics reduce the
gut flora and thereby there is, in theory, an
increased risk of pill failure. As there is no
easy way of determining the effect of the
gut flora in reducing circulating levels of
oestrogen, all women taking the COC pill
should be considered at risk from pill failure
if prescribed systemic antibiotics. The overall
failure rate of oral contraceptives in women
taking systemic antibiotics may be no greater
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DentalPharmacology

than when taking oral contraceptives alone.

It is recommended that all female patients
taking the pill are warned of the risk of pill
failure if prescribed systemic antibiotics and
to use additional methods of contraception
during the antibiotic therapy, and for at least
one week after the last antibiotic dose.11 If
these seven days run beyond the end of a
packet, the next packet should be started
immediately without a break.

Drug interactions involving

analgesic agents

Figure 5. Schematic diagram to illustrate interaction between aspirin and NSAIDs with SSRIs leading to
an increased risk of bleeding.

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In dental practice, analgesics

are frequently prescribed as short 35 day
courses for the management of post-operative
pain after a dental or oral surgical procedure.
Drug interactions involving analgesics are
summarized in Table 3.
Combinations of non-steroidal
anti-inflammatory drugs (NSAIDs) to
control post-operative pain will not result in
additional analgesia, however, it will increase
the risk of adverse effects. For example, using
both aspirin and ibuprofen to treat postoperative pain increases the risk of gastrointestinal problems and ulceration. There is
also an interaction between ibuprofen or
other NSAIDs and low dose aspirin taken for
vascular and cerebrovascular protection.12 A
single dose of ibuprofen 400 mg, when taken
before aspirin, has been shown to reduce
aspirins antiplatelet effect by up to 50%. If
ibuprofen is taken after aspirin, the effect on
aspirin-induced antiplatelet activity is minimal.
If ibuprofen or other NSAIDs are prescribed
to a patient taking low dose aspirin, then the
patient should be advised to take the aspirin
before the NSAID.13
NSAIDs, aspirin and selective
serotonin re-uptake inhibitors (SSRIs) can
interact to increase the risk of bleeding. SSRIs,
eg fluoxetine (Prozac), citalopram, paroxetine,
and sertraline also inhibit serotonin re-uptake
in platelets. Serotonin is normally released
from platelets as a response to injury and
has an important role in regulating the
haemostatic response by potentiating
platelet aggregation. NSAIDs and aspirin
also affect platelet aggregation by blocking
thromboxane synthesis and release. This
interaction is illustrated in Figure 5. The major
significant risk from this interaction is a
gastro-intestinal bleed; when both drugs are
used concurrently the risk of a bleed increases
1516 fold.14 This increased risk of a GIT bleed
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Analgesic

Interacting drug

Outcome and recommendation

Paracetamol
(acetaminophen)

Alcohol

Increased risk of paracetamol toxicity and liver damage. Daily

dose of paracetamol should not exceed 4000 g (8 tablets) and
for alcoholics this should not exceed 2000 g (4 tablets).

Aspirin and other non-selective

cyclo-oxygenase inhibitors, eg
ibuprofen

Alcohol

Increased risk of gastro-intestinal toxicity. Analgesic intake and

alcohol consumption should be separated by 12 hours.

Non-steroidal anti-inflammatory
drugs, eg ibuprofen

Antihypertensive drugs,
especially beta-blockers
(atenolol), ACE inhibitors
(lisinopril) and diuretics

NSAIDs can affect renal function and causes salt and water
retention which can antagonize antihypertensive drugs. This
only becomes a clinical problem if such analgesics are
prescribed for more than 5 days. Limit analgesic usage to this
timeframe for patients on antihypertensives.

NSAIDs, eg ibuprofen

Methotrexate

The effects of NSAIDs on renal perfusion are described above.

This increases the risk of methotrexate toxicity. Avoid NSAIDs
whenever possible in patients taking methotrexate.

NSAIDs, aspirin

Selective serotonin
reuptake inhibitors, eg
fluoxetine

Both drugs affect platelet function and increase the risk of postoperative bleeding and bleeding from the gastro-intestinal tract.
Avoid concomitant use.

Aspirin

Warfarin

Increased risk of bleeding: displacement of warfarin from

protein-binding sites and both drugs affect haemostasis. Avoid
aspirin in patients taking warfarin.

Aspirin

Clopidogrel

Both drugs affect platelet function and therefore increase risk of

bleeding. Avoid analgesic doses of aspirin.

Aspirin, NSAIDs

Systemic corticosteroids

Both categories of drugs are ulcerogenic and increase the risk

of gastro-intestinal bleeding. Avoid aspirin and NSAIDs in
patients on systemic corticosteroids unless they are taking antiulcer drugs.

Table 3. Synopsis of drug interactions with commonly prescribed analgesics.

should be compared with a 45 fold increase

when NSAIDs are used alone. In view of the
significance of this interaction, NSAIDs should
be prescribed with caution to patients taking
SSRI. The addition of a gastroprotective agent,
eg a proton pump inhibitor (omeprazole),
should be considered if this combination
is essential. Paracetamol can be used as an
alternative.

Drug interactions involving local

anaesthetic agents
The three main local anaesthetic
drugs used in dental practice are lidocaine,
prilocaine and articaine. All are amide agents
and, when used at normal doses, have

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an excellent safety record. Most of the

concerns with local anaesthetic agents
and drug interactions reside with the
vasoconstrictor component, in particular,
adrenaline. This vasoconstrictor is an
agonist at both A-1 and B2 adrenergic
receptors. A-1 stimulation causes
vasoconstriction in the skin and mucous
membranes, whilst B2 activity results in
vasodilatation in skeletal muscles. These
actions of adrenaline are short lived owing
to its short half-life in the bloodstream.
A considerable amount of
conjecture has surrounded many possible
drug interactions involving adrenaline
and related compounds and these will be
discussed below.

Adrenaline and B-adrenoreceptor blockers (Beta

-blockers)

Beta-blockers are widely

used for the treatment of a range of
cardiovascular problems, in particular
hypertension, angina and disorders of
cardiac rhythm. They are categorized as
being either selective (block B1 receptors
only) or non-selective, blocking both B1
and B2 receptors. Potential interactions
between adrenaline and beta-blockers
depend upon the type of beta-blocker
and the systemic absorption of adrenaline.
For example, an intravenous infusion of
adrenaline (0.0160.032 g), when given
to hypertensive patients on propanolol
therapy (a non-selective beta-blocker),
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cause a significant rise in both systolic

and diastolic blood pressure.15 The
dose of adrenaline used in this study
is equivalent to 12 cartridges of
adrenaline-containing local anaesthetic
solution (2550 g). By contrast, when
the same group of patients were treated
with a cardio-selective beta-blocker
(atenolol), there was only a slight rise in
blood pressure.
Whilst these findings
were in hypertensive patients, similar
observations have been found in health
volunteers; selective beta-blockers, such
as atenolol, metoprolol, and acebutolol,
can block an adrenaline-stimulated
increase in blood pressure.16
The interaction between
adrenaline and non-selective betablockers (eg propanolol, nadolol, sotalol)
is potentially serious, but is doserelated and will be more pronounced
if adrenaline is given, inadvertently,
intravenously.15 Some authors
recommend that patients on nonselective beta-blockers are given a test
dose of 1 cartridge of an adrenalinecontaining local anaesthetic solution. If
there is no significant increase in blood
pressure, then it is safe to give up to two
cartridges of this anaesthetic agent. A
25% increase in either systolic or diastolic
blood pressure would be considered
significant.17
Whilst caution should
always be exhibited when giving local
anaesthetics, it is important to ensure
adequate analgesia for the dental
procedure to be undertaken. Inadequate
pain control can bring about a significant
increase in endogenous adrenaline
production.
An adrenaline-containing
retraction cord should be completely
avoided in patients taking non-selective
beta-blockers. Such a cord can contain as
much as 0.5 mg of adrenaline, equivalent
to 0.2 mg/cm.18
Adrenaline and tricyclic antidepressants

Tricyclic antidepressants
produce their therapeutic effect by
blocking the reuptake of noradrenaline
at central synapse. The excess of
noradrenaline in the synapse means
that administration of adrenaline can
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have a significant effect, notably in the

cardiovascular system, leading to an
increase in blood pressure.
Animal experiments have
shown that such an interaction can occur,
but only if the adrenaline dose exceeds
the equivalent of seven cartridges of local
anaesthetic solution.19 It is recommended
that no more than three cartridges of
adrenaline-containing local anaesthetic
solution should be given at any one time
to patients on tricyclic antidepressants.20
There is also a suggestion that chronic
dosing of tricyclic antidepressants can
result in desensitization in response to
adrenaline as a consequence of down
regulation of post synaptic receptors.21
Atomoxetine is used
in the management of attention
deficit hyperactivity disorder. It has a
similar mode of action to the tricyclic
antidepressants and the same caution,
with respect to the number of cartridges
of adrenaline-containing local anaesthetic
solution used, should also apply to
patients on this medication.

patients at every visit. Many patients know

their drugs only by the trade name and it
must then be checked in the Formulary.
If in doubt, contact the patients general
medical practitioner. There are certain
categories of drugs that are more likely to
be involved in drug interactions, notably
those that are extensively protein-bound,
those with a low therapeutic index, and
those drugs metabolized by the CYP450
enzymes. Drug interactions can be
minimized in the dental setting by taking
a full drug history and using alternative
drugs where indicated, or dose reductions.

References
1.

2.

3.
Adrenaline and non-potassium sparing
diuretics

Adrenaline has an impact

upon metabolism and, in particular,
causes a decrease in plasma potassium
levels.22 Such fluctuations in potassium
levels may be significant in those patients
taking non-potassium sparing diuretics.
Such diuretics include the thiazide
group, eg bendroflumethiazide, and loop
diuretics, eg furosemide. Adrenalinecontaining local anaesthetics are likely
to cause disorders of cardiac rhythm in
patients taking these diuretics and the
recommendation is not to exceed three
cartridges of anaesthetic solution in those
patients.23

4.

5.

6.

7.

Conclusions
Drug interactions are
important and can lead to significant
morbidity and even mortality. Fortunately,
the latter is a rare occurrence in
connection with dental prescribing.
Dentists prescribe a limited range of drugs
and, for the most part, these are safe.
However, interactions can occur and it is
essential to take a full drug history from

8.

9.

Seymour RA. Dentistry and the

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