drug form (eg tablet, capsule or mixture) quantity of drug to be supplied drug dose, route of administration, frequency, and

nd duration of treatment (if necessary) clear instructions for the patient (in English)-it is not appropriate to write 'take as directed' any further instructions necessary for the pharmacist the words 'for dental treatment only' signature of the prescriber-handwritten. Figure I (p.9) is an example ofthe format required for a legal prescription written by a dentist. If the prescription is for an item included in the Pharmaceutical Benefits Scheme (PBS), the dentist's unique prescriber number must be on the prescription. PBS prescription pads are available from Medicare Australia.
1

Figure 1. Example of the format required for a legal prescription written by a dentist
Dr J Smith BDSc Address Telephone number PBS prescribing number

Patient's Medicare number Patient's name Patient's address Patient's date of birth Ms lane Citizen

11

Points to note when writing a prescription are as follows: Make the prescription as tamper-proof (unalterable) as possible and use indelible ink. Do not write prescriptions for more than one person on the same form. Use standard language for instruction. Do not use abbreviations or Latin terms. Avoid using decimal points if possible (eg write quantities less than 1 gram as milligrams, and quantities less than I milligram as micrograms). Ifusing a decimal point, put a '0' in front of the point (eg '0.5', not '.5'). Do not abbreviate microgram, nanogram, international or unit. Limit the number of items on a prescription to two or, at the most, three. Use computer-generated prescriptions (if possible). If using brand or trade names, ensure that you know the approved or generic name as well. If any space is unused on the prescription, put a line across the area to prevent the addition of items. Dentists may not order repeat prescriptions. Prescribers and pharmacists have complementary roles in ensuring optimum patient outcomes. This is enhanced by mutual respect for each other's skills.
8

Rx Phenoxymethylpenicillin

500 mg capsules

20
Take 1 capsule 4 times a day at 6-hourly intervals for 5 days

s~,,"re~
Date For dental treatment only

..
.

~ Cl.
';:
C) I/)

c o

e
"tl

Cl.

THE PRESCRIPTION AND THE PATIENT

When prescribing drugs, give the patient specific information about the drug, including: the brand name and the approved name of the drug the effects of the drug and why it is needed possible adverse effects and what to do if they occur instructions on how to take the drug

c:
IV
I/)

c:

~
.;:

C)c: 1/).-

'Q/)

c.~
9

Q):!:: ....

 warnings (eg possible interactions, maximum dose) when to return for review permission to ring you if concerned about any issues. Patients often do not remember the details or instructions they are given during a consultation, so it is desirable to give written instructions as well. Consumer medicine information (CMI) leaflets are available for the majority of medicines prescribed in Australia, and should be offered every time a drug is dispensed. They are available from pharmacies and some clinical software packages. Consumers can access CMIs directly via the NPS: Better choices, Better health website <www.nps.org.au>.

Websites Pharmaceutical Benefits Scheme (PBS) website <www.pbs.gov.au> Australian Dental Association website <www.ada.org.au> Pharmacist-relevant website <http://auspharmacist.net.au/>, to a large number of sites with drug information NPS: Better Choices, Better Health website <www.nps.org.au> which has links

LEGISLATION ABOUT PRESCRIPTIONS PRESCRIBING

AND

SOURCES OF DRUG INFORMATION

Recommended sources of drug information include journals, books, electronic resources and websites: Journals
Australian Dental Journal (ADJ)-see 'Medications in dentistry supplement' in December 2005 edition (can be accessed via the Australian Dental Association website <www.ada.org.au Prescriber

the following

For legislation pertaining to prescriptions and prescribing in each of the states and territories, see p.12. Overall, there are no significant differences in the requirements for what constitutes a legal prescription between the states and territories, but there are some minor differences. If dentists are in doubt, they should consult the appropriate legislation for their state or territory. A 'prescription-only' drug is a drug that can only be obtained with a prescription; it cannot be purchased over-the-counter. Dentists may prescribe any prescription-only drug provided it is for the dental treatment of a patient under their care. Dentists may prescribe any drug Additional caution should be of dependence (in most states and exercised when prescribing territories) for a patient under their drugs of dependence. care provided they do so in accordance with legal requirements, and have taken all reasonable steps to ascertain the identity ofthat person and to ensure that a therapeutic need exists, and the drug is required for dental treatment. Additional caution should be exercised when prescribing drugs of dependence. Dentists may not order repeat prescriptions. Legislation regarding prescribing for the purpose of self-administration varies between the states and territories; however, generally, selfprescribing is not recommended. The Pharmaceutical Benefits Schedule includes a number of medicines that are subsidised by the Pharmaceutical Benefits Scheme (PBS) if prescribed by a dentist. For more information, see <www.pbs.gov.au>.

Australian

<www.australianprescriber.com>

Books and electronic resources

Australian Medicines Handbook (AM H)-independently prepared source of evidence-based drug information; also includes a section on prescription-writing and drug interactions (updated electronically biannually and in print annually) GUidelines-Analgesic, Gastrointestinal, Antibiotic, Neurology, Cardiovascular, Dermatology,

Therapeutic Respiratory,

Endocrinology, Disability

Psychotropic,

Palliative Care,

Rheumatology, Toxicology & Wildemess, and Developmental management guideline. Allprint titles are available through the electronic products, eTG complete and miniTG

MIMS-contains product information as provided by pharmaceutical companies and approved by the Therapeutic Goods Administration (can be accessed via the Australian Dental Association website <www.ada.org.au (Tatro DS, editor. St Louis: Facts and comparisons)-this is an excellent resource on drug interactions (updated electronically quarterly and in print annually)
Drug Interaction Facts

Any recent textbook on clinical pharmacology

10 11

Relevant regulations
The following are the relevant Acts and Regulations for each state and territory. They can be accessed via the Australian Health Practitioner Regulation Agency (AHPRA) website <www.ahpra.gov.au> (choose 'Legislation & Publications I Legislation'). The Poisons Standard lists the classification of medicines and chemicals into schedules for inclusion in the relevant legislation. For more information, see <www.tga.gov.au/industry/scheduling-poisons-standard.htm#susmp>. Australian Capital Territory

Getting to know your drugs

Dentists may prescribe any drug approved by the Therapeutic Goods Administration (TGA), provided the drug is prescribed as part of the dental treatment for a patient that the dentist has established (by examination) needs the drug. Most ofthe drugs discussed in this chapter are subsidised by the Pharmaceutical Benefits Scheme (PBS). Dentists must know the beneficial they prescribe (see 'Sources of as the patient's medical history prescription, over-the-counter and and the adverse effects of the drugs drug information', p.IO), as well and current medications, including complementary medicines.

Drugs of Dependence Act 1989 Drugs of Dependence Regulation 2009 Medicines, Poisons and Therapeutics Goods Act 2008 Medicines, Poisons and Therapeutics Goods Regulation 2008 New South Wales Poisons and Therapeutic Goods Act 1966 Poisons and Therapeutic Goods Regulation 2008 Northern Territory

ANTI MICROBIALS Principles of antimicrobial use

The problems posed by pathogenic organisms resistant to antimicrobial drugs are increasing globally. Adherence to the principles of antimicrobial use outlined in Box 3 (p.15) and summarised in the antimicrobial creed (see Box 4, p.16) is important. It must first be determined if an antimicrobial drug is needed. The majority of infections that present in the dental clinic require active dental treatment to remove the source of infection, and this is usually the most effective method of treating the problem. It should also be kept in mind that most viral and minor bacterial infections are selflimiting and do not require an antimicrobial. Unnecessary prescription of antimicrobials exposes patients to adverse drug effects, is costly, and creates conditions that favour the proliferation of resistant organisms in the patient and the community. Only antimicrobials with an oral and dental indication are discussed in this chapter. Refer to Therapeutic Guidelines: Antibiotic for information on other antimicrobials.

Poisons and Dangerous Drugs Act Poisons and Dangerous Drugs Regulations Therapeutic Goods and Cosmetics Act Queensland
(ij
Cl)

... c::
't:I

Health Act 1937 Health (Drugs and Poisons) Regulation 1996 South Australia Controlled Substances Act 1984 Controlled Substances (Poisons) Regulations 201 I Tasmania Poisons Act 1971 Poisons Regulations 2008 Victoria Drugs, Poisons and Controlled Substances Act 1981 Drugs, Poisons and Controlled Substances Regulations 2006 Western Australia Poisons Act 1964 Poisons Regulations 1965

Cl

c::
ell

s
Ui c
Q)

(ij

Q)

-0

:3
G
'';:::;

o
::::J
Q)

0..

~
..c
IQ)

12

13

Antimicrobial resistance
Antimicrobial drugs are different from other drugs in that their use in one patient can influence their future effects in other patients. The development and spread of bacterial resistance to antimicrobials is a major problem within hospitals and in the community. Although the mechanisms are complex, resistance is essentially due to selective pressure exerted by the widespread presence of antimicrobial drugs in the biosphere, together with the facilitated transfer of organisms between staff and patients. Antimicrobial resistance is increasing in many pathogens. As there are only a limited number of new antimicrobial drugs becoming available, they are a particularly valuable resource. Restraint in prescribing and adherence to the principles outlined in these guidelines are essential to ensure that antimicrobials remain effective in treating important infections. Appropriate antimicrobial use delays the emergence of resistance and minim ises resistance prevalence after it has emerged (see Box 3, p.lS). The Centers for Disease Control and Prevention website has useful information on Restraint in the use of all how to prevent antimicrobial resistantimicrobials is the best way to ance in health care settings-see ensure their continuing efficacy. <www.cdc.gov/drugresistance/ healthcare/patients.htm>.

Box 3. General principles of antimicrobial use

Prophylactic therapy
Restrict use of prophylactic antimicrobial therapy to situations in which prophylaxis has been shown to be effective or where the consequences of infection would be disastrous. Base choice of antimicrobial (s) on known or likely target pathogen(s). For most surgical prophylaxis indications, use a single perioperative dose sufficient to achieve therapeutic tissue concentrations at the time contamination is most likely. To maintain adequate tissue concentrations, a repeat dose is only required if a short half-life drug is used and the procedure is prolonged.

Empirical therapy
Use antimicrobials only where proven benefits are substantial. Avoid use in minor use is a significant driver of antimicrobial or self-limiting illness-unnecessary resistance.

Base therapy on the most likely and/or important potential pathogen(s) and their likely antimicrobial susceptibilities. In general, use the narrowest spectrum antimicrobial to treat the likely pathogen(s). Use a dose that is high enough to ensure efficacy and minimise the risk of resistance selection, and low enough to minimise the risk of dose-related toxicity. Before commencing therapy, where appropriate, obtain specimens for blood culture (at least two sets from clinically septic patients) and other cultures. If possible, direct therapy from the start through antigen detection tests, nucleic acid tests and/or Gram stain results. Cease therapy if a noninfective diagnosis is confirmed. In the absence of a proven causative organism at 48 hours, evaluate the clinical and microbiological justification for continuing therapy. Liaise regularly with local pathology providers to obtain up-to-date local antimicrobial resistance patterns for significant pathogens. information on

Prophylactic, empirical or directed antimicrobial therapy

Antimicrobial use can be prophylactic, empirical, or directed against a known organism. Prophylactic use aims to prevent infection in clinical situations where there is significant risk of infection. Empirical antimicrobials are used when the causative organism is proven. This may occur if treatment must be commenced before culture susceptibility results are available, the clinical situation is serious enough to warrant taking cultures, or appropriate material culture cannot be obtained. not the not for

Directed therapy
Critically evaluate culture and other microbiological results to distinguish infection from colonisation or contamination that does not require specific antimicrobial treatment. If necessary, obtain advice from an infectious diseases physician or a clinical microbiologist. Based on a demonstrated microbial cause and its antimicrobial susceptibility, direct antimicrobial therapy in accordance with recommendations using the most effective, least toxic, narrowest spectrum drug available. Use a single drug unless it has been proven that combination therapy is required to ensure efficacy (eg a proven mixed infection), for synergy, or to reduce the selection of clinically significant resistance (eg treatment of tuberculosis, HIV infection). Keep duration of therapy as short as possible. Do not exceed 7 days without a proven indication for a longer duration (eg for treatment of endocarditis). For most odontogenic infections 5 days of therapy with appropriate dental treatment is sufficient.

Directed use occurs when culture susceptibility results are used to guide therapy. In all three of these circumstances, the principles listed in Box 3 (p.lS) and summarised in the antimicrobial creed (see Box 4, p.16) should be closely adhered to.
14

Classes of antimicrobial drugs commonly used in dentistry examples of drugs from each class are shown in Table I (p.l7).

and

15

Box 4. The antimicrobial creed

M microbiology guides therapy wherever possible indications should be evidence-based N narrowest spectrum required dosage appropriate to the site and type of infection

Antibiotics may be used within the tooth (ie intra dental therapy). Commercial intradental antibiotic preparations usually also contain a corticosteroid. These preparations are used to manage intracanal infections and apical periodontitis, and to reduce inflammatory root resorption. Table 1. Common antimicrobial drugs used in dentistry
Examples

M
E

minimise duration of therapy ensure monotherapy in most situations

Antibacterial drugs beta lactams

Route of administration
The oral route of administration is preferred, where possible, because it is usually associated with less serious adverse effects, has a cheaper drug product cost and has lower administration costs than parenteral therapy. Antimicrobials that have a high oral bioavailability (eg clindamycin and metronidazole) can usually be given orally rather than intravenously. There is no basis to the common bel ief that injections are more 'powerful' than tablets. However, parenteral administration (usually intravenous) is required in certain circumstances: oral administration is not tolerated or is not possible (eg a patient with swallowing difficulties) gastrointestinal absorption is likely to be significantly reduced (eg vomiting, gastrointestinal pathology), or reduced absorption might accentuate already poor bioavailability an oral antimicrobial with a suitable spectrum of activity is not available higher doses than can conveniently be administered orally are required to achieve effective concentrations at the site of infection (eg spreading deep odontogenic infections) urgent treatment is required because of severe and rapidly progressive infection (although rarely would the hour or two required for oral absorption significantly alter the outcome). Ifparenteral administration is used, reassess the need daily and convert to oral therapy as soon as possible. To reduce the development of resistant organisms, topical therapy should be restricted to proven indications (eg miconazole for oral candidosis).

penicillins narrow-spectrum narrow-spectrum with anti staphylococcal activity moderate-spectrum broad-spectrum (beta-Iactamase inhibitor combinations) cephalosporins moderate-spectrum glycopeptides lincosamides macrolides nitroimidazo/es tetracyclines Antifungal drugs azo/es pOlyenes Antiviral drugs guanine analogues aciclovir, famciclovir, penciclovir, valaciclovir fluconazole, itraconazole, miconazole amphotericin, nystatin cephalexin, cephazolin teicoplanin, vancomycin clindamycin, lincomycin roxithromycin metronidazole, tinidazole doxycycline benzylpenicillin, phenoxymethylpenicillin dicloxacillin, flucloxacillin

amoxycillin, ampicillin amoxycillin+clavulanate

16

17

Adverse effects of antimicrobials

All anti microbials can cause adverse effects so the possibility of harm must always be considered when deciding whether to prescribe an antimicrobial. Usually the adverse effects are minor and/or self-limiting; however, some can be more significant. For more information on antimicrobial hypersensitivity and antibiotic-associated diarrhoea, see discussion below and p.20. Particular care should be taken in the elderly, who often have altered pharmacokinetic or toxicodynamic profiles making them more likely to suffer an adverse effect. In patients with renal or hepatic impairment, dose and/or dose interval adjustment may be required to prevent concentration-related adverse effects (toxicity). A history of hypersensitivity or other adverse response to the drug should always be sought before prescribing an antimicrobial drug.
Always check if the patient has a history of hypersensitivity before prescribing an antimicrobial.

IgE-independent reactions-mimicking conditions of 'pseudoallergy' (eg responses to vancomycin infusions such as 'red-man' syndrome) involving the direct release of vasoactive mediators. These reactions may be ameliorated by prophylactic antihistamines and slowing the infusion rate. Delayed reactions-macular, papular, or morbilliform rashes occurring several days after commencement of treatment are more common than immediate reactions, and may be caused by the infection or its treatment. Such reactions are usually T-cell (not IgE) mediated. Skin testing often proves negative, particularly when performed several months or years after the event. Delayed reactions commonly occur in patients with intercurrent Epstein-Barr virus or HIV infection and such reactions are often not reproducible with deliberate challenge when the patient is well. Delayed rashes due to penicillin, especially amoxy/ampicillin, are not strongly predictive of future reactions and repeat exposure to beta lactams is not necessarily contraindicated. Patients with known hypersensitivity should be strongly advised to wear an alert bracelet or necklace advising of their allergy.
~ Diagnosis of antimicrobial hypersensitivity

Antimicrobial hypersensitivity (allergy)

It is common for a patient to give a history of being 'allergic' to an antimicrobial-usually penicillin-and this can present a dilemma. If penicillin is administered to a highly allergic patient, fatal anaphylaxis can occur. However, many patients who report a penicillin allergy have a vague history and are not allergic at all. Also, it is important not to deny patients treatment with an antimicrobial unnecessarily, especially if they have a serious infection for which that antimicrobial would be the most effective treatment.
~ Types of hypersensitivity

s c
Q)

Antimicrobial hypersensitivity is usually diagnosed based on clinical history (especially its timing after antimicrobial use). If the patient reports an allergy, seek specific details about the nature of the reaction, the timing and the outcome. For information on diagnosis of antimicrobial hypersensitivity and protocols for desensitisation, see Therapeutic Guidelines: Antibiotic.
~ Penicillin hypersensitivity

C
"Cl

re

IgE-mediated immediate hypersensitivity-while many reactions are labelled as 'allergic', true IgE-mediated immediate hypersensitivity is characterised by the development of urticaria, angioedema, bronchospasm or anaphylaxis (with objectively demonstrated hypotension, hypoxia or tryptase elevation) within 1 to 2 hours of drug administration. Anaphylaxis is mainly associated with parenteral rather than oral administration. For penicillin, anaphylaxis occurs at an estimated frequency of 1 to 4 cases per 10000 courses, with 10% of these reactions being fatal. Ifthere is a clear history of an Igfi-mediated reaction, the drug should not be administered again without appropriate precautions (eg desensitisation).

Patients with penicillin hypersensitivity are more likely also to be hypersensitive to other structurally related drugs. However, the exact prevalence and importance of cross-reactivity is not known. For example, in patients who report penicillin allergy, subsequent administration of a cephalosporin has been reported to result in an adverse reaction in 0.17% to 8.4% of patients. Cross-reactivity between penicillins and meropenem (a carbapenem) appears to be low (0.9% in one study"),

'Romano A, Viola M, Gueant-Roddiguez RM, Gaeta F,Valluzi R, Gueant JL. Brief communication: tolerability of meropenem in patients with IgE-mediated hypersensitivity to penicillins. Ann Intern Med 2007;146(4):266-0.

18

19

A clear history of an IgE-mediated immediate hypersensitivity reaction (urticaria, angioedema, bronchospasm or anaphylaxis within I to 2 hours of drug administration) contraindicates further exposure to penicillins, cephalosporins or carbapenems, unless desensitisation is undertaken. For detailed information on the management of patients reporting penicillin hypersensitivity, see Therapeutic Guidelines: Antibiotic.

Antibacterial drugs
Beta lactams Penicillins
The most common adverse effects of the penicillins are nausea, diarrhoea, rash, urticaria, pain and inflammation (at the injection site), and superinfection (after prolonged treatment and/or with broadspectrum penicillins). See also 'Antimicrobial hypersensitivity 'Antibiotic-associated diarrhoea' (p.20).
~ Narrow-spectrum penicillins

Antibiotic-associated diarrhoea
Diarrhoea is an adverse effect of many antibiotics. In most cases, no pathogen is identified. If possible, cease treatment with any antibiotic likely to be causing the symptoms. Clostridium difficile is responsible for the most serious cases of antibiotic-associated diarrhoea. Exposure to broad-spectrum antibiotics such as cephalosporins, quinolones and lincosamides is an important predisposing factor. For more information, see Therapeutic Guidelines: Gastrointestinal.

(allergy)'

(p.18)

and

Narrow-spectrum penicillins are active mainly against Gram-positive organisms, and they are inactivated by beta-lactamases. Phenoxymethylpenicillin (penici IIin V) is acid-stable, so it can be given orally, although food impairs absorption. It is intrinsically less active than benzylpenicillin. Phenoxymethylpenicillin is the drug of choice in acute odontogenic infections due to its narrow (and appropriate) spectrum of activity, with 85% of oral bacteria susceptible. Although susceptibility to amoxycillin is marginally higher (91 %), its use should be reserved to prevent the development of resistance in infections caused by Streptococcus pneumoniae. Phenoxymethylpenicillin has fewer gastrointestinal problems than amoxycillin and is less likely to cause a rash. Benzylpenicillin (penicillin G) is administered parenterally and is the treatment of choice for susceptible infections if parenteral treatment is warranted.
~ Narrow-spectrum penicillins with antistaphylococcal activity

Antimicrobial drug interactions

Some antimicrobials can interact with other drugs, which may affect the dose or choice of antimicrobial. Antimicrobials commonly implicated in drug interactions include rifampicin, linezolid, erythromycin, systemic azoles and antiretrovirals.

s s:::
Q)

C
"C

s:::

(Il

Studies have failed to show a significant interaction between oral contraceptives and common anti microbials used in dentistry. Additional contraceptive precautions are required in patients taking hormonal contraceptives who are treated with antimicrobials that are enzyme inducers (eg rifampicin, some antiretrovirals). * A comprehensive listing of interactions between antimicrobials and other drugs is beyond the scope of these guidelines, but relevant interactions are referred to in the text when considered particularly important. For more detailed information, see the product information for individual drugs or an appropriate drug interactions reference (eg Australian Medicines Handbook).

iii

<5
(f)

QJ

c
Q) ::::l CJ
'.;:0

o
QJ Cl.

::::l

.c
I-

~ QJ
* Faculty
of Sexual and Reproductive London: Healthcare. Drug interactions with hormonal 2011. contraception. Royal College of Obstetricians & Gynaecologists; <www.ffprhc.org.uk/pdfslCEUGuidanceDruglnteractionsHonmonal.pdf>

Dicloxacillin and flucloxacillin are stable to beta-Iactamases produced by staphylococci. They are reliably absorbed by the oral route; however, food reduces absorption and they are best taken half to one hour before food. Ideally, they should be dosed at 6-hourly intervals, but for practical purposes (eg in children) four-times-a-day dosing, evenly spaced during waking hours, can be given. They are rarely indicated in general dental practice. Flucloxacillin is generally well tolerated but, rarely, is associated with cholestatic jaundice, particularly in older patients on prolonged 21

20

therapy. This may occur after oral or intravenous administration and up to 6 weeks after treatment. It may last for months, can be irreversible and, rarely, may be fatal. Dicloxacillin appears to cause less irreversible hepatotoxicity but results in more infusion phlebitis and interstitial nephritis. Dicloxacillin may be preferable to ftucloxacillin for oral therapy or in patients requiring prolonged therapy. In these guidelines, ftucloxacillin. ~ Moderate-spectrum dilftucloxacillin refers to dicloxacillin or

streptococci and staphylococci, including beta-Iactamase-producing staphylococci. Their Gram-negative spectrum includes E. coli and most Klebsiella species, but they are inactive against many Gram-negative aerobes (eg Serratia, Enterobacter and Pseudomonas species). They are not useful against the Gram-negative anaerobe Bacteroides fragilis and related species. The common adverse effects are diarrhoea, nausea, rash, eosinophilia, drug fever, electrolyte disturbances, and pain and inflammation (at the injection site). See also 'Antimicrobial hypersensitivity (allergy)' (p.IS) and' Antibiotic-associated diarrhoea' (p.20). Glycopeptides Teicoplanin and vancomycin are active against a wide range of Grampositive organisms; Gram-negative organisms are not susceptible. Glycopeptides are sometimes used to treat severe infection with susceptible organisms in patients hypersensitive to penicillin. Vancomycin or teicoplanin may be used for prophylaxis of endocarditis in patients hypersensitive to penicillin. Teicoplanin can be given by intramuscular injection, or slow intravenous injection or infusion. Vancomycin is given by slow intravenous infusion to avoid producing a histamine-release reaction, commonly known as 'red-man' syndrome. Lincosamides Clindamycin and lincomycin are active against Gram-positive aerobes and most anaerobes. They are used as second-line therapy in those intolerant to conventional therapy or where resistance is of concern. Oral clindamycin and intravenous formulations of both clindamycin and lincomycin are available. There is no oral liquid formulation of clindamycin currently marketed in Australia; however, a 50 mgimL clindamycin solution can be made before each dose by dissolving the contents of alSO mg capsule in 2 mL of water. Draw this solution into a syringe and make the volume up to 3 mL (if necessary). The required volume of solution should be mixed with juice or soft food to disguise the taste before administration. Clindamycin is well absorbed orally. Intravenous doses should be administered slowly to avoid producing serious arrhythmias. The most common adverse effects of lincosamides are diarrhoea (see 'Antibiotic-associated diarrhoea', p.20), nausea, vomiting, 23

peniciliins

The aminopenicillins, amoxycillin and ampicillin, have greater activity than benzylpenicillin against some Gram-negative organisms (eg Escherichia coli, Haemophilus injluenzae), but are destroyed by betalactamase-producing strains. Amoxycillin is better absorbed orally than ampicillin, is not affected significantly by food and requires fewer oral doses per day, but when administered parenterally they are equivalent. Amoxycillin and ampicillin can increase the likelihood of rash In patients taking allopurinol (used in the prevention of gout). In these guidelines, ampicillin. ~ Broad-spectrum amoxy/ampicillin refers to amoxycillin or

peniciliins (beta-Iactamase

inhibitor combinations)

The beta-Iactamase inhibitor cIavulanate inhibits the enzymes produced by Staphylococcus aureus, Bacteroides fragilis and H injluenzae, and also most ofthe beta-Iactamase enzymes found in E. coli and Klebsiella species. Clavulanate possesses little Amoxycillin+clavulanate inherent antibacterial activity, but should not be used as first-line significantly extends the spectrum of treatment for odontogenic activity of amoxycillin when given infections. with it. This combination should be reserved for the treatment of beta-Iactamase-producing organisms. Additional anaerobic cover (eg metronidazole) is not required with beta-Iactamase inhibitor combinations. Amoxycillin+clavulanate can cause diarrhoea and hepatotoxicity, which occur more frequently than with amoxycillin alone.

Cephalosporins
Cepbalexin and cephazolin are moderate-spectrum cephalosporins with a similar range of antimicrobial activity. They are active against 22

abdominal cramps, abdominal pain, metallic taste (with intravenous administration), itch and rash.

Macrolides
Macrolides are rarely indicated in dental practice, although roxithromycin may be used to treat acute odontogenic infecti?ns in patients with penicillin hypersensitivity. ~n vitro, roxlthr~mycm has reasonable activity against some oral organisms, such. as vll:ldans group streptococci and Gram-positive anaerobes. However, Its activity against Gram-negative anaerobic organisms is more vanable; Bacteroides fragilis and Fusobacterium species are resistant. Roxithromycin is preferred to erythromycin because it has a ~~re benign adverse effect profile, fewer drug interactions and better activity against oral pathogens. The most common adverse effects of macrolides are nausea, vomiting, diarrhoea, abdominal pain, cramps, headache, dyspnoea, cough and candidal infections.

avoid alcohol during treatment, and for at least 24 hours after treatment with metronidazole or 72 hours after treatment with tinidazole. Metronidazole also inhibits the metabolism of warfarin, increasing its concentration and the risk of bleeding, so patients taking warfarin should have their international normalised ratio (INR) monitored.

Tetracyclines
Tetracyclines are usually bacteriostatic and have a broad spectrum of activity, which includes Gram-positive and Gram-negative bacteria, Chlamydia, Rickettsia, Mycoplasma, spirochaetes, some nontuberculous mycobacteria and some protozoa. Tetracyclines are rarely indicated in general dental practice, but may be used in the management of tooth avulsion to help prevent root resorption. Doxycycline is the preferred tetracycline in most situations, as oncedaily dosing enhances patient adherence and dosage adjustment is not required in patients with renal impairment. Demeclocycline is available in combination with triamcinolone acetonide as an intracanal paste (see 'Intradental corticosteroids', p.34). Tetracyclines are contraindicated in children 8 years of age or less as they chelate calcium ions and are incorporated into the hydroxyapatite of the developing enamel and dentine, leading to tooth discolouration and enamel dysplasia. They are also deposited in bone, causing deformities and inhibiting bone growth. As dentine development may continue beyond 8 years of age, some practitioners avoid tetracyclines in children up to 12 years of age. Tetracyclines are safe for use during the first 18 weeks of pregnancy (16 weeks postconception) after which they may affect the formation of the baby's teeth and cause discolouration. There have been rare occurrences of hepatic necrosis in pregnant women. Tetracyclines may be used for short courses (eg 7 to 10 days) in breastfeeding women if there are no appropriate alternatives. All tetracyclines cause some gastrointestinal symptoms. Oesophagitis can occur with any tetracycline so they should be taken after food with a full glass of water and the patient should be instructed to remain upright for at least 30 minutes after oral administration. Photosensitivity reactions can occur with any tetracycline, but are most likely with doxycycline, and sun protection should be recommended. Candidal overgrowth can also occur with any tetracycline. There are several important interactions with tetracyclines. Antacids decrease the absorption oftetracyclines, and oral doses oftetracyclines and antacids should be separated by 2 hours. Some drugs (eg

Nitroimidazoles
Metronidazole and tinidazole have a spectrum of activity that encompasses Gram-negative anaerobes such as B~cteroides fragili~, Gram-positive anaerobes such as Clostridium. species, and ~naeroblc protozoa. Metronidazole is the drug of choice for spreading neck infections and acute ulcerative gingivitis. Metronidazole is available as an intravenous preparation; however, excellent absorption means that tablets or suppositories ~an often be used instead. In these guidelines, for the treatment of mixed aerobic and anaerobic infection, metronidazole is recommended at a dose. of 400 mg orally and SOO mg intravenously, with. a 12-~ourly. dosing schedule to increase patient adherence. This dosing regimen IS based on pharmacokinetic data and minimum in.hi.bitory c~ncentratlOns of the pathogens involved, rather than formal clinical studies. Tinidazole is available only as an oral preparation. It has a longer halflife than metronidazole so it can be administered less frequently or as a single dose. The most common adverse effects of nitroimidazoles are nausea, diarrhoea and a metallic taste. Nitroimidazoles can interact with alcohol causing a disulfiram-like reaction (severe intestinal cramping, flushing, tachycardia, nausea and vomiting). Patients should be counselled to
24

carbamazepine, phenytoin) reduce the plasma concentrations of doxycycline. Tetracyclines can enhance the activity of warfarin so patients taking warfarin should have their international normalised ratio (INR) monitored.

erratically from the gut, and even less through the skin. Valaciclovir, a prodrug of aciclovir, has improved oral bioavailability compared with aciclovir. Famciclovir is well absorbed from the gut. Famciclovir and valaciclovir require fewer oral doses per day than aciclovir. They are all generally well tolerated. Topical aciclovir and penciciovir are indicated for the treatment of herpes simplex virus infection of the lips (herpes simplex labial is). For best effect, they should be applied to the lesions or impending lesions as early as possible, particularly for treatment of recurrent episodes. Common adverse effects include a transient stinging or burning sensation. Application of topical aciclovir and penciclovir to mucous membranes (eg in the mouth, eye or vagina) should be avoided as they may be irritant.

Antifungal
Miconazole

drugs

Miconazole is an imidazole derivative with broad antifungal activity. It is available as a topical 2% oral gel, which is used to treat oral candidosis. Patients should be counselled to use the gel after food and retain the gel in their mouth for as long as possible before swallowing. Treatment should be continued for 7 days after symptoms disappear to prevent the germination of remaining spores, which are invariably present. Topical imidazole preparations can cause local irritation but sensitisation is uncommon. Miconazole use on the oral mucosa may cause a significant increase in the international normalised ratio (INR) in patients taking warfarin. Polyenes Nystatin and amphotericin are highly effective against Candida species. They can be used topically on the oral mucosa to treat candidosis, as they are not absorbed through the mucosa or the gastrointestinal tract to any significant extent. Amphotericin is available as a lozenge-advise patients to suck the lozenge after food to reduce the adverse effect of nausea. Nystatin is available as oral drops-advise patients to take the drops after food and to swish the medicine around the mouth for as long as possible before swallowing. Topical intraoral polyenes have few adverse effects. The most common are mild gastrointestinal symptoms (eg nausea, vomiting, diarrhoea).

ANALGESICS
Three broad groups of drugs are used as analgesics for oral and dental pain-nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol and opioids.

Nonsteroidal

anti-inflammatory

drugs

General considerations Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs for pain relief. Many patients use NSAIDs for self-management of common pain problems (eg headaches, muscular aches, period pain, toothache). SAIDs relieve nociceptive pain associated with inflammation due to tissue damage, as well as having a direct anti-inflammatory action. They exert their main effect by inhibiting cyclo-oxygenase (COX), which in turn reduces the synthesis of pro-inflammatory mediators (prostaglandins) from arachidonic acid. NSAIDs act both at peripheral sites in the body (ie where the tissue damage has occurred) and in the central nervous system. As the majority of dental pain is inflammatory in origin, NSAIDs are the drug class of choice for the treatment of acute dental pain. They are also effective in treating bone pain, which makes them very useful for dental pain. NSAIDs can be used alone for mild to moderate pain; however, severe pain usually requires the addition of another analgesic, such as paracetamol. 27

Antiviral drugs
Guanine analogues 26 Aciclovir, famciciovir and valaciclovir are active against herpes simplex and varicella-zoster virus. Aciclovir is absorbed poorly and

The analgesic and, particularly, anti-inflammatory actions ofNSAlDs are dose-related. Lower doses can provide pain relief, but higher doses are required for effective anti-inflammatory action (eg a single dose of 200 mg of ibuprofen may relieve pain temporarily, but at least 400 mg is required to reduce the inflammatory response; 600 mg is even more effective). However, adverse effects are also dose-related, and the analgesic needs of the patient must be balanced against the risk of adverse effects (see below for adverse effects). The dosing interval is important to maintain therapeutic blood concentrations. These drugs should be used as a 'course of treatment' with regular doses at specified time intervals rather than when the patient feels pain or discomfort. It is important to educate the patient about how to use NSAIDs properly. Many different NSAIDs are available and they have similar efficacy. Therefore, the choice of drug is largely based on safety, availability, cost and the required route of administration. The pharmacokinetic profiles of individual NSAIDs vary considerably. The most commonly used NSAlDs for dental, oral and facial pain are ibuprofen and aspirin. Ibuprofen produces greater analgesia than paracetamol+codeine combinations.

NSAIDs are available as over-the-counter medications and on prescription; they are packaged in different dosages for different markets. It is important that the correct dosage is prescribed and the potential problems are explained to the patient. Some commercial formulations combine SAIDs with other drugs; a careful medication history needs to be taken to determine the total daily dose of each component. Table 2. Adverse effects of nonsteroidal anti-inflammatory drugs
System cardiovascular neurological Adverse effects

ris.~.in. blood pressure. fluid retention. myocardial infarction. stroke

headaches. confusion. hallucinations. depersonalisation reactions depression. tremor. aseptic meningitis. tinnitus. vertigo. neuropathy. ...................................... t?XIGamblyopia. transient transparent corneal deposits gastrointestinal nausea. vomiting. dyspepsia. diarrhoea. constipation. gastnc mucosal irritation. superficial erosions. peptic ulceration. oesophagitis and strictures. faecal blood loss. major gastrointestinal haemorrhage. penetrating ulcers. small bowel erosions anaerrua, bone marrow depression. decreased platelet aggregation hepatotoxicity. fulminant hepatic failure glomerulopathy. interstitial nephritis. changes in renal blood flow leading to a fall in glomerular filtration rate. alterations in tubular function. reduction in diuretic-induced natriuresis. inhibition of renin release. oedema precipitation of asthma in patients with nasal polyps. skin rashes

haematological hepatic renal

Adverse effects, interactions and precautions

All NSAIDs have potential adverse effects and these should be discussed with the patient (see Table 2, p.29). Older patients have a higher risk ofNSAID-related adverse effects and their need for NSAID therapy should be assessed carefully. NSAIDs may cause gastric erosions and peptic ulcers (gastric and duodenal) and increase the risk of upper gastrointestinal complications (bleeds, perforation). These lesions may occur in the presence or absence of symptoms. The relative risk of a serious gastrointestinal adverse event varies between NSAlDs and is dose-related. The risk is also related to patient-specific factors (see Box 5, p.29). NSAIDs are typically contraindicated in patients with a definite history ofNSAID allergy (particularly NSAlD-induced asthma), active peptic ulcer disease or gastrointestinal bleeding. Aspirin should not be used for analgesia in children less than 16 years of age because of its rare association with Reye syndrome. NSAIDs interact with many drugs, including angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, inhibitors of some cytochrome P450 enzymes, some diuretics, lithium and warfarin.
28

other

Box 5. Risk factors for NSAID-induced upper gastrointestinal bleeding or perforation

older age past history of upper gastrointestinal past history of peptic ulcer disease Helicobacter pylori infection concomitant drugs. including (in order of risk) anticoagulants. SSRls and corticosteroids significant comorbidity smoking.
NSAID =

bleeding

antiplatelet

drugs.

nonsteroidalanti-inflammatorydrug; SSRI = selectiveserotoninreuptake inhibitor

29

Paracetamol
General considerations
Paracetamol (acetaminophen) has analgesic and antipyretic actions through inhibition of prostaglandin synthesis in the central nervous system. In therapeutic doses, inhibition of prostaglandin synthesis is not significant in peripheral tissues, so paracetamol has minimal antiinflammatory action. Paracetamol may be used to reduce the required daily dose of nonsteroidal anti-inflammatory drugs (NSAIDs) or opioids, thus reducing the risk oftheir adverse effects. Other indications include: an alternative to NSAlDs, including when NSAIDs are contraindicated (see 'NSAIDs: Adverse effects, interactions and precautions', p.28) mild procedural pain management of fever. Paracetamol is rapidly absorbed after oral administration, with peak blood concentrations reached within 10 to 60 minutes; its half-life is 1 to 3 hours. It readily crosses into the cerebrospinal fluid and into the brain where it has its major analgesic effect. It undergoes extensive firstpass metabolism in the liver, and the kidneys excrete its metabolites. The typical dose schedule for healthy adult patients is 0.5 to 1 g every 4 to 6 hours up to 4 g per day (less in the elderly and the frail). Some oral preparations are modified for slow release and can be taken every 8 hours. Formulations of paracetamol include immediate-release tablets and capsules, modified-release tablets, chewable tablets, soluble and effervescent tablets, oral solutions and suspensions, suppositories, and an injectable formulation. Paracetamol may be combined with other analgesics (eg NSAIDs, codeine), decongestants, antihistamines and antiemetics. Some combination products are available without a prescription. Clinicians should be familiar with the range ofpreparations available so they can advise patients.

metastases; however, paracetamol should be administered cautiously in patients with renal or hepatic dysfunction. Tolerance and dependence to paracetamol have not been reported. Paracetamol doses of more than 3.5 g per week may interact with warfarin to increase the international normalised ratio (lNR) so patients taking warfarin should have their INR monitored. Inadvertent overdose is a possibility (see below). Due to the variety of paracetamol-containing products available, patients should be advised to consider the paracetamol content of all medications taken. A careful medication history should be taken to determine the total daily dose of paracetamol. Care is required when prescribing paracetamol and the dose should be stated in grams or milligrams rather than as number of tablets or volume of liquid.

Overdose
Acute paracetamol overdose (in adults with a single ingestion of more than 10 g and children with a single ingestion of more than 200 mg/kg) is a potentially life-threatening event. Excessive metabolite production in overdose may overwhelm the availability of hepatic glutathione to detoxify the harmful metabolite, leading to severe toxicity with hepatic necrosis. Much lower doses of paracetamol may be toxic in patients who already have reduced hepatic glutathione due to starvation, fasting or other acute hepatic insult. A paracetamol overdose is a medical emergency that requires recognition and prompt management (see Therapeutic Guidelines: Toxicology & Wilderness for assessment and management). Clinical signs of overdose may take several days to develop so liver biochemistry, renal function tests and plasma paracetamol concentration should be performed immediately and monitored.

Opioids General considerations

Opioids (narcotics) are generally used for severe pain (eg severe postoperative pain, severe acute trauma, chronic cancer-related pain). Opioids include codeine (the most commonly prescribed opioid in dental practice) (see p.32), morphine, oxycodone and tramadol. Opioids have many significant adverse effects in all major systems of the body (see Table 3, p.33) and should be used with caution. Safe use requires knowledge of the available opioids and their relative

Adverse effects, interactions and precautions

Paracetamol is generally considered a safe analgesic with a low incidence of adverse effects compared with other drugs. Rarely, patients may experience urticarial or erythematous rashes, fever or blood dyscrasias. Long-term use of paracetamol alone does not seem to cause analgesic nephropathy and it can be used in patients with liver

31

30

indications, formulations and routes of administration, as well as awareness of their potential adverse effects and how to manage these. Opioids act on specific receptors at supraspinal, spinal and peripheral sites. They can block all forms of pain, not just pain arising from tissue damage and inflammatory processes. The normal clinical doses used also dampen the patient's emotional response to the pain, perhaps more effectively than blocking the pain (ie pain may still be noted by patients but they can tolerate it or cope with it better).

Table 3. Adverse effects of opioids

System
cardiovascular

Adverse effects
bradycardia due to stimulation of the vagal nucleus in the medulla histamine release by morphine and morphine analogues, which may cause vasodilation and hypotension during intravenous administration postural hypotension from peripheral vasodilation and baroreflex inhibition

dermatological

sweating, flushing urticaria and pruritus due to histamine release

Adverse effects, interactions and precautions

The adverse effects of opioids are summarised in Table 3 (p.33). Hypersensitivity may manifest as pruritus, urticaria, rash or bronchospasm. Opioid withdrawal syndrome includes body aches, diarrhoea, 'goose flesh', loss of appetite, nervousness or restlessness, runny nose, sneezing, tremors or shivering, stomach cramps, nausea, sleeplessness, diaphoresis, yawning, asthenia, tachycardia and unexplained fever. Concomitant use of central nervous system depressant drugs (eg sedatives, hypnotics, antipsychotics, antidepressants, anaesthetics, alcohol) may increase the sedative and respiratory depressant effects of opioids. Concomitant use of drugs with anticholinergic activity (eg tricyclic antidepressants, atropine) may increase the risk of severe constipation, urinary retention and delirium. Drugs that induce or inhibit the hepatic cytochrome P450 system may affect the blood concentrations of opioids, leading to either decreased effectiveness or toxicity. Opioids affected include tramadol and codeine. Optimal analgesia is difficult to achieve in an opioid-dependent and specialist advice may be needed. person
gastrointestinal

vomiting, anorexia, decreased gastric motility, increased antral tone, delayed gastric emptying, slowed digestion, prolonged large bowel transit time, increased anal sphincter tone, constipation (these are caused by mu and delta receptor agonists acting locally and centrally) chest wall rigidity (with fentanyl and fentanyl analogues), myoclonus hypothalamic effects (including inhibition of gonadotrophin- releasing hormone and corticotrophin-releasing factor) leading to decreased gonadotrophins, adrenocorticotrophic hormone, beta-endorphin, testosterone and cortisol, and increased prolactin antidiuretic hormone release is variably increased by mu receptor agonists (leading to fluid retention or oedema), and inhibited by kappa receptor agonists

musculoskeletal neuroendocrine

neurological

dose-dependent mental clouding, delirium, sedation, nausea and vomiting, cough suppression, miosis, respiratory depression or apnoea, excitatory phenomena with myoclonus with high doses relative to renal function, reactivation of herpes simplex (with spinal and epidural morphine) following intraspinal use of morphine or hydromorphone, central adverse effects may be considerably delayed (6 to 12 hours)

respiratory

Codeine
Codeine is metabolised to morphine, which is responsible for most of codeine's analgesic action. Approximately 7% to 10% of Caucasians and 1% to 2% of Asians are poor metabolisers of codeine, and have no detectable analgesic effect from codeine. In these individuals, there is no benefit in increasing the dose, and it is potentially harmful because codeine itself can cause constipation and drowsiness. Codeine is available for oral use, and has a duration of action of 4 to 6 hours. For opioid adverse effects, interactions and precautions, see above.
32

dose-related respiratory depression (which is more marked during sleep or with concomitant sedatives, hypnotics, alcohol and general anaesthetics) bronchospasm due to histamine release

urinary

urinary retention and difficulty with micturition, increased external sphincter tone, decreased detrusor muscle tone, antidiuretic effect

33

CORTICOSTEROIDS
Corticosteroids are useful drugs for the management of many dental and oral mucosal inflammatory conditions. Their use must be prefaced by a complete medical and medication history, and an accurate diagnosis of the presenting condition. In dentistry, corticosteroids can be used intradentally (within a tooth), topically on the oral mucosa or systemically. The most effective route of administration should be chosen. Intradental or topical intraoral corticosteroids are preferred as the drug is placed at the site of action, which generally results in a more rapid onset of action and less systemic adverse effects.

The corticosteroid-antibiotic cements are used within the crown of a tooth as part of a cavity lining or base, as an indirect pulp cap, as a direct pulp cap, or as a pulpotomy agent before restoration of cavities in teeth that have reversible pulpitis. Commercial preparations typically also contain various other substances (eg calcium hydroxide, zinc oxide, eugenol). The cement is presented as a powder and liquid, which are mixed to form a paste that is placed on the dentine or exposed pulp; it then sets to form the hard cement.

Topical corticosteroids General considerations

Intradental

corticosteroids

Corticosteroids have been combined with antibiotics for intradental application in the management of pulp and periapical diseases. The corticosteroid component is included as almost all pulp and periapical diseases are inflammatory in nature. The antibiotic component is included as these diseases are usually caused by the presence of bacteria within the tooth, pulp or root canal system. There are two forms of corticosteroid-antibiotic compounds commercially available for intradental use-a water-soluble paste and a hardsetting cement. The form used depends on the condition being treated and where the material is to be placed.
(ij
Cl)

... c
ca

C
'C C

The corticosteroid-antibiotic pastes are used as an intracanal medication (within the root canal system of a tooth) during endodontic treatment. The paste can be used as an initial medication for rapid and reliable relief of pain associated with irreversible pulpitis. It is also used as an intracanal medication to reduce the periapical inflammation (acute or chronic apical periodontitis)-and hence the pain-that is often associated with irreversible pulpitis and always associated with an infected root canal system. The pastes are also used as an intracanal medication to prevent and manage several forms of inflammatory root resorption (eg internal inflammatory resorption, external apical inflammatory resorption, external lateral inflammatory resorption). An additional effect of intracanal corticosteroid pastes is a reduction in external replacement resorption following tooth avulsion and intrusive luxation injuries, as corticosteroids inhibit the action of clastic cells. Commercial preparations of pastes include clindamycin or demeclocycline with triamcinolone acetonide.

Topical corticosteroids have anti-inflammatory and immunosuppressant effects that are useful in a number of skin, mucosal and mucocutaneous diseases. Modifications of the naturally occurring hydrocortisone molecule have produced a range of drugs with varying anti-inflammatory potency for topical use (see Table 4, p.36). An understanding of this potency is critical to their effective and safe clinical use. The potency depends on the concentration used, the intrinsic activity ofthe compound, and its ability to penetrate the barrier of the epidermis or mucosa, which may be influenced by the vehicle in which it is applied and the method of application. The permeability of the oral mucosa varies at different sites. Keratinised masticatory mucosa (palate, dorsum of tongue and gingivae) is less permeable than nonkeratinised lining mucosa (floor of mouth and ventral surface of tongue). The cumulative effect of corticosteroids depends on the frequency and duration of application . Topical corticosteroids should not be used unless a clinical diagnosis that requires the use of corticosteroids has been made. It is important that the pathogenesis of the condition is understood so an appropriate regimen can be determined and, equally, the outcome of this regimen can be defined and discussed with the patient. For example, the indications and outcome with oral lichen planus are quite distinct from pemphigoid and aphthous ulcerative disease. Most mucosal lesions progress through several stages (eg an aphthous ulcer may be prodromal, preulcerative, ulcerative, or show signs of healing or advanced healing). The stage of the disease must be identified to assist in determining the treatment. Consideration of the stage helps establish if a corticosteroid is indicated and, if so, the appropriate potency, the method of application, the frequency and duration of treatment, and the expected treatment outcome.
continued p.37

34

35

Table 4. Properties of topical corticosteroids oral mucosa

Drug Strength Form* Clinical potency on oral
mucosa" hydrocortisone acetate 1% ointment mild

used on the

Oral uses

Most mucosal diseases respond best to a topical corticosteroid when it is applied at the earliest stage (eg topical corticosteroids are most useful for aphthous ulcers when they are in the prodromal and preulcerative stages, as this disease has a well established cell-mediated immunopathogenesis ). The topical corticosteroids that can be applied intraorally and their suggested uses are outlined in Table 4 (p.36). In the mouth, ointments are preferred, as creams are less effective in enhancing contact time. Generally, twice-daily application is adequate and there is no additional benefit from more frequent use. Most areas receive adequate coverage with frugal application and brief gentle rubbing without abrading tissues. If prolonged application is indicated, for example in gingival erosive conditions, custom-made applicators can be worn by the patient. Clinicians should exercise caution with the entire range of corticosteroids, and avoid potent drugs unless familiar with their use and there is a clear indication for this level of drug. The prolonged use of high potency corticosteroids requires careful control. Often their use indicates a lack of understanding of the disease mechanisms and an unrealistic expectation of the treatment by the patient and clinician (ie expect cure/lesion resolution, as opposed to symptom reduction and control).

minor mucosal inflammation, cheilitis (not suitable for angular cheilitis) inflammatory mucosal conditions inflammatory mucosal conditions (eg aphthous ulceration, lichen planus) (use with caution) inflammatory mucosal conditions (eg aphthous ulceration, lichen planus) (use with caution) inflammatory mucosal conditions (eg aphthous ulceration, lichen planus, pemphigoid, pemphigus) (use with caution) inflammatory mucosal conditions (eg aphthOUS ulceration, lichen planus) (use with caution) severe inflammatory mucosal conditions (eg erosive lichen planus) (use with caution)

triamcinolone acetonide betamethasone valerate

0.02%

ointment

moderate

0.02%, 0.05%

ointment

moderate

betamethasone valerate

0.1%

ointment

potent

General principles of use

Most topical corticosteroids available in Australia are marketed for external use on the skin and packaging is marked accordingly. Therefore, it is important patients are made aware of the nature of the prescribed medication and are reassured that the medication is safe for intraoral application when used as instructed. Patients also benefit from written confirmation of verbal instructions separate from the prescription, as the dispensing pharmacist or attending medical practitioner may not be familiar with the intraoral use ofthese drugs and may provide conflicting advice. (On occasion, the drug may not be dispensed on the basis that it is 'for external use only'.) Points to consider when prescribing topical intraoral corticosteroids are outlined in Box 6 (p.38). Caution must be taken with corticosteroid use in patients with certain conditions, and patients must be advised of potential adverse effects and be reviewed regularly (see p.38 for adverse effects). The use of topical corticosteroids must be precise and controlled. Many commonly prescribed topical corticosteroids are medium to high potency and this is not appreciated by the patient and, on occasion, by 37

betamethasone dipropionate

0.05%

ointment

potent

S c:
Q)

Q
'C

c:

ca

(ij 0

..
Vi Q)
c :::J o :::J
D.
Q)

methylprednisolone aceponate

0.1%

ointment

moderate

(j)

:Q

mometasone furoate

0.1%

ointment

potent

(!) '.p

In the mouth, ointments

are preferred, as creams are less effective in enhancing contact time. when applied to the oral mucosa are not the same as when they

~
s:
tQ)

t Potencies of corticosteroids are appliedto the skin.

36

the prescriber. A general guideline is to prescribe the lowest potency clinically indicated, with a minimal amount applied as infrequently as possible for the minimum time. Extending use outside of this guideline requires special ist advice. The goal of treatment should be defined and explained to the patient. This may be: symptomatic relief only complete lesion resolution (eg for minor aphthous ulceration) resolution but with residual visible tissue changes (eg for major aphthous ulceration) clinical management of a chronic condition (eg for atrophic lichen planus). Box 6. Points to consider when prescribing topical intraoral corticosteroids
Corticosteroids are best applied with the pad of a washed finger. Applicators, including cotton tips, are fibrous and may inadvertently damage the fragile atrophic mucosa. Corticosteroids should be applied to wet mucosa. Drying the tissues before application is a natural instinct, but tissue trauma must be balanced against any benefit of drying (which is minimal). Prolonged avoidance of food and drink after topical corticosteroid rapid. A convenient time for application is after oral hygiene in the morning and at night. Patients readily become frustrated when ointments do not adhere effectively. This is overcome by frugal application, brief gentle rubbing with the finger pad, and reassurance that this method of application is adequate. Patients using special methods of application (eg sprays, adhesives) require additional written explanation. application seems logical, but is not required as corticosteroid absorption is reasonably

Intraorally, adverse effects are somewhat hidden, but they are noticeable on the face and the vermilion of the lips. Penetration of corticosteroid into the dermis is greater on the face and only mild corticosteroids (eg hydrocortisone) should be used on this site. In certain circumstances, more potent corticosteroids (eg methylprednisolone aceponate) may be used intermittently for up to 2 weeks. If improvement does not occur after 2 weeks, do not persevere with treatment-reconsider the diagnosis and seek specialist advice. Potential local skin effects include: loss of dermal collagen, leading to skin atrophy, formation of striae, fragility and easy bruising telangiectasia (development of prominent blood vessels) promotion of infection idiosyncratic reactions (eg allergic contact dermatitis, perioral dermatitis). The most common adverse reactions to topical intraoral corticosteroids are secondary oral candidosis, nausea, intolerability (eg because of unpl.easant taste), refractory response, mucosal atrophy and delayed healing, Secondary oral candidosis imposes a treatment interruption and delays effective management. In many cases, it can be anticipated, and preventive and interceptive strategies can be used concurrently. For ~xample, patients with salivary gland hypofunction or atrophic candidosis under prostheses, or patients who are using corticosteroid inhalers or have hyperkeratotic lesions (Candida is keratinophilic) are more likely to develop candidosis. A number of oral mucosal diseases cause tissue atrophy, particularly on the tongue (eg lichen planus), which can persist even with lesion resolution or entry into a quiescent phase. Long-term use of topical corticosteroids compounds the disease-related atrophy. Monitor patient use and adherence, and regulate use against the level of tissue and sensory morbidity experienced by the patient. With greater potency, there is also an increased risk of rebound on withdrawal. Many conditions benefit from a tapered dose reduction to complete cessation or, on occasion, a maintenance level. Topical corticosteroids should not be used in the presence of infection without appropriate antimicrobial cover. Generally, infections ?r .. a predisposition to develop an infection should be managed initially before commencing topical corticosteroids. Avoid topical corticosteroids if a viral disease is suspected as they prevent cytotoxic T Iymphocytes attaching to virally infected cells and do not control
39

Adverse effects, precautions and contra indications

Adverse effects of topical corticosteroids may be due to local effects on the skin or mucosa at the site of application, or due to systemic effects following absorption of the drug (see 'Systemic corticosteroids' for a discussion of systemic adverse effects, pAD). The intensity of adverse effects increases with the potency of the preparation. When topical corti eo steroids are used on the oral mucosa, systemic absorption is generally limited; however, caution is required when potent topical preparations are used.

38

the local inflammatory component of conditions such as herpes zoster. Systemic contraindications, including the possibility of reactivation of tuberculosis, should be considered when using methods likely to enhance contact time and systemic absorption. These include occlusive devices, such as custom applicators, and corticosteroid mouthwashes. Caution is also required in patients with hypertension or diabetes.

(anxiolytic effect), promote drowsiness (sedative effect) and induce sleep (hypnotic effect). All anxiolytic and sedative drugs are central nervous system (CNS) depressants. The most commonly used drugs for oral anxiolysis and sedation in dentistry are benzodiazepines (see below). The development of substance dependence, tolerance and withdrawal can be a major concern to both patients and prescribers. For more information, see p.42.

Systemic corticosteroids
Systemic corticosteroids are usually inappropriate for general dental practice. They represent a highly potent class of medication, and while adverse events are uncommon and of short duration, they are significant. Wherever possible, the topical corticosteroids are preferred because their immunosuppressive effects are much less (see 'Topical corticosteroids', p.3S). Some oral inflammatory mucosal conditions, however, do require systemic corticosteroids. Systemic corticosteroids should only be used in patients who have been assessed as suitable for treatment (eg there are no contraindications to their use) and in whom they are the treatment of choice. Systemic corticosteroids may be useful in the management of severe postoperative swelling, severe trauma, and periapical nerve sprouting and acute apical periodontitis following removal of acutely inflamed pulp. All of these conditions usually require specialist management.

Benzodiazepines
General considerations
Benzodiazepines are the most commonly prescribed anxiolytic and sedative drugs because of their efficiency and relatively low incidence of adverse effects. They act by potentiating the action of gammaaminobutyric acid (GABA) at the GABAA receptor resulting in neuronal inhibition. Benzodiazepines are generally rapidly and fully absorbed after oral ingestion with peak plasma concentrations occurring from 0.5 to 2 hours after administration. They There is little basis for the use of are metabolised by glucuronidation, more than one benzodiazepine which inactivates them, and by oxiconcurrently in any patient. dation, which may produce active metabolites. Most differences between benzodiazepines are explicable in terms of different pharmacokinetic properties. There is little basis for the use of more than one benzodiazepine concurrently in any patient.

iV ...
s:::
Q)

C
'C

s:::

(Il

iV ..
Ui Q)
c
Q)

The major limiting factor in the use of systemic corticosteroids is the development of adverse effects, which may be extensive and are largely dose-related. Treatment with prednisolone or prednisone at doses greater than 10 mg daily for more than 3 weeks may be sufficient to cause adrenal suppression. A patient taking corticosteroids should have their dose increased before surgery. Addisonian (adrenal) crisis can present 6 to 12 hours after surgical stress in a patient taking corticosteroids who has not had the dose increased before the surgery (see 'Adrenal disorders: Dental issues', p.1S1).

Adverse effects, interactions and precautions

Drowsiness is a common initial reaction to benzodiazepines. Psychomotor performance may be impaired, as may some memory functions. Older people are particularly vulnerable to the adverse effects of ataxia (with consequent falls and injury), confusion, memory loss and cognitive impairment. Benzodiazepines can precipitate delirium. In younger patients, ataxia, nystagmus, muscle weakness and dysarthria are reported less often. Dry mouth and blurred vision are sometimes troublesome. Sedation may persist the following day after benzodiazepine dosing (even with short-acting drugs) and the effects of alcohol and other CNS depressants (eg opioids) can be potentiated. Warn patients that this may affect their ability to drive and operate machinery safely.

:2
:::J 0 o ~ :::J
Q) Q)

LOCAL ANAESTHETICS
See the 'Local anaesthesia' chapter (pp.11l-l9) for detailed information.

0.

~
s:
I-

ANXIOLYTIC AND SEDATIVE DRUGS

Depending on the dose administered, drugs classified as anxiolytics and sedative-hypnotics have the ability to calm a patient and relieve anxiety

40

41

The potential for developing tolerance, dependence and withdrawal symptoms is an important consideration (see below). Dependence develops rarely in patients taking therapeutic doses ofbenzodiazepines for short periods (eg I to 2 weeks). All benzodiazepines can produce withdrawal symptoms; these can be physical and psychological and are related to the dose and duration of use. Tolerance occurs more with the sedative and hypnotic effects of benzodiazepines than with other effects; the degree of tolerance differs between patients. Patients with a history of dependence on alcohol and other drugs are more likely to become dependent or intentionally misuse benzodiazepines. Avoid benzodiazepines in patients with myasthenia respiratory impairment or severe hepatic impairment. gravis, severe

Psychotropic for more information). Some drug classes (eg selective serotonin reuptake inhibitors) are associated with a withdrawal syndrome, but patients taking these drugs do not show development of dependence. Patients with a substance use disorder, particularly alcohol- or opioidrelated, or a history of such a disorder, are at particular risk of developing benzodiazepine dependence. If a drug use problem is identified, it is important to investigate the use of other substances as multiple drug use is very common. A range of psychiatric disorders also occurs with greater frequency among patients with problem drug use. The most common are depression, anxiety disorders (particularly social phobias) and personality disorders. It should also be recognised that many psychiatric patients use drugs such as alcohol, cannabis and amphetamines. See also 'Legislation about prescriptions prescribing drugs of dependence. and prescribing' (p.ll) for

Diazepam and temazepam

Diazepam and temazepam are widely used as anxiolytics and sedatives. Diazepam is also used as a muscle relaxant and as an antiepileptic. Diazepam is available as tablets, an oral liquid and an injection. It is reliably absorbed from the gut and its optimum clinical effect is reached after 1 hour. Diazepam's half-life is between 14 and 70 hours; its primary metabolite, nordiazepam, retains significant eNS depressant activity. Temazepam also has a rapid onset of action, but has a relatively short half-life (3 to 25 hours) and no active metabolites. Temazepam is only available as tablets. For benzodiazepine pAl. adverse effects, interactions and precautions, see

MOUTHWASHES
A mouthwash may be recommended as: an antiseptic to decrease the number of microorganisms in the oral cavity (eg for periodontal disease, halitosis, dental caries) fluoride treatment for dental caries an anti-inflammatory (eg for oral mucosal disease) an analgesic (eg for oral mucositis). The use of antiseptic mouthwashes in periodontal disease is controversial; however, there are specific instances where they can be beneficial (eg for short-term use in patients with gingivitis when inflammation restricts normal toothbrushing). These mouthwashes are only effective against supragingival plaque, and are not effective beyond the gingival crevice or periodontal pocket. Therefore, they are not appropriate as the sole treatment for periodontal disease. Patients should be informed that the principal treatment for chronic periodontal disease is professional intervention with root planing of involved teeth and meticulous oral hygiene (see 'Gingivitis', p.55, and 'Periodontitis', p.56). The use of mouthwash alone for oral hygiene is not recommended. Oral hygiene must be, principally, toothbrushing and dental f1ossing. Nevertheless, the use of mouthwashes containing fluoride has significant benefits in patients at high risk of caries (see 'Fluoride', p.50).
43

Dependence, tolerance and withdrawal

Tolerance is a physical state whereby, after repeated administration, a given dose of drug produces a decreased effect, or increasingly larger doses must be taken to obtain the effects observed with the original dose. Physiological dependence occurs when repeated administration of the drug is necessary to prevent a characteristic withdrawal syndrome. Substance dependence is a behavioural syndrome in which individuals have an overwhelming drive to use a substance, often despite medical or social consequences, and they behave as if the effects of the drug are needed for continued wellbeing. The term 'addiction' is best used synonymously with dependence. Tolerance and withdrawal represent only 2 of the 7 criteria for substance dependence in the most commonly used diagnostic criteria of DSM-IV- TR (see Therapeutic Guidelines:
42

Although anti-inflammatory mouthwashes can provide symptomatic relief of oral inflammatory mucosal disease, the use of topical corticosteroids is often the most effective treatment; this is discussed in the 'Oral mucosal disease' chapter (pp.71-90) and in the 'Topical corticosteroids' monograph (p.35).

Povidone-iodine Povidone-iodine is an iodine complex that has antibacterial, antifungal and antiviral properties. It is used in mouthwashes and gargles. It is also used in skin cleansers; antiseptic creams, ointments, powders, solutions and paints; and in some antiseptic swabs and wound dressings. Povidone-iodine can cause irritation of skin and mucous membranes. It is absorbed through damaged skin so application over a large broken skin surface is not recommended. Povidone-iodine should not be used during pregnancy or lactation as it has the potential to cause hypothyroidism in the neonate. Triclosan Triclosan is a broad-spectrum antibacterial used in mouthwashes and toothpastes. It effectively inhibits plaque build-up. It also has anti-inflammatory properties, which further helps to reduce gingival inflammation. Triclosan is also used in medicated soaps and topical skin preparations. Allergic contact dermatitis has been reported.

Use of alcohol in mouthwashes

Alcohol causes profound drying of the oral mucosa. Advise patients with oral mucosal disease and dry mouth to avoid alcohol-containing mouthwashes, as they will exacerbate their condition. There is currently controversy surrounding a possible link between alcohol-containing mouthwashes and oral cancer. Until this is resolved, it is recommended that alcohol-containing mouthwashes be used with care.

Antiseptic mouthwashes
Chlorhexidine Chlorhexidine, an antiseptic commonly used in mouthwashes, is bactericidal and effective against fungi (including yeasts). Chlorhexidine adsorbs onto oral surfaces so it is effective over a prolonged period. By these mechanisms, it prevents plaque formation on a clean tooth surface, but does not reduce pre-existing plaque. Therefore, where possible, chlorhexidine should not be recommended without mechanical oral hygiene measures. In a mouthwash, it is available as chlorhexidine gluconate in concentrations of 0.12% and 0.2%. It is also used in sprays, creams, gels, solutions, dressings and powders. A slow-release formulation is available for local delivery into periodontal pockets. Chlorhexidine salts can cause skin reactions, irritate mucosal surfaces and interrupt wound healing. Chlorhexidine mouthwash and intraoral gel can discolour teeth, margins of restorations, the tongue and buccal cavity; this extrinsic staining is not permanent and can be professionally removed. Chlorhexidine can also cause a burning sensation, altered taste and increased calculus formation. For these reasons, particularly to prevent the adverse effect of staining, chlorhexidine is usually recommended for short periods of up to 2 weeks.

Fluoride mouthwashes
Mouthwashes containing fluoride are discussed on p.50.

Benzydamine
Benzydamine is a nonsteroidal anti-inflammatory drug (NSAID) and therefore has anti-inflammatory and analgesic properties. It can be used for the temporary relief of painful inflamed oral mucosal conditions. It is available in mouthwashes, mouth gels and sprays, sometimes in combination with chlorhexidine, in concentrations of 0.15% to 1%. Local adverse reactions of benzydamine, such as numbness, burning, erythema and rash, have been occasionally reported. Systemic adverse reactions are uncommon and not serious. Further reading
Sources of drug information are given on p.10.

44

45