effect of drugs on oral mucosa and their management

EFFECT OF DRUGS ON ORAL

MUCOSA AND THEIR

MANAGEMENT

By:-

Rajsandeep Singh

Roll no.71

4th year

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Introduction

About 10% of ambulant outpatients may be having systemic drug treatment. Though not

a common source of difficulties, some drugs can complicate dental management,

occasionally catastrophically. Drug addicts are also a growing clinical problem The

effects of systemically administered drugs on dental management are varied.

Significance of drug treatment to dental management.

Drugs may complicate dental treatment itself.

Drugs may react with drugs given for dental purposes.

Drugs may cause stomatitis or have other oral effects.

Etiology and Pathogenesis of Oral Adverse Drug Reactions

Although the skin is more commonly involved in adverse reactions to drugs, the oral

mucosa is also frequently affected. Virtually any drug has the potential to cause an

untoward reaction, but some have a greater ability to do so than others. Pathogenesis of

drugs are mediated by the immune system and are drug allergies. Three mechanisms have

been proposed for drug allergies. Firstly, IgE-mediated reactions occur when the drug

reacts with IgE antibodies bound to mast cells. Secondly, drug allergies can involve a

cytotoxic reaction in which an antibody binds to a drug that is already attached to a cell

surface. The third mechanism in a drug allergy involves circulation of the antigen for

extended periods allowing sensitization of the patient’s immune system and production of

a new antibody. Nonimmunologic drug reactions are not antibody dependent and may

directly affect mast cells causing the release of chemical mediators. Also some

nonimmunologic drug-induced result from a drug overdose or toxicity.

Clinical Features of Oral Adverse Drug Reactions

Manifestations of drug reactions are dependent on the type of drug, dose and individual

patient differences. These reactions can be seen either rapidly or several days after drug

use. Acquired angioedema is an IgE-mediate drug allergy that is commonly observed as

drug and food reactions. Other cutaneous manifestations of drug reactions include

urticaria, maculopapular rash, erythema, vesicles, ulcers, and target lesions. An unusual

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form of drug reaction is known as fixed drug reaction during which an erythematous

lesion appears in the same location with each antigenic challenge. Oral manifestations of

drug reactions may be erythematous, vesicular, or ulcerative in nature. They may also

mimic erosive lichen planus known as lichenoid drug reactions.

Histopathology of Oral Adverse Drug Reations

Histologic features or findings of drug reactions include nonspecific features as

spongiosis, apoptotic keratinocytes, lymphoid infiltrates, eosinophils, and ulceration.

Also, mononuclear of pllymorphonuclear infiltrations in a subepithelial or perivascular

distribution, basal cell destruction, edema, and keratinocyte necrosis are seen.

Diagnosis of Adverse Drug Reactions

The diagnosis of drug reactions requires a high index of suspicion and careful history

taking. Recent use of a drug is important. Withdrawal of the suspected drug should result

in improvement, and reinstitution of the drug should exacerbate the patient’s condition.

The clinical expression of lesions in drug reactions is generally allergic in nature that can

help with the diagnosis.

BRIEF DESCRIPTION OF DRUGS HAVING DENTALLY RELEVANT

ADVERSE REACTIONS

I) Tetracyclines

These are a class of antibioties having a nucleus of 4 cyclic rings. They are

obtained from soil actinomycetes.

These are primarily bacteriostatic. They interfere with a attachment of

aminoacyl-t-RNA to the mRNA – ribosome complex by binding to 30S

ribosomes in susceptible organisms.

Indications :

a) Empirical therapy or in mixed infections although combination of B-

lactams & an aminoglycocide or 3rd generation cephalosporin on

flouroquinolone are preferred.

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b) Many organisms have developed resistance however they are still

preferred for Venereal diseases like lymphogranuloma venereum &

granuloma inguinale, ataypical pneumonia caused by mycoplasma,

cholera, brucellosis, plague, relapsing fever (cause by B recurrentis),

Rickettseal infections like typhus, rocky fever, Q-fever.

Effect on oral mucosa : It causes superinfection as they cause marked

suppression of the resident flora causing the more virulent organism to flare

up.

II) Chloramphenicol:

It is synthesized chemically and it inhibits bacterial protein synthesis by

interfering with transfer of the elongating peptide chain to the newly attached

aminoacyl - tRNA to acceptor site at the ribosome-mRNA complex.

Indications :

It is never used for infections treatable by other agents. It is however used for

the following purposes:

In enteric fever caused by sensitive strains

H.influenzae meningitis

Anaerobic infections caused by Bact.fragilis and others(wound

infections, pelvic and brain abscesses).

Intraocular infections

Effects on oral mucosa:

Bone marrow depression: This leads to opportunistic infections, necrotizing

gingival diseases or purpuric spots on the mucosa.

Hypersensitivity reactions may cause atrophic glossitis, angiodema.

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Superinfections similar to the ones caused by tetracyclines are seen but are less

common as compared to tetracyclines.

When high doses are given to neonates it causes grey baby syndrome ashen-grey

cyanosis which is also manifested in the oral mucosa.

III) Penicillin

These are chemically β-lactams and one of the first antibiotics to be used

clinically.

These in a bit transpiptidases and therefore destroy the cell wall repair mechanism

of organisms.

Indications :

a) Streptecocal infection

b) Meningococal infection

c) Gonorrhoea

d) Syphilis

e) In diphtheria & tetanus as adjuvant therapy

f) Prophylactic uses for Rheumatic fever, gonorrhoea / syphilis, Bacterial

Endocarditis, surgical infections.

Effect on oral mucosa: It causes type1 hypersensitivity reactions. There is

generalized slight oedema of face, rashes, pallor and may cause angiodema.

IV) Nefedipine

It is a calcium channel blocker and is a potent vasodilator & anti-anginal drug. It

causes preferential dilatation of coronary vessels & increases coronary blood

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flow. It also exerts a potent vasodilator effect on arterial bed & produces

reduction in both systolic & diastolic blood pressure & causes reflex tachycardia.

Indications:

Vasospastic angina, chronic stable angina, hypertension, hypertrophic

cardiomyopathy, peripheral vascular diseases, congestive heart failure, acute

myocardial infarction, myocardial preservation, during surgery, migrane,

oesophageal sparsm, exercise induced bronchial asthma.

Effect on oral mucosa – gingival hyperplasia

V) Diltiazem:

It is a less potent vasodilator thannefedipine & has a modest direct negative

chronotropic, inotropic, dromotropic effect. It produces a modest fall in bp

with no change in heart rate. Large doses decrease total peripheral resistance

markedly & elicit reflex cardiac effects. It is a potent coronary dilator.

Indications: Angina pectoris due to coronary spasm & chronic stable angina.

Effect on oral mucosa:

Gingival hyperplasia.

VI Phenytoin

Most outstanding action is abolition of tonic phase of maxima electro shock

seizures, with no effect / prologation of chronic phase. It stabilizes neuronal

membranes & therefore, limits spread of seizure activity & is also effective in

neuralgias & cardiac arrythmias.

Indications :

Grandmal, cortical focal & Psychomotor epilepsy.

Migraine

Trigeminal neuralgia6

Cardiac arrythmias especially diagoxin induced.

Effects on oral mucosa & perioral structures:

Gingival hyperplasia, neutropenia, DLE, Rashes, megaloblastic anaemia.

VII Aspirin

It is acetyl salicylic acid which is a potent anti-inflammatory & a good analgesic.

It is rapidly converted to salicylic acid which is responsible for most of its actions.

Other actions result from acetylation of macromolecules like COX.

Indications:

Analgesic (headache, backache, myalgia, joint pain, tooth ache,

neuralgias, dysmenorrhoea).

Antipyretic

Acute Rheumatic fever

Rheumatoid arthritis

Osteoarthritis

Post myocardial infarction & post stroke patients, transient ischemic

attacks.

Coronary bypass, Trans-luminal angio-plasty


Potentiation of any haemorrhagic tendencies, avoid in children because of risk of

Reye’s syndrome.

VIII Other NSAIDs occasionally cause lichenoid drug reactions

IX Hypnotics & sedatives cause potentiation of general anaesthetics & other

sedating drugs.

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X Barbiturates

They are known as minor tranquilizers. They are general depressants for all

neurons and produce dose dependant effecys on CNS ranging from sedation to

coma. They besides acting on the CNS act on the CVS. They have a dual mode of

action on skeletal muscles acting directly on them & also by acting on

neuromuscular transmission.

Indications: Except for thiopentone in anesthesia and phenobarbitone in epilepsy

they are rarely used now. As hypnotics and anxiolytics they have been superseded

by BZDs.

Effects on oral mucosa :

They cause Erythema multiforme which may progress to toxic epidermal

necrolysis.

XI Phenothiazine antipsychotics

These are called ‘major tranquilizers’

Indications:

Psychoses (Schizophrenia, Mania, organic brain syndromes)

Anxiety

As antiemetics

To potentiate Hypnotics, analgesics, anaesthetics

Intractable hiccoughs

Tetanus

Alcoholic hallucinosis, huntington’s diease, Gilles de la Tourette’s

syndrome.


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Dry mouth in due to their anti cholinergic properties, however, clozapine causes

hypersalivation due to its central actions.

They also cause rigidity, tremos, hypokinesia and mask like facies.

Acute Myotonias: Bizarre muscle spasms, mostly involving linguo-facial muscles.

Which cause grimacing, torticollis, locked jaw and occur within few hours of a

single dose or at the most in the first week of therapy.

Tardive dyskinesia occur late in therapy include constant chewing, pouting,

puffing of cheeks, lip licking, choreoathetoid movements.

XII Metoclopramide:

It is a prokinetic drug & acts by D2 antagonism 5HT4 agonism & 5HT3

antagonism.

Indications: It is used as an anti-emetic, gastrokinetic, in dyspepsia and in

GERD.


Can cause muscle dystonias. Can lead to clenching of jaws.

XIII Tricyclic antidepressants (eg. Amitryptyline)

They inhibit the active uptake of biogenic amines(NA & 5-HT3) into their

respective neurons and thus potentiate them.

Effec on oral mucosa :

They cause a dry mouth and bad taste. In the perioral tissues sweating and fine

tremors can be seen.

XIV MAO inhititors:

They as the name suggest, inhibit mitochondrial oxidative deamination of

biogenic amines and potentiates their effects. Therefore is used in various forms

of depression.9


They cause dry mouth.

Opiod therapy particularly with pethidine is contra indicated because it

causes high fever, sweating, excitation, detirium, convulsions & sense

respiratory depression. This is because MAO inhibitors retard hydroysis of

pethidine but not its demethylation. Thus norpethidine accumulates.

XV Antihistamines:

These have histamine antagonist, antiallergic, CNS depressant & anti –

cholinergic actions.

Indications: they are used in various allergic disorders, as pruritides, common

cold, motion sickness and vertigo.


They cause a dry mouth

Other dentally relevant adverse effects are drowsiness & potentiation of sedatives.

XVI Corticosteroids

They have glucocorticoid & mineralocorticoid actions, however, they are mainly

used for their glucocorticoid actions. They are catabolic in most of their functions

except they promote gluconeogenesis, glycogenesis. They increase the destruction

of lymphocytes(t-cells primarily). However their main action is anti-

inflammatory. The action is non-specific and covers all components and stages of

inflammation.

Indications:

Replacement therapies

Arthritides

Collagen diseases10

Severe allergies reactions

Autoimmune diseases

asthma


They progressively bring down the systemic & local immune defenses &

causes opportunistic infections in the mouth(e.g.candida)

It decreases wound healing.

Foetal abnormalities: Cleft palate and other defects are produced in

animals, but have never been encountered in clinical use in pregnant

women.

XVII Other immunosuppressive & cytotoxic drugs

Methotrexate causes oral ulceration.

Cisplatin causes grey gingival line.

Vincristine can cause jaw pain & weakness of facial muscles.

Besides all of these would cause opportunistic infections.

XVIII Cyclosporin

It is a cyclic polypeptide obtained from a fungus & is a highly selective

immunosuppressant. It profoundly & selectively inhibits T lymphocyte

proliferation, IL2 and other cytokine production and response of inducer T-cells

to IL-1 without any effect on suppressor T-cells. Lymphocytes are arrested in G0-

or G1 phase.

Indications: It is the most effective drug for preservation and treatment of graft

rejection reaction. It is routinely used in renal, hepatic, cardiac, bone marrow &

other transplantations.

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Gum hyperplasia

IMPORTANT TYPES OF ORAL DRUG REACTIONS

I Local reactions to drugs

Chemical irritation

Interference with the oral flora

II Systemically mediated reactions

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Depression of marrow function

Depression of cell mediated immunity

Lichenoid reactions

Erythema multiforme (Stevens-Johnson syndrome)

Fixed drug reactions

Toxic epidermal necrolysis

III Other effects

1. Gingival hyperplasia

2. Pigmentation

3. Dry mouth

LOCAL REACTIONS TO DRUGS

1. Chemical burns. The best known example is that of aspirin tablets held against the

mucosa close to an aching tooth. This causes superficial necrosis and a white

patch.

Other irritant chemicals are acid etchants or phenol dropped on oral mucosa

during dental treatment.

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2. Interference with the oral flora: superinfection. Prolonged therapy use of

antibiotics(particularly tetracyclines) in the mouth kills off sensitive organisms

and allows resistant ones, particularly Candida albicans , to proliferate , causing

thrush. In susceptible patients use of a topical antibiotic may precipitate candidal

infection within 48 hours

SYSTEMICALLY MEDIATED REACTIONS

1) Depression of marrow function . Few drugs significantly depress red cell

production alone, though any drug which causes anemia might give rise to oral

signs. E.g. phenytoin which, in susceptible patients, can occasionally cause severe

aphthous stomatitis.

Management: Response promptly follows administration of folate, and the blood

picture returns to normal.

Necrotizing Ulcerative Gingivitis: White cell production is depressed by a variety

of drugs. Leucopenia can be severe enough to produce a picture of agranulocytosis,

with necrotizing ulceration of the gingivae and throat which can go onto a severe

prostrating illness and septicaemia if untreated. Drugs which may have this effect

are:

Antibacterials, particularly co-trimoxazole, chloramphenicol.

Analgesics, particularly amidopyrine(obsolete in most countries)

Phenothiazines

Anti-thyroid drugs

When the main effect is on granulocytes, the low-grade pathogens, particularly of

the gingival margins, are able to overcome local resistance and produce necrotizing

ulceration.

Oral manifestatrions:14

It has a rapid and acute onset.

First symptoms include excessive salivation, a metallic taste, and sensitivity

of the ginivae

This is followed by extremely red and painful gingivae with punched out

crater like ulcerations usually on the on the inter-dental gingivae but any

part of the marginal gingivae can be involved.

There is accompanying malodor and gingival bleeding.

Management:

This is directed towards supportive care and pain control, definitive treatment and

identification of predisposing factors.

Definitive treatment consists of gentle debridement of as much plaque and calculus as

possible; bets accomplished under local anesthesia.

Use of chlorhexidine mouth washes is very helpful.

In extensive cases antibiotics against gram –ve bacteria (β-lactams)are essential.

Metronidazole though ineffective against spirochetes is helpful.

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necrotizing ulcerative infection in neutreopenic patient

Other drugs may affect haemostasis and cause oral purpura. Drug induced purpura is an

early sign of aplastic anemia caused by drugs like chloramphenicol. It can produce severe

gingival bleeding or blood blisters or extensive submucosal ecchymoses.

2) Aphthous Stomatits:

Aphthous stomatitis is commonly observed and is mediated by the immune system.

Lesions usually appear as painful, tiny, discrete, or grouped papules and vesicles. These

vesicles are small in diameter with round, shallow ulcerations predominantly seen over

the buccal and labial mucosa. The ulcers seen are usually of minor type. The reactions

usually heal without scarring in 10-14 day, however, recurrence is common.

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recurrent aphthous stomatitis

Drugs with potential to cause aphthous

stomatitis

Azathiopurine Losartan

Captopril NSAIDs

Cyclosporine Fluoxetine

Penicillamine Gold compounds

Sertaline Indinavir

Sulphonamides Interferones

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Management:

In mild cases with two or three small lesions, use of a protective emollient such as

Orabase or Zilactin, a topical anesthetic is all that’s necessary. Pain can be relieved by

topical anesthetic agent or topical diclofenac.

In more severe cases a high potency topical steroid preparation, such as fluocinonide,

betamethasons, or clobetasol is necessary which shortens healing time and reduces the

size of the ulcers.

3) Depression of cell-mediated immunity:

Immunosuppresion by drugs as corticosteroids is induced in patients having organ

transplants or with immunologically mediated diseases. Viral and fungal infections of

the mouth are common in patients and can be severe. Recurrences of childhood

infections like measles and chicken pox are possible.

4) Lichenoid reactions:

Etiology and pathogenesis:

It has been postulated that DLIRs may result from poor drug metabolism because

genetic variation of the major cytochrome p-450 enzymes

As the clinical and histopathological picture resembles a delayed type

hypersensitivity reaction, it has been suggested that drugs or their metabolites act

as haptens and trigger a lichenoid reaction against the cell components.

Drugs with potential to cause LIchenoid Eruptions

penicillin gold sulfonamides

Merciry(amalgam) allopurinol ACE inhibitors

methyldopa Arsenical compounds NSAIDs

Β-blockers palladium Bismuth

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penicillamine chloroquine Primaquine

Cholera vaccine HBV vaccine Quinine

quinidine .hydroxychloroquine Chlorpropamide.

Propranolol Phenothiazines furosemide

streptomycin tetracyclines Lithium carbonate

BCG vaccine captopril Carbamazepine

griseofulvin ketoconazole Interferon-{157}

metformin Protease inhibitors Oral contraceptives

Clinical findings:

It has been suggested that they are predominantly unilateral and present with an

ulcerative reaction pattern. However, these findings are not consistant and not enough to

differentiate them from lichen planus.

They show a homogenous well demarcated white plaque often but not always surrounded

by striae, appearing similar to lichen rubber planus, and may be severely pruritic.

Management:

Discontinuance of the drug and symptomatic treatment with topical steroids is usually

enough. The patient should be properly educated about the responsible drug to prevent

future DILRs.

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The picture shows a lichenoid reaction following 1 month of medication with a

cholestyramine-containing drug. The adjacent picture shows regression following

withdrawl.

5) Acute erythema multiforme

Erythema multiforme is an acute, self-limited, inflammatory mucocutaneous disease that

manifests on skin and often oral mucosa, although other mucosal surfaces are also may

involved.

In general, EM is classified as EM minor if less than of skin involvement is there and

there is minimal to no skin involvement.

It is classified as major if it has more extensive but characteristic skin involvement, with

the oral mucosa and other mucosal surfaces involved.


EM is an hypersensitivity reaction and the most common enticing factors are infection,

particularly with HSV, or drug reactions to NSAIDS, anticonvulsants, or other drugs.

It has been postulated that these agents incite a t-cell mediated delayed hypersensitivity

reaction that generates interferon-γ, with the amplified immune response recruiting more 20

T-cells to the area. Cytotoxic T cells, natural killer cells, and/or cytokines destroy the

epithelial cells.

Clinical features:

Episodes usually last several weeks

There is a prolonged prodrome of fever, malaise, headache.

Skin lesions rapidly appear over few days starting usually from hands and spreading

centripetally to the trunk. Skin lesions take several forms and hence the name multiforme.

Typical target lesions of the hand

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target lesions if the leg

Oral findings range from mild erythema and erosions to painful ulcerations.

When severe, ulcers may be large and confluent, causing difficulty in eating,

drinking, and swallowing.

Patients with severe EM may drool blood-tinged saliva.

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Intra oral lesions of EM in an 18-year old

Management:

There are no specific laboratory tests that are useful but diagnosis is made primarily on

clinical findings.

Mild EM can be managed with systemic or topical analgesics for painand

supportive care as the disease is self-limiting and resolves within a few weeks.

More severe cases are treated with systemic corticosteroids.

Topical corticosteroids may also help resolve the lesions.

Dugs with potential to cause erythema multiforme

NSAIDS carbamazepine phenytoin Sulphonamides

barbiturates Iodine containing

mouth washes

chlorpropamide rifampicin

Combination of anti Estrogens/progestins clindamycin Tetracyclines

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malarials-

chloroquine and

sulfadoxine-

pyrimethamine

6) Toxic epidermal necrolysis:

This which probably represents the extreme end of the spectrum of erythema multiforme,

is one of the most dangerous a severe forms of drug reactions.

Mucosal involvement is common and causes widespread erosions due to epithelial

destructions. Oral ulcerations may precede the dermal changes, and cause the patient to

seek treatment for extreme soreness of mouth.healing of the lesions may leave a pattern

of lichen planus.

Causative drugs: metals such as gold salts are important causes but phenylbutazone,

barbiturates have also been implicated.

Because of the severity of the disease, treatment is generally with high doses of systemic

corticosteroids., intravenous immunoglobulins, and thalidomide.

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7) Fixed drug eruptions:

These consist of sharply circumscribed skin lesions recurring in the same site or sites

each time the drug is given. Involvement of the oral mucous membrane has been

described but is exceedingly rare. Phenolphphthalein, a component of purgatives is most

commonly implicated.

Oral mucosal membranes may be the sole site of involvement, or they may be a

part of a more generalized skin reaction to the offending drug.

The main type of hypersensitivity reaction that affects oral mucosa is a delayed

reaction mediated by sensitized T-lymphocyte.

Stomatitis medicamentosa, or fixed drug eruption, occurs with systemic drug

usage and stomatitis venenata appears with contact hypersensitivity.

Lesions associated with fixed drug eruption are erythematous in mild cases and

appear ulcerated in severe cases.

The reactions usually appear in 24 hours post-ingestion of the drug. Delayed

reaction (up to two weeks) has been noted after use of ampicillin. Withdrawal of

the causative drug results in resolution of the lesions.

Other drugs implicated are:

Barbiturates Lidocaine Chlorhexidine Penicillamine

Gold Salicylates Indomethacin Sulphonamides

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Fixed eruption on the tongue

OTHER DRUG EFECTS

1) Gingival hyperplasia:

The growth starts as a painless, beadlike enlargement of the interdental papilla and extends to the facial and lingual gingival margin. The enlargement is usually generalized throughout the mouth but is more severe in the maxillary and mandibular anterior regions.


It is hypothesized that in non-inflamed gingiva, fibroblasts are less active or even quiescent and do not respond to circulating drugs; fibroblasts within inflamed tissue are in an active state as a result of inflammatory mediators and the endogenous growth factors. It is known that causative drugs inhibit Ca2+ uptake on gingival fibroblasts that correlates with the rate of fibroblast proliferation. Drug variables, plaque-induced inflammatory changes in the gingival tissues, and genetic factors should be considered. The last determines the heterogeneity of the gingival fibroblast and could also influence drug pharmacokinetics and pharmacodynamics.

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Phenytoin, cyclosporine-A, calcium channel blockers, and oral contraceptives are the main causative agents of gingival hyperplasia. Several mechanisms have been suggested for drug-induced gingival hyperplasia.

Cyclosporine-A has been shown to increase the fibroblast production of collagen and protein, leading to extra cellular collagen and matrix formation and to decrease collagenase activity. The increased levels of interlukin-6 and TGF-ß and the decreased levels of gamma-interferon observed during cyclosporine-A therapy may favor the fibroblast synthesis of collagen. Also, it has been reported the keratinocyte growth factor receptor is up-regulated by cyclosporine-A25, and there is evidence that cyclosporine-A regulates cytokine expression in gingival tissue.

There is evidence that mast cell mediated androgen action in the gingiva in response to phenytoin could contribute to gingival overgrowth The incidence of phenytoin-induced gingival overgrowth is approximately 50 percent, but it is higher in both teenagers and institutionalized epileptics. Gingival overgrowth usually becomes apparent during the first 3 months after starting phenytoin and is most rapid in the first year. Unlike phenytoin hyperplasia, cyclosporine-induced hyperplasia is reversible following cessation of drug use

Nifedipine, the most commonly used calcium channel blocker, induces gingival enlargement in 20% of the cases. Amlodipine, diltiazem, felodipine, nitrendipine, and verapamil also induce gingival overgrowth. The dihydropyridine derivative isradipidine does not induce gingival overgrowth. Inhibition of apoptosis by nifedipine and resultant epithelial hyperplasia has been reported There is also evidence that nifedipine inhibits both adherence- and lipoploysaccharide-stimulated macrophage-induced death of fibroblasts which results in gingival overgrowth Nifedipine is frequently prescribed to organ transplant patients to reduce the nephrotoxic effects of cyclosporine and, thus, an additive effect on the gingival tissues is usually observed

The incidence of gingival overgrowth by oral contraceptives is not rare and resolves when the drug is withdrawn. There is evidence the accumulation of metabolic products of the naturally occurring sex hormones in gingiva is an important factor in the pathogenesis of chronic gingivitis. The prevalence and percentage of incidence is uncertain. Maintenance of adequate plaque control is important for gingival health during the administration of oral contraceptives.

Other drugs with potential to cause gingival hyperplasia are listed below

Other drugs with potential to cause gingival hyperplasia

Cotrimoxazole Phenobarbital

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Cyclosporine Primidone

Erythromycin Sertraline

Ethosuximide Sodium valproate

Ketoconazole Topiramate

Lamotrigine Vigabatrin

Lithium

Management:

Plaque removal and good oral hygiene may benefit in a fast recovery and limits the severity of the lesion but the lesion does not completely resolve. Extreme cases need surgery and long term oral hygiene maintenance is essential.

cases of drug induced gingival hyperplasia

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2) Pigmentation: Heavy metals such as mercury, bismuth and lead can cause black or brown deposits

in the gingival sulcus by interaction with bacterial products to form sulphides.The blue lead line may be particularly sharply well defined and indicate the floor of the pocket.

Cisplatin, a cytotoxic drug, can cause a blue line. Topical antibiotics and antiseptics can cause dark pigmentation.

.Black Hairy Tongue (Lingua villosa nigra)

In this condition there is an elongation of the filiform papillae of the tongue to form hair-like overgrowth that becomes stained brown or black due to proliferation of chromogenic microorganisms. Black hairy tongue can be seen with the administration of oral antibiotics, poor dental hygiene, and excessive smoking in adults. Drugs and chemicals with potential to cause black tongue include those listed in below.

Drugs and chemicals with potential to cause black tongue

Amitriptyline Lansoprazole

Benztropine Methyldopa

Cephalosporines Maprotilline

Chloramphenicol Nortriptyline

Clarithromycin Penicillins

Clomipramine Streptomycin

Clonazepam Sulfonamides

Corticosteroids Tobacco

Desipramine Tetracyclines

Fluoxetine Thiothixene

Griseofulvin Tranylcypromine

Imipramine Vegetable dyes

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Black hairy tingue

3) Effect on salivary glands:

The salivary glands are under control of the autonomic nervous system, mainly the parasympathetic division. Salivary gland function can be affected by a variety of drugs that can produce xerostomia or ptyalism. It is suggested this is due to both the reduced salivary flow rate and to a decrease in salivary calcium and phosphate concentration caused by such drugs as amphetamines. Submandibular and parotid glands, the major salivary glands of the body, have important roles in maintaining the health of the oral cavity and gastrointestinal tract. Altered salivary flow rate and levels of secretory proteins or enzymes may cause destructive effects on oral and dental health and wound healing rates directly through lower levels of specific growth factors being present. It is known that salivary mucins and growth factors are involved in the maintenance of mucosal integrity due to their ability to trap water, thereby, preventing injury through desiccation; growth factors may assist in tissue regeneration. The epidermal growth factor that is secreted from salivary glands has a potential role in oral wound healing. Common oral manifestations resulting from decreased salivary flow include increased dental caries, fungal infections, bacterial infections, aphthous lesions, and dysphagia. Systemic drug therapy can also produce pain and swelling of the salivary glands. The following table lists drugs and chemicals with potential to inhibit the function of salivary glands.

xerostomia

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Drugs and chemicals with potential to inhibit the function of salivary glands including secretion of proteins and enzymes into saliva

Benzodiazepines Morphine

Cadmium Nifedipine

Cyclosporine Nitric oxide inhibitors

Diltiazem Ofloxacin

Gentamicin Rubidium

Lead Verapamil

Lithium

Drugs that can cause dryness of mouth

Amphetamine Omeprazole

Anticholinergics Ondansetron

Antihistamines Selective serotonin reuptake inhibitors

Antineoplastic drugs Thiabendazole

Anti-HIV protease inhibitors Tramadol

Didanosine Tricyclic antidepressants

Levodopa

Drugs that can cause sialorrhea

Alprazolam Levodopa

Amiodarone Lithium

Bethanechol Mefenamic Acid

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Buspirone Mercurial salts

Clozapine Niridazole

Diazoxide Pentoxifylline

Edrophonium Pilocarpine

Gentamycin Risperidone

Guanethidine Rivastigmine

Imipenem/Cilastatin Succinylcholine

Iodides Tacrine

Kanamycin Tobramycin

Ketamine Venlafaxine

Lamotrigine Zaleplon

Drugs that have potential to cause swelling and/or pain in salivary

Bretylium Naproxen

Catecholamine inhalation Nifedipine

Chlorhexidine Nitrofurantoin

Cimetidine Phenytoin

Clonidine Ranitidine

Deoxycycline Ritodrine

Famotidine Sulfonamides

Iodine Trimipramine

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Methyldopa WarfarinSjogren's Syndrome includes parotid swelling. However, parotid enlargement in Sjogren’s

Syndrome occurs relatively late in the course of rheumatoid arthritis. Its sudden appearance in the early stages of the disease may well indicate an adverse reaction to an anti-inflammatory drug since the H2–receptor antagonists have been reported to aggravate the disease. The swelling is quite common in rheumatoid arthritis, for which NSAIDs are frequently used, therefore, salivary gland swelling could be part of the disease rather than a complication of its treatment. Sjogren's Syndrome is often (30%) seen in association with other autoimmune rheumatic diseases.

4) Muscular and Neurological Disorders

Tardive dyskinesia that affects the elderly, particularly women, taking antipsychotic drugs for many years, is an uncommon and sometimes unrecognized cause of orofacial pain. Tardive dyskinesia is a painless syndrome in itself, but secondary orofacial pain can result from chronic mild trauma between a denture-bearing mucosa and dentures with abnormal movement.

Facial pain has also been reported following the use of a controlled–release theophylline preparation. The following table lists drugs reported to cause sensation of numbness, tingling, or burning in the face or mouth.

Drugs reported to cause sensation of numbness, tingling, or burning in the face or mouth

Acetazolamide Nicotinic acid

Amitriptyline Nitrofurantoin

Chlorpropamide Pentamidine

Ergotamine Polymyxin B

Gonadotropin-releasing-hormone analogues

Propranolol

Hydralazine Streptomycin

Isoniazid Tolbutamide

Nalidixic acid

5) Taste Disturbance33

Many drugs induce abnormalities of taste by processes not yet fully understood. The alteration in taste may be simply a blunting or decreased sensitivity in taste perception (hypogeusia), a total loss of the ability to taste (ageusia), or a distortion in perception of the correct taste of a substance, for example, sour for sweet (dysgeusia). A wide-range of drugs give rise to dysgeusia or hypogeusia either by interfering in chemical composition or flow of saliva, or, more specifically, affecting taste receptor function or signal transduction. Sulfhydryl compounds are a common cause of taste disturbance. Drugs with the potential for affecting taste are listed in Table 15.

Drugs with potential to cause ageusia

Acarbose Dicyclomine Pentamidine

Acetazolamide Enalapril Phenytoin

Amitriptyline Etidronate Propantheline

Aspirin Fluoxetine Propylthiouracil

Atrovastatin Fluvoxamine Rifabutin

Captopril Indomethacin Ritonavir

Ceftirizine Isotretinoin Rivastigmine

Cisplatin Levodopa Spironolactone

Clidinium Losartan Sulfadoxine

Clomipramine Methimazole Topiramate

Cocaine Penicillamine Venlafaxine

Diazoxide

Drugs with potential to cause dysgeusia

Acetaminophen Dipyridamole Minoxidil

Acetazolamide Donepezil Naratriptan

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Acyclovir Dorzolamide Nifedipine

Albuterol Doxepin Nortriptyline

Alendronate Deoxycycline Ofloxacin

Allopurinol Enalapril Olanzapine

Alprazolam Etidronate Omeprazole

Amiloride Famotidine Pamidronate

Amiodarone Fenfluramine Penicillamine

Amitriptyline Fentanyl Penicillins

Amlodipine Flecainide Pentazocine

Amoxicillin Fluconazole Pentoxifylline

Aspirin Fluorouracil Pergolide

Atrovastatin Fluoxetine Perindopril

Atropine sulfate Flurazepam Phytonadione

Baclofen Fluvastatin Pilocarpine

Benztropine Fluvoxamine Potassium iodide

Bromocriptine Gancyclovir Procainamide

Buspirone Gemfibrozil Propantheline

Busulfan Glyburide Propranolol

Calcitonin Gold compounds Propylthiouracil

Captopril Granisetron Pyrimethamine

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Carbamazepine Griseofulvin Quinidine

Cephalosporines Hydrochlorothiazide Ranitidine

Celecoxib Hydroxychloroquine Ribavirin

Chlorhexidine Imipenem/Cilastatin Riluzole

Chlorothiazide Imipramine Risperidone

Cholestyramine Indinavir Ritonavir

Ciprofloxacin Interferons Rivastigmine

Citalopram Isotretinoin Saccharin

Clarithromycin Ketoprofen Selegiline

Clidinium Ketorolac Serteraline

Clindamycin Labetalol Simvastatin

Clofazimine Lamotrigine Sulfonamides

Clofibrate Lansoprazole Sumatriptan

Clomipramine Leuprolide Tacrine

Clonazepam Levodopa Tamoxifen

Clonidine Lisinopril Terbutaline

Clozapine Lithium Timolol

Codeine Loratadine Tocainde

Cotrimoxazole Losartan Tolazamide

Cromolyn Lovastatin Tolbutamide

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Cyproheptadine Maprotilline Tolmetin

Dacarbazine Mesalamine Topiramate

Dantrolene Mesna Tramadol

Desipramine Metformin Triamteren

Dexfenfluramine Methamphetamine Trimipramine

Dextroamphetamine Methimazole Ursodiol

Diazoxide Methocarbamol Vancomycin

Diclofenac Methotrexate Venlafaxine

Dicyclomine Metoprolol Vinblastine

Dihydroergotamine Metronidazole Vincristine

Diltiazem Midazolam Zidovudine

.

6) Halitosis

Halitosis is the offensive breath resulting from poor oral hygiene, dental or oral infections, ingestion of certain foods, use of tobacco, and some systemic diseases. Disulfiram and sublingual isosorbide dinitrate can cause halitosis. Drugs causing xerostomia, discussed earlier, may indirectly cause or aggravate this problem.

7) Alveolar Osteitis (Dry Socket)

The use of contraceptives has been associated with a significant increase in the frequency of dry sockets (alveolar osteitis) after removal of impacted lower third molars. The probability of dry sockets increases with the estrogen dose in the oral contraceptive. The dry sockets can be minimized by carrying out the extractions during days 23-28 of the tablet cycle.

Conclusion

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Since most drug reactions occur within 1 to 2 weeks following initiation of therapy, reactions seen after 2 weeks are less likely to be due to medication use. Some reactions are dependent on dosage or cumulative toxicity. The majority of drug-induced oral reactions are moderate in severity. However, severe reactions necessitate rapid withdrawal of the suspected drug. In most cases, the oral reaction will be resolved by symptomatic treatment. Readministration of the offending drug helps to establish whether the oral eruption is drug-induced. Reactions after rechallenge may be more severe and, therefore, rechallenge should not be performed without medical supervision. Many clients take multiple medications; therefore, dentists must be aware of the issues related to drug use including indications, interactions, and adverse drug effects. The ability to evaluate these issues is necessary to accurately assess client status and prevent situations that compromise client safety. Oral side effects interfere with client function and increase risks for infection, pain, and possible tooth loss. It has been reported the most frequent side-effects of drugs are xerostomia, dysgeusia, and stomatitis.

As a final note, rapid progress in pharmacotherapeutics requires clinicians to constantly update their knowledge of drugs used by their patients. Attention must be paid to their toxic and unwanted effects that in many cases may be similar to characteristics of common diseases.

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