mini - reviewcontrol.slda.lk/media/sldj/48_01_2018/mini_review_481.pdfglands has been reported with...

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Mini - Review

Oral adverse reactions to systemic medications - mini review

Niroshani S. Soysa and Neranjan Fonseka

Niroshani S. Soysa

Neranjan Fonseka

Division of Pharmacology, Faculty of Dental Sciences, University of Peradeniya, Sri Lanka. E-mail: [email protected]

Division of Pharmacology, Faculty of Dental Sciences, University of Peradeniya, Sri Lanka.

Sri Lanka Dental Journal 2018; 48(01) 05-17

AbstractDose-related and time-related adverse effects of drugs can occur with almost all drugs irrespective of their mode of application even though they are used in a standard dose. Due to the increase in geriatric population today, the number of polymedicated patients is on the rise making it difficult to identify clinically the exact adverse effects of a particular drug. There are a large number of drugs that can induce adverse effects on oral cavity and many of them mimic the local and systemic diseases making it difficult to manage patients unless the clinician identify the drug as the culprit causing the oral lesion or condition. Therefore, the main aim of this mini review is to briefly outline the oral adverse effects of commonly used systemic drugs.

IntroductionWorld Health organization (WHO) has defined an adverse drug reaction (ADR) as “a response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for the modification of physiologic function” 1. However, ADR can be categorized into several types, Type A to Type F. Type A (augmented) reactions are induced by the same pharmacological mechanisms which cause the drug’s therapeutic effect (augmentation of effect). Augmentation of effect can be due to increase of the therapeutic or other pharmacological effect of the drug.

Type A reactions are directly dose-dependent. Type B (bizarre) reactions can develop due to the immunological reaction to a drug (allergy) or genetic predisposition (idiosyncratic reactions).

Type B reactions are generally unexpected and unpredictable. Type C reactions are time and dose-related. Chronic use of therapy may give rise to adverse effects due to cumulative-long term exposure. Type D effects are time-related and can be dose-related as well. They encompass teratogenic, mutagenic and carcinogenic reactions. Type E or end of use type of reactions occurs due to the drug withdrawal syndrome and rebound phenomenons.

Lesions in the oral cavity could arise due to many reactions including inflammation, infections and neoplasms. Majority of the lesions are reported to arise as a result of adverse effects of drugs (Table 1). Most of the adverse effects of drugs on oral cavity mimic systemic diseases making it difficult to differentiate from the systemic conditions. The most frequent adverse effects of drugs on oral cavity can be categorized as effects on oral mucosa, salivary glands, gingiva, oral pigmentation, alteration of taste sensation, halitosis, osteonecrosis, infections, necrotizing stomatitis, hemorrhagic diatheses, and movement disorders and so on. Xerostomia or dry mouth is the commonest adverse effect in the oral cavity.

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Effects on salivary glandsDrug-related xerostomia/hyposalivationXerostomia or dry mouth occurs due to insufficient secretion of saliva or due to qualitative changes in saliva without any actual change in salivary flow 2. The drugs commonly cause xerostomia are given in Table 2. The mechanisms underline xerostomia include, sympathomimetic action or anticholinergic action of the drugs 3. However, persistent hyposalivation may lead to oral candidiasis and dental caries. The loss of lubrication within the oral cavity results in discomfort, erythema and susceptibility of oral mucosa to frictional trauma against teeth. Elderly patients and patients who are on polypharmacy are more likely to develop xerostomia. Moreover, smoking, alcohol consumption and even long-term use of caffeinated drinks are implicated in causing oral dryness or the perception of dryness4.

Drug-related sialorrhea / hypersalivation /ptyalismParasympathomimetics cause ptyalism or excessive secretion of saliva by direct action on acetylcholine receptors or inhibition of enzyme acetylcholine esterase. Few classes of drugs implicated in causing hypersalivation include antipsychotics, particularly clozapine and direct and indirect cholinergic agonists that are used in Alzheimer’s disease and myasthenia gravis. Hypersalivation is also reported to occur with drugs such as cocaine, risperidone, clozapine, clonazepam, yohimbine and ketamine by directly acting on central nervous system 5. The treatment is basically symptomatic and therapeutics are used to reduce cholinergic activity by giving systemic oral anticholinergics such as atropine and related drugs and administering sublingual ipratropium spray. Clonidine patch can be also used to

Table 1. Drug-related oral reactions

General effects on oral cavity

Effects on salivary glands

Effects on mucosa

Effects of nerves

Effects on gingiva

Effects on bones (jaws)

HalitosisOral infectionsAlteration of taste sensationHemorrhagic diathesis

Xerostomia/ hyposalivationSialorrhea/hypersalivation/ptyalismSalivary gland swellingSalivary gland painDiscoloration of salivaNecrotizing sialometaplasia

Oral mucosal ulcerationLichenoid reactionsErythema multiformeBullous diseasesLupus like disordersAngioedemaKeratosis/epithelial hyperplasiaMucosal Pigmentation

Movement disordersDysesthesia

Fibrovascular hyperplasia

Osteonecrosis

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Table 2. Drug-related xerostomia

Drugs causing severe xerostomia

AntidepressantsAmitriptylineCitalopramDuloxetineFluoxetineImipramineAripiprazoleOlanzapineQuetiapineChlorpromazineLithiumAntimuscuranic agentsAtropineOxybutyninSkeletal muscle relaxantsBaclofenLoop diureticsFurosemideAnticonvulsantsGabapentinPsychostimulantsMethylphenidate Antiparkinson drugsRotigotineAntihypertensive/ antianginas Verapamil

Drugs causing moderate xerostomia

Anti-hypertensivesEnalaprilAtenololMetoprololMethyldopaAntidepressantsDoxepinDosulepinDesvenlafaxineOpioid-analgesicsFentanylMorphineTapentadolTramadolAntipsychoticsHaloperidolSertindoleHypnotic-sedativesEszopicloneDexmedetomidineAnti-convulsantsClobazamPregabalinSodiumvalproateAnti-obesity drugsOrlistat

enhance the sympathetic activity. Botulinum injections into the major salivary glands such as parotid gland have been used successfully to treat hypersalivation which cannot be managed with the aforementioned drugs.

Drug-related salivary gland swellingDrug-related salivary gland swelling is not a common adverse drug effect of drugs and usually painless and involved bilaterally. Using a modified Naranjo probability scale Brooks and Thomson reported that L-asparaginase, clozapine, and phenylbutazone showed causality between aforementioned drugs and parotid swelling 6. Parotid swelling is an occasional side effect of

chlorhexidine. Parotid swelling consequent to chlorhexidine is ascribed to vigorous rinsing 7. One reason for this observation could be the possible mechanical obstruction of the ducts due to the negative pressure created by vigorous rinsing causing aspiration of chlorhexidine into the gland 8. Painful bilateral swelling of parotid glands has been reported with oxyphenbutazone, nitrofurantoin, doxycycline, terbinafine, warfarin, nifedipine and α-methyl dopa 9. Sialadenitis may occur due to enalaprilat which is attributed to a type B idiosyncratic adverse drug reaction 10. Though the exact mechanism is not known, it is postulated that salivary gland swelling may occur as a result of oedema or spasm of

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smooth muscle in the salivary glands or due to an allergic reaction. Drug-induced parotitis may occur as a probable cause for interferon, ramipril, trimethoprim/sulfamethoxazole, nicardipine, chlormethiazole, methimazole, naproxen, sulfadiazine, captopril, cytarabine, cimetidine, ranitidine, and thioridazine 11.

Drug-related salivary gland PainDrugs such as antihypertensives, antithyroid agents, chlorhexidine, cytotoxic drugs, iodine, phenothiazines, bethanidine, clonidine, methyldopa and sulphur can cause salivary gland pain 11.

Drug-related discoloration of salivaDrugs may change the color of saliva and other body fluids either into red or orange color. The drugs implicated include clofazimine, levodopa, rifabutin and rifampicin.

Drug-related necrotizing sialometaplasiaNecrotising sialometaplasia is defined as “necrotising inflammatory reactions that affect minor salivary glands in the hard palate”. Nevertheless, it may also occur in other sites such as gingiva, cheek, lip, retromolar pad, tongue, nasal cavity, sinuses, larynx and trachea where the salivary gland tissue is located. Though pathogenesis is not delineated yet it is postulated to occur as a result of ischemia of vasculature supplying the salivary gland lobules. Necrotizing

sialometaplasia can occur as an adverse effect following injection of a vasoconstrictor with local anesthetic agent to the palate (Figure 1). It is a rare benign and self-limiting condition that resolves spontaneously without leaving functional or anatomical sequelae. However, biopsy is needed to confirm the diagnosis, as it can mimic squamous cell carcinoma or mucoepidermoid carcinoma, both clinically and histologically 12.

Drug-related alteration of taste sensationTaste disorders can be categorized into two depending on quantitative and qualitative differences. Quantitative changes include hypergeusia (increased taste responsiveness), hypogeusia (partial taste loss), and ageusia (total loss of taste). Qualitative taste changes include dysgeusia (distortion in the perception of the correct taste of a substance where a bitter, salty, rancid, or metallic taste sensation persists in the mouth) and phantogeusia (taste sensation without a stimuli, i.e. “taste phantoms” or “oral phantoms”) 13. Mechanisms behind drug-related altered taste could be due to the excretion of parent drug or its metabolites into saliva that changes the chemical composition/ salivary flow or by affecting the taste receptor and transduction of taste signals effecting in an unpleasant taste.

Alteration of taste is most commonly observed with angiotensin converting enzyme inhibitors (ACEI), beta lactam antibiotics such as penicillins,

Figure 1. Drug-related necrotizing sialometaplasia

Figure 2. Drug-related oral ulceration


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Figure 3. Drug-related lichenoid reaction Figure 4. Phenytoin-induced gingival overgrowth

biguanides, chlorhexidine, anti-thyroid drugs, chemotherapeutic agents, statins, diuretics, tricyclic antidepressants, anti-inflammatory agents, and opioids 14. ACEI has been reported to exert an assortment of taste changes from sweetness or saltiness to metallic or bitter taste. Angiotensin receptor blockers may give rise to ageusia 13. Diuretics may cause a foul or rancid taste in the mouth, and statins are known to produce dysgeusia or ageusia 15. Most of these effects are self-limiting and reversible within few months or once the drug is stopped; however the dysgeusia may persist in patients who are on long term continued therapy with ACEI.

Effect on oral mucosaDrug-related oral mucosal ulcerationDrug-related oral mucosal ulceration ranges from drug-related burns to vesiculobullous lesions. Oral mucosal burns commonly occur due to inappropriate use of drugs such as placing a tablet against mucosa (e.g., aspirin) or with some topical agents such as hydrogen peroxide 16. Recurrent aphthous stomatitis (RAS) is a condition which usually starts in childhood or adolescence. These ulcers are small round or ovoid ulcers with well-circumscribed margins, erythematous surrounding, and yellow or gray fibrinous membrane involving non keratinized mucosa 17. Aphthous-like ulcers arise as a result of drugs such as NSAIDs, labetalol, alendronate, captopril and nicorandil 18 (Figure 2). Sodium lauryl sulfate

which is an anionic detergent which is used as a surfactant in most dentifrices is implicated in causing mucosal irritation and ulceration. Other common groups of drugs causing oral ulcers are listed in Table 3.

A fixed drug eruption is described as an allergic reaction to a drug that characteristically recurs in the same site or sites each time a particular drug is taken. Fixed drug eruption or contact stomatitis is common and may recur with each exposure to particular drug including antibiotics, antiseptics and barbiturates 19 (Table 4). These lesions can be localized to the mouth or be associated with lesions at other mucocutaneous sites and manifest as ulceration, bullae, erythematous patches, or superficial erosions.

Chemotherapeutic agents such as methotrexate, 5- fluorouracil, blecomycin and doxorubicin may affect the gastrointestinal epithelium and may manifest as mucositis and ulcerations. These drugs affect the rapidly dividing cancer cells and inhibit the cell replication and also these drugs act on rapidly dividing oral mucosal cells and cause mucosal disruption 20. Widespread sloughing and ulceration arise within days of commencement of therapy and the associated pain often requires potent analgesics such as opioids. Methotrexate-induced oral ulceration due to the inhibition of folate metabolism can be overcome by exogenous intake of folinic acid.


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Table 3. Drug-related oral ulceration

Table 4. Drug-related fixed drug eruption

Table 5. Drug-related lichenoid reactions

Drug class

AntihypertensivesAnticonvulsants

Analgesics-NSAIDs

BisphosphonatePsychotropicAntibiotics

The mammalian target of rapamycin (mTOR) inhibitors

Examples

Losartan, nicorandil, captoprilcarbamazepine, phenytoin

piroxocam, naproxen, diclofenac,indomethacinalendronate

sertraline, olanzapinepenicillin, vancomycin

sirolimus, temsirolimus, everolimus, ridaforolimus

Drug class

AnalgesicsAntibacterials

Sedative-hypnoticsLeprostatic agents

Examples

Paracetamol, phenacetin, acetylsalicylic acid/aspirin, ibuprofen Tetracycline antibiotics - doxycycline, minocycline

Sulphonamide antibiotics - cotrimoxazole, sulfasalazine barbiturates, benzodiazepines, chlordiazepoxide

Dapsone

Drug class

AnalgesicsAntidiabetics

AnticonvulsantsAntihypertensives

AntifungalsAntimalarials

Antimicrobials

Oral contraceptives

Examples

NSAIDs, phenylbutazone, piroxicamchlorpropamide, metformin, olbutamide

carbamazepine, phenytoincaptopril, flunarizine, labetalol, methyldopa, oxprenolol, prazosin,

procainamide, propranololgriseofulvin, ketoconazole

chloroquine, colchicine, dapsone, hydroxychloroquine, quininelevamisole, lincomycin, metronidazole, niridazole, penicillamine,

penicillins, prothionamide, rifampicin, streptomycin, sulfonamides, tetracycline


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Table 6. Drug-related erythema multiforme

Drug class

Analgesics

AnticonvulsantsAntifungals

AntihypertensivesAntimicrobials

Diuretics

Examples

acetylsalicylic acid, codeine, diclofenac, phenylbutazone, piroxicam, tenoxicam

carbamazepine, phenytoingriseofulvin, fluconazole

amlodipine, digitalis, diltiazem, nifedipine, verapamilclindamycin, chloramphenicol, ethambutol, penicillin derivatives,

rifampicin, streptomycin, tetracyclines, vancomycin, cotrimoxazolefurosemide, hydrochlorothiazide

Drug-related lichenoid reactionsOral Lichen planus (LP) is an inflammatory mucocutaneous disease with well-established clinical and microscopic features. The oral mucosa and skin may present clinical and microscopic lesions mimicking those observed in LP, called lichenoid reactions (LRs), which are triggered by systemic or topical aetiological agents (Figure 3). While the aetiology of LRs is related to the contact with specific agents, such as restorative materials, resins, and drugs, with a cause-effect relationship, the aetiopathogenesis of LP is not fully delineated and postulated to be T cell-mediated auto-inflammatory process to a still unknown antigen. Drugs which most commonly cause lichenoid reactions are given in Table 5 21. The most reliable means to diagnose lichenoid reactions is by withdrawing the drug and the lesion will erupt with the re-administration of the culprit drug.

Drug-related erythema multiformeErythema multiforme is an acute, recurring and self-limiting mucocutaneous condition and

is considered to be a hypersensitivity reaction associated with certain drugs, infections and toxins. It involves the oral mucosa, lips and leads to crust formation. Erythema multiforme usually occurs within days to weeks after the drug administration 22. Drugs which are most

commonly associated with erythema multiforme are given in Table 6. Depending on the intensity and tissue distribution erythema multiforme is categorized into erythema multiforme major and minor forms. Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) differ only in their severity and can be life-threatening as well and they are distinct from that of erythema multiforme contrary to the earlier thinking that they constitute the same entity23. Drug-associated erythema multiforme is managed by withdrawing the suspected drug and by using anti-inflammatory agents.

Drug-related bullous diseasesDrug-induced pemphigus is a well-established variant of bullous disease. Drug-induced pemphigus mimics the pemphigus vulgaris or foliaceus and occur as a result of type II hypersensitivity reaction and antibody production against the desmoglein 1 and desmoglein 3 in desmosomes, a type of junctional complex in epithelial cells of skin and mucosa. This gives rise to blisters which erode into

ulcerated lesions and erosions. Drugs which are capable of inducing pemphigus are divided into ‘thiol’ and ‘non thiol’ group of drugs depending on whether the drug is having a thiol group (-SH group) 11. Drugs having a thiol group are the most frequently involved and examples


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include phencyclidine and acetylcholine esterase inhibitors 24.

Drug-related lupus like disorders Drugs such as procainamide, hydralazine, chlorpromazine, isoniazid, methyldopa, penicil lamine and quinine may induce systemic lupus erythematosus (SLE) 25. Pathogenesis underlying the drug-induced lupus erythematosus (DILE) is postulated to be immunologically mediated. Though SLE and DILE share similar clinical and laboratory findings, the pathophysiology can be due to different mechanisms of action. Patients who are on the above mentioned drugs have a higher predisposition to systemic lupus erythematosus than normal population.

Drug-related angioedemaAngioedema is a clinical manifestation of allergic disorders and is characterized by swelling of mucus membranes and tissues underneath the skin. Drug-induced angioedema can arise due to a wide range of drugs including non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor antagonists, proton pump inhibitors, statins, antibiotics, fibrinolytic agents, estrogens, diuretics, calcium channel blockers, beta blockers, and psychotropic drugs (serotonin reuptake inhibitors). Drug-induced angioedema occur more frequently with the beta-lactam antibiotics such as penicillins and NSAIDs 26. Drug-induced angioedema which is also coupled with urticaria may be complicated by life-threatening anaphylaxis. ACEI-induced angioedema is thought to occur due to high levels of bradykinin while histamine acts as the main culprit in allergic angioedema. Correct diagnosis is vital in managing the patients as standard treatments such as glucocorticoids and antihistamines may be ineffective in treating non-allergic forms of angioedema.

Effects on gingivaGingival enlargement can be brought by drugs such

as phenytoin, cyclosporine A, calcium channel blockers (verapamil and nifedipine) due to the enhanced extracellular matrix 27. Less commonly, drugs such as norethisterone (progestogen hormone), erythromycin, ketoconazole, lithium, lamotrigine and phenobarbitone may cause gingival enlargement. The postulated mechanism underlying gingival enlargement due to drugs such as phenytoin (Figure 4) is thought to occur as a result of decreased uptake of folic acid by cells and by reducing the production of active collagenase and matrix metalloproteinases (MMPs) which are necessary for collagen degradation 28. Arya et al (2011) 29 have shown that administration oral folic acid can decrease the incidence of PHT-induced gingival overgrowth (PIGO) in children who are on phenytoin therapy. Furthermore, fibroblasts in the presence of phenytoin increase the synthesis of cytokines such as IL-6, IL-1, and IL-8 which in turn induce the activation and proliferation of T cells and the recruitment of neutrophils 28. Dental plaque enhances the fibrosis by inducing a local inflammatory response. Other than the aforementioned cytokines growth factors such as connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), fibroblast growth factors (FGF) and transforming growth factor beta (TGF)-b are up regulated and may play a role in the pathogenesis of drug-induced gingival overgrowth 28.

Gingival enlargement usually results following long-term therapy with the abovementioned drugs and get aggravated with poor oral hygiene. Therefore, such patients require frequent dental checkups and treatments for gingival hyperplasia in order to obtain a better cosmetic outcome. Rarely Kaposi’s sarcoma or squamous cell carcinoma may arise within the areas of cyclosporine A-induced areas of gingival enlargement 30.

Drug-related pigmentationDrugs can cause oral mucosal pigmentation, dental staining or both. Oral pigmentation is associated with both the dosage and duration of drug therapy. Dental staining can be intrinsic


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or extrinsic. Extrinsic stains cover up the tooth surface and can be removed easily by scaling or brushing (e.g., chlorhexidine) whereas intrinsic stains are entrapped within the dental structures, requiring teeth whitening (e.g., tetracycline) 17. Intrinsic discoloration by tetracycline is prominent when given to children under 8 years. In addition to teeth, tetracycline may also get deposited in thyroid, bone, sclera and nails.

Oral mucosal pigmentation may arise as a result of many mechanisms. Certain drugs may stimulate the activity of melanocytes, while drugs like phenothiazines and heavy metals may deposit

within the oral mucosa and alter the pigmentation directly31. Table 7 list the drugs that involved in pigmentation of oral mucosa.

The “black hairy tongue ˮ which is characterized by the elongation and blackish/brownish discoloration of filiform papillae occurs due to the chromogenic bacteria, tobacco and long term use of oral antibiotics such as linezolid and antacids32.

Drug-related halitosisHalitosis or bad breath is commonly results due to poor oral hygiene, oral and dental infections and some systemic diseases. In addition, halitosis

Table 7. Drug-related oral mucosal pigmentation

Table 8. Drugs causing haemorrhagic diathesis

Drug class

AnalgesicsAntihypertensives

Antimicrobials

AntimalarialsAntiretrovirals

Chemotherapeutic agentsHormone replacement therapy

Oral ContraceptivesPsychotropic drugs

Examples

aminophenazonemethyldopa, propranolol, quinidine

clofazimine, doxorubicin, doxycycline, ketoconazole,minocycline

chloroquine, hydroxychloroquininezidovudine

busulfan, cyclophosphamide, fluorouracil

fluoxetine

Drug class

AnticoagulantsDiuretics

AntimalarialsAntibiotics

Examples

heparin, warfarinthiazidesquinine

sulphonamides


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can arise as a direct or indirect effect of certain drugs. Isosorbide dinitrate, dimethyl sulfoxide and disulfiram can directly induce halitosis. Drugs causing xerostomia may indirectly cause or aggravate this condition.

Drug-related osteonecrosisOsteonecrosis is defined as “an area of exposed bone that persists for more than 8 weeks in the absence of prior radiation and or metastasis in the mandible” 33. Osteonecrosis of the jaws is identified as an adverse effect due to bisphosphonate therapy. Bisphosphonates inhibit the bone resorbing activity of osteoclasts and used to treat post-menopausal osteoporosis and reduce skeletal related events during cancer therapy. However, medications other than antiresorptive agents such as antiangiogenic agents may also be involved in osteonecrosis 34.

Presence of necrotic bone in the maxilla/mandible may be asymptomatic or be associated with significant pain and infection. In addition to its antiresorptive effect, bisphosphonates have antitumor effects and antiangiogenetic effects which cause decreased circulating levels of vascular endothelial growth factor (VEGF). Therefore, bisphosphonates make bone healing more difficult in the presence of infection/trauma 33.

Drug-related oral InfectionsAlteration of the oral flora following treatment with systemic drugs predisposes to oral fungal and bacterial infections. The most frequently identified, opportunistic infection in oral cavity is candidiasis caused by Candida albican 35. While glucocorticoids, broad spectrum antibiotics, immunosuppressants, antineoplastics may alter the oral flora, drugs that cause xerostomia favor the occurrence of oral candidiasis and suppurative parotitis. Patients who are on long term immunosuppressive therapy and patients having immunodeficiency viral infection (HIV) are susceptible to opportunistic infections in the oral cavity. Drugs such as disease-modifying

antirheumatic drugs (DMARDs) can cause neutropenia, thus making favorable environment for viral infections such as herpes simplex, herpes zoster and deep fungal infections.

Hemorrhagic diathesisIntraoral hemorrhages can be occurred as a result of thrombocytopenia, defective vascular integrity or coagulopathy 36. The drugs which can give rise to above condition are listed in Table 8. Intraoral hemorrhages clinically manifest as petechiae in lips, buccal mucosa, junction of hard palate and soft palate and also appearance of petechiae following minor trauma to the lateral edge of the tongue.

Effects on nervesDrug-related movement disordersDrugs such as phenothiazines, tricyclic antidepressants, and antidopeminergics may cause several types of movement disorders principally affecting the face and mouth. Long-term use of dopaminergic antagonists result in abnormal, involuntary, repetitive, purposeless movement in oro-facial region which is called tardive dyskinesia 36. It is clinically characterized by tongue protrusion, lip smacking, grimacing, rapid eye blinking and soon. Dystonia (uncontrollable muscle contraction) can be also caused by metoclopramide and carbamazepine therapy.

Drug-related oral dysaesthesia Oral dysaesthesia is a painful, burning feeling in the mouth and can be divided into primary dysaesthesia and secondary dysaesthesia. Primary dysaesthesia is also known as ‘burning mouth syndrome’. Secondary dysaesthesia arises as a result of underlying systemic condition or due to a causative agent such as drugs. ACE inhibitors, angiotensin receptor blockers, antiretroviral agents, chemotherapy, and clonazepam cause oral burning. Drugs which cause xerostomia such as anticholinergics, psychotropic drugs, tricyclic antidepressants, amitriptyline and antihistamines may indirectly cause oral burning 37.


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SynopsisA wide variety of drugs can give rise to numerous adverse effects on oral cavity. Oral ulcerations, xerostomia, taste alterations and gingival over growth are the most common among them. Most of the naturally occurring oral manifestations of systemic diseases can be mimicked by adverse effects due to drugs. On the other hand, drug-induced disorders may initiate painful, destructive and harmful processes that will not be successfully managed unless culprit drug is identified. This may require alteration of the dose or withdrawal of the drug to improve the quality of life of the patient. Therefore, practicing clinician should have an adequate knowledge on adverse effects of drugs and thereby a clinician would be able to individually prevent, diagnose and treat those adverse effects.

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