Local Reactions to Drugs

• Reactions to drugs are classified into local reactions, systematically mediated reactions, and other effects.

Local Reactions to Drugs

• Chemical irritation and interference with the oral flora are local drug reactions.
• Chemical irritation can happen when an Aspirin tablet is held against the mucosa near a tooth that aches.
• A white patch that has superficial necrosis and shedding of dead epithelium can occur.
• The mucosa heals after removing the cause of the chemical irritation.
• Other chemicals like acid etchants, Phenol, CMCP, and NaOCl can cause irritation if accidentally dropped on the mucosa, especially without proper isolation.
• Prolonged use of antibiotics can alter the normal oral flora by killing sensitive organisms, leaving resistant ones.
• Candida albicans can proliferate, resulting in thrush or acute atrophic candidiasis.
• Topical steroids can have adverse effects on the immune response locally when used for a long time or in large doses, or systemically due to absorption.

Systemically Mediated Reactions

• Depression of bone marrow function, depression of cell-mediated immunity, lichenoid drug reaction, erythema multiforme, toxic epidermal necrolysis, and fixed drug eruptions are systematically mediated reactions.
• Some medications can cause anemia, which can cause oral signs, few drugs significantly depress RBCs production alone.
• Prolonged use of Phenytoin can cause Foliate Deficiency and Macrocytic Anemia in susceptible patients.
• Severe Aphthous Stomatitis like ulcers can be caused by Foliate Deficiency and Macrocytic Anemia, administration of Foliate can resolve the Aphthous Stomatitis.
• A variety of drugs can depress WBCs production.
• Agranulocytosis, with necrotizing ulceration of the gingivae and throat, can be the clinical picture of WBCs production depression.
• Untreated Agranulocytosis can lead to severe illness and Septicemia.
• Drugs that may cause WBCs production depression include antibacterials, analgesics, antipsychotics, and antithyroid agents.
• Low-grade oral pathogens can produce necrotizing ulceration (such as NUG) when the effect is on Granulocytes.
• Drug-induced purpura can be an early sign of Aplastic Anemia from medications that depress marrow function such as Chloramphenicol.
• Drug-induced purpura can cause severe spontaneous gingival bleeding, blood blisters, and submucosal ecchymosis.
• Aspirin affects platelets, can cause oral purpura.
• Immunosuppression by drugs like Corticosteroids is induced in patients with organ transplants or immunologically mediated diseases, who receive high doses of corticosteroids for prolonged time.
• Viral and fungal infections of the mouth are common and can be severe in immunosuppressed patients.
• Recurrences of childhood viral infections such as Recurrent Herpes, Measles, and Chickenpox are possible.
• Gold Salts, antimalarials, antihypertensive agents like Methyldopa and Captopril can cause lichenoid drug reactions, meaning lesions indistinguishable from Lichen planus clinically and histologically.
• Grinspan's syndrome includes hypertension, diabetes mellitus, and Lichen planus.
• Erythema multiforme & Stevens-Johnson syndrome may be caused by Penicillin, Sulphonamides, NSAIDS, Anticonvulsants, Barbiturates.
• Toxic epidermal necrolysis is the extreme end of the spectrum of Erythema multiforme, which is one of the most dangerous and severe types of drug reactions.
• Mucosal involvement is common and causes widespread erosions due to epithelial destructions in Toxic epidermal necrolysis.
• Early diagnosis and treatment are important (Lifesaving) as Toxic epidermal necrolysis reaction can be lethal.
• Toxic epidermal necrolysis (TEN) may occur along with Stevens–Johnson syndrome (SJS).
• Drugs implicated in Toxic epidermal necrolysis include Sulfonamides, Beta-lactams, NSAIDs, Allopurinol, Antimetabolites, Antiretroviral drugs, Anxiolytics, and Anticonvulsants.
• Sharply circumscribed skin lesions (mostly painful purple patches) recurring at the same site each time the drug is given are fixed drug eruptions.
• Cotrimoxazole, Trimethoprim, Tetracycline, Doxycycline, Ciprofloxacin, Clarithromycin, Fluconazole, NSAIDs, Phenytoin, Pseudoephedrine, and Phenolphthalein can cause fixed drug eruptions.
• Involvement of the oral mucous membrane is exceedingly rare in fixed drug eruptions.

Other Drug Effects

• Gingival hyperplasia, oral pigmentation, and dry mouth are other drug effects.
• Anticonvulsants, antihypertensive agents including ACE inhibitors and Calcium channel blockers, and Immunosuppressant medications can cause fibrous hyperplasia of the gingivae particularly concentrated at the interdental papillae.
• Heavy metals such as Mercury, Bismuth and Lead can cause black or brown deposits in the gingival margins by the interaction with bacterial byproducts to form metal Sulfides.
• The blue Lead line indicates the level of the floor of the pocket.
• Mercury and Bismuth are no longer used in medicine and Lead is no longer a major industrial hazard, thus the effects of the heavy metals are rarely seen nowadays.
• Cisplatin, a cytotoxic drug, can cause a blue line.
• Topical antibiotics & antiseptics may cause dark pigmentation, particularly of the dorsum of the tongue, due to over growth of the pigment forming bacteria.
• Excessive use of Chlorhexidine can cause extrinsic yellow or brownish-dark pigmentation of the teeth, oral mucosa and dorsal surface of the tongue.
• Dry mouth is a relatively common side effect of some drugs, particularly those with an Anticholinergic or Atropine like action, such as the Tricyclic antidepressants, MAO inhibitors, Phenothiazine antipsychotics, and Antihistamines.

Management Considerations

• History is the key for diagnosis.
• Oral reactions to drugs are not overall common; nevertheless, they may be important as an early sign of a dangerous or lethal reaction.
• A drug being taken by a patient is not necessarily the cause of any oral symptom.
• Coincidence is often difficult to exclude, particularly with common oral disease such as Lichen planus.
• The problem is made more difficult by multiple drugs treatment.
• A detailed history of medications is essential as it may affect other aspects of dental treatment.