All of the following posts are copied and pasted from the Medscape link.

An estimated 2-4% of hospital admissions are related to adverse drug reactions. Mucocutaneous eruptions are often central to these untoward reactions, and an ever-expanding list of medications is linked to pathologic reactions in the oral and perioral region. These adverse drug reactions have a broad spectrum of clinical manifestations that can mimic those of other disease states, including both local and systemic conditions.^{[1, 2, 3, 4, 5]}

Fortunately, several patterns of disease have been identified, and these can assist the clinician in determining a possible cause-and-effect relationship with a particular medication or group of medications. The clinical patterns of adverse drug reactions of the oral cavity include xerostomia, swelling, nonspecific ulceration, vesiculobullous or ulcerative mucositis that mimics other disease states, nonspecific vesiculoulcerative mucositis, pigmentation, gingival enlargement, and medication-related osteonecrosis of the jaws.

Oral drug-reaction patterns with associated drugs and drug classes

Xerostomia

Agents include antidepressants and antipsychotics, antihypertensives, antihistamines, anticholinergics, and decongestants.

Swelling

Agents include penicillins, aspirin, sulfa drugs, and ACE inhibitors.

Nonspecific ulceration and mucositis

Agents include antineoplastics (methotrexate, 5-fluorouracil, doxorubicin, and melphalan); barbiturates; dapsone; phenazone derivatives; phenolphthalein; sulfonamides; tetracyclines; NSAIDs (indomethacin, salicylates, gold salts, naproxen); meprobamate; methyldopa; penicillamine; phenylbutazone; propranolol; spironolactone; thiazides; tolbutamide; alendronate; captopril; phenytoin; and (by direct contact) compounds containing aspirin, hydrogen peroxide, or phenol.

Vesiculobullous or ulcerative lesions that mimic other immunologic diseases

Reactions may include lichen planus–like, erythema multiforme (EM)–like, pemphigoid-like, pemphigus -like, and lupus erythematosus (LE)–like reactions.

Lichen planus–like^{[6, 7, 8]} agents may include the following:

• Antialcoholism (cyanamide)
• Antibiotics (aminosalicylate sodium, isoniazid, rifampin, streptomycin, tetracyclines)
• Anticonvulsants (carbamazepine, oxacarbazepine, phenytoin, valproate)
• Antidiabetics (chlorpropamide, glipizide, insulin, tolbutamide)
• Antidiarrheals (bismuth)
• Antifungals (amphotericin B, ketoconazole)
• Antihistamines (cimetidine, cinnarizine, triprolidine)
• Antihypertensives (atenolol, captopril, chlorothiazide, enalapril, furosemide, hydrochlorothiazide, methyldopa, metoprolol, oxprenolol, propranolol, spironolactone)
• Antihyperuremics (allopurinol)
• Antimalarials (chloroquine, hydroxychloroquine, pyrimethamine, quinacrine, quinidine)
• Antiretroviral (zidovudine)
• Calcium channel blocker (flunarizine)
• Chemotherapeutics (dactinomycin, imatinib, palladium)
• Diuretic (furosemide)
• Immunomodulators (dapsone, gold salts, interferon alfa, levamisole, penicillamine)
• NSAIDs (acetylsalicylic acid, para-aminosalicylic acid, diflunisal, ibuprofen, indomethacin, naproxen, rofecoxib, sulindac)
• Psychiatrics (benzodiazepines, tricyclic antidepressants, levopromazine, lithium, lorazepam, phenothiazines, pyritinol)

Erythema multiforme (EM)–like agents may include the following:

• Antibiotics (antimalarials, penicillins, sulfonamides, tetracyclines)
• Allopurinol
• Barbiturates
• Protease inhibitors
• NSAIDs

Pemphigoid-like^[9] agents may include the following:

• Antirheumatics (penicillamine, ibuprofen, phenacetin)
• Cardiovascular drugs (furosemide, captopril, clonidine)
• Antibiotics (penicillins, sulfonamides)
• Antimicrobials
• Thiol-containing drugs
• Sulfonamide derivatives

Pemphigus -like^[10] agents may include the following:

• Alpha-mercaptopropionylglycine
• Ampicillin
• Captopril
• Cephalexin
• Ethambutol
• Glibenclamide
• Gold
• Heroin
• Ibuprofen
• Penicillamine
• Phenobarbital
• Phenylbutazone
• Piroxicam
• Practolol
• Propranolol
• Pyritinol chlorohydrate
• Rifampin
• Theobromine

Lupus erythematosus (LE)–like agents may include the following:

• Carbamazepine
• Chlorpromazine
• Ethosuximide
• Gold
• Griseofulvin
• Hydantoins
• Hydralazine
• Isoniazid
• Lithium
• Methyldopa
• Penicillamine
• Primidone
• Procainamide
• Quinidine
• Reserpine
• Streptomycin
• Thiouracils
• Trimethadione

Pigmentation

Agents include amiodarone; antimalarials (chloroquine, hydrochloroquine, hydroxychloroquine, quinacrine, quinidine); busulfan; clofazimine; cyclophosphamide; estrogen; imatinib; ketoconazole; minocycline; phenolphthalein; chlorpromazine; and zidovudine.

Gingival enlargement

Agents include calcium channel blockers (amlodipine, bepridil, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, nitrendipine, oxidipine, verapamil); other dihydropyridines (bleomycin); cyclosporine; phenytoin; and sodium valproate.

Swelling

Several drugs can induce type I hypersensitivity reactions, or disease mediated by immunoglobulin E mast cells, that can range from isolated swelling of the oral tissues to full-blown anaphylaxis. Around the mouth, the lips are the most frequently involved site, followed by the tongue. Among the most common offending agents are ACE inhibitors, penicillin and penicillin derivatives, cephalosporins, barbiturates, and aspirin and other NSAIDs. Affected mucosa typically appears edematous and erythematous within minutes or hours after exposure to the offending drug. Similar contact reactions to latex had become increasingly problematic in oral health care settings until the recent shift towards non-latex replacement materials such as vinyl or nitrile rubber.

ACE inhibitors are also associated with oral swelling of a nonallergic nature. This reaction, which is possibly secondary to alterations in local bradykinin levels or C1 esterase inhibitor function, is reported in less than 1% of patients, with an increased risk noted among blacks in the United States. Although swelling is most commonly seen in the first weeks of therapy, it may occur within hours of the initial exposure or after an extended period of drug use. As with the type I reactions, the lips are the most typical site of involvement. The tongue and oropharyngeal tissues can also be affected, with a potentially fatal outcome.

Vesiculobullous or Ulcerative Lesions That Mimic Other Immunologic Diseases

Oral drug reactions that bear striking clinical, histopathologic, and even immunopathologic resemblance to idiopathic lichen planus, erythema multiforme (EM), pemphigoid, pemphigus, and lupus erythematosus (LE) are well recognized, and the list of reactions in each category is constantly expanding. Clinically, any oral site can be affected; however, the posterior buccal mucosa (cheeks), the lateral borders of the tongue, and the alveolar mucosa are most commonly involved. Lesions may be isolated, although bilateral and occasionally symmetric involvement is not uncommon.

Lichen planus – like (lichenoid) reactions

Initially described in association with antimalarial medications, lichen planus–like or lichenoid drug reactions have subsequently been reported in association with many other agents. Both papuloreticular and erosive manifestations may be observed; the latter is characterized by shallow irregular ulcerations or erosions with a peripheral border of fine keratotic striae that often appear to radiate from the center of the lesion. Although drug-induced lichenoid reactions tend to be erosive and unilateral compared with the typical bilateral presentation in idiopathic lichen planus, these associations are not consistently observed.

Currently, NSAIDs and ACE inhibitors appear to be among the most frequently cited offenders (see Oral drug-reaction patterns and associated drugs and drug classes in Introduction). Interestingly, agents used in the treatment of lichen planus (eg, hydroxychloroquine, dapsone, levamisole) have themselves led to adverse lichenoid eruptions.

Erythema multiforme (EM) – like reactions

Drug-induced EM represents approximately 25% of all reported cases. As with idiopathic or virally induced cases (the latter often due to the herpes simplex virus), the disease has a rapid onset with a variable expression that can range from lesions limited to the oral mucosa to widespread mucocutaneous involvement. Drug-induced EM is frequently linked to agents such as sulfonamides, sulfonylureas, and barbiturates, among others (see Oral drug-reaction patterns and associated drugs and drug classes in Introduction).

Oral lesions start as erythematous macules or patches that lead to short-lived vesicles or bullae, followed by ragged and shallow ulcerations that may become extensive. Hemorrhagic ulceration and crusting of the labial vermilion zone is common. Any intraoral site can be involved, but the attached gingival and palatal tissues are often relatively spared. Lesional discomfort can lead to decreased fluid intake and dehydration. A variety of lesions, including classic target or bull's eye lesions, can affect the skin.

More severe forms of disease include EM major (Stevens-Johnson syndrome) and toxic epidermal necrolysis (TEN, Lyell syndrome). In addition to the oral and skin lesions, conjunctivitis of the ocular mucosa and urethritis of the genital mucosa are typical findings in patients with EM major. Over three-quarters of EM major cases and virtually all cases of TEN represent adverse drug reactions. In TEN, widespread mucocutaneous epidermolysis results in diffuse bullae formation and subsequent denudation that affects significant proportions of the skin and mucosal surfaces. Severe dehydration, electrolyte imbalances, and secondary infections are potentially life-threatening sequelae, and even with aggressive therapy the mortality rate is greater than 30%.

Pemphigoid-like reactions

Pemphigoid-like reactions can be limited to the oral mucosa, or they can affect other mucosal or cutaneous sites. Clinically, lesions appear as relatively sturdy vesicles or bullae that break down into shallow ulcerations. Generalized or multifocal involvement of the gingival tissues may be observed, with marked erythema and erosion of the superficial gingiva, a pattern that has been called desquamative gingivitis. Thiol-containing drugs and sulfonamide derivatives are among the most commonly involved medications, as are the therapeutic classes of NSAIDs, cardiovascular agents, antimicrobials, and antirheumatics (see Oral drug reaction patterns with associated drugs and drug classes in Introduction).

Circulating autoantibodies to basement membrane components may or may not be detectable. The relatively young age of the patients at onset (usually less than 70 years) may help distinguish this disease from idiopathic bullous pemphigoid or idiopathic cicatricial pemphigoid, because these latter conditions typically appear in persons aged 60-80 years. In addition, oral involvement may be more common in drug-induced bullous pemphigoid than in the idiopathic counterpart.

Pemphigus-like reactions

Pemphigusike reactions can have features of either pemphigus vulgaris or pemphigus foliaceous, although pemphigus foliaceous is uncommon in the oral cavity. Thiol-containing drugs are the most common cause of pemphiguslike reactions (see Oral drug-reaction patterns and associated drugs and drug classes in Introduction). In drug-induced pemphigus vulgaris, the relatively fragile vesicles are rarely observed at clinical examination, and most cases are characterized by irregular ulcerations with ragged borders that may coalesce to involve large areas of the mucosa. Patients may have circulating autoantibodies to the desmosomal components.

Lupus erythematosus (LE) – like reactions

Drug-induced LE is a well-recognized adverse reaction that is most commonly associated with procainamide and hydralazine, although more than 70 medications are implicated (see Oral drug-reaction patterns and associated drugs and drug classes in Introduction). Clinically, the oral lesions of drug-induced LE may simulate those of erosive lichen planus, with irregular areas of erythema or ulceration bordered by radiating keratotic striae. These lesions may affect the palate, buccal mucosa, and gingival or alveolar tissues. The rarity of lichen planus on the hard palate may be helpful in differentiating it from drug-induced LE.

Gingival Enlargement

Diffuse, non-neoplastic enlargement or overgrowth of the gingival tissues was initially recognized in patients who were using phenytoin. More recently, calcium channel blockers (members of the dihydropyridine class of medications), cyclosporine, and the antiepileptic drug sodium valproate have been associated with this reaction. Within the calcium channel blocker family, nifedipine, diltiazem, verapamil, and amlodipine are among the most commonly reported causative agents (see Oral drug-reaction patterns and associated drugs and drug classes in Introduction).

Gingival enlargement is not observed in all patients. The prevalence is 25-50%, and no clear relationship has been established between the dose of the drug and the severity of the overgrowth. Synergistic effects have been reported with the use of 2 or more suspected agents. Tissue enlargement typically occurs by 1-3 months after drug therapy is initiated and begins in the superficial gum tissues between the teeth (interdental papillae). Anterior segments are more frequently involved than posterior areas, but generalized involvement is not uncommon.

An inverse relationship exists between oral hygiene and the degree of gingival enlargement associated with these drugs. Although good oral hygiene typically does not prevent enlargement in susceptible individuals, it can often limit the severity of the response to acceptable levels. Although cessation or substitution of the drug may lead to regression, surgical removal of the excess tissue (ie, gingivectomy) may be necessary to permit adequate oral hygiene in certain individuals.

Bump

Bump

Bump

Bump

Your welcome Mel. Please, consider bumping this once and awhile if I haven't

Transferred post written by LoverofLife. Esophageal reflux/GERDS can impact the mouth and the posterior throat

Sep 29, 2017 10:55PM Loveroflife wrote:

Oooh the light bulb just came on. May I add my thoughts....,some drugs can actually cause reflux ( calcium channel blockers, potassium supplements for example).

From Mayo:

Bump