News for pharmacy professionals
29 Sep 2016
Adverse drug reactions are those that produce a harmful, unintended response. They can be classified into two types:
Type “A” reactions: directly related to an enhanced pharmacological action of the drug administered (e.g. hypoglycaemia from an anti-diabetic drug).
Type “B” reactions: those that are unexpected from the know pharmacological action of the drug (e.g., anaphylaxis from penicillin).
Just as in the rest of the body, these adverse reactions may occur in the oral cavity affecting different parts of the mouth.
There are over 500 drugs that may cause dry mouth - or xerostomia - up to 80% of those most commonly prescribed. Salivary glands are very sensitive to strict anticholinergics (atropine, belladonna, scopolamine, etc.). Other pharmacological groups which also produce xerostomia are: antidepressants and antipsychotics (serotonin reuptake inhibitors, tricyclic and heterocyclic antidepressants), antihypertensives (ACE inhibitors, diuretics, beta blockers, etc.), anxiolytics and sedatives, muscle relaxants, analgesics (CNS/opioids), antihistamines, appetite suppressants, acne medications, anticonvulsants, antiparkinson agents, bronchodilators, migraine medications and hypnotics.
A reduction in saliva has consequences for the oral cavity, since its pH buffer effect and microbial inhibition is lost. It may thus lead to the development of diseases such as caries and periodontal disease or disorders like halitosis and dental hypersensitivity.
There are other drugs that can cause the opposite effect—hypersalivation—also known as ptyalism or sialorrhea. This is much less frequent and less severe, although it may be bothersome for those who have to endure it. It is fundamentally attributed to parasympathomimetic drugs, which act directly on the acetylcholine receptors (pilocarpine, cevimeline, bethanechol, carbachol) or by inhibiting acetylcholinesterase (neostigmine, physostigmine). In some countries pilocarpine is in fact used as a treatment for xerostomia, although it is necessary to evaluate the side effects that may arise. Catecholamines and other drugs that act on the central nervous system (CNS) also cause this effect through other mechanisms of action, such as epinephrine, clonazepam, bromine, mercury and iodine compounds.
Inflammation and pain in the salivary glands
Chemical burns to the mucosa are produced most commonly by misuse of analgesics and antiseptics. An example is acetylsalicylic acid, which is used topically to relieve dental pain and produces a superficial necrosis of the epithelium, with the appearance of white lesions with irregular edges on an area showing painful erythema.
Other drugs such as phenylbutazone, indomethacin, silver nitrate, hydrogen peroxide, isoproterenol and potassium chloride also cause ulcers if applied in the same way. In addition, these may be produced by the use of products with high alcohol content, like some mouthwashes (if abused) or certain benzocaine-based anaesthetic solutions.
Chemotherapy may cause mucositis (inflammation and ulceration of the mucosa with pseudomembrane formation) after 5-7 days of treatment. The antineoplastics that produce these reactions most frequently are methotrexate and 5-fluorouracil. They cause such pain as to interfere with patients' daily lives, affecting their eating habits. Topical anaesthetics and oral analgesics are used to treat mucositis.
Allergic stomatitis may be due to the systemic administration of, or direct contact with, certain drugs. Drugs with which this occurs most often are barbiturates, acetaminophen, phenacetin, pyrazolones, sulfonamides and tetracyclines.
Certain medications may cause lichenoid reactions; these are similar to lichen planus, but are associated with the use of medicines. Their aetiopathogenesis is undetermined, and the reactions disappear after ceasing medication. They may mainly be caused by non-steroidal anti-inflammatory drugs (NSAIDs) (such as piroxicam) and angiotensin-converting enzyme inhibitors (ACE inhibitors), but may also be produced by antimalarials, other antihypertensive agents (diuretics such as hydrochlorothiazide, beta blockers, etc.), psychotropic drugs, metal salts (gold- or bismuth-based) and drugs for rheumatoid arthritis (monoclonal antibodies).
Oral iron supplements (in the form of ferrous salts), used for the treatment of iron deficiency anaemia may cause the appearance of black spots on the teeth.
Cisplatin, a drug used for certain antineoplastic therapies, may produce a linear bluish staining on the gum margin.
Bisphosphonates are the drugs most commonly associated with osteonecrosis, especially if used intravenously. This condition occurs with the exposure of the maxillary bone due to a lack of blood supply, and inhibition of bone resorption. Most cases occur in patients taking bisphosphonates in cancer therapy, as tumours such as multiple myeloma or breast carcinoma tend to involve the skeleton. However, osteonecrosis may also occur with the use of biphosphonates for osteoporosis. Multidisciplinary management of these patients is required to prevent occurrence of this very serious complication.
There are over 200 drugs that produce alterations to the sense of taste, either diminishing it (hypogeusia), distorting it (dysgeusia) or causing its total loss (ageusia). The list of drugs that produces this is very long, and may include antibiotics, anti-rheumatics, anti-inflammatories, antithyroid drugs, antihypertensives, diuretics, local anaesthetics, antineoplastic treatments, oral antiseptics, anxiolytics, antidepressants, etc. These problems disappear after discontinued use of the drug responsible for causing the alteration.
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