DRUG REACTIONS

Classification of drug reactions: Reactions to drugs

:classified into

:I. Local reactions to drugs

Chemical irritation .1
Interference with the oral flora .2

:II. Systematically mediated reactions

Depression of bone marrow function .1
Depression of cell-mediated immunity .2
Lichenoid drug reaction .3
Erythema multiforme (Stevens-Johnson syndrome) .4
Toxic epidermal necrolysis .5
Fixed drug eruptions .6

:III. Other effects (reactions)

Gingival hyperplasia .1
Oral pigmentation .2
Dry mouth .3

:Local reactions

Chemical irritation (burn): The best known example is that of .1

Aspirin tablet held against the mucosa close to an aching tooth
which will cause a white patch characterized by superficial
necrosis with dead epithelium shedding/sloughing. Mucosa
.heals after removal of cause

Other irritant chemicals used in dental treatment such as acid

etchants, Phenol, CMCP, NaOCl and others dropped on the
mucosa accidently during work especially in bad isolation (no
.rubber dam)

1
Interference with the oral flora (Super infection): Prolonged .2
use of antibiotics (or topical antibiotics) may alter the normal
oral flora by killing sensitive organisms leaving resistant ones,
particularly opportunistic organisms such as Candida albicans
.to proliferate resulting in thrush in susceptible patients

Systemically mediated reactions

:Depression of bone marrow function .1

a. Anemia and RBCs effects: Some drugs cause anemia might

give rise to oral signs. Few drugs significantly depress RBCs
.production alone

The main example is a prolonged use of Phenytoin (for

epilepsy) which in susceptible patients can cause Foliate
.Deficiency and Macrocytic Anemia

This in turn can cause severe Aphthous Stomatitis like ulcers,

which respond promptly to the administration of Foliate, and the
.blood picture returns to normal

b. WBCs production depression: WBCs production is

depressed by a variety of drugs. Leukopenia may be severe
enough to produce the clinical picture of Agranulocytosis, with
necrotizing ulceration of the gingivae and throat which can go
.on to a severe prostrating illness and Septicemia if untreated

:Drugs which may have this effect include

Antibacterials: particularly Co-trimoxazole, Chloramphenicol .1

Analgesics: Particularly Aminopyrine (Aminophenazone) .2

Antipsychotics: Phenothiazines .3

Antithyroid agents .4

2
When the main effect is on Granulocytes, low-grade oral
pathogens, particularly of the gingival margins, are able to
overcome local resistance and produce necrotizing ulceration
.(such as NUG)

:c. Other drugs may affect hemostasis and cause oral purpura

Drug-induced purpura is often also an early sign of Aplastic

Anemia caused by drugs such as Chloramphenicol, which
.depress marrow function

Purpura can produce severe spontaneous gingival bleeding or

.blood blisters and widespread submucosal ecchymosis

Aspirin with its known effect on the platelets (not on the bone
.marrow)

Depression of cell-mediated immunity: lmmunosuppression .2

by drugs as such Corticosteroids is induced in patients having
.organ transplants or with immunologically-mediated diseases

Viral and fungal infections of the mouth are common in

.immunosuppressed patients and can be severe

Recurrences of childhood viral infections such as Measles and

.Chickenpox are also possible

Lichenoid drug reactions: Several drugs such as Gold salts .3

and Antimalarials (both previously used in the treatment of
Rheumatoid Arthritis or other collagen diseases), the
antihypertensive agents such as Methyldopa (Aldomet ®) and
Captopril can cause lesions indistinguishable from Lichen
planus, both clinically and histologically. The mechanism of
.such reactions is unknown

Grinspan’s syndrome: Hypertension (Antihypertensives),

.Diabetes Mellitus and Lichen planus

3
Erythema multiforme (Stevens-Johnson syndrome): Which .4
:may be caused by some drugs such as

Sulphonamides, Barbiturates. Other drugs are occasionally

implicated, but the mechanisms are unknown and more
.frequently there is no evidence of such a drug reaction

Toxic epidermal necrolysis: This reaction probably represents .5

the extreme end of the spectrum of Erythema multiforme, it’s
one of the most dangerous and severe types of drug reactions.
Mucosal involvement is common and causes widespread
erosions due to epithelial destructions. Oral ulceration may
precede the dermal changes, and cause the patient to seek
treatment for the extreme soreness of the mouth. Early
diagnosis and treatment is important as the reaction can be
.lethal

Note: Toxic epidermal necrolysis (TEN) may occur along with

.Stevens–Johnson syndrome (SJS)

:Drugs implicated include

Antibiotics: Sulfonamides (Sulfamethoxazole, Sulfadiazine, *

Sulfapyridine)

Beta-lactams (Cephalosporins, Penicillins, Carbapenems)

Non-steroidal anti-inflammatory drugs such as *

Phenylbutazone

Allopurinol (used to treat Gout and certain types of kidney *

stones as it decreases uric acid levels)

Antimetabolites (Methotrexate) *

Antiretroviral drugs (Nevirapine) *

Anxiolytics (Chlormezanone) *

Anticonvulsants (Phenobarbital, Phenytoin, Carbamazepine, *

Lamotrigine, and Valproic acid)

Metals such as Gold salts *

4
Barbiturates (CNS depressants) *

Fixed drug eruptions: These consist of sharply circumscribed .6

skin lesions (mostly painful purple patches) recurring in the
.same site or sites each time the drug is given

:Many drugs are capable of causing this reaction such as

Cotrimixazole, Trimethoprim *

Tetracycline, Doxycycline, Ciprofloxacin *

Clarithromycin *

Fluconazole *

NSAIDs (e.g. Ibuprofen) *

Phenytoin *

Pseudoephedrine (used as nasal/sinus decongestant and in *

combinations such as Sudafed)

Phenolphthaline (used as laxative or purgative) *

Involvement of the oral mucous membrane has been described

.but is exceedingly rare

Other drug effects

:Gingival hyperplasia: Drugs such as .1

Anticonvulsants: Phenytoin (Dilantine Sodium).

Antihypertensive agents and Calcium channel blockers such as
.Nifidipine (Adalat)

.Immunosuppressant: Cyclosporine

All can cause fibrous hyperplasia of the gingivae particularly

.concentrated at the inter dental papillae

5
Oral pigmentation: Heavy metals such as Mercury, Bismuth .2
and Lead can cause black or brown deposits in the gingival
margin by the interaction with bacterial byproducts to form metal
Sulphides. The blue Lead line may be particularly sharply
.defined and indicate the level of the floor of the pocket

These effects are rarely seen nowadays because Mercury and

Bismuth are no longer used in medicine and Lead is no longer
.a major industrial hazard

.However, 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

Dry mouth: Is a relatively common side effect of some drugs, .3

particularly those with an Anticholinergic or Atropine like action,
such as the Tricyclic antidepressants which are widely used, MAO
inhibitors, Antihistamines, Phenothiazine antipsychotics (major
.tranquilizers)

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

However, 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 drug treatment.

However, it is essential to get a detailed history of drug treatment
.as this may affect other aspects of dental treatment