W19 69 adverse drug reactions and the oral mucosa

Question 1

What are the 2 types of adverse drug reactions?

Answer 1

Type A reactions (augmented) - exaggerated effected to what was intended
Type B reactions (bizarre) - bizarre, not exaggerated
(most oral ADRs are likely to be Type B)

Question 2

Are ADRs systemic or local?

Answer 2

Some oral ADRs will be part of a wider systemic manifestation, eg Stevens Johnson syndrome
Some drug eruptions will also be only one part of wider multi organ involvement, eg drug induced lupus

Question 3

How do we detect an ADR was caused by the drug?

Answer 3

Challenge - at or after treatment started?
‘De-challenge’ - did it stop when treatment stopped?
‘Re-challenge’ - began again on re-starting
Known with drugs but not disease.

Question 4

Why is detecting ADRs difficult?

Answer 4

Reactions are rare, like treated illness, novel, delayed, affect offspring

Question 5

How can dermatological ADRs manifest?

Answer 5

Skin reactions
Mucocutaneous changes (in oral mucosa)
Severe ones might involve lips and peri-oral area (angioedema)

Question 6

What drug classes have increased frequencies of drug eruptions?

Answer 6

NSAIDs, Abx (antibiotics), AEDs (anti epileptic drugs)

Question 7

List the specific adverse effects that occur in the oral cavity from drugs

Answer 7

Tooth staining/discolouration
Mucosal pigmentation
Drug-induced gingival overgrowth
Drug-induced thrombocytopenia
Drug-induced oral ulceration
Fixed drug eruptions
Generalised oral mucositis
Lichenoid reactions
Oral candidiasis
Drug-induced taste disorders
Salivary glands
Xerostomia
Hypersalivation (sialorrhoea or ptyalism)
Sialadenitis
Angioedema
Drug-induced vesticulo-bullous disorders
Stevens-Johnson syndrome

Question 8

What might cause tooth staining/discolouration?

Answer 8

Chlorhexidine - brown staining
Iron salts - stain enamel black
Co-amoxiclav suspension - superficial staining
Tetracyclines - yellowish (intrinsic) staining
Fluoride (excessive ingestion) - dental fluorosis - white speckling on teeth

Question 9

How might drugs cause mucosal pigmentation?

Answer 9

Via accumulation of melatonin, iron or drug metabolites within the mucosa

Question 10

What drugs might cause mucosal pigmentation?

Answer 10

Amiodarone
Bleomycin
Chloroquine
Chlorpromazine
Gold
Hydroxychloroquine
Mepacrine
Methyldopa
Minocycline
Premarin
Quinidine

Question 11

What is drug-induced gingival overgrowth?

Answer 11

Characterised by inflammatory overgrowth (hypertrophy) of soft tissue between the teeth (buccal and labial gingivae predominant)
Can induce abnormal fibrogenesis of the gums causing the appearance
Characteristic thickened, lobulated appearance

Question 12

What are some associated symptoms of drug-induced gingival overgrowth?

Answer 12

Pain, tenderness, bleeding of the gums
Negates people from brushing - can mask gingivitis

Question 13

What drugs can cause drug-induced gingival overgrowth?

Answer 13

Nifedipine (and other dihydropyridine CCBs)
Ciclosporin
Phenytoin

Question 14

Pathologically what do the drugs do to cause gingival overgrowth?

Answer 14

Cause dysregulation of cytokines and growth factors leading to fibrosis and hypercellularity.
Usually occurs within 1-3 months of starting drugs.

Question 15

What drugs can cause drug-induced thrombocytopenia?

Answer 15

Quinine (rarely used, for malaria)
Sulphonamides (rarely)
Heparin

Question 16

What might thrombocytopenia cause in the oral cavity?

Answer 16

Bleeding at the gingival margins, which may be spontaneous or may follow mild trauma (eg tooth brushing)

Question 17

What is the effect of drugs causing the thrombocytopenia?

Answer 17

Accelerated platelet destruction

Question 18

What drugs can cause drug-induced oral ulceration?

Answer 18

Methotrexate
Nicorandil - can cause widespread ulceration
NSAIDs
Gold
Penicillamine

Question 19

What are the different effects that can occur of drugs causing drug-induced oral ulceration?

Answer 19

Oral use of caustic agent can cause erosions and ulcers
Chemical burns (eg prolonged buccal administration) can cause local lesions

Question 20

How can you treat the symptoms of drug-induced oral ulceration?

Answer 20

Symptomatic treatment with topical benzydamine +/- chlorhexidine

Question 21

What are fixed drug eruptions and how can they manifest?

Answer 21

FDEs are recurrent site-specific lesions on the skin and/or mucosa each time the responsible drug is taken.
They can manifest as mouth ulcerations, particularly on repeated exposure to the causative agent.

Question 22

What drugs can cause fixed drug eruptions?

Answer 22

Barbiturates, NSAIDs, sulfonamides and tetracyclines

Question 23

What is generalised oral mucositis?

Answer 23

Chemotherapy-associated mucositis and ulceration often widespread.
Sloughing and oedema (accelerated detachment of oral epithelial cells)
Immunsuppression increases susceptibility to oral infections
Grades into 4 stages, with 1 being soreness and redness but no ulcerations, and 4 being ulceration so bad patients can eat solids only fluids.

Question 24

What are lichenoid reactions?

Answer 24

Identifiable causes of lichen planus
Eg drug induced lichen planus = lichenoid reaction

Question 25

What is lichen planus?

Answer 25

Autoimmune, mucocutaneous disorder with oral, genital and or skin lesions (typically white).
Affects the T cells.

Question 26

How does a lichenoid reaction typically present?

Answer 26

Typical striae (Wickhams striae) on the mucosa

Question 27

What are drugs can cause lichenoid reactions/lichen planus?

Answer 27

NSAIDs, antihypertensives (all classes), dental amalgams, penicillamine, anti-malarials

Question 28

What is oral candidiasis?

Answer 28

Fungal overgrowth - disruption of normal oral flora.
Superficial infection of the oral mucosa.
Presents as creamy white patches easily scraped from epithelium.

Question 29

What can cause pseudomembranous candidiasis (thrush)?

Answer 29

Use of broad spectrum antibiotics
Immunosuppressants (including corticosteroids)
Cytotoxic therapies

Question 30

What are the different types of taste disorders?

Answer 30

Dysgeusia - distorted taste eg sweet things taste sour
Hypogeusia/ageusia - blunted or lost taste
Parageusia - perverted taste eg a sense of splint food instead of normal

Question 31

If not an abscess, taste disorders are usually drug-induced. What drugs can cause taste disturbances?

Answer 31

Captopril (and other ACE inhibitors)
Calcium channel blockers
Clopidogrel
Griseofulvin
Omeprazole
Penicillamine
Terbinafine

Question 32

A metallic taste is usually a frequent complaint. What drugs can cause a metallic taste?

Answer 32

Amiodarone, gold compounds, lithium salts, metformin metronidazole, tetracyclines and zopiclone

Question 33

What drugs might reduce flow from the salivary glands causing xerostomia?

Answer 33

Particularly antimuscarinics (anticholinergics), antidepressants (TCAs, SSRIs), baclofen, clonidine and tizanidine
Excessive use of diuretics

Question 34

Which drugs can increase saliva production from the salivary glands (rarely a problem unless pt has associated difficulty in swallowing)?

Answer 34

Clozapine, neostigmine

Question 35

What drugs can cause pain in salivary glands?

Answer 35

Some antihypertensives (clonidine, Methyldopa)
Vinca alkaloids

Question 36

Many many (>500) drugs are implicated for drug-induced xerostomia. What patients and drugs especially?

Answer 36

Elderly patients, patients treated for cardiac disease (esp diuretics) or mental illness, or palliative patients
Anticholinergic drugs (M3 muscarinic receptors) are a very common cause of xerostomia

Question 37

What can xerostomia cause?

Answer 37

Tongue or mucosal cracking, increasing the risk of secondary infection

Question 38

What is the symptomatic treatment of xerostomia?

Answer 38

Chewing sugar free gun
Sialogogue (eg pilocarpine)
Mouthwashes to alleviate discomfort
Saliva substitutes (for short periods)

Question 39

What is another word for hypersalivation?

Answer 39

Sialorrhea or pytalism

Question 40

What drugs can cause hypersalivation/sialorrhea/ptyalism)?

Answer 40

Parasympathomimetics (eg pilocarpine)
Antipsychotics eg clozapine

Question 41

What is pilocarpine usually used for?

Answer 41

The treatment of xerostomia following irradiation for head and neck cancer

Question 42

What is hypersalivation sometimes treated with?

Answer 42

Amitriptyline or antimuscarinics

Question 43

What is Sialadenitis?

Answer 43

Inflammation/enlargement of the major salivary glands

Question 44

What drugs can cause sialadenitis?

Answer 44

ACE inhibitors
Antithyroid drugs
Methyldopa
Sulfonamides
Phenothiazines
Protease inhibitors

Question 45

What is angioedema?

Answer 45

Localised swelling of lipids, tongue and mucous membranes of the mouth

Question 46

What drug varieties might cause angioedema (unrelated to anaphylaxis)?

Answer 46

ACE inhibitors
Angiotensin receptor blockers (more rarely)
NSAIDs

Question 47

What diseases cause vesiculobullous lesions?

Answer 47

Pemphigus vulgaris = intraepithelial blisters which rupture to form painful erosions
Pemphigoid = tense bullae that heal without scarring

Question 48

What drugs can mimic vesiculobullous diseases causing drug-induced vesiculobullous disorders?

Answer 48

Penicillamine

Question 49

Mucous membranes of the mouth often involved in erythema multiforme. What is the severe form of this called?

Answer 49

Stevens-Johnson syndrome

Question 50

How might SJS be life-threatening?

Answer 50

If widespread and life threatening = TEN - toxic epidermal necrolysis
Massive mucous membrane ulceration throughout the whole gut. Might affect genitals, eye mucosa (conjunctivitis), oral ulceration

Question 51

What drugs might cause SJS?

Answer 51

Antibiotics (esp penicillins and sulfonamides)
Anti-epileptic drugs (eg carbamazepine)

Question 52

How are most ADRs resolved/managed?

Answer 52

Cessation of the drug
Good oral hygiene and pain relief where necessary