The document discusses adverse drug reactions (ADRs), defining them as unintended harmful effects that occur from drugs used for treatment or diagnosis. It classifies ADRs into different types based on predictability (Type A/predictable vs. Type B/unpredictable) and timing (Type C associated with long-term use, Type D delayed effects, Type E withdrawal effects). It also discusses hypersensitivity reactions, drug abuse/dependence, teratogenicity, photosensitivity, iatrogenic disease, and effects on oral tissues like dry mouth, aphthous ulcers, and teeth discoloration.

1. A
• ADVERSE
D • DRUG
R • REACTIONS

2. ADVERSE DRUG REACTIONS
WHO DEFINITION
Any noxious, unintended & undesired effect of a drug
which occurs at a dose used in humans
for prophylactic, diagnostic or therapeutic
purposes
FDA Definition
 an adverse event occurring in the course of the use
of drug in professional practice
 an adverse event from drug overdose whether
accidental or intentional
 an adverse event occurring from drug abuse
 an adverse event from drug withdrawal
 any significant failure of expected pharmacological
action.

3. Classification
• Type A (predictable)
 extension of pharmacologic effect
 often predictable and dose dependent
 responsible for at least two-thirds of ADRs
 e.g. anticholinergics and dry mouth
• Type B (unpredictable)
 idiosyncratic or immunologic reactions
 rare and unpredictable
 e.g., chloramphenicol and aplastic anemia
 Penicillin induced anaphylactic shock

4. Predictable
Pharmacologic side effect Dry mouth from antihistaminics
Secondary pharmacologic side effect Thrush while taking antibiotics
Drug toxicity Hepatotoxicity from diclofenac
Drug-drug interactions Seizure from theophylline while taking
erythromycin (increased thephylline
level)
Drug overdose Seizure from excessive lidocaine
(Xylocaine)

5. Unpredictable
Pseudoallergic Anaphylactoid reaction after ASPIRIN
Idiosyncratic Hemolytic anemia in a patient with
G6PD deficiency after ciprofloxacin
therapy
Intolerance Tinnitus after a single, small dose of
aspirin

6. • Type C
 associated with long-term use
 involves dose accumulation
 e.g., NSAID induced nephropathy
• Type D
 delayed effects (dose independent)
 Carcinogenicity
 Teratogenicity

7.  Type E: End-of-use
◦ Withdrawal
◦ Related to discontinuation which is too abrupt
◦ Examples:
 Addisonian crisis after steroid withdrawal
 Angina pectoris after stopping -blockers

8. CLASSIFICATION OF ADRs
~According to SEVERITY~
 Mild
Does not affect patient’s day-to-day activity
 Moderate
Affects patient’s day-to-day activity to some
extent
 Severe
Adversely affects patient’s health may
lead to death

9. ADVERSE DRUG EFFECTS
1. Side Effects
 Unwanted but unavoidable
pharmacodynamic effects
occuring at therapeutic doses.
 Side effect may be based on same
action as therapeutic effect.
 Eg. Atropine and dry mouth
 Codeine and constipation

10. 2. SECONDARY EFFECTS
 Indirect consequences of a primary action
of the drug.
a.Super infection due to tetracyclines.
b.Latent tuberculosis activated by
corticosteroids.

11. 3. Idiosyncratic reactions
 Gentically determined abnormal reactivity to a
chemical.
 Chloramphenicol – aplastic anemia
4. INTOLERANCE
 Failure to tolerate even a single dose of the drug
 Appearance of characteristic toxic effects of a drug
in an individual at therapeutic doses.
 Aspirin - gastric bleeding

13. Poisons and Poisoning
 chemical
substance that
endangers life by
affecting one or
more vital functions
of the body.

14. Accidental?
Suicidal Homicidal

15. Deliberate?

16. hypersenstivity:

17. Immunological
Type I reaction (IgE-mediated)
Anaphylaxis from
β-lactam antibiotic
Type II reaction (cytotoxic) Hemolytic anemia from
penicillin
Type III reaction (immune complex) SLE, RHEUMATOID
ARTHRITIS
Type IV reaction (delayed, cell-mediated) Contact dermatitis from
topical antihistamine

18. Immune reaction Mechanism Clinical
manifestation
Timing of
reactions
Type I (IgE-mediated) Drug-IgE complex
binding to mast cells
with release of
histamine,
inflammatory
mediators
Urticaria, angioedema,
bronchospasm,
pruritus, vomiting,
diarrhea, anaphylaxis
Minutes to hours after
drug exposure
Type II (cytotoxic) Specific IgG or IgM
antibodies directed at
drug-hapten coated
cells
Hemolytic anemia,
neutropenia,
thrombocytopenia
Variable
Type III (immune
complex)
Tissue deposition of
drug-antibody
complexes with
complement activation
and inflammation
Serum sickness,
fever, rash,
arthralgias,
lymphadenopathy,
urticaria,
glomerulonephritis,
vasculitis
1 to 3 weeks after
drug exposure
Type IV (delayed,
cell-mediated)
MHC presentation of
drug molecules to T
cells with cytokine and
inflammatory mediator
release
Allergic contact
dermatitis,
2 to 7 days after
cutaneous drug
exposure

19. Drug abuse
 It is the use of a drug for a
nontherapeutic effect.
 Some of the most commonly abused drugs
are alcohol; nicotine; marijuana;
amphetamines; barbiturates;
cocaine;opium alkaloids; synthetic opioids;
benzodiazepines, phencyclidine; ketamine;
and anabolic steroids.
 Drug abuse may lead to organ damage,
addiction, and disturbed patterns of
behavior.
 Use of these drugs often incurs criminal
penalty in addition to the potential for
physical, social, and psychologic harm

20. Drug dependence
 Drug dependence is the body's
physical need, or addiction, to a
specific agent.
 It is a state in which use of
drugs for personal satisfaction
often in the face of known risk
to health.
Types:
 Psychological dependence
 Physical dependence.

21. Psychological dependence
develops when the individuals
believe that optimal state of
well being is achieved through
the action of the drug.
 It results in compulsive drug
use in some individuals.
 Intensity of dependence vary
from desire to craving.

22. Physical dependence
 it is manifested by a withdrawal
(abstinence) syndrome, in which
untoward physical effects occur when the
drug is stopped or when its effect is
counteracted by a specific antagonist.
 Drugs that cause strong physical
dependence include heroin, alcohol,
benzodiazepines, and cocaine.
Reinforcement :
Ability of the drug to produce effects that make the
user wish to take it again.
Ex., opiods,cocaine,LSD,benzodiazepines.

23. Drug addiction Drug habituation
 Drug addiction is a state of periodic
or chronic intoxication produced by
the repeated consumption of a drug
(natural or synthetic).
Its characteristics include:
1) An overpowering desire or need
(compulsion) to continue taking the
drug and to obtain it by any means;
2) A tendency to increase the dose;
3) A psychic (psychological) and
generally a physical dependence
on the effects of the drug;
 Drug habituation (habit) is a
condition resulting from the
repeated consumption of a
drug.
Its characteristics include:
1) A desire (but not a
compulsion)to continue taking
the drug for the sense
of improved wellbeing which it
engenders:
2) Little or no tendency to increase
the dose;
3) Some degree of psychic
dependence on the effect of the
drug,but absence of physical
dependence and hence of an
abstinence syndrome;

24. Addiction habituation

25. Teratogenicity
 Definition :
 Ability of a drug to
cause fetal
abnormalities when
administered to a
pregnant women.

26. PHOTOSENSITIVITY
 Cutaneous reaction resulting from drug induced
sensitisation of the skin to UV radiation
 Phototoxic
◦ Photochemical
◦ Erythema, edema, hyperpigmentation, desquamation
◦ Fluroquinolones, sulfonamides, tetracyclines,
ibuprofen, naproxen
 Photoallergic
◦ Cell mediated immune reaction
◦ Papule or contact dermatitis
◦ Sulfonamides, ketoprofen, and celecoxib, grasofulvin

27. Sun burn

28. Hyperpigmentation Desquamation

29. Contact Dermatitis

30.  Any adverse condition in a
patient occurring as the result
of treatment by a physician,
surgeon, or other health
professional, especially
infections acquired by the patient
during the course of treatment.
 drug induced / physician
induced disease.
 Ex.,hepatitis by isoniazid
 Peptic ulcer by salicylates and
corticosteroid.
Iatrogenic disease

31.  "The term carcinogen denotes a chemical
substance or a mixture of chemical substances
which induce cancer or increase its incidence“
 Mutagen is An agent, such as a chemical,
ultraviolet light, or a radioactive element, that can
induce or increase the frequency of mutation in
an organism.
Carcinogenicity &
mutagenicity.

32. Effects of Medication on Oral
Tissues
 Most but not all drugs have effect on the
health of oral .
 One of the most common and the earliest
known adverse/side effect involved the use of
tetracycline.
 The administration of tetracycline to pregnant
women resulted in tooth staining/discoloration
in their children. It resulted in yellow brown
stains on the teeth of these children.
 Most common oral effects of medications
include dry mouth, a common condition that
may lead to decay of teeth, opportunistic
infections like candidiasis and/or difficulty in
speaking and swallowing. .

33.  Contact stomatitis
 It is a localized reaction of the oral
mucosa usually after repeated contact
with the causative agent.
 It may result in erythema or ulcerative
lesions with or without burning sensation.
 The reaction may occur as early as one
day after the drug usage
 Antibiotics, iodine, mouthwashes,
toothpastes, certain cosmetics, etc
have the potential to cause contact
somatitis.

35. aphthous ulcers
 aphthous ulcers or more commonly
known as the canker sores. These are
tiny, painful lesions which occur either
singly or in groups on the labial or buccal
mucosa.
 These usually heal without scar
formation within 14 days.
 Various drugs including NSAIDs,
captopril, losarton and penicillamine
can cause aphthous ulcers.

36.  Dry mouth
 Certain drugs such as sedatives,
anticholinergics, omeprazole, anti
cancer drugs, antidepressants etc
cause dry mouth as these affect the
function of the saliva glands reducing the
saliva.
 Some of the common problems
associated with it are burning sensation,
constant sore throat, speech problems,
difficulty in swallowing and hoarseness.
 Drugs that cause xerostomia most
commonly are benzodiazepines,
morphine, calcium channel blockers,
etc

37. Teeth discoloration
 Tooth discoloration may be intrinsic or
extrinsic.
 Intrinsic stains are usually caused by
drugs which are taken during and affect
the tooth development, more so during
the stages of enamel and dentin
formation. Such drugs, for example,
tetracycline gets accumulated in the
dentin and enamel of the developing
tooth and appears as yellow or brown
stains on the tooth.
 Extrinsic stains are the ones which are
taken up by the tooth after development.
These include tea and coffee stains and
stains caused by some drugs such as
chlorhexidine, tobacco

38. Oral pigmentation
 Pigmentation may occur either due to
systemic absorption or local use of drugs
in the oral cavity.
 Pigmentation has been reported in cases
taking mercury, arsenic, gold, cupper,
zinc etc, especially around the gingival
margins around the teeth.
 These are more prominent in the
presence of plaque and inflammation.
 These may be temporary or permanent
but usually most of the pigmentation
disappears with the discontinuation of
the drug.

39.  Burning mouth syndrome
This syndrome may occur due to hormonal
withdrawal, iron or vitamin deficiencies,
psychogenic factors or hypersensitivity
reactions to various dental materials or
drugs.
 Glossitis
Glossitis or inflammation of the tongue is
characterized by intense pain and swelling
that may be referred to the ear. It usually
results in difficulty in speaking, swallowing
along with systemic signs such fever and
enlarged lymph nodes. Glossitis though not a
common side effect is usually associated with
penicillin, bleomycin, lansoprazole, etc.

41.  Oral Ulceration
 More commonly referred to as burns of
the oral mucosa. Aspirin, cocaine,
hydrogen peroxide, phenytoin,
penicillin, etc can cause either local
irritation or ulceration in the oral cavity.
 Ptyalism
 Some drugs alter the function of salivary
glands by increasing the rate of
formation of saliva, commonly known as
ptyalism. The saliva is thin and watery
without its usual buffering properties
leading to decay of hard and soft tissues
of the oral cavity. Example: pilocarpine

42.  Drug induced Gingival hyperplasia
 It is the painless overgrowth of the gingival
tissues, usually the interdentally papilla is
more affected, later extending to other areas
of the gingival.
 The common drugs causing the drug induced
gingival enlargement are cyclosporine,
phenytoin, calcium channel blockers like
nidefine and oral contraceptives.
 Reducing the dose of the offending drug
along with the maintenance of good oral
hygiene usually suffices the treatment for
gingival hyperplasia. In severe cases
complete stoppage and/or changing to an
alternative drug is required to treat the case.

44.  Taste disturbance
 this may include alteration in taste by reducing
the sensitivity in taste perception, or a total loss
of taste or a disturbance in correct identification
of taste.
 Drugs that are capable of affecting/altering the
taste sensation are aspirin, cetrizine, various
antibiotics like penicillamine, ofloxacin,
metronidazole, etc.
 Halitosis
 Halitosis or bad breadth can result from poor oral
hygiene, ingestion of certain drugs, use of
tobacco products, oral or dental infections, and
some systemic disorders. Sublingual nitrate
and disulfiram have the potential to cause
halitosis.

45.  Oral candidiasis
 At times the systemic drug therapy alters the
oral micro flora predisposing the mouth to
various bacterial and fungal infections. Also
the drugs that reduce/suppress the immunity
of the individual make the individual
susceptible to opportunistic infections such
as candidiasis. Such drugs include
corticosteroids, antimicrobials,
immunosuppressive agents, anticancer
drugs,
 Abnormal bleeding
 Abnormal bleeding is caused by drugs such
as aspirin, NSAIDs, anticoagulants and
steroids which thin the blood, used in
conditions of stroke, myocardial infarctions
and arrhythmias

47.  Alveolar osteitis or, a dry socket, is a
complication of wound healing following extraction
of a tooth. It is known as "dry socket" as after the
clot is lost, the socket has dry appearance
because of exposed bone. The blood clot helps in
stopping the bleeding and lays framework for new
tissues to develop there but in case of dry socket,
the clot is dislodged and the bone is exposed. This
bare bone is exposed to bacteria in the saliva and
the food which the patient consumes and the bone
becomes infected and painful. The uses of oral
contraceptives have also been associated with
significant increase in the frequency
of dry socket.

48. Aphthous ulcer treatment
 Treatment is symptomatic and
includes oral pain relievers, mouth
rinses, topical creams with or without
steroids, diphenhydramine, and
tetracycline suspension mixed with
nystatin and diphenhydramine.
 Aphthasol is a new topical drug which
decreases the duration of healing and
ulcer pain.