Download - 5ee1 adverse drug reaction
A• ADVERSE
D • DRUG
R• REACTIONS
ADVERSE DRUG REACTIONSWHO DEFINITION
Any noxious, unintended & undesired effect of a drugwhich occurs at a dose used in humansfor prophylactic, diagnostic or therapeutic
purposes
FDA Definition
an adverse event occurring in the course of the useof drug in professional practice
an adverse event from drug overdose whetheraccidental or intentional
an adverse event occurring from drug abuse
an adverse event from drug withdrawal
any significant failure of expected pharmacological action.
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
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)
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
• Type C
associated with long-term use
involves dose accumulation
e.g., NSAID induced nephropathy
• Type D
delayed effects (dose independent)
Carcinogenicity
Teratogenicity
Type E: End-of-use
◦ Withdrawal
◦ Related to discontinuation which is too abrupt
◦ Examples:
Addisonian crisis after steroid withdrawal
Angina pectoris after stopping -blockers
CLASSIFICATION OF ADRs
~According to SEVERITY~ Mild
Does not affect patient’s day-to-day activity
ModerateAffects patient’s day-to-day activity to some extent
SevereAdversely affects patient’s health may lead to death
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
2. SECONDARY EFFECTS
Indirect consequences of a primary action
of the drug.
a.Super infection due to tetracyclines.
b.Latent tuberculosis activated by
corticosteroids.
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
Poisons and Poisoning
chemical
substance that
endangers life by
affecting one or
more vital functions
of the body.
Accidental?
Suicidal Homicidal
Deliberate?
hypersenstivity:
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
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
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
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.
Psychological dependencedevelops when the individualsbelieve that optimal state ofwell being is achieved throughthe action of the drug.
It results in compulsive druguse in some individuals.
Intensity of dependence varyfrom desire to craving.
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.
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 acondition resulting from therepeated consumption of adrug.
Its characteristics include:
1) A desire (but not acompulsion)to continue takingthe drug for the sense
of improved wellbeing which itengenders:
2) Little or no tendency to increasethe dose;
3) Some degree of psychicdependence on the effect of thedrug,but absence of physicaldependence and hence of anabstinence syndrome;
Addiction habituation
Teratogenicity
Definition :
Ability of a drug to
cause fetal
abnormalities when
administered to a
pregnant women.
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
Sun burn
HyperpigmentationDesquamation
Contact Dermatitis
Iatrogenic disease
Any adverse condition in apatient occurring as the resultof treatment by a physician,surgeon, or other healthprofessional, especiallyinfections acquired by the patientduring the course of treatment.
drug induced / physician induced disease.
Ex.,hepatitis by isoniazid
Peptic ulcer by salicylates and corticosteroid.
Carcinogenicity &
mutagenicity.
"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.
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 earliestknown adverse/side effect involved the use oftetracycline.
The administration of tetracycline to pregnantwomen resulted in tooth staining/discolorationin their children. It resulted in yellow brownstains on the teeth of these children.
Most common oral effects of medicationsinclude dry mouth, a common condition thatmay lead to decay of teeth, opportunisticinfections like candidiasis and/or difficulty inspeaking and swallowing. .
Contact stomatitis
It is a localized reaction of the oralmucosa usually after repeated contactwith the causative agent.
It may result in erythema or ulcerativelesions with or without burning sensation.
The reaction may occur as early as oneday after the drug usage
Antibiotics, iodine, mouthwashes,toothpastes, certain cosmetics, etchave the potential to cause contactsomatitis.
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.
Dry mouth Certain drugs such as sedatives,
anticholinergics, omeprazole, anticancer drugs, antidepressants etccause dry mouth as these affect thefunction of the saliva glands reducing thesaliva.
Some of the common problemsassociated with it are burning sensation,constant sore throat, speech problems,difficulty in swallowing and hoarseness.
Drugs that cause xerostomia mostcommonly are benzodiazepines,morphine, calcium channel blockers,etc
Teeth discoloration Tooth discoloration may be intrinsic or
extrinsic. Intrinsic stains are usually caused by
drugs which are taken during and affectthe tooth development, more so duringthe stages of enamel and dentinformation. Such drugs, for example,tetracycline gets accumulated in thedentin and enamel of the developingtooth and appears as yellow or brownstains on the tooth.
Extrinsic stains are the ones which aretaken up by the tooth after development.These include tea and coffee stains andstains caused by some drugs such aschlorhexidine, tobacco
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.
Burning mouth syndrome
This syndrome may occur due to hormonalwithdrawal, iron or vitamin deficiencies,psychogenic factors or hypersensitivityreactions to various dental materials ordrugs.
Glossitis
Glossitis or inflammation of the tongue ischaracterized by intense pain and swellingthat may be referred to the ear. It usuallyresults in difficulty in speaking, swallowingalong with systemic signs such fever andenlarged lymph nodes. Glossitis though not acommon side effect is usually associated withpenicillin, bleomycin, lansoprazole, etc.
Oral Ulceration More commonly referred to as burns of
the oral mucosa. Aspirin, cocaine,hydrogen peroxide, phenytoin,penicillin, etc can cause either localirritation or ulceration in the oral cavity.
Ptyalism Some drugs alter the function of salivary
glands by increasing the rate offormation of saliva, commonly known asptyalism. The saliva is thin and waterywithout its usual buffering propertiesleading to decay of hard and soft tissuesof the oral cavity. Example: pilocarpine
Drug induced Gingival hyperplasia
It is the painless overgrowth of the gingivaltissues, usually the interdentally papilla ismore affected, later extending to other areasof the gingival.
The common drugs causing the drug inducedgingival enlargement are cyclosporine,phenytoin, calcium channel blockers likenidefine and oral contraceptives.
Reducing the dose of the offending drugalong with the maintenance of good oralhygiene usually suffices the treatment forgingival hyperplasia. In severe casescomplete stoppage and/or changing to analternative drug is required to treat the case.
Taste disturbance
this may include alteration in taste by reducingthe sensitivity in taste perception, or a total lossof taste or a disturbance in correct identificationof taste.
Drugs that are capable of affecting/altering thetaste sensation are aspirin, cetrizine, variousantibiotics like penicillamine, ofloxacin,metronidazole, etc.
Halitosis
Halitosis or bad breadth can result from poor oralhygiene, ingestion of certain drugs, use oftobacco products, oral or dental infections, andsome systemic disorders. Sublingual nitrateand disulfiram have the potential to causehalitosis.
Oral candidiasis
At times the systemic drug therapy alters theoral micro flora predisposing the mouth tovarious bacterial and fungal infections. Alsothe drugs that reduce/suppress the immunityof the individual make the individualsusceptible to opportunistic infections suchas candidiasis. Such drugs includecorticosteroids, antimicrobials,immunosuppressive agents, anticancerdrugs,
Abnormal bleeding
Abnormal bleeding is caused by drugs suchas aspirin, NSAIDs, anticoagulants andsteroids which thin the blood, used inconditions of stroke, myocardial infarctionsand arrhythmias
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.
Aphthous ulcer treatment
Treatment is symptomatic andincludes oral pain relievers, mouthrinses, topical creams with or withoutsteroids, diphenhydramine, andtetracycline suspension mixed withnystatin and diphenhydramine.
Aphthasol is a new topical drug which decreases the duration of healing and ulcer pain.