Adverse Drug Reactions

Adverse Drug Reactions (ADRs)

• A response to a medicinal product that is
noxious or potentially harmful and
unintended and which occurs at doses
normally used in human for prophylaxis,
diagnosis or therapy of a disease or for the
modification of physiological function in which
individual factors may play an important role.
 Cont…
• The meaning of this expression differs from
the meaning of "side effect", as this last
expression might also imply that the effects
can be beneficial. The study of ADRs is the
concern of the field known as
pharmacovigilance.
 My note
• Pharmacovigilance (abbreviated PV or PhV) is the pharmacological
science relating to the detection, assessment, understanding and
prevention of adverse effects, particularly long term and short term side
effects of medicines. Generally speaking, pharmacovigilance is the science
of collecting, monitoring, researching, assessing and evaluating
information from healthcare providers and patients on the adverse effects
of medications, biological products, herbalism and traditional medicines
with a view to:
• identifying new information about hazards associated with medicines
• preventing harm to patients
 Examples of ADRs include:
Medicines
• Erythromycin estolate
(antibacterial)
• Oral contraceptives
• Statins (for controlling
cholesterol)
• Thalidomide (for managing
morning sickness)
Reactions
• hepatitis (liver disorder)
• thromboembolism (blood
clots)
• muscle degeneration
• phocomelia (disfigured
infants)
 Classification

• ADRs may be classified as:

Type A: Augmented pharmacologic effects - dose
dependent and predictable ,management is by dosage
adjustment.
Type B: Bizarre effects (or idiosyncratic) - dose independent
and unpredictable,managanament is by stoping the drug.
Other types:
Type C: Chronic effects
Type D: Delayed effects
Type E: End-of-treatment effects
Type F: Failure of therapy
 Predisposing factors
• Multiple drug therapy
• Age
• Gender:female more prone to Adr.probably due to..gender related
differences in pharmacokinetics,and hormonal factors

• Intercurrent of disease:impared renal/hepatic function

• Race/genetic polymorphism:genes for drug metabolizing
enzymes,drug receptors and drug transporters.
 MECHANISM OF ADVERSE DRUG
REACTIONS.
• TYPE A:
pharmaceutical causes: dosage form-quantity of
drug/its release partens.
pharmacokinetic causes: ADME
Absorption-factor influence :-dosage form,pharmaceutical
factors,GIT factors,first pass metabolism
Distribution-blood flow, plasma protein and tissue binding
Elimanation-drug toxicity(reduced elimination),therapeutic
failure (enhanced elimination)
Metabolism-phase i(oxidation ,reduction, hydrolysis),phase
ii (sulphonation, glucuronidation, acetylation, methylation)
 Cont..
pharmacodynamics:
ADR which are dose related have a pharmacokinetics basis,
Some due to altered sensitivity of target organs/tissues
In Some people, the ADR May results from combination of two mechanism
 Cont…
TYPE B:
pharmaceutical causes: degradation of an active
ingredients, effect of non drug components, the effect of synthetic by
product of Active Pharmaceutical ingredients (API).
pharmacokinetic causes:
ADME}differ in orally bioavailability due to genetics
polymorphism of some genes eg..for transporter.
Pharmacodynamic causes:
mainly genetically abnormality eg G6PD(stability of red
blood cells)
 Cont..
...Exposed to hemolysis with oxidant drugs like
primaquine,sulphonamides.
Type C; Malignant hyperthermia: rise in temperature 2degree/hour
E.g anaethetics/muscle relaxants.

Type D; Delayed adverse effects of drugs: effect may be produced

after years eg. Phenothiazine- melanin deposits in lens and cornea.
Type E; Adverse effect associated with case withdrawal: e.g.
benzodiazepines ,rebound hypertension eg clonidine, acute adrenal
insufficiency on acute withdrawal of corticosteroids.
 DETECTION AND MORNITORING ADR

• Case reports, series in medical journals

• Cohort studies: monitor effect of drugs on a large group of
patients
• Case-control studies: effect of drug on people with deceased and
the one who are not.
• Spontaneous reporting schemes:
doctors,nurses,pharmacist,patient-to report any ADR
 MANAGING OF ADR
• An 81 year old man with an old valve
replacement and recent heart failure.

• Digoxin 0.25 mg daily

• Warfarin 4mg daily
• Frusemide 80 mg daily
• Potassium supplements
 CONT..
• Develops a deep bleeding ulcer
– Eventually looks like this:
 CONT..
• How serious is the patient's clinical state?
• If very serious:
– Stop all drugs which may POSSIBLY cause
condition
– Treat, as necessary
– Consider step-wise re-introduction, later
• If not serious:
– Proceed logically
 CONT..
• Diagnosis
– Possible bleeding tendency: over-
anticoagulated
• Action
– Stop warfarin
– Check prothrombin ratio
Stevens-Johnson syndrome and Toxic
epidermal necrosis
• Caused by nevirapine
stop offending drug
intravenous fluid replacement with
macromolecules/saline
the patient must be transferred to an
intensive care unit or a burn center.
 Cont..
• General principles:
• initiation of oral nutrition by nasogastric tube,
anticoagulation, prevention of stress ulcer,
and medication administration for pain and
anxiety control are all essential.
 PHARMACIST’S ROLE
• Ensure prescribing is safe
• Educate other health care professionals about prevention ,detection and
reporting ADR.
• Monitoring the patients who are in greater risk of developing ADR
• Monitoring the patient who are prescribed with highly susceptible to
cause ADR
• Assessing the patients drug therapy for its appropriateness
• Assessing and documenting the patients previous allergic status
• Assessing possible drug interaction in case of multiple therapies
• Educating the patient
• Conduct workshop/training/seminars on ADR for health personnel
• Obtain feed back about reported ADR.