adverse drug reactions

1. BY
Prathyusha.k
Pharm D II Yr

2. ADVERSE DRUG REACTIONS:
A response to a drug which is noxious &
Unintended & which occurs at normal doses used
in man.
ADVERSE DRUG EVENTS:
Any untoward medical occurance that may present
during treatment with a pharmaceutical
product(drug),but which does not necessarily have
a causal relationship with this treatment.

3.  WHO defined it as the “science & activities related
to the detection,assessment,understanding &
prevention ofadverse effects or any other drug
related problems.”
 The information generated by pharmacovigilance is
useful in educating doctors about ADRs & in the
official regulation of drug use.
 It has important role in rational use of medicines &
assessing safety of medicines.

4. ADRs can be minimised but not eliminated by
observing the following practices:
 Avoid all inappropriate use of drugs in the context
of patient’s clinical condition.
 Use correct dose,route & frequency of drug
administration based on patient’s specific
variables.
 Take into consideration about previous history of
drug reactions,allergic diseases &exercise
caution(drug allergy is more common in allergic
patients)

5.  Rule out possibility of drug interactions
when more than one drug is prescribed.
 Adopt correct drug administration technique
(eg:iv inj of vancomycin must be slow).
 Carry out appropriate laboratory monitoring
(serum drug levels with lithium).
SEVERITY OF ADVERSE DRUG REACTIONS:
Minor:No therapy,antidode or prolongation of
hospitalization is required.
Moderate:Requires change in drug therapy,specific
treatment or prolongs hospital stay atleast one
day.
Severe:Potentially life threatening,causes
permanent damage/requires intensive medical
treatment.
Lethal:Directly/indirectly contributes to death of
the patient.

7. Adverse drug effects may be categorized into:
1).Side effects:
Unwanted & unavoidable p’dynamic effects occurs
at therapeutic doses.
 Reduction of dose generally ameliorates the
symptoms.
 Side effects may be based on same action as the
therapeutic effect.
eg;Atropine is used as preanaesthetic for its
antisecretory action,the same action produces
dryness of mouth as side effect.
 Many drugs have been developed from observation
of side effects.eg;sulfonamides(antibacterial) used
as hypoglycemic sulfonylureas.

8.  These are indirect consequences of a primary
action of drug.
Eg;corticosteroids weekens host defence
mechanisms so that latent TB gets activated.
3).Toxic effects:
 Due to excessive p’cological action of the drug
due to overdose & prolonged use.The effects are
predictable & dose related.
 They result from functional alteration(high dose of
ATROPINE causes DELIRIUM)or drug induced tissue
damage(Hepatic necrosis from PARACETAMOL
overdose).

9. Poisoning:
 Due to large doses of drugs.
 Poison endangers life by severely affecting one or
more vital functions.
MEASURES:
 Resuscitation & maintenance of vital functions:
Adequate ventilation,artificial respiration,
maintenance of BP,heart beat,body temperature
& blood sugar level.
 Termination of exposure:
Removing patient to fresh air,washing skin &
eyes,induction of emesis with syrup ipecac/gastric
lavage [avoided in kerosine & CNS poisoning]

10.  Prevention of absorption of ingested poisons:
 20-40g(1g/kg) of activated charcoal suspension
should be administered in 200ml of water.
 Strong acids& alkalies,metallic salts,iodine,
cyanides,alcohol,organic solvents are not adsorbed
by charcoal.
 Hastening elimination:
Quick removal of poison from the body by
haemodialysis,inducing diuresis/altering urinary
pH.

11. 4).Intolerance:
known as inability to withstand/consume the drug.
Eg;only few doses of carbamazepine may cause
ataxia in some people.
5).Idiosyncrasy:
It is genitically determined abnormal reactivity to a
chemical.Peculiar to an individual because the drug
reacts with the specific gene which is specific to an
individual.
Eg;Barbiturates causes excitement & mental
confusion in some individuals.

12. 6).Drug allergy:
 A medical condition that makes a individual to
feel ill when a drug is taken.
 Allergic reactions occur only in a small proportion
of the population exposed to the drug & cannot be
produced in other individuals.
 Occur even with smaller doses & have a different
time course of onset & duration,also called as
HYPERSENSITIVITY but not supersensitivity.
 The drug/its metabolites acts as AG/HAPTEN &
induce production of AB/sensitized lymphocytes.
 They are of two types:HUMORAL & CELLMEDIATED.

13. A. HUMORAL:
 TYPE-I(anaphylactic)REACTIONS:
On exposure to the drug,AG:AB reaction takes
place on the mast cell surface releasing mediators
likehistamine,5HT,leukotrienes Prostaglandins
etc.,resulting in itching,
angioedema,bronchospasm,rhinitis.
 TYPE-II(cytolytic)REACTIONS:
Drug+component of a specific tissue cells act
as AG.The resulting antibodies(IgG,IgM)bind to the
target cells on reexposure AG:AB reaction takes
place on the surface of these cells,complement is
activated and cytolysis occurs.

14.  TYPE-III(retarded)REACTIONS:
AG:AB complexes bind complement & precipitate
on vascular endothelium giving rise to a destructive
inflammatory response.
Manifestations are rashes,serum sickness,mental
symptoms,myocarditis,
nephritis(usually in 1-2weeks)
B.CELL MEDIATED:
 TYPE-IV(delayed hypersensitivity)REACTIONS:
These are mediated through production of
sensitized T-lymphocytes carrying receptors for the
AG.They form inflammatory response.
Eg:dermatitis,rashes,fever,photosensitization
takes>12hrs to develop.

15. TREATMENT:
 Administration of oxygen.
 0.5mg adrenaline i.m injection.
 Administer a H1 antihistaminic i.m/slow i.v.
 I.V of glucocorticoids should be added in many
cases.
 Adrenaline followed by a short course of
glucocorticoids is indicated for bronchospasm
attending drug hypersensitivity.Glucocorticoids are
the only drug in type II,III,IV reactions.

16. 7).Photosensitivity:
It is a cutaneous reaction resulting from drug
induced sensitization of the skin to Uvrays.the
reactions are of two types:
a) Phototoxic:
Drugs/its metabolites accumulates in the
skin,absorbs light & undergoes a photochemical
reaction followed by a photobiological reaction
resulting in local tissue
damage.[edema,blistering etc drugs involved are
tetracyclines,thiazides]
b) Photoallergic:
Rarely AB mediate photoallergy & the
reaction takes form of flare&wheal on exposure
to sun drugs involved are
sulfonamides,chloroquines etc.

17. 8).Drug dependence:
It is a state in which use of drugs for personal
satisfaction is accorded a higher priority than
other basic needs,often in the face of known risks
to health.
a].Psychological dependance:individual believes
optimal state of wellbeing is achieved only
through the actions of the
drugs[cocaine,opioids,BZPs].
b].Physical dependance:an altered physiological
state produced by repeated administration of a
drug which necessitates the continued presence
of the drug to maintain physiological equilibrium.
 Discontinuation of the drug leads to withdrawl
syndrome.[BZDs,alcohol,cocaine].

18. c].Drug abuse:social disapproval of the manner
& purpose of drug use.
d].Drug addiction:strong physiological &
psycological dependence on a drug.
Eg;Narcotics,cocaine,Amphetamines.
e].Drug habituation:a psychological dependence
on drug due to repeated consumption with a
desire to continue its use,withdrawal produces
only mild discomfort.
Eg:coffee,tea,social drinking.

19. 9).Drug withdrawal reactions:
These reactions are produced when there
is sudden cessation of the drug or
interruption of therapy with certain other
drugs.
Eg;precipitation of MI may result from stoppage
of beta blockers.
10).Teratogenicity:
It refers to capacity of a drug to cause
foetal abnormalities when administered to the
pregnant mother.
Eg; Anticancer drug-cleft palate,multipledefects
Warfarindepressed nose,growth
retardation.

20. 11).Mutagenicity & Carcinogenicity:
The capacity of a drug to cause genitic
defects &cancer respectively.Usually oxidation of
the drug results in the production of reactive
intermediates which effects genes & may cause
structural changes in the chromosomes.
Eg;anticancerdrugs,tobacco,estrogens,radioisotope
s.
12).Drug induced diseases:
These are iatrogenic(physician
induced)diseases & functional
distrubances(disease)caused by drugs which
persists even after the offending drug has been
withdrawn & largely eliminated.
eg:peptic ulcer by salicylates & corticosteroids.

21.  If a new drug causes a bizarre effect in 1
in 6000 patients it would need 18000
patients to use the drug for it to occur in
3 patients
 It would take twice as many before there
was any suspicion that the effect was due
to the drug
 If the effect also occurs naturally then it
would take many times more patients
 Most early trials involve about 2000
patients

22.  MRHA (Medicine and Healthcare products
Regulatory Agency) freephone service for
reporting and information about suspected
ADRs
 Self reporting by patients and relatives
using Yellow cards available at pharmacies
 Prescription event monitoring
 New drugs – black triangles and yellow
cards
 Established drugs

26. References
 www.authorstream.com
 http://www.google.co.in/images
 Essentials of Medical pharmacology by K.D Tripathi
pg;no :78-86