ADVERSE DRUG REACTIONSBY

Prathyusha.kPharm D II Yr

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.

INTRODUCTION:

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.

PHARMACOVIGILANCE:

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)

Prevention of adverse effects to drugs:

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.

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.

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).

2).Secondary effects:

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]

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.

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.

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.

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.

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.

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.

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.

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].

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.

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 Warfarindepressed nose,growth retardation.

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,radioisotopes.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.

Detecting Adverse Effects 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

Detecting Adverse Effects

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

References

www.authorstream.com http://www.google.co.in/images Essentials of Medical pharmacology by K.D

Tripathi pg;no :78-86

THANK YOU….