Adverse drug interactions

1. Adverse Drug Reactions

2. Adverse Drug Reactions
• It is a response to a drug which is noxious & unintended & which
occurs at dose normally used in man/animals for prophylaxis,
diagnosis or therapy of disease or modification of physiological
functions.

3. ADVERSE DRUG EVENTS
• It is an injury resulting from the use of a drug.
• The term Adverse drug event includes harm caused by the drug
(adverse drug reactions & over doses) and harm from the use of the
drug (including dose reductions and discontinuation of drug therapy)

4. MEDICATION ERRORS
• Medication errors are mishaps that
occur during prescribing, dispensing,
administering, or monitoring a drug.
• Medication errors are more common
than adverse drug events.
• About 25% of adverse drug events are
due to medication error.
• This figure shows the relation between
medication errors, adverse drug events
& adverse drug reactions.

5. ADVERSE DRUG EFFECT
• Any undesirable or unintended consequence of drug administration.
• It is a broad term, includes all kinds of noxious effects:
• All drugs are capable of producing adverse effects & whenever a drug
is given a risk is taken.
• The magnitude of risk has to be considered along with the magnitude of
expected therapeutic benefit in deciding whether to use or not to use a
particular drug in a given patient.
• e.g. risk of bone marrow depression may be justified in treating cancer,
while mild drowsiness caused by an antihistaminic in treating common
cold is unacceptable.
• Adverse effects may develop promptly or only after prolonged
medication or even after stoppage of the drug.
• Adverse effects are not rare, an incidence of 10-25% has been
documented.
• They are more common with multiple drug therapy and in elder
patients.

6. CLASSIFICATION
• TYPE A (AUGMENTED OR PREDICTABLE REACTION)
• These are based on the pharmacological properties of drug and are dose
related.
• These are mostly preventable and reversible; It includes :-
a. Side effects
b. Toxic effects
c. Intolerance
• TYPE B (UNPREDICTABLE REACTIONS)
• These are based on peculiarities (genotype) of the patient and not on the
drug dose.
• These are less common , generally more serious & require withdrawal of
the drug. It includes :-
1. Allergy
2. Idiosyncrasy

7. • TYPE C Reaction
• These reactions occur due to chronic effect of drug.
• TYPE D
• These are delayed adverse effect of drug.
• TYPE E
• These adverse effects appear at the end of treatment.
• TYPE F
• These adverse effects are associated with failure of treatment.
• TYPE G
• These adverse effects are produced due to effect of drug on genes.
• Type A & B were proposed in 1970 & other types were
proposed subsequently.

8. SEVERITY OF ADVERSE DRUG
REACTION
• MINOR
• No therapy , antidote or prolongation of hospitalization is
required.
• MODERATE
• It requires change in drug therapy, specific treatment or
prolong hospital stay by at least one day.
• SEVERE
• It is life threatening, cause permanent damage or requires
intensive medical treatment.
• LETHAL
• It directly or indirectly contributes to death of the patient.

9. PHARMACOVIGILANCE
• Parmacovigilance has been defined by the WHO as the science &
activities relating to the detection, assessment, understanding &
prevention of adverse effects or any other drug related problems.
• The information generated is useful in educating doctors about ADRs
& in the official regulation of drug use

10. The Activities Involved In Pharmacovigilance
• Premarketing surveillance
• It is done during clinical trials of drug.
• Side-effects & ADRs are often unknown at the time drug enters the market because clinical
trials involve some thousands patients only.
• Postmarketing surveillance
• It includes:
• i. Voluntary reporting by doctors
• ii. Prescription event monitoring
• iii. Computerized medical records monitoring
• iv. Case control studies.
• Dissemination of ADR data through ‘drug alerts’ ‘medical letters’ advisories sent to
doctors by pharmaceuticals and regulatory agencies (such as FDA in USA).
• Changes in the labelling of medicines indicating restrictions in use or warnings,
precautions, or even withdrawal of drug.
• Pharmacovigilance centers have been set up in most countries, The Uppsala Monitoring
Centre (Sweden) is the international collaborating centre.

11. SIDE EFFECTS
• These are unwanted but often unavoidable pharmacodynamic effects that
occur at therapeutic doses.
• A side effect may be based on the same action as the therapeutic effect.
e.g.
a) Atropine is used in preanaesthetic medication for its antisecretory
action, the same action produces dryness of mouth as a side effect.
b) Acetazolamide acts as diuretic by promoting bicarbonate excretion
acidosis occur as side effect.
• An effect may be therapeutic in one context but side effect in another
context.
• E.g. Codeine used for cough produces constipation as a side effect but
the latter is its therapeutic effect in travelers diarrhea

12. INTOLERANCE
• It is the appearance of characteristic toxic
effects of a drug in an individual at therapeutic
doses.
• It indicates a low threshold of the individual to
the action of a drug.
• A single dose of triflupromazine induces
muscular dystonias in some individuals
specially children.
• Only few doses of carbamazepine may cause
ataxia in some people.
• One tablet of chloroquine may cause vomiting
& abdominal pain.

13. IDIOSYNCRASY
• It is a genetically determined abnormal reactivity to a chemical.
• The drug interact with some unique feature of the individual, not found in
majority of subjects & produces the uncharacteristic reaction.
• As such, the type of reaction is restricted to individuals with a particular
genotype.
• Quinine cause cramps, diarrhoea, asthma & vascular collapse in some
patients.

14. DRUG ALLERGY
• It is an immunologically mediated reaction producing serotype symptoms
which are unrelated to the pharmacodynamics profile of the drug, this is also
called Drug hypersensitivity.
• Generally occurs even with much smaller doses and have a different time
course of onset and duration.
• Prior sensitization is needed and a latent period of at least 1-2 week is requires
after the first exposure.
• The drug or its metabolites act as an antigen and induced production of
antibodies.
• Chemically Related drugs often show cross sensitivity, one drug can produce
different type of allergic reactions in different individuals.
• While widely different drugs can also produce the same reaction.
• The course of drug allergy is variable, an individuals previously sensitive to a
drug may subsequently tolerated without a reaction and vice versa.

15. Mechanism & Type Of Allergic Reactions
• ON BASIS OF HUMORAL RESPONCEthere are three types
of reactions
i. type-I anaphylatcic reactions
ii. type-II cytolytic reaction
iii. type-III retarded arthus reaction
• ON BASIS OF CELL MEDIATED RESPONCE
a. type-IV delayed hypersensitivity

16. Type-I Anaphylatcic Reactions
• In this reaction antibodies (IgE) are produced which get fixed to the
mast cells.
• On exposure to the drug antigen : antibody reaction takes place on the
mast cell surface .
• Which leads to releasing mediators like histamine, leukotrienes, and
prostaglandin.
• Resulting in urticaria, itching, bronchospasm, rhinitis or anaphylactic
shock.
• Antihistaminic drugs are benificial in some of this cases .

17. Type-II Cytolytic Reaction
• Drug+ component of a specific tissue cell act as Ag. The resulting
antibodies (IgG, IgM) bind to the target cells, on re-exposure Ag:Ab
reaction takes place on the surface of these cells, complement is activated
and cytolysis occurs .
• e.g thrombocytopenia, agranulocytosis, aplastic anemia, haemolysis, organ
damage (liver, kidney, muscle) etc. may occur
Type-III Retarded Arthus Reaction
• These are mediated by circulating antibodies (predominantly IgG). Antigen
antibody complex binds complement and precipitate on vascular
endothelium giving rise to a destructive inflammatory response
manifestations are rashes, serum sickness etc.

18. Type-IV Delayed Hypersensitivity
• These reactions are mediated through production of sensitized T-
lymphocytes carrying receptors for antigens.
• On contact with antigens, these T-cells produce lymphokines which
attract granulocytes and generate an inflammatory response .
• Eg. contact dermatitis, rashes, fever, photosensitization.
• These reactions generally takes more than 12 hours to develop

19. Treatment of Drug Allergy
• Most mild reactions like skin rashes subside by themselves and do not required specific
treatment.
• Antihistimines are beneficial in some type 1 reactions & some skin rashes.
• In case of anaphylactic shock and angioedema of larynx, following measures are adopted:
i. Put the patient straigth, administer oxygen at high flow rate and perform
cardiopulmonary resuscitation if required.
ii. Inject adrenaline , repeat every 5-10 min in case patient does not improve, this is the
only life saving measure.
• Adrenaline should not be injected IV (can itself be fatal) unless shock is immediately life
threatening. It should be diluted to 1:10,000 or 1:100,000 & slowly with constant
monitoring
iii. Administer a H1 antihistaminic (chlorpheniramine) i.m/i.v.
iv. Intravenous glucocorticoids (hydrocortisone sodium succinate) should be added in
severe/recurrent cases . It acts slowly, but is specially valuable in asthmatic cases.
• Glucocorticoids are the only drugs effective in type II,III,IV reactions.

20. Drugs Frequently Causing Allergic Reactions
• Cephalosporin
• Penicillin
• Salicylates
• Sulfonamide
• Tetracyclines
• Anesthetics
• Quinolones
• Antitubercular drug
• Hydralazine
• Phenothiazines
• Local anaesthetics

21. DRUG ABUSE
• Drug abuse refers to use of a drug by self medication in a manner and
amount that deviates from the approved medical & social pattern in a
given culture at a given time.
• The terms have a huge range of definitions related to taking a
psychoactive drug or performance enhancing drugs for a
nontherapeutic or non-medical effect.
• Some of the drugs most often associated with this term include
alcohol, barbiturates, benzodiazepines, cocaine and opioids etc.

22. DRUG ADDICTION
• It is a pattern of compulsive use of drug characterized by
overwhelming involvement with use of drug.
• Is defined as a drug user's compulsive need to use drug in order to
function normally. When such drugs are unobtainable, the user suffers
from drug withdrawal.
• Examples: cannabis, amphetamine etc.

23. DRUG HABITUATION
• It denotes less intensive involvement with the drug so that its
withdrawal produces only mild discomfort.
• Consumption of tea coffee, tobacco, social drinking are regarded
habituating.
• Basically habituation & addiction imply different degree of
psychological dependence , it may be difficult to draw a clear cut line
between these two.

24. DRUG WITHDRAWAL REACTION
• Stopping or discontinuing any drug that was taken from long time can lead
to appearance of many adverse symptoms ,which are called drug
withdrawal reaction of drug.
• Withdrawal from many drugs can bring symptoms such as agitation,
sweating, an inability to sleep, and high blood pressure.
• Opiate and narcotic withdrawal symptoms can be among the most difficult.
• Opiates and narcotics are classes of drugs that include heroin, codeine etc.
which are taken to achieve a sense of euphoria .
• Other substances that tend to cause more severe withdrawal symptoms, and
potentially life-threatening symptoms, are barbiturates, alcohol, and
benzodiazepines
• E.g. Acute adrenal insufficiency may be precipitated by abrupt cessation of
corticoid therapy.