Adverse Drug Reactions.ppt

Adverse Drug reactions
By
Dr. Faraza Javaid

INTRODUCTION
 The drugs prescribed for disease may
themselves be the cause of diseases (adverse
reactions). This may range from mere
inconvenience to permanent disability to and
death.
such as
 Nausea and vomiting with any of the drug
 Deafness with aminoglycosides
 Death with penicillin's

 How much diseases they cause and why they cause ?
So that preventive measures can be taken.
 Which adverse effects are avoidable and which are
not ?
 Some patients with history of allergy to drugs, are up
to 4 times more likely to have another adverse
reaction.
 It is also useful to discover the cause of adverse
reaction ,so that ,that can be avoided.

 Side effects: Many unwanted effects , are
medically minor and need not to stop the drug,
called side effects.
 Adverse reactions: Harmful or seriously
unpleasant effects occurring at therapeutic
doses and which call for reduction of dose or
withdrawal of the drug and /or forecast hazards
from future administration.

 Toxicity: Direct action of the drug, often at high dose
, damaging cell.
e.g. liver damage from paracetamol over dose,
8th cranial nerve damage from gentamicin .
All the drugs are said to be toxic in over dose
Some times drugs in ordinary dose may become
toxic due to under lying abnormality in patient
e.g. in renal impairments

Classification
 Type “A” OR Type “1”
 75% of all adverse reactions.
 they can occur in every one
 they are common
 they are predictable
 they are dose dependent
 skill management can reduce their incidence
 they are mostly part of normal pharmacology of drug.
e.g. Hypoglycemia
Hypotension
Hypocalcaemia

These adverse effects may be
 irreversible
aminoglyside 8th cranial nerve damage
Or
 Reversible
like morphine poisoning reversed by administration
of Naloxone.

 Type “B” ( Bizarre)
 they are less than 25% of adverse effects
 only occur in some people
 not a part of normal pharmacology of drug
 can not be predicted.

 Adverse effects may be unrelated to normal
pharmacology of the drug.
 As paracetamol hepatotoxicity
 Aspirin induced tinitus
 Primaquine induced haemolysis.

 These are due to unusual attributes of patient
interacting with drug.
 These may be inherited abnormalities
(idiosyncrasy) and immunological process
(drug allergy)
 These accounts for most drug fatalities.

 Type “C”( continuous) due to long term use
of drugs
e.g. analgesic nephropathy
tardive dyskinesia with neuroleptics
 Type”D” (delayed)
e.g. teratogenesis, thalidomide causing
phecomelia

 Type “E”( ending of use) where discontinuous
is too abrupt.
e.g. Rebound adrenal insufficiency.
over shoot of blood pressure due to
propranolol withdrawal.
Note : some authors include Type C,D&E as
type “B”

Variations in Drug
responsiveness

 When a drug is administered usually there is
normal predicted response or
there may be
 reduced response
 or increased response
 or altered response
what are the factors which may produce
these unwanted responses.

Variation in drug response
 Desensitazation
 tachyphylaxis
 tolerance
 Drug resistance
 change in receptor
 loss of receptor
 exhaustion of mediators
 increased metabolic degradation
 physiologic adaptation
 active extrusion of drug from cells.

Qualitative variations
Individuals may vary considerably in their responsiveness
1. A single individual may respond differently to the same drug
at different times
2. Occasionally individuals exhibit an unusual or
IDIOSYNRATIC drug response , this is infrequent.
3. Theses are caused by genetic difference in metabolism of
Drug like Fast acetylators and slow acetylators
OR by Immunologic mechanisms. Including allergic reactions

Idiosyncratic reactions
 It is qualitatively abnormal and usually harmful,
occurs in small proportion of populations e.g.
chlormaphenicol causes aplastic anemia 1 in 50,000.
 G6PD deficiency leads to hemolysis caused by
primaquaine.
 Hepatic porphyria (abnormal haem synthesis) caused
by carbamzepine.
 Malignant hyperthermia caused by suxamethonium
and inhalational anesthetics.

 Anaphylaxis:
 it is immediate hypersensitivity reaction on
exposure to specific antigen or hapten leading
to life threatening respiratory distress
followed by vascular collapse.

QUANTITATIVE
variations
 More common
 More clinically important
 Patient may be
Hypo reactive:
Hyper-reactive: to drug to a given dose
 Hypersensitivity:
allergic or other immunologic responsiveness to
drugs
e.g. Pencillins

 Tolerance
with some drugs intensity of response to given dose
may change during course of therapy, usually
decrease in response to continued administration of
drug.
e.g. Salbutamol (β-adrenergic agonist)
Opium ,barbiturates , Alcohol
 Tachyphylaxis:
when responsiveness diminishes rapidly after
administration of drug
e.g. ephedrine
Amphetamine

 Keeping this responsiveness of individual
drug, so there should be change of the drug or
dose. These includes propensity of particular
drug to produce tolerance or tachyphylaxis as
well as effects of age, sex ,body size , diseases
state and simultaneous administration of other
drugs.

 Mechanism: which may contribute to variations in
drug responsiveness among patients or among
individual patient at different times.
 A) Alteration in concentration of drug that
reaches receptor.
 B) Variation in concentration of an endogenous
receptor ligand.
 C) Alteration in number of function of Receptors
 D) Changes in components of response distal to
receptor

A) Alteration in drug concentration
 A) Patient may differ in rate of absorption,
distribution, and elimination of drug. By
alteration of concentration of drug that
reaches relevant receptor may alter clinical
response.
 some difference can be produced on the basis of
age, weight, diseases state, liver and kidney function,
drug metabolizing enzymes.

Alteration in number of receptors
There occurs change in responsiveness caused by increase or
decrease in number of receptor sites or alteration in efficiency of
coupling of receptor to distal effectors mechanism.
e.g.Receptors for hormones
Thyroid hormones cause increase in number of β-adrenergic
receptors and hence increase in cardiac sensitivity to
catecholamines

ii) Receptor specific desensitization mechanism act
physiologically to allow cells to adopt to changes in rates
of stimulation by hormones or neurotransmitters .
These mechanisms contribute to tacyphylaxis or tolerance and
over shoot phenomena that follows with drawl of
certain drugs .
Antagonists (up regulation) increase the number of receptors
e.g. Propranolol
Agonists (Down regulation) decrease the number of receptors.
This may be dangerous to discontinue certain drugs.
Therefore drugs are to be with drawn slowly

Adverse Drug Reactions.ppt

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