LESSON 4: Adverse Drug Reactions and Interactions

Question 1

Any response to a drug that is noxious and unintended and that
occurs at doses of an appropriately given drug used in man for
prophylaxis, diagnosis or therapy (WHO)

Answer 1

ADVERSE DRUG REACTIONS

Question 2

No history of adverse drug reaction does not mean that the patient
won’t develop any untoward reaction in the future
● Includes:
○ Age
○ Sex
○ Genetic influences
○ Concurrent diseases (renal,liver, cardiac)
○ Previous adverse drug reactions
○ Compliance with dosing regimen
○ Total number of medications
○ Misc. (diet, smoking, environmental exposure)

Answer 2

Patient-related factors

Question 3

● Intrinsic characteristic of the drug, dose and duration of intake may
affect the patient’s response to the drug
● Includes:
○ Dose
○ Duration
○ Inherent toxicity of the agent
○ Pharmacodynamic properties
○ Pharmacokinetic properties

Answer 3

Drug-related factors

Question 4

Predictable, dose-related responses arising from an extension of
therapeutic effect

Answer 4

Extension Effect

Question 5

Predictable, dose-dependent reactions unrelated to the goal of
therapy

Answer 5

Side Effect

Question 6

● No formal dose-response curve and very small doses of the drug
may elicit the reaction once allergy is established
● Reaction disappears on discontinuation of the drug
● Illness is often recognizable as an immunological reaction
● Undetectable during conventional testing
● No relation to the usual pharmacological effects of the drug
● Delay between first exposure to the drug and the occurrence of the
subsequent adverse reaction

Answer 6

Type B (Bizarre)

Question 7

● Genetically determined abnormal response to a drug
● Although dose-dependent, such reactions are unpredictable in most
instances
● Cannot be attributed to drug allergy

Answer 7

Idiosyncrasy

Question 8

● Long term effects are usually related to the dose and duration of
treatment
● Occur with long term use of medicines such as maintenance drugs for
months around 3 months

Answer 8

Type C (Continuous or Chronic)

Question 9

● Include teratogenic and carcinogenic effects that are seen in the
offspring of individuals who took the culprit drugs
● Carcinogenesis - causes cancer
● Teratogenicity - drug-induced birth defect.
● Immunotoxicity

Answer 9

Type D (Delayed)

Question 10

● Withdrawal Syndromes
● Sudden discontinuation of a drug brings adverse reactions as a result
of drug dependence
● Commonly encountered withdrawal syndromes

Answer 10

Type E (Ending of Use)

Question 11

● Substandard drug
● No actual drug in the formulation
● Toxic excipients, adjuvants or impurities are present in formulation
● Tolerance effects
● Antimicrobial resistance

Answer 11

Type F (Failure of Treatment)

Question 12

● International Conference on Harmonisation E2A Guideline (1994):
○ Any untoward medical occurrence that at any dose:
■ Results in death
■ Is life-threatening
■ Requires inpatient hospitalization or prolongation of existing
hospitalization
■ Results in persistent or significant disability/incapacity
■ Is a congenital anomaly/birth defect

Answer 12

Serious Adverse Event (SAE) or
Serious Adverse Drug Reaction (SADR)

Question 13

Is any reaction between a drug and a second substance interactant
(e.g. another drug, food, chemical)

Answer 13

DRUG INTERACTIONS

Question 14

increased toxicity or decreased or loss of
efficacy

Answer 14

Adverse interaction

Question 15

reduction of toxicity or enhancement of
efficacy

Answer 15

Beneficial interaction

Question 16

● Drug whose function is affected
● Narrow margin of safety (low therapeutic ratio)
● Steep dose response curve

Answer 16

Object Drug

Question 17

● Drug that causes the reaction
● Highly protein bound
● Affects metabolism of other drugs
● Affects excretion of other drugs

Answer 17

Precipitant/Interactant Drugs

Question 18

physicochemical interactions either of a drug with an intravenous
solution or two drugs in the same solution

Answer 18

Pharmaceutical

Question 19

occurs when the absorption, distribution, metabolism or excretion
of the object drug is altered by the interactant drug

Answer 19

Pharmacokinetic

Question 20

occurs when the interactant drug alters the effect of the object drug
at it sites of action

Answer 20

Pharmacodynamic

Question 21

● Physicochemical interactions
○ includes physical and chemical interactions vital for maintaining
homeostasis

Answer 21

Pharmaceutical Drug Interaction

Question 22

Commonly observed pharmaceutical interaction
in clinical practice

Answer 22

IV incompatibilities

Question 23

Occurs when the absorption, distribution, metabolism, or excretion of
the object drug is altered by the precipitant/interactant drug

Answer 23

Pharmacokinetic Drug Interactions

Question 24

Antimuscarinic drugs will decrease gastrointestinal motility → slow
rate of gastric emptying → increased gastric retention → increased
absorption of drugs absorbed in the stomach

Answer 24

Alteration of motility

Question 25

○ Food + isoniazid/penicillin/rifampicin decreased absorption

Answer 25

● Alteration of contents

Question 26

Majority of metabolism interactions occur with induction or inhibition
of the hepatic microsomal P-450 system.

Answer 26

Metabolism

Question 27

Involves enhancement or inhibition of drug clearance, resulting in
decreased efficacy or increased toxicity of drugs

Answer 27

Excretion

Question 28

○ interactions at the drug receptor
○ E.g. Antagonism at the same site:
■ Naloxone & opiate
■ Flumazenil & benzodiazepine

Answer 28

● Pharmacologic

Question 29

○ interactions due to different cellular mechanisms acting in concert
or in opposition

Answer 29

● Physiologic

Question 30

● Precipitant drug possesses an effect which is not related to the effects of the object drugs

Answer 30

Indirect Pharmacodynamic Interaction

Question 31

○ The combined effect of two or more drugs that have the same
activity equals the sum of their individual effects
○ 1+1=2

Answer 31

Summation/Addition

Question 32

○ The combined effect of two active drugs is greater than the sum of
their effects
○ 1+1=3

Answer 32

Synergism

Question 33

○ The activity of one drug is increased by another drug that does not
possess the same activity
○ 0+1=2

Answer 33

Potentiation

Question 34

○ The activity of one drug is decreased or totally negated by the
activity of another drug
○ 1+2=1 or 1+0=0

Answer 34

● Antagonism

Question 35

Also called voluntary reporting

Answer 35

SPONTANEOUS REPORTING

Question 36

● Stands for Registry of Admission and Discharges
● An electronic medical record system used in PGH

Answer 36

RADISH