LESSON 4: Adverse Drug Reactions and Interactions Flashcards
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)
ADVERSE DRUG REACTIONS
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)
Patient-related factors
● 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
Drug-related factors
Predictable, dose-related responses arising from an extension of
therapeutic effect
Extension Effect
Predictable, dose-dependent reactions unrelated to the goal of
therapy
Side Effect
● 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
Type B (Bizarre)
● Genetically determined abnormal response to a drug
● Although dose-dependent, such reactions are unpredictable in most
instances
● Cannot be attributed to drug allergy
Idiosyncrasy
● 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
Type C (Continuous or Chronic)
● 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
Type D (Delayed)
● Withdrawal Syndromes
● Sudden discontinuation of a drug brings adverse reactions as a result
of drug dependence
● Commonly encountered withdrawal syndromes
Type E (Ending of Use)
● Substandard drug
● No actual drug in the formulation
● Toxic excipients, adjuvants or impurities are present in formulation
● Tolerance effects
● Antimicrobial resistance
Type F (Failure of Treatment)
● 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
Serious Adverse Event (SAE) or
Serious Adverse Drug Reaction (SADR)
Is any reaction between a drug and a second substance interactant
(e.g. another drug, food, chemical)
DRUG INTERACTIONS
increased toxicity or decreased or loss of
efficacy
Adverse interaction
reduction of toxicity or enhancement of
efficacy
Beneficial interaction
● Drug whose function is affected
● Narrow margin of safety (low therapeutic ratio)
● Steep dose response curve
Object Drug
● Drug that causes the reaction
● Highly protein bound
● Affects metabolism of other drugs
● Affects excretion of other drugs
Precipitant/Interactant Drugs
physicochemical interactions either of a drug with an intravenous
solution or two drugs in the same solution
Pharmaceutical
occurs when the absorption, distribution, metabolism or excretion
of the object drug is altered by the interactant drug
Pharmacokinetic
occurs when the interactant drug alters the effect of the object drug
at it sites of action
Pharmacodynamic
● Physicochemical interactions
○ includes physical and chemical interactions vital for maintaining
homeostasis
Pharmaceutical Drug Interaction
Commonly observed pharmaceutical interaction
in clinical practice
IV incompatibilities
Occurs when the absorption, distribution, metabolism, or excretion of
the object drug is altered by the precipitant/interactant drug
Pharmacokinetic Drug Interactions
Antimuscarinic drugs will decrease gastrointestinal motility → slow
rate of gastric emptying → increased gastric retention → increased
absorption of drugs absorbed in the stomach
Alteration of motility
○ Food + isoniazid/penicillin/rifampicin decreased absorption
● Alteration of contents
Majority of metabolism interactions occur with induction or inhibition
of the hepatic microsomal P-450 system.
Metabolism
Involves enhancement or inhibition of drug clearance, resulting in
decreased efficacy or increased toxicity of drugs
Excretion
○ interactions at the drug receptor
○ E.g. Antagonism at the same site:
■ Naloxone & opiate
■ Flumazenil & benzodiazepine
● Pharmacologic
○ interactions due to different cellular mechanisms acting in concert
or in opposition
● Physiologic
● Precipitant drug possesses an effect which is not related to the effects of the object drugs
Indirect Pharmacodynamic Interaction
○ The combined effect of two or more drugs that have the same
activity equals the sum of their individual effects
○ 1+1=2
Summation/Addition
○ The combined effect of two active drugs is greater than the sum of
their effects
○ 1+1=3
Synergism
○ The activity of one drug is increased by another drug that does not
possess the same activity
○ 0+1=2
Potentiation
○ The activity of one drug is decreased or totally negated by the
activity of another drug
○ 1+2=1 or 1+0=0
● Antagonism
Also called voluntary reporting
SPONTANEOUS REPORTING
● Stands for Registry of Admission and Discharges
● An electronic medical record system used in PGH
RADISH
