Adverse Drug Reactions Flashcards
The WHO defines an adverse drug reaction (ADR) as:
A response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease, or for modification of physiological function
The use of the phrase “at doses normally used in man” distinguishes what from what?
The noxious effect during normal medical use from the toxic effect caused by poisoning (over dose)
There is ___(A need/No need) to prove a pharmacological
mechanism for any noxious response to be termed as ADR.
No need
What is a side effect?
An unintended effect of a drug
related to its pharmacological properties and can include unexpected benefits of treatment
The revised ADR definition is “A harmful or unpleasant reaction, resulting from the intervention related to the use of a medicinal product, which: (4 points)
1) Predicts hazard for future administration
2) Warrants prevention or specific treatment
3) Requires alteration of dosage regimen
4) Requires withdrawal of the product
What is an adverse drug event (ADE)?
An adverse outcome that occurs after the use of the drug, but which may or may not be
linked to this use.
All ___(ADEs/ADRs) are ___(ADEs/ADRs), but not all ___(ADEs/ADRs) will be ___(ADEs/ADRs).
All ADRs are ADEs, but not all ADEs will be ADRs
ADE can be used when:
It is NOT possible to suggest a causal link between a drug treatment and an adverse outcome.
Rawlins-Thompson Classification of ADRs:
1) Type A
2) Type B
3) Type C
4) Type D
5) Type E
6) Type F
What is Type A ADRs?
Normal but exaggerated (augmented) pharmacological effects of the drug. (Common)
Give an example of Type A ADRs.
Bradycardia associated with βadrenergic blockers
What is Type B ADRs?
Abnormal (bizarre) effects not related to the pharmacological effects of the drug
Give an example of Type B ADRs.
Hepatotoxicity of isoniazid, and
allergic reactions
What is Type C ADRs?
Dose-related and time related
Give an example of Type C ADRs.
Hypothalamic-pituitary adrenal axis suppression by corticosteroids
What is Type D ADRs?
Time-related, usually dose
related, occurs or becomes apparent some time after the use of the drug.
Give an example of Type D ADRs.
Carcinogenesis
What is Type E (End of use) ADRs?
Occurs soon after withdrawal of the drug
Give an example of Type E ADRs.
Opiate withdrawal syndrome
What is Type F ADRs?
Common, unexpected failure of therapy, dose-related
Type F ADRs are often cause by:
Drug interactions
Give an example of Type F ADRs.
Failure of contraceptives in the
presence of metabolizing enzyme inducers
What are the factors that affect the susceptibility to ADRs?
1) Age
2) Gender
3) Co-morbidities and concomitant drug use
4) Ethnicity
5) Pharmacogenetics
Why are children more susceptible to ADRs?
1) Differ in drug response
2) Body composition, metabolism, and other physiological parameters
3) Higher body water content can increase the volume of distribution of water soluble drugs
4) Reduced albumin may be associated with high free concentrations of highly protein-bound drugs.
5) Immature blood-brain barrier can increase sensitivity to morphine and other drugs.
Which drugs have higher risks of toxicity in the first weeks of life?
1) Chloramphenicol
2) Digoxin
3) Ototoxic antibiotics
Older children and young adults are more susceptible to some ADRs, such as:
1) Increased risk of extrapyramidal effects associated with metoclopramide.
2) Aspirin is restricted under age of 12 years because of association with Reye’s syndrome.
3) Heightened probability of dosing errors and the relative lack of evidence for both safety and efficacy put children at high risk.
Which gender is more susceptible to ADRs?
Women
Which ADRs are more common in women?
1) Impairment of concentration and psychiatric adverse events associated with anti-malarial agent Mefloquine.
2) Drug-induced torsade de pointes
There is increased risk of ___ with the use of ACE-inhibitors in Africans.
Angioedema
There is increased susceptibility of whites and blacks to CNS adverse effects of ___ compared to Chinese and Japanese.
Mefloquine
There is increased risk of myopathy after ___ in Asians.
Rosuvastatin
There is increased risk of ___ after Rosuvastatin in Asians.
Myopathy
What is Pharmacogenetics?
The science of understanding how variability in a single gene can influence drug treatment outcomes
Genomic Variations led to the concept of:
“Personalized Medicine”
Variation can be caused by:
1) Different concentrations at sites of drug action-pharmacokinetic variation.
2) Different responses to the same drug concentration–pharmacodynamics variation
Genetic variation in drug metabolism examples:
1) Atypical plasma cholinesterase
2) Genetic deficiency in acetylation: “slow” “intermediate” and “rapid” acetylators
3) Polymorphic oxidation: ultrarapid, extensive,
intermediate, or poor metabolizers.
Inherited Variation in Pharmacodynamics examples:
1) Hereditary Warfarin Resistance
2) Heparin Resistance
3) Vitamin D resistance
4) Favism (drug-induced hemolytic anemia)
5) Malignant Hyperthermia with Muscle Rigidity
6) Glaucoma due to abnormal response to intraocular steroids
The immune response is NOT related to:
The pharmacological action of the drug
What is required for a drug to cause an immunological reaction?
Prior exposure to the drug
Patients with a history of ___ are at higher risk of developing immunological reactions to drugs.
Atopic or allergic disorders
Which types of immunological reaction may occur with drug use?
All types
Causality is very difficult to prove and needs what for “Regulatory Authority” action?
High degree of suspicion
What is the Naranjo algorithm?
An objective method to assess causality that reduces assessor bias
Clozapine is used for:
Treatment–resistant schizophrenia
An adverse effect of Clozapine is:
Agranulocytosis
What should we monitor when giving Clozapine?
White blood cells (WBCs)
What are the conditions of a serious adverse event?
1) Results in death
2) Is life-threatening
3) Results in inpatient hospitalization or prolongation of existing hospitalization
4) Results in a persistent or significant disability/incapacity
5) Results in a congenital anomaly/birth defect
What is a mild adverse event?
Causing no limitation of usual activities, the participant may experience slight discomfort
What is a moderate adverse event?
Causing some limitation of usual activities, the participant may experience annoying discomfort
What is a severe adverse event?
Causing inability to carry out usual activities, the participant may experience intolerable discomfort or pain
What is a very common adverse event?
> 10%
What is a common adverse event?
> 1% - <10%
What is an uncommon adverse event?
> 0.1% - <1%
What is a rare adverse event?
< 0.1%
