21. Drug epidemiology and drug safety. Adverse drug reactions (ADRs). Classification, registration, clinical detection of ADRs. Flashcards
what is Pharmacoepidemiology
clinical pharmacology and epidemiology, which studies the use of and the effects of drugs in large numbers of people.
what is Pharmacoepidemiology used for
Studies of drug safety
Studies of drug utilization
Studies of drug induced birth defects
study medication errors
improving physician prescribing
Methods in pharmacoepidemiology
A DOSE
Spontaneous reporting- (yellow card scheme), most common
Observational studies
Experimental (interventional) studies
Descriptive studies-
Analytical study-
what is Spontaneous reporting- (yellow card scheme),
used to collect information on ADRs from healthcare professionals and patients.
3 stages;
collection of data,
analysis
feedback
advantages of spontaneous reporting
cheap
collects data from large populations
how do observational studies differ from exp
difference in study groups is created experimentally and outcomes are observed.
Observational studies- the differences in the study groups are only observed and analysed NOT created experimentally.
examples of observ studies
case-control studies
cohort studies.
what is analysed in Analytical study
relationships between health status and other variables
Descriptive studies- describe what?
occurrence of a disease (ADR) in a population.
what is an adverse drug event
unwanted medical event during rx w. a ddrug but isnt directly caused by the rx
adr
oxious and unintended response to a drug which occurs at normal doses
causal relationship expected
Unexpected ADR
an ADR whose a nature or severity is not compatible with the drug information or cannot be predicted from the characteristics of the drug
Side-effects
unwanted but unavoidable pharmacodynamic effects, occurring at therapeutic doses.
Secondary effects
indirect consequences of a primary action of the drug
Eg disbacteriosis due to broad spectrum antibiotics
types of ADR
Minor ADRs: no therapy, antidote or prolongation of hospitalization is required.
Moderate ADRs: Require change in drug therapy, specific treatment or prolong hospital stay by at least 1 day.
Severe ADRs: Potentially life threatening, cause permanent damage or require intensive medical treatment.
Lethal: Directly or indirectly contributes to death of the patient.
ADR classification
type A: Augmented dose related
Type B (Bizarre) Unrelated to dose
Type C (Chronic) Dose and time-related
Type D (Delayed) Delayed in time
Type E (End of treatment) After drug discontinuation
Type F (Failure) Unexpected failure of therapy
Type U (Unclassified)
Type A (augmented) Dose-related features
Common and predictable
Augmentations of known pharmacologic effects
can be alleviated by a dose reduction
Associated with high doses
Low mortality
Common in patients with liver and kidney failure
Minor type A reaction= side-effect
Type A ADR examples
obvious ones
antihypertensive medications- orthostatic hypotension
beta blockers-
bradycardia
nitrates-
headache,
flushing
reflex tachycardia
Type B (Bizarre) Unrelated to dose
Uncommon and unpredictable
affects a small population
not related to the main pharmacologic action of the drug
high mortality
TYPE B ADR EXAMPLES
immunologic reactions (allergy)
intolerance
hemolytic anemia
serum sickness
Type C (Chronic) Dose and time-related
Reactions due to long-term drug use
Related to the cumulative dose
type c ADR examples
Neuroleptic-related tardive dyskinesia.
corticosteroids-(Cushing’s)
Analgesic nephropathy
Type D (Delayed) Delayed in time
occur after many years of treatment
carcinogenic, mutagenic and teratogenic effects
Type D ADR examples
Tetracyclines-yellow staining of the primary or deciduous teeth
Retinoic acid or vitamin A-extremely teratogenic
anticancer drugs- carcinogenesis and may cause secondary tumors
Type E (End of treatment) After drug discontinuation
Drug withdrawal syndrome
ADRs, mostly in the form of worsening of the clinical condition for which the drug was being used
Type E ADR examples
benzodiazepines w/drawal symp- insomnia, anxiety
withdrawn abruptly beta blockers- Worsening of angina pectoris or acute myocardial infarction
withdrawal of glucocorticosteroids.-Adrenocortical insufficiency
Type F (Failure) Unexpected failure of therapy
Common
Often caused by drug interactions.
Type F examples
Inadequate dosage of an oral contraceptive when used with an enzyme inducer.
Resistance to antimicrobial agents
PATIENT factors predisposing ADR
AGE
- pediatric age
- geriatric age
renal/hepatic impairment
gender
- women> men
- hormonal diff to met
comorbidities
genetic abnormalities
-altered met
history of ADR
drug factors
higher incidence of ADRs,
high allergenicity,
Prescriber factors
inappropriate drug or drug combination
inappropriate dose,
route of administration
duration of treatment.
Criteria for causality assessment
Timing
- time between drug administration and reaction
Pharmacological properties of the drug, data on ADR
Investigations (clinical and lab) contributing to plausibility of ADRs
Presence or lack of other causes of the reaction
Response to drug withdrawal(dechallenge) and provocation (rechallenge- controlled administration of the drug))tests
WHO criteria for the degree of causality of a drug w/ the ADR
Certain
Probable
Possible
Unlikely
Unclassified
Management of ADRs
Drug withdrawal
decrease dose
change Route of admin
Systemic, topical or combined therapy
Hospitalization
Selection and administration of different drugs
Pharmacovigilance
collection, detection, assessment, monitoring, and prevention of adverse effects with pharmaceutical products. I
