Principles of Drug Toxicology Flashcards
How do you study adverse effects of chemicals on living systems?
Mechanisms of action Understanding physiology + pharmacology Recognition + quantification of hazards Discovery of new drugs Development of standards + regulations
What are the different types of adverse drug reactions?
Type A (augmented) Type B Type C (chemical) Type D (delayed) Type E (end of treatment)
What is the difference between Type A + B?
A can be predicted from pharmacology of drug B cannot
A typically dose-dependent
B can effect almost any organ system
What is Type A induced by?
Same pharmacological mechanism as therapeutic effect
How can Type A arise?
Changes in drug pharmacokinetics = pathology or aging
Changes in pharmacodynamics = concomitant pathology or non-compliance
Which is the most frequent of all adverse reactions?
Type A
Which is relatively less dangerous + why?
Type A = lower mortality rate
What is the intervention for Type A?
Dose reduction
Use of antagonist
What is the prevention for Type A?
Dose titration
Monitoring
Pharmacotherapy monitoring (PK/PD)
What is Type B?
Allergy to the drug
What is Type B caused by?
Genetic predisposition
Does Type B have an relation to dose of drug?
NO
Why does Type B have a higher serious clinical outcome?
Higher mortality rate
What is the intervention for Type B?
Instant drug withdrawal
Symptomatic treatment
What can be used for Type B since it is an allergy?
Antihistamines
Adrenaline
What is the prevention for Type B?
Avoiding certain drugs with known risks
What does Type B (allergic reactions) require?
Previous exposition before manifestation
What are the two different Type B?
Allergic reactions Idiosyncratic reactions (genetics)
How can immunogenicity be acquired in Type B (allergic reactions)?
Binding of drug on macromolecular carrier
Covalent bond
Carrier = protein
What does idiosyncratic not require?
Prior exposure
What is idiosyncratic primarily determined by?
Genetic deviations
Are the effects of idiosyncratic related to pharmacological properties of drug?
NO
Is Type C as frequent as B?
NO
What is Type C associated with?
Cumulative-long term exposure inducing toxic response
What is most accumulation in Type C?
Functional NOT immune
What does Type C have a direct relationship with?
Cumulative dose
What is Type C treatment?
Troublesome, largely irreversible in higher cumulative dose
What is Type C prevention?
Cumulative dose reduction
Limitation of time exposure
Monitoring
Prevention of non-compliance + drug abuse
What is part of Type D?
Teratogenesis
Mutagenicity + carcinogenicity
What is teratogenesis?
Embryo/foetus death, morphologic malformations, functional defects
= penetration of placenta barrier
Describe teratogenesis
Homogenous distribution between mother + foetus
What is mutagenicity + carcinogenicity?
Mutation
Describe mutagenicity + carcinogenicity
Impair regulation of cellular proliferation + differentiation = tumour formation
What % of carcinogenic events are induced by chemical compounds?
60-70%
What is Type E (end of use)?
Drug withdrawal syndromes
What is Type E due to?
Up-regulation of receptors during chronic treatment
Withdrawal of long-term systemic treatment with glucocorticoids
What is Type E prevention?
Avoid abrupt withdrawals
Slow decrease in dose
Avoid long treatment
