Clinical Pharm Adverse Drug Effects

Front 1

Discuss the pre-marketing drug evaluation process for efficacy and adverse drug events.

Back 1

FDA clinical trials of 3000-4000 subjects, to uncover adverse events which occur more frequently than 1 in 1000

Front 2

Which adverse drug effects are likely to be associated with the administratino of therapeutic dosages of a drug, and are usually predictable and avoidable?

Back 2

Type A reactions
Dose dependent, most ADEs, exaggeration of direct effects of a drug

Front 3

The formation of unstable or reactive drug metabolites, which may interact with O2 and overwhelm antioxidant defense systems or covalently bind to cellular macromolecules are characteristic of what type of adverse drug effects?

Back 3

Cytotoxic effects
oxidative pathway: dormation of electrophillic cpd, which covalently bind to cellular macromolecules
Reductive pathway: intermediate cpd w/excess electrons, which interact w/O2 producing free radicals

Front 4

Which adverse drug effects have pharmocodynamic basis?

Back 4

drug-drug interactions
pharmacologic: same receptor
physiologic: different receptors, which affect each other's outcomes
chemical: direct interaction
receptor alterations: chronic drug exposure alters reception expression

Front 5

A pharmacokinetic drug-drug interaction characterized by drug A, usually a weak acid, competing for plasma protein binding with drug B and resulting in increased plasma level of drug B is an example of an interaction that will primarily affect which pharmacokinetic parameter?

Back 5

Distribution

Front 6

A pharmacokinetic drug-drug interaction characterized by drug A increasing bile flow and the synthesis of proteins, which function in conjugation reaction reactions and results in decreased plasma level of drug B is an example of an interaction that will primarily affect which pharmacokinetic parameter?

Back 6

Metabolism

Front 7

An adverse drug event associated with isoforms of the CYP450 enzyme system (genetic polymorphism), which may lead to significant differences in the efficacy or toxicity of a drug among individuals is an example of what type of adverse drug effect?

Back 7

Idiosyncratic reaction (type B)
mechanism of most idiosyncratic drug reactions is immune mediated toxicity. To create an immune response, you must have a foreign molecule that antibodies can bind to (ie. the antigen) and you must have cellular damage. Very often, drugs will not be immunogenic because they are too small to bind antibodies. However, a drug can cause an immune response if the drug binds a larger molecule. Some unaltered drugs such as penicillin will bind avidly to proteins. Others must be bioactivated into a toxic compound that will in turn bind to proteins. The second criteria of cellular damage can come either from a toxic drug/drug metabolite or it may come from an injury or infection. These will sensitize the immune system to the drug and cause a response.

Front 8

Initial exposure to drug A resulted in antigen (drug A)-specific antibody production dominated by the immunoglobulin E (IgE) isotype. Upon re-exposure to drug A what type of reaction is the patient likely to experience?

Back 8

Type I (immediate) hypersensitivity

Front 9

Discuss the mechanisms responsible for teratogenic drug effects.

Back 9

Accumulation of a drug or its metabolites in the fetus at critical time periods (3rd-12th weeks); depends on fetal age, drug potency, dosage.

Constriction of placental vessels -> gas and nutrient exchange impairment -> hypertonia, resulting in anoxic injury -> indirectly changing biochemical dynamics of the mother

Front 10

Discuss the mechanisms responsible for oncogenic drug effects.

Back 10

Primary: procarcinogenic drugs, which have been converted into carcinogens by polymorphic oxidative reaction; reactive metabolites bind covalently to DNA
Secondary: therapeutic immunosuppresion in the presence of infection w/oncogenic viruses (HBV, HCV, CMV, HSV, HPV, EMV); pattern of cancer differs from general population