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Rx2013
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Types of DI/ADR
- augmented pharmacologic effect
- Bizarre effects
- chronic effects
- delayed effects
- end of treatment effects
- failure of therapy
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Chronic effect example
- reversible
- hairloss due to drug
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Delayed effect example
- damage to DNA caused by chemo which later causes cancer
- birth defects
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levels of severity of ADR
- Death
- Life-threatening
- disability
- congenital anomaly
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Prevalence of ADR
- 2 million ADR/year
- 100,000 deaths / year
- 6th leading cause of death
- 350,000 per year in nursing homes
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Costs associated with ADR
- 136 billion /year
- cost of bringing drugs to market and then having them removed due to ADR
- increasing hospital stay, cost and mortality for ADR pts.
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Common Drug classes of ADR
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Drugs eliminated from development due to ADR
38%
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Stages at which drug interactions occur
- pharmacodynamics
- pharmaceuticals
- pharmacokinetics
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Pharmacodynamic
- Antagonists/agonist competition
- Additive/synergistic effects
- Fluid/e- imbalance
- Indirect interactions
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Pharmaceutical
- incompatibility between two drugs
- precipitation (physical)
- change in the nature of the drug (chemical)
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Pharmacokinetic
- Altered absorption
- Altered distribution
- Altered metabolism
- Altered elimination
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Altered absorption (non transporter based)
- changes in GI pH
- chelation
- changes in GI flora
- change in GI motility
- malabsorption caused by other drug
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Altered absorption (transporter based)
- modulation of transporter activity (inh. or ind. by other drug)
- polymorphisms of transporters (genetic)
- nonlinear kinetics result
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P-glycoprotein inhibition
increased plasma levels of digoxin
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p-glycoprotein induction
decreases plasma digoxin
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Altered metabolism
- toxic drug metabolites
- inhibition or induction of CYP 450
- CYP polymorphism
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Reason for toxic metabolite formations with drugs metabolized by CYP
80% of drugs are metabolized by CYP
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induction of CYP
- increased metabolism
- changes efficacy
- increases toxicity
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inhibition of cyp
- decreases metabolism
- changes efficacy
- increases toxicity
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CYP304
50%of drugs metabolized
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Polymorphism with no CYP2D6
- slow metabolism
- high drug levels
- high risk for ADR
- no response from some prodrugs
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Polymorphism with increased CYP2D6
- too rapid metabolism
- no drug response at normal dose
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Altered Excretion
- 1-2% of DI
- change in active excretion
- change in biliary excretion
- change in renal blood flow
- change in urine pH
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Which of the following are examples of DI/ADR due to non-transport mediated altered absorption?
A. Physical interaction
B. change in GI pH, Chelation and GI Flora
C. change in GI pH
D. GI Flora
E. Chelation
B. change in GI pH, Chelation and GI Flora (this multiple choice question has been scrambled)
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What is the most prevalent stage of DI?
A.Pharmacokinetics
B. Pharmaceutical
C. Pharmacodynamics
A.Pharmacokinetics (metabolism) (this multiple choice question has been scrambled)
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