Pharmacology Exam 2

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Internal risk factors for ADR
- Age
- Disease
- Species differences
- Gender
- Pregnancy
Elderly
- decreased metabolism and excretion
- decreased enzyme induction
- usually take multiple drugs
Very Young
- metabolism not fully developed
- no phase II enzymes
Fetus

only has CYP3A
Diseases

general decrease in CYP enzymes
Species differences

different enzymes
Use of rats in clinical trials
- rats have six CYP2D
- Humans have 1
Erythromycin in females vs. males

Female metabolizes faster than male
Propranolol oxidation in m vs. f

M>F
Nicotine metabolism in M vs. F
- F>M
- females may become addicted faster
Pregnancy
- 50% of drugs are metabolized by CYP3A4
- fetus does not have this enzyme!
Consequences to fetus or neonate given wrong drugs
- teratogenicity
- carcinogenicity
- hepatotoxicity
External risk factors
- Multiple drugs
- Diet, supplements, and alternative medicines
- Alcohol
- Tobacco
- substances of abuse
Multiple drug risks
- Disease co-existance
- Combination therapy
Diet and supplements
- special diet due to disease or culture
- OTC products
Alternative medicine vs. Antiretrovirals may inhibit or induce CYP
- inhibitors increase ARV concentration
- Inducers decrease ARV concentration
All ARVs except 1 are metabolized by

CYP3A4
Alcohol, tobacco and other substance of abuse
- induce CYP
- produce oxidative stress
- decrease response to ARVs
Alcohol induces

CYP2E1 and CYP3A4
Tobacco induces

CYP 2A6 and CYP 2E1
Pharmacogenetics as risk factors
- variation of metabolizing enzymes
- variation of drug transporters
- variation in drug targets
Genetic polymorphism

>1% incidence in the population
Poor metabolizers via CYP2D6
- 5-10% of caucasians
- 1-2% of asians
decreased CYP2D6 function
- increase in drug levels
- lower dose to avoid toxicity
Increase in CYP2A...
- increase nicotine dependance
- increased cancer risk

Author

Rx2013

39024

Card Set

Pharmacology Exam 2

Description

Factos affecting DI/ADR

Updated

2010-10-02T03:27:07Z

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