NESC 3237 Lecture Notes - Drug Tolerance, Grapefruit Juice, Hypothermia

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Published on 17 Apr 2013
School
Dalhousie University
Department
Neuroscience
Course
NESC 3237
Professor
January 15th, 2013
January-15-13
2:31 PM
Factors that alter metabolism
Stimulation and depression of enzymes
o Enzymes are responsible for changing the composition of molecules and making them
usually more safe for the body and facilitating its elimination
o There are drugs that can increase or reduce function of these enzymes
o Sometimes by using the drug a lot, your body may increase the production of the drug
involved
Age
o As you get older, function of the liver decreases, which makes your much more sensitive to
drugs that affect your metabolism
Species
o Not all species metabolize all drugs in the same fashion, so the effects of drugs on
metabolism between species may be different
Stimulation of enzymes
Heavy drinkers have higher levels of alcohol dehydrogenase
o Which is why the more you drink, the more alcohol you can tolerate
Causes metabolic tolerance
o So if you're heavy drinker for many years and then quit, you'll still have this abundance of
alcohol dehydrogenase
St John's Word
o Used as a natural antidepressant
o Works by stimulating an enzyme that is associated with the metabolism of oral
contraceptives
So can make your birth control ineffective
Depression of enzyme activity
Grapefruit juice can block the enzyme that destroys many drugs in the intestine (blocks first pass
metabolism)
o Will increase effectiveness of drugs like viagra
Species differences
Many species have different enzymes and different levels of them
o Very important when developing new drug and testing safety of new drug
So effects of drugs may not translate perfectly between species
Age
As organisms grow and as they age enzyme levels change and different enzymes are used causing
different concentrations of the drug and different metabolism
Elderly people more sensitive to drugs because of their decreased liver function
Time course for blood level of drugs
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Time course for absorption and excretion summed into the resultant, which is the effect of the
drug you actually feel
Fast absorption causes high peaks and short duration
Slow absorption causes low peaks and long duration
Therapeutic window
Require that a certain blood level be maintained, but not so high that the effects are toxic
Hard to do with rapidly absorbing drugs
So many drugs for therapeutic effects designed to release slowly over an extended period of time
**Start of Lecture 2**
Within-subject design
Each subject is their own control
Each subject tested in each condition
Advantages
o Better control condition - no individual variation
Disadvantages
o Take more time, but uses fewer subjects
o possible interactions between conditions
o Attrition
o Carry-over effects possible
Between-subject design
Subjects randomly assigned to different condition
Advantage
o No interaction between conditions
o Faster
Disadvantage
o Need more subjects to average out between subject variation
Balanced placebo design
Cross expectation with pharmacology
Involves 4 groups
o Expect drug, get drug
o Expect drug, get placebo
o Expect placebo, get drug
o Expect placebo, get placebo
Three group design
Often used when testing new therapeutic drug
o Placebo control
o Experimental drug
o Treatment with known effectiveness
Becoming less and less commonly used
o Because of ethical considerations regarding the use of placebo groups in some cases, such
as conditions where not treating can prove fatal, or conditions such as depression
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Document Summary

Age: as you get older, function of the liver decreases, which makes your much more sensitive to drugs that affect your metabolism. Species: not all species metabolize all drugs in the same fashion, so the effects of drugs on metabolism between species may be different. Heavy drinkers have higher levels of alcohol dehydrogenase: which is why the more you drink, the more alcohol you can tolerate. Causes metabolic tolerance: so if you"re heavy drinker for many years and then quit, you"ll still have this abundance of alcohol dehydrogenase. St john"s word: used as a natural antidepressant, works by stimulating an enzyme that is associated with the metabolism of oral contraceptives. Grapefruit juice can block the enzyme that destroys many drugs in the intestine (blocks first pass metabolism: will increase effectiveness of drugs like viagra. Many species have different enzymes and different levels of them: very important when developing new drug and testing safety of new drug.

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