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Let’s extend our understanding of dose/response curves and toxicity.
Cholesterol is an unavoidable component of every human diet. But,
because of the risks commonly associated with a diet that’s too high in cholesterol,
we tend to have strong associations between cholesterol and ill health.
We tend to think of cholesterol as “bad for you.”
On the other hand, we tend to think of vitamins as “good for you.” Many people
take vitamin supplements expecting them to provide health benefits.
High levels of dietary cholesterol can lead to clogged blood vessels and heart
disease. But cholesterol is an indispensable component of the plasma
membrane of many cells, particularly nerve cells,
so extremely low levels of cholesterol in the body can lead to neurological disorders.
Vitamin D regulates calcium metabolism. So a
common symptom of insufficient vitamin D (as with insufficient calcium)
is weak bones. On the other hand, a common symptom of overdose
of vitamin D (or calcium) is kidney stones, caused by calcium
crystals being deposited in the tubules of the kidney.Therefore,
for any given substance, toxicologists think not just in terms of
“good” versus “bad,” but rather in terms of “how much?”
And we make these judgments by measuring dose/response curves.
If you look closely, though, you will notice that
all the responses we have examined so far—both beneficial and harmful
effects—have all been short-term responses. What about
the long term?Notice, for example, that very high doses
of cholesterol in your diet will have essentially no immediate effect on your
risk for coronary disease. But high levels of cholesterol in your diet
over the course of many years are very likely to have a harmful effect.
Toxicologists and pharmacologists refer to short-term or
immediate responses to substances as acute effects.
And they refer to long-term responses as chronic effects.
As a matter of fact, cholesterol overdose, cholesterol deficiency,
vitamin D overdose, and Vitamin D deficiency, are all
chronic responses. You won’t observe harmful effects within
hours, but over weeks, or months, or even years.
Let’s consider an important chronic effect
of a drug we have already examined: aspirin.
People take aspirin to relieve moderate pain, like a headache. But you may also know
that people who have suffered a stroke or a heart attack may take low doses
of aspirin, every day, in order to lower their risk of another cardiovascular
episode.If you have a headache, you might take
two pills and receive an exposure of 650 mg of aspirin
—which you might repeat four hours later. But you might
only take aspirin for a headache a few times a year.On the other hand,
if you have had a heart attack, you might take 80 mg of aspirin
every single day.These two exposure patterns
are very different. Notice that although about 8 days’
worth of the chronic preventative dose adds up to a single
acute pain relief dose, your body responds to these exposures
very differently: the acute doses have no protective
effect for future heart attacks, and the chronic doses would not
relieve a headache.