Acute versus Chronic Toxicity

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.