It has long been known that vitamin A has a regulatory effect
on growth and differentiation of epithelial tissue. Since the
1940's, high doses of vitamin A have been employed in the
treatment of severe acne and various disorders of keratinization.
Vitamin A's use, however, was limited by its side effects - liver
toxicity and pseudotumor cerebri in particular. In an attempt to
find a drug with a better therapeutic index than vitamin A,
several synthetic retinoids have been developed.
One of these, accutane (13-cis-retinoic acid), was first
synthesized in 1955. It was largely ignored until the results of
the first major clinical trial demonstrating its efficacy in the
treatment of severe recalcitrant cystic acne were published in
1972. in 1982, accutane was approved in the United States
for that single indication only. Its trade name is Accutane. A
major feature of this drug is that it produces a prolonged
remission in patients with severe cystic acne, many of whom had
not responded to other therapies. The most striking discovery,
however, is that the remission is often sustained for months or
years after the four- to five-month treatment course has been
completed.
Transport and metabolism of vitamin A (retinol) and accutane
Significant differences between vitamin A and accutane
with regard to their transport and metabolism account for their
difference in toxicity. The major source of vitamin A
(retinol) is the conversion of dietary plant carotenoids in the
intestinal mucosa. Retinol is stored in the liver, which contains
over 90% of body stores. Mobilization from the liver is
accomplished when retinol is bound to a specific transport
protein, retinol binding protein, that delivers it to tissues.
Plasma levels of vitamin A tend to remain constant despite wide
variations in diet. Extremely high dietary intake (eg. polar bear
liver, vitamin A tablets) produces hypervitaminosis A.
Hypervitaminosis A results in greatly increased hepatic stores
and subsequent toxicity.
In contrast, accutane binds to serum albumin. Accutane
is readily absorbed orally and put into circulation via the
portal system. It is not significantly stored in any organ
system, and plasma levels vary with the amount ingested.
Wash the skin
Avoid oily substances
Shampoo the hair daily
Don`t "pop" pimples
Exercise regularly
Don't stop the acne medicine
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