The Hole Story:
Drugs and Sunlight
A number of commonly used drugs cause a reaction in people who go out in the sun. Dr Douglas Moore of the Department of Pharmacy at the University of Sydney is studying how these drugs react with materials in the human body after they have been stimulated by Ultra Violet radiation.
The main thrust of Douglas Moore’s work is a study of the photochemistry of drugs, that is how drugs react to light. There are a number of drugs used to treat people that have side affects in a small percentage of the population by causing a reaction when they go out in the sun. It manifests as an exaggerated sunburn and is called phototoxicity. Moore’s research involves looking at the reactions of those drugs as they are exposed to UV light.
When a drug is ingested by an individual it is carried around the body in the blood stream. The blood flows to the skin where it is used by the body as a means of heat transfer for cooling the body. So the blood flow to the skin is relatively high and it gets even higher when a person goes out in the sun. Near the surface of the skin the blood capillaries carry a measurable amount of the drug. UV light penetrates the skin into those blood capillaries where it can be absorbed by the drug molecules.
As it turns out most drug molecules don’t absorb light in the visible region of the spectrum. In other words they look either white as solids or colourless when dissolved. Something that is coloured has a characteristic absorption in the visible region of the spectrum. However, many drug molecules, although they may be white or colourless, do absorb light in the UV region. That is found out using a spectrophotometer which determines how much light the compound will absorb at particular wavelengths. All the drug compounds that Moore looks at have some capacity to absorb UV light in the sunlight region.
Molecules are normally in their lowest or ground state energy level but they are excited to higher energy levels when they absorb sunlight. The extra energy means the molecules can be vibrating much more vigorously and they are therefore much more liable to fall apart, react with oxygen or interact with other molecules. It is possible to induce a variety of processes by making the molecules absorb light. Observing what these processes are is basically what Moore’s work is all about.
Oxidation reactions where the molecules react with oxygen are one of the principal forms of reaction. Oxidation also occurs with naturally occuring molecules in the body such as proteins and components of cell membranes. The body, of course, has a lot of defence mechanisms. There are species such as vitamins which are travelling around in the blood system and they are able to interact with the unwanted products of these reactions to scavenge them before they can do any harm. This may be the reason the problem isn’t more wide-spreads than it is. These natural defence mechanisms usually prevent the problem from getting out of hand.
But in some people that additional absorption of light by the drug generates new compounds in larger amounts that the biological scavengers cannot cope with. The result is exaggerated sunburn, skin rashes or blistering occurring in a time period less than that which would normally cause a sunburn. The result can look a little different to normal sunburn, and also different compounds cause effects with slightly differing appearances. Some compounds cause what are called wheals and flares, with colouring in circular patterns on the skin. Sometimes there are spots like flares of redness on various areas of the body while others are characterised by being intensely red.
These are the only visible effects. The difficulty with this sort of symptom is that experiencing a bit of sunburn is a part of our culture. This means that a lot of these effects may be experienced by people but are not being reported. There may also be other things happening which people don’t associate with the combination of a particular drug with sunlight. Someone who has side effects from a drug may not associate these effects with going out in the sun. There are a lot of drugs, for instance, that have skin rashes listed as their side effects but the association with the sun is not necessarily made.
The sunburn response is an inflammation which occurs because of the impact on the skin of something which is foreign to it. In an insect bite for instance, a toxin is injected, the skin reacts against it - it itches and the defense mechanisms go to work which results in an inflamed site. Sunburn is like that too. The UV light is being absorbed by the molecules in the skin and they undergo chemical change and as a result you get an inflammatory response. When a drug molecule is also present which is capable of other reactions then a second inflammatory response is generated. It could be an altogether different response to sunburn.
“It is interesting that you can take a laboratory animal, which is usually immune deficient, feed it anyone of these particular drugs, irradiate it with UV light and lo and behold out will come a nice vigorous sunburn which ultimately can lead to skin cancer as well,” says Moore. “The important thing is that skin cancer is endemic in our society, with our white skins, with our closeness to the equator, with our high level of solar energy that we are all loving and soaking up because it feels healthy. You’ve got about a 60% chance of experiencing skin cancer by the age of 50. There are a number of contributing factors. Sunlight is of course the major factor but there is an additional contributing factor for people who are having these interactions with drugs. If you suffer from an exaggerated sunburn it will clearly initiate some processes in the skin which could ultimately lead to skin cancer.”
But why would the inflammation from a drug be likely to cause skin cancer? Well, what does cause skin cancer, after all? The generally held view is that skin cancer is caused by excessive continual exposure to sunlight. The sunlight triggers off changes in the genetic material, the DNA, and there are cells which are left in the skin which ultimately are triggered to start dividing excessively and so a cancer is formed. Some drugs produce a photochemical reaction capable of causing similar sorts of things and so they exacerbate the problem.