Topical and local routes

A tablet produces a peak: the drug is absorbed quickly, blood levels rise, then fall as the liver and kidneys remove it, and the patient may swing between too much and too little before the next dose. A transdermal patch changes that shape. The skin is a barrier, and the rate at which a drug crosses it is limited and fairly constant, so the patch behaves like a slow, continuous infusion through a large surface. The result is a blood level that stays within a narrow band for many hours or days, which is precisely what is wanted for a drug that the body eliminates quickly and that would otherwise need several doses a day. This explains the choice of drugs used in patches: nitroglycerin, scopolamine, nicotine, clonidine and fentanyl are all drugs that act at low doses and are cleared rapidly if given another way. It also explains the limits. Because the skin is the rate-limiting step, a drug that penetrates poorly can never be delivered in useful amounts, so only relatively small daily doses are possible. The patch must be placed on clean, intact, hairless skin, since damaged or hairy skin changes absorption unpredictably, and rotating the site prevents irritation. Finally, the ease of stopping is both a safety feature and a limitation: removing the patch ends delivery at once, but the drug already in the skin and blood continues to act for some time, so a patient cannot expect instant reversal of every effect.

The topical routes are taught as local, and for the skin and the ear this is largely true: an ointment on eczema or drops in an infected ear canal act where they are placed, and very little drug reaches the blood. But the same principle breaks down at three surfaces. The nasal mucosa is thin, extremely well supplied with blood, and directly connected to the general circulation, which is why nasal sprays can be used deliberately for systemic effects such as nicotine for smoking cessation, calcitonin for osteoporosis or sumatriptan for migraine — and why their side effects include irritation of the passages and damage to the cilia. The conjunctiva and cornea also allow absorption; a drug placed in the eye can travel through the tear duct into the nose and thence into the blood, which is why some eye drops produce effects elsewhere in the body, and why patients are taught to press the inner corner of the eye after instilling drops. The vaginal wall absorbs slowly but steadily, so vaginal forms can produce systemic effects as well as local ones, and substances absorbed here may partly avoid first-pass metabolism. The practical lesson is to stop equating the site of application with the site of action. Ask three questions of any topical order: where is the drug meant to act, can it cross this surface into the blood, and if it can, what else in the body might be affected? The answers decide whether the prescriber is using a local treatment or an unusual systemic route.