Sublingual (abbreviated SL), literally 'under the tongue', from Latin, refers to the pharmacological route of administration by which drugs diffuse into the blood through tissues under the tongue. Many pharmaceuticals are designed for sublingual administration, including cardiovascular drugs, steroids, barbiturates, enzymes, and increasingly, vitamins and minerals.
When a chemical comes in contact with the mucous membrane beneath the tongue, it diffuses through it. Because the connective tissue beneath the epithelium contains a profusion of capillaries, the substance then diffuses into them and enters the venous circulation. In contrast, substances absorbed in the intestines are subject to "first pass metabolism" in the liver before entering the general circulation.
Sublingual administration has certain advantages over oral administration. Being more direct, it is often faster, and it ensures that the substance will risk degradation only by salivary enzymes before entering the bloodstream, whereas orally administered drugs must survive passage through the hostile environment of the gastrointestinal tract, which risks degrading them, either by stomach acid or bile, or by the many enzymes therein, such as monoamine oxidase (MAO). Furthermore, after absorption from the gastrointestinal tract, such drugs must pass to the liver, where they may be extensively altered; this is known as the first pass effect of drug metabolism. Due to the digestive activity of the stomach and intestines and the solubility of the GI tract, the oral route is unsuitable for certain substances, such as salvinorin A .
Almost any form of substance may be amenable to sublingual administration if it dissolves easily in saliva. Powders and aerosols may all take advantage of this method. However, a number of factors, such as pH, molecular weight, and lipid solubility, may determine whether the route is practical. Based on these properties, a suitably soluble drug may diffuse too slowly through the mucosa to be effective. However, many drugs are much more potent taken sublingually, and it is generally a safer alternative than administration via the nasal mucosa. This method is also extensively used by people administering certain psychoactive drugs. One drawback, however, is tooth discoloration and decay caused by long-term use of this method with acidic or otherwise caustic drugs and fillers.
In addition to Salvinorin A, other psychoactives may also be applied sublingually. LSD, MDMA, morphine, alprazolam, clonazepam, and many other drugs including the psychedelic tryptamines and phenethylamines are all viable candidates for administration via this route. Most often, the drug in question is powdered and placed in the mouth (often directly under the tongue). If held there long enough, the drug will diffuse into the blood stream, bypassing the GI tract. This is definitely a preferred method to simple oral administration, because MAO is known to oxidize many drugs (especially the tryptamines such as DMT) and because this route translates the chemical directly to the brain, where most psychoactives act. The method is limited by excessive salivation washing the chemical down the throat. Also, many alkaloids have an unpleasant taste which makes them difficult to hold in the mouth. Tablets of psychoactive pharmaceuticals usually include bitter chemicals such as denatonium in order to discourage abuse and also to discourage children from eating them.
Allergens may also be applied under the tongue, and the FDA is reviewing this method of allergen immunotherapy but it is not yet approved in the US. In 2007, Roder published work showing sublingual immunotherapy with grass pollen is not effective in symptomatic youngsters in primary care.
The sublingual route may also be used for vaccines against various infectious diseases. Thus, preclinical studies have found that sublingual vaccines can be highly immunogenic and may protect against influenza virus  and Helicobacter pylori, but sublingual administration may also be used for vaccines against other infectious diseases.
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