Sublingual
Encyclopedia
Sublingual, literally 'under the tongue
', from Latin
, refers to the pharmacological route of administration
by which drug
s 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.
beneath the tongue, or buccal mucosa, 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 enzyme
s 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
.
, 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 to administration via the nasal mucosa. Many people are forced by the high cost of pharmaceuticals to split their pills and take them sublingually. One drawback, however, is tooth discoloration and decay caused by long-term use of this method with acidic or otherwise caustic drugs and fillers.
, MDMA, morphine
, alprazolam
, clonazepam
, and many other drugs including the psychedelic tryptamine
s and phenethylamine
s 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 a repulsive taste which makes them difficult to hold in the mouth. Tablets of psychoactive pharmaceuticals often include bitter chemicals such as denatonium
in order to discourage abuse and also to discourage children from eating them..
Tongue
The tongue is a muscular hydrostat on the floors of the mouths of most vertebrates which manipulates food for mastication. It is the primary organ of taste , as much of the upper surface of the tongue is covered in papillae and taste buds. It is sensitive and kept moist by saliva, and is richly...
', from Latin
Latin
Latin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...
, refers to the pharmacological route of administration
Route of administration
A route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is taken into the body.-Classification:Routes of administration are usually classified by application location...
by which drug
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
s 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.
Principle
When a chemical comes in contact with the mucous membraneMucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
beneath the tongue, or buccal mucosa, it diffuses through it. Because the connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
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
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
, which risks degrading them, either by stomach acid or bile, or by the many enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s therein, such as monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...
(MAO). Furthermore, after absorption from the gastrointestinal tract, such drugs must pass to the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, where they may be extensively altered; this is known as the first pass effect
First pass effect
The first-pass effect is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption which is generally related to the liver and gut wall...
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
Salvinorin A
Salvinorin A is the main active psychotropic molecule in Salvia divinorum, a Mexican plant which has a long history of use as an entheogen by indigenous Mazatec shamans...
.
Substance
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 pHPH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
, 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 to administration via the nasal mucosa. Many people are forced by the high cost of pharmaceuticals to split their pills and take them sublingually. One drawback, however, is tooth discoloration and decay caused by long-term use of this method with acidic or otherwise caustic drugs and fillers.
Psychoactives
In addition to Salvinorin A, other psychoactives may too be applied sublingually. LSDLSD
Lysergic acid diethylamide, abbreviated LSD or LSD-25, also known as lysergide and colloquially as acid, is a semisynthetic psychedelic drug of the ergoline family, well known for its psychological effects which can include altered thinking processes, closed and open eye visuals, synaesthesia, an...
, MDMA, morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, alprazolam
Alprazolam
Alprazolam is a short-acting anxiolytic of the benzodiazepine class of psychoactive drugs. Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA gamma-amino-butyric acid receptor...
, clonazepam
Clonazepam
Clonazepamis a benzodiazepine drug having anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties. It is marketed by Roche under the trade name Klonopin in the United States and Rivotril in Australia, Brazil, Canada and Europe...
, and many other drugs including the psychedelic tryptamine
Tryptamine
Tryptamine is a monoamine alkaloid found in plants, fungi, and animals. It is based around the indole ring structure, and is chemically related to the amino acid tryptophan, from which its name is derived...
s and phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...
s 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
Dimethyltryptamine
N,N-Dimethyltryptamine is a naturally occurring psychedelic compound of the tryptamine family. DMT is found in several plants, and also in trace amounts in humans and other mammals, where it is originally derived from the essential amino acid tryptophan, and ultimately produced by the enzyme INMT...
) 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 a repulsive taste which makes them difficult to hold in the mouth. Tablets of psychoactive pharmaceuticals often include bitter chemicals such as denatonium
Denatonium
Denatonium, usually available as denatonium benzoate and as denatonium saccharide, is the bitterest chemical compound known; with bitterness thresholds of 0.05 ppm for the benzoate and 0.01 ppm for the saccharide.It was discovered in 1958 during research on local anesthetics by Macfarlan...
in order to discourage abuse and also to discourage children from eating them..