Sublingual (
abbreviated SL), from the
Latin
Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through ...
for "under the
tongue", refers to the
pharmacological route of administration by which substances diffuse into the
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
through
tissues under the tongue.
The
sublingual glands receive their primary blood supply from the sublingual and submental arteries, which are branches of the
lingual artery
The lingual artery arises from the external carotid artery between the superior thyroid artery and facial artery. It can be located easily in the tongue.
Structure
The lingual artery first branches off from the external carotid artery. It runs ...
and
facial artery, respectively. These arteries are both branches of the
external carotid artery. The
sublingual vein
The sublingual vein is a vein which drains the tongue
The tongue is a muscular organ in the mouth of a typical tetrapod. It manipulates food for mastication and swallowing as part of the digestive process, and is the primary organ of taste. Th ...
drains into the
lingual vein, which then flows into the
internal jugular system
Internal may refer to:
*Internality as a concept in behavioural economics
*Neijia, internal styles of Chinese martial arts
*Neigong or "internal skills", a type of exercise in meditation associated with Daoism
*''Internal (album)'' by Safia, 2016
...
.
The sublingual glands receive their parasympathetic input via the
chorda tympani nerve, which is a branch of the
facial nerve via the
submandibular ganglion. The nerve functions in a
secretomotor capacity. The chorda tympani branches from the motor branch of the facial nerve in the
middle ear cavity
Middle or The Middle may refer to:
* Centre (geometry), the point equally distant from the outer limits.
Places
* Middle (sheading), a subdivision of the Isle of Man
* Middle Bay (disambiguation)
* Middle Brook (disambiguation)
* Middle Creek ( ...
, which then exits the middle ear through the
petrotympanic fissure. The chorda tympani then travels with the
lingual nerve to synapse at the submandibular ganglion. The
postganglionic fibers reach the sublingual gland, and release
acetylcholine and
substance P. Acetylcholine, the primary neurotransmitter and the
muscarinic receptor
Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...
s work to increase
salivation.
Many drugs are absorbed through sublingual administration, including
cardiovascular drugs,
steroid
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
s,
barbiturate
Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential a ...
s, benzodiazepines,
opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
analgesics,
THC,
CBD, some
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s and increasingly,
vitamins and
minerals
In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid chemical compound with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed ...
.
Principle
When a chemical comes in contact with the
mucous membrane beneath the tongue, it is absorbed. Because the
connective tissue
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
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, by either stomach acid or bile, or by
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s such as
monoamine oxidase (MAO). Furthermore, after absorption from the gastrointestinal tract, such drugs must pass to the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
, 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, the oral route is unsuitable for certain substances, such as
salvinorin A.
Forms
Pharmaceutical preparations for sublingual administration are manufactured in the form of:
* Sublingual tablets—tablets which easily melt in the mouth, dissolve rapidly and with little or no residue. Nitroglycerine tablets are an example, the anti-emetic
ondansetron is another.
* Sublingual strips—similar to tablets in that they easily melt in the mouth and dissolve rapidly.
Suboxone is an example of medication that comes in a sublingual strip.
* Multi-purpose tablets—Soluble tablets for either oral or sublingual (or
buccal) administration, often also suitable for preparation of injections, Hydrostat (
hydromorphone) and a number of brands of morphine tablets and cubes.
* Sublingual drops—a concentrated solution to be dropped under the tongue, as with some nicocodeine cough preparations,
* Sublingual spray—spray for the tongue; certain human and veterinary drugs are dispensed as such.
*
Lozenge
Lozenge or losange may refer to:
*Lozenge (shape), a type of rhombus
*Throat lozenge, a tablet intended to be dissolved slowly in the mouth to suppress throat ailments
*Lozenge (heraldry), a diamond-shaped object that can be placed on the field of ...
—effects a metred and patient-controlled-rate combination of sublingual, buccal, and oral administration, as with the Actiq
fentanyl
Fentanyl, also spelled fentanil, is a very potent synthetic opioid used as a pain medication. Together with other drugs, fentanyl is used for anesthesia. It is also used illicitly as a recreational drug, sometimes mixed with heroin, cocain ...
.
* Effervescent buccal or sublingual tablets—this method drives the drug through the mucous membranes much faster (this is the case in the stomach with carbonated or effervescent liquids as well) and is used in the Fentora fentanyl buccal tablet.
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
pH,
molecular weight
A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bio ...
, 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.
Psychoactives
In addition to
salvinorin A, other psychoactives may also be applied sublingually.
LSD,
MDMA
3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for recreational purposes. The desire ...
,
morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies ('' Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...
,
alprazolam,
clonazepam,
diazepam, and many other substances including the psychedelic
tryptamines and
phenethylamines, and even recreational
cannabis edibles
A cannabis edible, also known as a cannabis-infused food or simply an edible, is a food product (either homemade or produced commercially) that contains decarboxylated cannabinoids (cannabinoid acids converted to their orally bioactive form) f ...
(
THC) 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 may be a preferred method to simple oral administration, because MAO is known to oxidize many drugs (especially the tryptamines such as
DMT
''N'',''N''-Dimethyltryptamine (DMT or ''N'',''N''-DMT, SPL026) is a substituted tryptamine that occurs in many plants and animals, including human beings, and which is both a derivative and a structural analog of tryptamine. It is used as a ...
) 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
Allergen
An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called allergies.
In technical t ...
s may also be applied under the tongue as a part of
allergen immunotherapy.
Therapeutic peptides and proteins
A relatively new way of administration of therapeutic
peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...
s and proteins (such as
cytokines, domain
antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of ...
,
Fab fragment
The fragment antigen-binding region (Fab region) is a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. The variable domain contains the paratope (the ant ...
s or single chain antibodies) is sublingual administration. Peptides and proteins are not stable in the
gastro-intestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
, mainly due to degradation by enzymes and pH differences. As a consequence, most peptides (such as
insulin,
exenatide,
vasopressin, etc.) or proteins (such as
interferon,
EPO and
interleukins) have to be administered by injection. Recently, new technologies have allowed sublingual administration of such molecules. Increased efforts are underway to deliver macromolecules (peptides, proteins and immunotherapies) by sublingual route, by companies such as
Novo Nordisk
Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, Denmark, with production facilities in nine countries, and affiliates or offices in five countries. Novo Nordisk is controlled by majority shareholder ...
,
Sanofi and BioLingus.
Sublingual delivery may be particularly effective for immuno-active medicines, due to the presence of immune-receptor cells close to the sublingual area.
Vaccines
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.
Footnotes
External links
*
{{Dosage forms, state=expanded
Routes of administration