Sublingual administration

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Sublingual (abbreviated SL), from the Latin for "under the tongue", refers to the pharmacological route of administration by which substances diffuse into the blood through tissues under the tongue. [1]

Contents

Many drugs are absorbed through sublingual administration, including cardiovascular drugs, steroids, barbiturates, benzodiazepines, [2] opioid analgesics, THC, CBD, some proteins and increasingly, vitamins and minerals.

Principle

When a chemical comes in contact with the mucous membrane beneath the tongue, it is absorbed. Because the connective tissue beneath the epithelium contains a profusion of capillaries, the substance then diffuses into them and enters the venous circulation. [1] 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 onset of action, 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 enzymes 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, the oral route is unsuitable for certain substances, such as salvinorin A.

Forms

Pharmaceutical preparations for sublingual administration are manufactured in the form of:

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, 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.[ citation needed ] 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, morphine, alprazolam, clonazepam, diazepam, and many other substances including the psychedelic tryptamines and phenethylamines, and even recreational cannabis edibles (THC) are all viable candidates for administration via this route.[ citation needed ] 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) 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.[ citation needed ]

Allergens

Allergens 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 peptides and proteins (such as cytokines, domain antibodies, Fab fragments or single chain antibodies) is sublingual administration. Peptides and proteins are not stable in the gastro-intestinal tract, 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, Sanofi and BioLingus. [3] 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 [4] [5] and Helicobacter pylori, [6] but sublingual administration may also be used for vaccines against other infectious diseases.[ citation needed ]

Footnotes

  1. 1 2 Grewal, JS; Bordoni, B; Ryan, J (2020), "article-36176", Anatomy, Head and Neck, Sublingual Gland, This book is distributed under the terms of the Creative Commons Attribution 4.0 International License (creativecommons.org), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, a link is provided to the Creative Commons license, and any changes made are indicated., Treasure Island (FL): StatPearls Publishing, PMID   30571047 , retrieved 2020-03-28{{citation}}: External link in |others= (help)
  2. "ATIVAN 1 mg SUBLINGUAL TABLETS; ATIVAN 2 mg SUBLINGUAL TABLETS". home.intekom.com. Retrieved 2016-07-08.
  3. "Biolingus". www.biolingus.ch.
  4. Sambhara, Suryaprakash; Pedersen, Gabriel Kristian; Ebensen, Thomas; Gjeraker, Ingrid Hjetland; Svindland, Signe; Bredholt, Geir; Guzmán, Carlos Alberto; Cox, Rebecca Jane (2011). "Evaluation of the Sublingual Route for Administration of Influenza H5N1 Virosomes in Combination with the Bacterial Second Messenger c-di-GMP". PLOS ONE. 6 (11): e26973. Bibcode:2011PLoSO...626973P. doi: 10.1371/journal.pone.0026973 . ISSN   1932-6203. PMC   3206068 . PMID   22069479.
  5. Song, J.-H.; Nguyen, H. H.; Cuburu, N.; Horimoto, T.; Ko, S.-Y.; Park, S.-H.; Czerkinsky, C.; Kweon, M.-N. (2008). "Sublingual vaccination with influenza virus protects mice against lethal viral infection". Proceedings of the National Academy of Sciences. 105 (5): 1644–1649. doi: 10.1073/pnas.0708684105 . ISSN   0027-8424. PMC   2234198 . PMID   18227512.
  6. Raghavan, S; Ostberg, AK; Flach, CF; Ekman, A; Blomquist, M; Czerkinsky, C; Holmgren, J (October 2010). "Sublingual immunization protects against Helicobacter pylori infection and induces T and B cell responses in the stomach". Infection and Immunity. 78 (10): 4251–60. doi:10.1128/IAI.00536-10. PMC   2950356 . PMID   20696831.

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