Molecular mechanism of action
The key feature of systemic retinoids is their ability to interact with specific nuclear (intracellular) receptors. In the body, the active form of vitamin A is retinoic acid. Having penetrated through the cell membrane into the cytoplasm and then into the nucleus, it finds its targets.
Pharmacologists distinguish two main types of such receptors:
- RAR (retinoic acid receptors);
- RXR (retinoid X receptors).
The resulting activated vitamin-nuclear receptor complex binds to specific regulatory DNA elements. As a result of this interaction, a change in gene transcription occurs. Thus, the ultimate pharmacological effect is realized through the fine regulation of specific protein synthesis. It is worth noting that biocatalytic activity is exhibited not by the original vitamins themselves, but by the products of their biotransformation (coenzymes). This intracellular mechanism of action makes retinoids akin to vitamin D preparations, which also work through nuclear structures.
Systemic effects
At the whole-organism level, retinoids perform a number of critically important functions:
- Epithelial regulation. The drugs strictly control the processes of division (proliferation) and maturation (differentiation) of epithelial cells. This applies to all epithelial tissues, including the cells of the corneal epithelium.
- Maintenance of vision. Vitamin A is absolutely essential for the normal functioning of the visual analyzer. It participates in the complex photochemical cycle of the retinal visual pigment, which provides a person with adequate scotopic vision.
- Immunomodulation. Retinoids have a pronounced effect on the immune system. They are able to modulate leukocyte activity and regulate lysozyme levels, thereby increasing the body's resistance to infectious agents.
Pharmacokinetics: absorption, transport, and storage
Since retinoids belong to the group of fat-soluble compounds, their metabolism has a number of specific features. For the full absorption of these drugs in the intestine, the participation of bile is mandatory. It is bile acids that provide the process of micelle formation, without which the assimilation of fat-soluble molecules is impossible.
After absorption, the delivery of vitamins to target tissues is carried out using specific blood transport proteins. The vast majority of these carrier proteins are synthesized by hepatocytes. Excess retinoids are not excreted immediately, but accumulate in the liver, forming a depot. From this reservoir, active substances are released gradually, strictly in accordance with the metabolic needs of the body.
Levels of retinoid metabolism disorders
In clinical practice, the effects of retinoids may not be properly realized. Violations occur at several successive stages:
- Failure of the release of the vitamin or its precursor (provitamin) from food products.
- Impaired intestinal absorption. Most often, this occurs due to bile deficiency in cholestasis syndrome, which is a critical factor specifically for fat-soluble vitamins.
- Decreased synthesis of specific blood transport proteins (e.g., in severe liver pathology), which disrupts delivery even with normal absorption.
- Inability to release the vitamin from the transport complex (disruption of the dissociation of the transport protein-vitamin complex).
- Receptor pathologies in which the interaction of the free ligand or complex with cellular nuclear receptors is disrupted.
- Blocking of intracellular metabolism when the transformation of the molecule into the active form or coenzyme is disrupted.
Application in dermatology: therapy of pyodermas
In dermatological practice, systemic retinoids occupy a special place in the treatment of severe pustular skin diseases (pyodermas). In particular, the drug Isotretinoinum (isotretinoin) has strict indications for prescription. It is used for dissecting folliculitis, as well as for perifolliculitis capitis abscedens et suffodiens.
Unlike milder forms of infections where topical antibacterial agents or antiseptics are sufficient, deep and stubborn processes require powerful systemic intervention aimed at changing the properties of the epithelium itself and the follicular apparatus.
In order not to confuse retinoid receptors, remember: RAR stands for Receptors of Active Retinol (retinoic acid), while RXR stands for Receptors with an "X-factor" (retinoid X receptors). Both groups are located deep inside the cell, in the nucleus.
Class and exam questions
Why is the assimilation of systemic retinoids impaired in cholestasis?
Retinoids are fat-soluble substances. For their absorption in the intestine, micelle formation with bile acids is necessary, so in case of bile deficiency, this process is blocked.
How do liver pathologies affect the transport of vitamin A?
Hepatocytes synthesize specific blood transport proteins. In liver diseases, their deficiency occurs, which disrupts the delivery of the vitamin to tissues even with its normal intake into the body.
What is the difference between the mechanism of action of retinoids and most other drugs?
They act not through rapid membrane receptors, but penetrate into the cell nucleus, where they bind to DNA and directly alter gene transcription and the synthesis of specific proteins.
In what forms of pyoderma is isotretinoin indicated?
The drug is prescribed strictly according to indications for severe lesions: dissecting folliculitis and scalp perifolliculitis.
What else to study on this topic
- Metabolism and activation of cholecalciferol (vitamin D) in the liver and kidneys
- Topical antibacterial drugs in the therapy of pyodermas
- Systemic and topical glucocorticosteroids in dermatology
- Immunobiological agents for the treatment of staphylococcal infections
- Antioxidant function of tocopherol (vitamin E) at the molecular level
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