STUDY - Technical - New Dacian's Medicine
Drug-Induced
Skin Reactions (2)
Translation Draft
I 'remained' to the pathogenicity of non-immunological drug reactions. Non-immunological mechanisms are responsible for most drug reactions (but, nevertheless, I will present only the most important of them).
And, I'm going to start with the non-immunological activity of the effector paths. Medicinal reactions can result from non-immunological activation of the effector pathways by three mechanisms: 1. drugs can release mediators directly from mastocytes and basophils, and manifest as anaphylactic or urticarian reaction and/ or angioedema (anaphylactic urticaria reactions induced by opiates, polymixin B, tubocurarin, radiological contrast media and dextrans may occur by this mechanism), 2. medicines can activate the complement in the absence of antibody (this is an additional mechanism by which radiological contrast media can act) and 3. drugs like aspirin and other nonsteroidal anti-inflammatory agents can alter the pathways of arachidonic metabolism (these drugs inhibit cyclooxygenase which catalyzes, in vitro, the generation of prostaglandins from arachidonic acid).
Phototoxic reactions may be drug-induced or may occur in metabolic disorders in which a corresponding photosensitizing chemical is produced in excess. In each case, the phototoxic reaction occurs when sufficient chromophorus (medicine or metabolic product) absorbs sufficient radiation into the reactive tissue. Medicinally induced phototoxic reactions may occur at first exposure, and the incidence of phototoxicity is directly proportional to the concentration of the sensitizer and the amount of light. At least three photochemical mechanisms have been described.
In the first laugh, the reaction between the excited state of a phototoxic molecule and a biological target can cause the formation of a covalent photoadition product. Secondly, the phototoxic molecule can absorb protons to form stable photoproducts that are toxic to biological substrates. Third, irradiating a phototoxic molecule can lead to the transfer of energy to oxygen molecules, causing the synthesis of toxic forms of oxygen, such as atomic oxygen, superoxide anion or hydroxyl radical.
Their interaction with biological targets produces photooxided molecules. Serum protein-dependent systems and circulating effector cells play a role, in vivo, in acute phototoxic tissue lesions due to exogenous agents (a normal number of polymorphonuclears and an intact complement system are required for the full development of demeclocicline-induced phototoxic lesions).
Various agents can exacerbate pre-existing diseases. For example, lithium can accentuate acne and psoriasis in a way that depends on the dose. Betablockers and lithium may induce psoriaziform dermatitis, and discontinuation of glucocorticoids may exacerbate psoriasis or atopic dermatitis. Exacerbations of skin lupus have been observed in the use of cimetidine. Vasodilators can exacerbate rosacea.
Now, a few things about hereditary enzyme or protein deficiencies. Genetically determined specific defects in an individual's ability to detoxify toxic drug metabolites may predispose these individuals to serious drug reactions, especially hypersensitivity syndrome and toxic epidermal necrolysis (NET) associated with the use of sulfonamides and anticonvulsants.
Changes in the immunological state of the patient may also alter the risk of skin reactions. Patients with bone marrow transplantation often experience medicinal skin reactions. These reactions can be difficult to differentiate from acute graft-to-host reactions, even when a skin biopsy is performed. People infected with HIV are 5-10 times more likely to develop skin reactions, and this increased risk is not only explained by the large number of drugs used by these patients, as the risk of these reactions increases as immunological functions deteriorate.
Skin reactions to trimetoprim-sulfamethoxazole occur in about one third of HIV-infected users of this drug. Dapsona, single trimetos and amoxicillin with clavulanic acid are also common causes of drug rashes in these patients. Some medicines cause specific problems in people infected with HIV. For example, phoscarnet causes a painful penian ulcer in a substantial number of patients. People infected with HIV are at greater risk for the most serious types of reactions, including toxic epidermal necrolysis (NET) and Stevens-Johnson syndrome.
To address now the characteristic features of drug skin reactions. Drug-induced skin disorders by known mechanisms include urticaria, photosensitivity, pigmentation changes, vasculitis, phenytoin hypersensitivity syndrome and warfarin necrosis of the skin. Uncertain mechanism reactions include morbid reactions, polymorphic erythema, fixed drug reactions, nodos erythema, lichenoid reactions, bullous drug reactions and NET.
Among the known reactions, urticaria is a skin reaction characterized by red, itchy papules. Injuries can range from a small point to a large area. Individual lesions rarely persist for more than 24 hours. When the tissues of the deep and subcutaneous dermis are edematized, this reaction is called angioedema. Angioedema may be of interest to the mucous membranes and may be a component of a life-threatening anaphylactic reaction.
Urticaria lesions along with pruritus and morbiliform (or maculopapular) rashes are among the most common types of skin reactions to drugs. Drug-induced urticaria can be caused by three mechanisms: 1. an dependent IgE mechanism, 2. circulating immune complexes (serum disease) and 3. non-immunological activation of effector paths. Dependent IgE urticaria reactions usually occur within 36 hours, but can also occur within minutes. Reactions that occur within minutes or hours of exposure to the medicine are designated as immediate reactions, and those that occur 12-36 hours after exposure to the medicine are called accelerated reactions.
Urticaria induced by immune complexes, associated with serum disease, can occur 4-12 days after exposure. In this syndrome, urticaria rash may be accompanied by fever, hematuria and arthralgia, liver dysfunction and neurological symptoms. Certain medicines, such as non-steroidal anti-inflammatory agents, angiotensin conversion enzyme (ACE) inhibitors and radioopaque substances, may induce urticaria, angioedema and anaphylaxis in the absence of drug-specific antibodies. Although aspirin, penicillin and blood-derived products are the most common causes of urticaria rash, urticaria has been observed in combination with almost all medications.
Medications can also cause chronic hives, which last over 6 weeks. The mechanisms of chronic urticaria are unclear. Aspirin frequently exacerbates this condition. Treatment of urticaria or angioedema depends on the severity of the reaction and the speed with which it evolves. In addition to stopping taking the drug, antihistamines are usually sufficient for patients who have only skin symptoms without symptoms of angioedema or anaphylaxis. For patients with anaphylaxis, systemic glucocorticoids are used, sometimes in intravenous administration. In cases with severe respiratory or cardiovascular alterations epinephrine is useful.
Eruptions produced by photosensitization are usually more pronounced in sun-exposed areas, but can spread to sun-protected areas. Phototoxic reactions are more common than photoallergic reactions. Phototoxic reactions usually resemble sunburn, can occur at first exposure to the drug and are dose dependent. The spectrum of action for phototoxicity is similar to the ultraviolet absorption spectrum of the drug. No test system seems to effectively estimate the potential for photosensitization for a particular compound.
The mechanism of photoallergy to systemic medications is not well defined. The drug, immune response and light are necessary to produce clinical photoallergy, and photoallergic reactions can be delayed hypersensitivity responses. Eruptions range from lichenoid papules to eczematous changes. Oral medicines that cause photoallergic or phototoxic reactions include chlorpromazine, tetracycline, thiazides, two non-steroidal anti-inflammatory agents (benoxaprofen and pyroxicam) and quinolonic antibiotics.
Based on test systems, most ordinary photosensitizers appear to have a spectrum of action located in the field of high wavelength ultraviolet (UV-A) and are usually phototoxic. This is favorable, as phototoxic reactions will disappear when removing either the drug or ultraviolet radiation, but some photoallergic reactions may persist after the drug has been discontinued.
Because the UV-A and the visible light that triggers these reactions are not easily absorbed by the opaque solar filters, these reactions can be difficult to block. Photosensitivity reactions are treated by avoiding exposure to ultraviolet (sunlight) and treatment similar to sunburn. It should be noted that individuals who experience serious photosensitivity reactions may react after several weeks of avoiding sunlight, as the medicine may persist in the skin for a while. Sometimes individuals develop persistent sensitivity of light, requiring long-term avoidance of sun exposure.
I will complete this post with a presentation of some details about the pigmentation changes. Medications can cause various pigmentation changes in the skin. Some drugs stimulate melanocytic activity and accentuate pigmentation. Drug deposits can also lead to pigmentation (a phenomenon that occurs in heavy metals). Phenothiazides can be stored in the skin and cause a gray coloration, like slate.
Antimalariars can cause yellow or grey pigmentation, such as slate. Long-term administration of minocycline may produce grey coloration (slate), especially in areas with chronic inflammation. Inorganic arsenic, once used for the treatment of psoriasis, is associated with diffuse macular pigmentation. Other heavy metals that cause pigmentation changes are silver, gold, bismuth and mercury. Long-term use of phenytoin can produce cloasma-like pigmentation in women.
Certain cytostatic agents can also cause pigmentation changes. Histological examination is often diagnosed for diseases with drug storage. Zidovudine (AZT) is a common cause of pigmentation, especially of the nails. Clofazimin, an aminophenazine dye used to treat leprea, causes a red skin coloration that is so marked that some patients discontinue therapy.
Metisergide produces a red skin color and a texture "in orange peel". Nicotinic acid in high doses can cause brown pigmentation. Oral contraceptives can produce cloasma, and adenocorticotropin can cause hypermelanosis similar to that of primary adrenal insufficiency. In addition, amiodarone can cause violaceous hyperpigmentation, which is more intense on sun-exposed skin. Medicines such as heavy metals, copper, antimalarial and arsenic agents and ACTH can also alter the color of the oral mucosa.
I'll keep going!
I 'remained' to the pathogenicity of non-immunological drug reactions. Non-immunological mechanisms are responsible for most drug reactions (but, nevertheless, I will present only the most important of them).
And, I'm going to start with the non-immunological activity of the effector paths. Medicinal reactions can result from non-immunological activation of the effector pathways by three mechanisms: 1. drugs can release mediators directly from mastocytes and basophils, and manifest as anaphylactic or urticarian reaction and/ or angioedema (anaphylactic urticaria reactions induced by opiates, polymixin B, tubocurarin, radiological contrast media and dextrans may occur by this mechanism), 2. medicines can activate the complement in the absence of antibody (this is an additional mechanism by which radiological contrast media can act) and 3. drugs like aspirin and other nonsteroidal anti-inflammatory agents can alter the pathways of arachidonic metabolism (these drugs inhibit cyclooxygenase which catalyzes, in vitro, the generation of prostaglandins from arachidonic acid).
Phototoxic reactions may be drug-induced or may occur in metabolic disorders in which a corresponding photosensitizing chemical is produced in excess. In each case, the phototoxic reaction occurs when sufficient chromophorus (medicine or metabolic product) absorbs sufficient radiation into the reactive tissue. Medicinally induced phototoxic reactions may occur at first exposure, and the incidence of phototoxicity is directly proportional to the concentration of the sensitizer and the amount of light. At least three photochemical mechanisms have been described.
In the first laugh, the reaction between the excited state of a phototoxic molecule and a biological target can cause the formation of a covalent photoadition product. Secondly, the phototoxic molecule can absorb protons to form stable photoproducts that are toxic to biological substrates. Third, irradiating a phototoxic molecule can lead to the transfer of energy to oxygen molecules, causing the synthesis of toxic forms of oxygen, such as atomic oxygen, superoxide anion or hydroxyl radical.
Their interaction with biological targets produces photooxided molecules. Serum protein-dependent systems and circulating effector cells play a role, in vivo, in acute phototoxic tissue lesions due to exogenous agents (a normal number of polymorphonuclears and an intact complement system are required for the full development of demeclocicline-induced phototoxic lesions).
Various agents can exacerbate pre-existing diseases. For example, lithium can accentuate acne and psoriasis in a way that depends on the dose. Betablockers and lithium may induce psoriaziform dermatitis, and discontinuation of glucocorticoids may exacerbate psoriasis or atopic dermatitis. Exacerbations of skin lupus have been observed in the use of cimetidine. Vasodilators can exacerbate rosacea.
Now, a few things about hereditary enzyme or protein deficiencies. Genetically determined specific defects in an individual's ability to detoxify toxic drug metabolites may predispose these individuals to serious drug reactions, especially hypersensitivity syndrome and toxic epidermal necrolysis (NET) associated with the use of sulfonamides and anticonvulsants.
Changes in the immunological state of the patient may also alter the risk of skin reactions. Patients with bone marrow transplantation often experience medicinal skin reactions. These reactions can be difficult to differentiate from acute graft-to-host reactions, even when a skin biopsy is performed. People infected with HIV are 5-10 times more likely to develop skin reactions, and this increased risk is not only explained by the large number of drugs used by these patients, as the risk of these reactions increases as immunological functions deteriorate.
Skin reactions to trimetoprim-sulfamethoxazole occur in about one third of HIV-infected users of this drug. Dapsona, single trimetos and amoxicillin with clavulanic acid are also common causes of drug rashes in these patients. Some medicines cause specific problems in people infected with HIV. For example, phoscarnet causes a painful penian ulcer in a substantial number of patients. People infected with HIV are at greater risk for the most serious types of reactions, including toxic epidermal necrolysis (NET) and Stevens-Johnson syndrome.
To address now the characteristic features of drug skin reactions. Drug-induced skin disorders by known mechanisms include urticaria, photosensitivity, pigmentation changes, vasculitis, phenytoin hypersensitivity syndrome and warfarin necrosis of the skin. Uncertain mechanism reactions include morbid reactions, polymorphic erythema, fixed drug reactions, nodos erythema, lichenoid reactions, bullous drug reactions and NET.
Among the known reactions, urticaria is a skin reaction characterized by red, itchy papules. Injuries can range from a small point to a large area. Individual lesions rarely persist for more than 24 hours. When the tissues of the deep and subcutaneous dermis are edematized, this reaction is called angioedema. Angioedema may be of interest to the mucous membranes and may be a component of a life-threatening anaphylactic reaction.
Urticaria lesions along with pruritus and morbiliform (or maculopapular) rashes are among the most common types of skin reactions to drugs. Drug-induced urticaria can be caused by three mechanisms: 1. an dependent IgE mechanism, 2. circulating immune complexes (serum disease) and 3. non-immunological activation of effector paths. Dependent IgE urticaria reactions usually occur within 36 hours, but can also occur within minutes. Reactions that occur within minutes or hours of exposure to the medicine are designated as immediate reactions, and those that occur 12-36 hours after exposure to the medicine are called accelerated reactions.
Urticaria induced by immune complexes, associated with serum disease, can occur 4-12 days after exposure. In this syndrome, urticaria rash may be accompanied by fever, hematuria and arthralgia, liver dysfunction and neurological symptoms. Certain medicines, such as non-steroidal anti-inflammatory agents, angiotensin conversion enzyme (ACE) inhibitors and radioopaque substances, may induce urticaria, angioedema and anaphylaxis in the absence of drug-specific antibodies. Although aspirin, penicillin and blood-derived products are the most common causes of urticaria rash, urticaria has been observed in combination with almost all medications.
Medications can also cause chronic hives, which last over 6 weeks. The mechanisms of chronic urticaria are unclear. Aspirin frequently exacerbates this condition. Treatment of urticaria or angioedema depends on the severity of the reaction and the speed with which it evolves. In addition to stopping taking the drug, antihistamines are usually sufficient for patients who have only skin symptoms without symptoms of angioedema or anaphylaxis. For patients with anaphylaxis, systemic glucocorticoids are used, sometimes in intravenous administration. In cases with severe respiratory or cardiovascular alterations epinephrine is useful.
Eruptions produced by photosensitization are usually more pronounced in sun-exposed areas, but can spread to sun-protected areas. Phototoxic reactions are more common than photoallergic reactions. Phototoxic reactions usually resemble sunburn, can occur at first exposure to the drug and are dose dependent. The spectrum of action for phototoxicity is similar to the ultraviolet absorption spectrum of the drug. No test system seems to effectively estimate the potential for photosensitization for a particular compound.
The mechanism of photoallergy to systemic medications is not well defined. The drug, immune response and light are necessary to produce clinical photoallergy, and photoallergic reactions can be delayed hypersensitivity responses. Eruptions range from lichenoid papules to eczematous changes. Oral medicines that cause photoallergic or phototoxic reactions include chlorpromazine, tetracycline, thiazides, two non-steroidal anti-inflammatory agents (benoxaprofen and pyroxicam) and quinolonic antibiotics.
Based on test systems, most ordinary photosensitizers appear to have a spectrum of action located in the field of high wavelength ultraviolet (UV-A) and are usually phototoxic. This is favorable, as phototoxic reactions will disappear when removing either the drug or ultraviolet radiation, but some photoallergic reactions may persist after the drug has been discontinued.
Because the UV-A and the visible light that triggers these reactions are not easily absorbed by the opaque solar filters, these reactions can be difficult to block. Photosensitivity reactions are treated by avoiding exposure to ultraviolet (sunlight) and treatment similar to sunburn. It should be noted that individuals who experience serious photosensitivity reactions may react after several weeks of avoiding sunlight, as the medicine may persist in the skin for a while. Sometimes individuals develop persistent sensitivity of light, requiring long-term avoidance of sun exposure.
I will complete this post with a presentation of some details about the pigmentation changes. Medications can cause various pigmentation changes in the skin. Some drugs stimulate melanocytic activity and accentuate pigmentation. Drug deposits can also lead to pigmentation (a phenomenon that occurs in heavy metals). Phenothiazides can be stored in the skin and cause a gray coloration, like slate.
Antimalariars can cause yellow or grey pigmentation, such as slate. Long-term administration of minocycline may produce grey coloration (slate), especially in areas with chronic inflammation. Inorganic arsenic, once used for the treatment of psoriasis, is associated with diffuse macular pigmentation. Other heavy metals that cause pigmentation changes are silver, gold, bismuth and mercury. Long-term use of phenytoin can produce cloasma-like pigmentation in women.
Certain cytostatic agents can also cause pigmentation changes. Histological examination is often diagnosed for diseases with drug storage. Zidovudine (AZT) is a common cause of pigmentation, especially of the nails. Clofazimin, an aminophenazine dye used to treat leprea, causes a red skin coloration that is so marked that some patients discontinue therapy.
Metisergide produces a red skin color and a texture "in orange peel". Nicotinic acid in high doses can cause brown pigmentation. Oral contraceptives can produce cloasma, and adenocorticotropin can cause hypermelanosis similar to that of primary adrenal insufficiency. In addition, amiodarone can cause violaceous hyperpigmentation, which is more intense on sun-exposed skin. Medicines such as heavy metals, copper, antimalarial and arsenic agents and ACTH can also alter the color of the oral mucosa.
I'll keep going!
Have a good day!
Dorin, Merticaru