The Kinetics and Dynamics of Hypersensitivity - Essay Example

Running head: Type I Hypersensitivity Severity of an Allergic Reaction: The Kinetics and Dynamics of Type I Hypersensitivity Table of Contents Introduction3 Type I Hypersensitivity.3 Anaphylaxis5 Treatment...6 Antihistamines...6 Pharmacodynamics..7 Pharmacokinetics.8 Corticosteroids..8 Pharmacodynamics..9 Pharmacokinetics...10 Bronchodilators...10 Beta 2 Agonists Pharmacodynamics..11 Pharmacokinetics...11 Chinese Herbal Medicines11 References..14 Introduction Hypersensitivity is used to describe the adverse reactions of the immune system to different allergens or substances. It is an abnormal condition typified by an overstressed and inapproporiate response of the immunse system to a second exposure to antigen or allergen (Allen et al., 2002; Holmes, 2003). These antigens are usually referred to as allergens, which are any foreign substance that is capable of yielding an immune response (Porth, 2002). Typically, the result is inflammation and damage to healthy tissue (Holmes, 2003). A lot of various chemicals, whether natural or man made, are known allergens, and complex natural organic chemicals like proteins, usually cause immediate hypersensitivity response. On the other hand, simple organic substances are more commonly known to cause delayed reactions. An individual may be exposed to these allergens through inhalation, ingestion, injection, or skin contact. (Porth, 2002) The classifications of hypersensitivity are not dependent on severity, but the type of cells, and location of tissues that is affected. Hypersensitivity reactions are classified into four types: type I (mediated by IgE), type II (tissue-specific), type III (immune-complex mediated), and type IV (cell-mediated) (Holmes, 2003). The first three types are mediated by antibodies, and the fourth type is mediated by T-cells, which produce a delayed reaction or onset of symptoms. However, it is seldom that one type occurs in isolation from the other (Nowak & Handford, 2004). During a hypersensitivity reaction or allergic reaction, an individual is usually prescribed with bronchodilators, steroids, and antihistamines. This paper will discuss type I hypersensitivity or anaphylactic hypersensitivity, as well as the pharmacokinetics and pharmacodynamics of the three agents mentioned above. In addition, Chinese herbal medicines will also be briefly discussed. Type I Hypersensitivity This type describes the allergy as the immediate hypersensitivty or anaphylactic hypersensitivity. It is mediated by the IgE antibody, which results to mast cell degranulation (Porth, 2003). The most common examples are systemic anaphylaxis, hay fever, allergic rhinitis, eczema, and asthma. The mucous membranes of the organs are very richly supplied with mast cells that are filled with IgE antibodies, and these mast cells are ideally located to be able to detect the entry of antigens. Upon initial entry, the individual or host will not manifest any symptoms or reactions. However, the cells have already captured and processed the allergen, and the antigen has then bound with IgE on mast cells, which have caused the cells to degranulate. These granules then spread into the circulation and binds with the mast cells throughout the body. Subsequently, the host is ready for the next contact with the allergen. (Nowak & Handford, 2004) Now during the second exposure, the mast cells are activated, causing the release of mediators, which then result to the immediate responses of the immune system, and this response is mostly cause by the release of preformed histamines (Ewan, 1998; Nowak & Handford, 2004). Kay (2001) gave a concise aetiology of acute allergy. She summarized that immediate hypersensitivity is brought about by the release of preformed granule-associated mediators, membrane derived lipids, cytokines, and chemokines when an allergen interacts with IgE that is bound to mast cells or basophils by the high affinity IgE receptors. In addition, the primary inducers of IgE are interleukin-4 and interleukin-13, which initiate the transcription of the gene (Kay, 2001). Early reaction usually ends in one hour, while the second wave or late phase reaction manifests itself in two to eight hours, and may last for two to three days (Nowak & Handford, 2004). Anaphylaxis Anaphylaxis is a general term, which refers to any severe systemic allergic reaction that could be life-threatening. It has a rapid onset and involves various organ-systems, and is usually caused by specific antigens in sensitised individuals (Ellis and Day, 2003). There is no exact and precise definitionfor anaphylaxis because it is a complex condition that comprises of different features, and affects multiple organ-systems. Beng a more severe allergic reaction, anaphylaxis occurs much less than the regular allergic reaction, which commonly manifests itself through urticaria or irregular-shaped red patches on the skin wth severe itching Clayton & Stock, 2001). Penicillin is an antibiotic that commonly causes anaphylaxis. However, Mosby's Medical Dictionary (2002) defines anaphylaxis as "an exaggerated hypersensitivity reaction due to a previously encountered antigen. It is mediated by antibodies of the E or G class of immunoglobulins and results in the release of chemical mediators from mast cells. The reaction may consist of a localised wheal and flare of generalized itching, hyperemia, angio-oedema, and in severe cases, vascular collapse, bronchospasm, and shock." (p. 70) As such, it requires immediate treatment and proper management. Preventive measures must also be observed. If an individual is aware of specific substances that they are allergic to, then measures must be observed to avoid being exposed to them. It is important to remember, however, that anaphylaxis is different from anaphylactoid reactions in the sense that anaphylaxis is mediated by IgE while anaphylactoid reactions are usually caused by opiates, radiocontrast agents, and Non-Steroidal Anti Inflammatory Drugs or NSAID (Ellis & Day, 2003). However, clinical features are similar and both are also countered by similar treatment. Anaphylaxis may be fatal as it may result to asphyxia, respiratory arrest, or shock. The common symptoms are urticaria or hives, dizziness and fainting, angio-oedema or swelling, swelling in the throat that maycause difficulty in swallowing or breathing, asthma symptoms, abdominal pains with diarrhea, or a tingling feeling in the skin (Stern, 2003). In addition, an individual may present with normal vital signs or otherwise with tachypnea, tachycardia, and hypotension (Stern, 2003). Death may also result from an excessively low blood pressure. Treatment Bronchodilators, steroids, and antihistamines are commonly given to a person who is experiencing an immediate hypersensistivity reaction. Other medications or forms of treatment depend upon the severity of the person's case, and the amount of antigen ingested or inhaled, and it is also dependent upon the localisation of the reaction. Each medication has a different drug action and the body may synthesize it differently from the other. Antihistamines Antihistamines are the most common medication given to individuals who are experiencing allergic reactions, since it blocks the effects of histamines at the H1 receptor, therefore relieving the clinical manifestations of the allergic reactions, and relieving the individual of its discomforts (Deglin & Vallerand, 2007). Pharmacodynamics Histamine is an important mediator in an immediate hypersensitivity reaction, or type I hypersensitivity, and it is a principal stimulator of gastric acid secretion and a significant neurotransmitter in the central nervous system. Histamine is stored in the secretory granules of mast cells, and when antigens bind with the high affinity IgE receptors, histamine is released. (Martens, 2005) When histamine is released, it is distributed widely in the lungs, skin, and gastrintestinal tract mucosa, and causes dilation of capillaries, decrease in blood pressure, increase in the secretion of gastric juice, and constriction of the smooth muscles of the bronchi and uterus (Martens, 2005; Allen et al., 2002). The uses of histamine as a drug create undesirable effects. However, antihistamines are very useful and therapeutic in its nature. Antihistamines are widely used to treat general allergic reactions. However, it is unable to block the histamines on cardiovascular H2 receptors (Martens, 2005). In addition to this, antihistamines do not actually inhibit the production of histamines; rather, it only treats and reduces the clinical symptoms or manifestations of a hypersensitivity reaction, but only if the concentration of the antihistamine is greater then the concentration of the histamine released (Clayton & Stock, 2001). Although the mechanisms for this is not very well established yet, it is believed that antihistamines also inhibit the release of mediators, the migration of basophils, and the recruitment of eosinophils, which can contribute to its antiallergy effects (Martens, 2005). Pharmacokinetics Antihistamines are most commonly taken through the oral route, and are known to have an effective and reliable bioavailabilty. The timeframe for the drug action to actually manifest its effects is about 30 minutes to an hour, yet there are others that take longer than that (Martens, 2005). Thus, orally administered antihistamine is not recommended for a person who is experienceing a more severe form of allergy or anaphylaxis, and in need of immediate treatment. There are two types of antihistamines. The first type or the first generation antihistamines have general distribution and readily infiltrates the central nervous system, which in turn gives it a sedative effect. On the other hand, the second generation antihistamines like fexofenadine, loratadine, and desloratadine do not readily permeate the CNS and are thus less sedative. (Martens, 2005) Metabolism takes place in the liver, and elimination is by renal excretion, and a typical side effect would be sedation. Corticosteroids Corticosteroids come in a large number of variances, with mostly similar chemical structure that is elaborated by the adrenal cortex (Allen et al., 2002). It is a sterol preparation for the treatment and control of edema and inflammation, and depresses the immune system. It comes in topical, systemic, nasal, and inhaled preparations, which is usually used to reverse beonchospasms and cutaneous effects of anaphylaxis (Deglin & Vallerand, 2007; Krause, 2006). Some also believe that corticosteroids help in the prevention of recurrent anaphylaxis; however, the exact incidence of this has not yet been identified precisely (Krause, 2006). The common uses of this drug are allergic reactions, skin diseases, breathing problems, blood disorders, eye problems, arthritis, digestive problems, and hormonal substitute ("Generic name: Corticosteroids-Oral," 2005). Glucocorticoids and mineralocorticoids are the corticosteroids that are synthesised by the adrenal glands, and the primary glucocorticoids are cortisol and corticosterone (Allen et al., 2002). Mineralocorticoids are usually used for the treatment of Addison's disease and for the maintenance of fluid and electrolyte imbalance, while glucocorticoids are for the relief of allergic reactions (Clayton & Stock, 2001). Pharmacodynamics Glucocorticoids have localised antiinflammatory and immunosuppressant reactions, wherein it effects the leukocyte movement, antigen processing, eosinophils, and lymphatic tissues. After administering this drug, the number of circulating neutrophils increases, and reduces the adherence of the neutrophils to the vascular endothelium, thus preventing the neutrophils from exiting towards the site of inflammation. It also blocks the production of the mediators of the inflammatory response. In summary, the effect of the drug to the body is that it prevents the accumulation of neutrophils and monocytes at sites of inflammation, while it also suppresses phagocytic, bactericidal, and antigen-processign activity of the cell. However, long term glucocorticoid use may compromise the immune system, and make and individual vulnerable to infection. (Minneman & Wecker, 2005) Paradoxically, as prolonged use may result to adrenal suppresion, corticosteroids must not be discontinued abruptly (Deglin & Vallerand, 2007). In addition to its antiimflammatory effect, corticosteroids also have various metabolic effects. Pharmacokinetics Most glucocorticoids are readily absorbed through the synovial and conjunctival spaces and the gastrointestinal tract because it has a lipophillic character wherein it binds with fats readily (Minneman & Wecker, 2005). If inhaled, the drug is distributed directly into the airways and respiratory tract. After inhalation, it is converted into an active metabolite that enhances its efficacy. After absorption in the lungs, it is metabolised by the liver, and may be eliminated through urination and defecation. (Deglin & Vallerand, 2007) If taken through a nasal preparation, it is immediately absorbed, and a minute amount is swallowed. After the absorption in the nasal mucosa, metabolism takes place in the liver and excretion follows in the renal system. (Deglin & Vallerand, 2007) On the other hand, if taken by mouth it is well-absorbed and if by intramuscular injection, it also well-absorbed, however more slowly. Metabolism occurs in the liver wherein cortisone is converted into hydrocortisone, and prednisone is converted into prednisolone. (Deglin & Vallerand, 2007) If the preparation is for topical administration, the distribution stays at the site of application. However, for prolonged use, the absorption may be systemic, resulting to adrenal suppression. It is most commonly metabolised in the skin. (Deglin & Vallerand, 2007) Bronchodilators Bronchodilators are prescribed because thye inhibit and relax the bronchial muscle allowing easy entry of oxygen. It could be indicated for any severe allergic reaction, not just asthma, because most allergic recations usually cause bronchospasm. Bronchodilators usually come in three groups: methylxanthines, beta adrenergic receptors, and muscarinic receptor antagonists (Minneman & Wecker, 2005). However, it is the beta 2 adrenergic drugs that are used for immediate hypersensitivity, because they relieve asthma symptoms very quickly, and as such is called "quick acting" or "rescue" relievers (Gerace, 2006). These medications usually come in inhalant preparations, and includes in its group terbutaline, metaprotrenol, albuterol, bitolterol, and pirbutrol (Minneman & Wecker, 2005). Beta 2 Agonists Pharmacodynamics Beta 2 adrenergic receptor agonists inhibit smooth muscle contraction and relax the bronchial smooth muscle. The substances derived from mast cell that stimulate the constriction of the bronchial tubes are also blocked. In addition, it also reduces microvascular permeability, and contains the parasympathetic ganglionic activity. (Minneman & Wecker, 2005). It binds with beta 2 adrenergic receptors in the smooth muscle of the airways, and activates adenyl cyclase, which eventually lead to decreased intracellular calcium and then results to the relaxation of the bronchial smooth muscles (Deglin & Vallerand, 2007). Pharmacokinetics Being a quick actin drug, it is rapidly absorbed after inhalation and immediately goes through extensive metabolism by the liver and other tissues (Deglin & Vallerand, 2007). Onset of action is fairly consistent between five to 30 minutes, and are effective for around four to six hours (Minneman & Wecker, 2005). Chinese Herbal Medicine In China, there are more than 3,200 herbs, 300 mineral and animal extracts, and more than 400 formulas used to come up with herbal medicine (Marcus American Cancer Society, 2005). It is said that the Chinese have formulated these medicines to restore a balance of energy, body, and spirit, making reference to the ying and the yang. There are a number of Chinese herbal medicines that may be used to help prevent or alleviate allergic reactions, depending on the site of reaction. To name a couple of the popular ones would be chamomile and ephedra. Chamomile (from Metricaria recutita), according to the Chinese, may be used to relieve inflammation in the gastrointestinal tract and skin irritation that may be brought about by exposure to allergens, while ephedra, whose active ingredient is alkaloid ephidrine) may be used as a nasal decongestant and a bronchodilator for asthma (Clayton & Stock, 2001). Chammomile has been declared safe. However, there are a few side effects of ephedra such as palpitations, nervousness, headaches, dizziness, and insomnia. Deaths have also been reported. In addition to this, some Chinese herbal medicines claim to be effective in treating atopic eczema, a type I hypersensitivity condition, which may be realated to food allergy, and is often followed by asthma (Barnetson & Rogers, 2002). The treatment mentioned involves drinking tea from a concoction of plant sources, which contains 10 herbs or more (Harper, 1994). Each formula differs from every patient. It has shown efficacy in children, but only temporary, lasting a period of six to 12 months. More than 600 clinics in the United Kingdom now offer Chinese herbal remedies. However, many are still skeptical about its efficacy and afraid of its side effects. Of the more than 10 herbal constituents of this treatment, some actually have a beneficial effect in the treatment of eczema. It has also been found that some of these drugs may have antiinflammatory efects. Some even proved to be more effective than western medicine. (Harper, 1994) Regarding a similar Chinese herbal remedy for the same skin problem, it has been reported that the topical preparation may contain steroids. Along with the oral preparation, a cream is also given by the hinese herbal medicine practitioners, and a woman has reported that the action of the cream was very similar to steroids Graham-Brown, Bourke, & Bumphrey, 1994). It is then very miuch questionable for a chinese herbal practitioner to prescribe steroids. References Allen, M.A. et al. (Eds.). (2002). Mosby's pocket dictionary of medicine, nursing, and allied health (4th ed.). Missouri: Mosby. Barnetson, R.S. & Rogers, M. (2002). Childhood atopic eczema. The British Medical Journal, 324. 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