Steroids Essays

Steroids Essays Steroids Essay Steroids Essay Introduction Background Steroids, more specifically glucocorticoids, for illustration hydrocortisone ( the construction of which is shown below in 1 ) are on a regular basis used in clinical pattern due to their anti inflammatory belongingss e.g. injected into inflamed articulations or sinews. ( 1 ) They achieve this inflammatory action by the suppression of the enzyme phospholipase A2. This enzyme converts cell membrane phospholipids into arachidonic acid – a cardinal molecule in the creative activity of all eicosanoids. ( 1 ) Eicosanoid is a general term for a group of molecules embracing prostaglandins, thromboxanes, prostacyclin, lipoxins, leukotrienes and derived functions. ( 1 ) Prostaglandins were discovered by a Swedish adult male named Ulf von Euler. He isolated them from a sample of seeds and so assumed they were synthesised by the prostate secretory organ, hence their name. ( 2 ) They have since been found, along with leukotrienes to be built-in to the inflammatory response and in the causing of hurting, while lipoxins signal the terminal of an inflammatory period. ( 3 ) Thromboxane is a lipid that promotes the collection of thrombocytes from which it is produced ; it is besides a powerful hypertensive agent that increases blood force per unit area by vasoconstriction, prostacyclin holding an counter consequence. ( 3 ) As steroids inhibit the production of all these molecules, they have a really broad scope of effects in the organic structure. They prevent vasocodilation, diminish the inflow and activity of leukocytes and mononucleate cells, suppress the procedure of angiogenesis, prevent extra fibrosis, decrease clonal enlargement of T and B cells and diminish the action of cytokine releasing T cells. ( 3 ) Non steroidal anti inflammatories ( NSAIDs ) for illustration acetylsalicylic acid ( the construction of which is shown below in 2 ) work to battle redness in a more specific mode than steroids. They inhibit the enzymes cyclooxygenase 1 and cyclooxygenase 2 therefore forestalling the oxidization of arachidonic acid to PGH2 which is an intermediary in the production of prostaglandins, thromboxanes and prostacyclin. ( 1 ) This allows the production of other eicosanoids ( e.g. leukotrienes and derived functions ) to go on uninhibited. This gives the drug a more targeted consequence. These drugs are known to hold anti pyretic, anti inflammatory and analgetic effects. ( 3 ) Cyclooxygenase 2 inhibitors ( for illustration Celebrex shown in 3 below ) are, once more, a much more targeted drug – merely suppressing the Cox 2 enzyme. ( 1 ) This has been shown to be good as the prostaglandins that are secreted into the gastro enteric piece of land ( GIT ) to protect against the potentially harmful low pH tend to be catalysed by the Cox 1 enzyme, i.e. the usage of traditional NSAIDs can take to ulceration in the GIT. ( 3 ) It has been suggested that all Cox enzyme suppressing drugs – but particularly cox-2 inhibitors increase the likeliness of thrombi forming, seting patients on these drugs at a higher hazard of holding myocardial infarctions, shots etc. ( 3 ) This is due to their suppression of prostacyclin, a lipoid that prevents curdling of blood. ( 1 ) An overview of the concatenation of reactions involved in the formation of eicosanoids and the action of steroids, NSAIDs and cox-2 inhibitors is shown below in 4. Connective tissue is a reasonably obscure term, split into three sub classs, connective tissue proper, unstable connective tissues and supportive tissues. ( 4 ) Connective tissue proper is so farther divided into loose and heavy conjunction tissues, depending on the figure of cells present and the comparative proportions of fibers and land substance. ( 4 ) All connective tissue proper contains fibroblasts, which secrete a substance called hyaluronan and assorted other proteins. Fibrocytes, Macrophages, Adipocytes, Mesenchymal cells, Melanocytes, Mast cells, Lymphocytes and Microphages are besides present in some but non all connective tissue proper. Forming a kind of web around the different cell types are fibers of which there are three types – collagen, reticulate and elastic. All three are created by the fibroblast cells from the proteins they secrete and maintained by fibrocytes. Collagen is a consecutive unbranching fiber that has unbelievable tensile strength that makes up about all of the composing of sinews and ligaments and is besides present in tegument. ( 4 ) Reticulate fibers are besides made of collagen but alternatively organize a heavy web like construction that is really strong and flexible. Elastic fibers are wholly different to the other two fibers, as they are made up of elastin. These fibers have the ability to stretch and return to their original size. An illustration of elastic fibers in the organic structure is the connexions between vertebrae. ( 4 ) Supporting all these constituent parts and filling in the spreads of connective tissue is ground substance. Ground substance is a clear, colorless extremely syrupy substance. This is good as it hinders the patterned advance of bacteriums and other pathogens through it and into the organic structure and besides aids phagocytosis. Purposes I intend to sketch the pros and cons of the clinical usage of steroids, not steroidal anti inflammatory drugs and Cox 2 inhibitors as anti inflammatories and anodynes when connective tissue injury is evident. aims To accomplish this I will turn up relevant research documents, critically measure their findings and explicate my ain decision sing their positive and negative effects in the organic structure, more specifically their effects on connective tissue fix and if their usage is good overall. Method Search I performed an electronic hunt of the MEDLINE ( 1950 to January Week 4 2009 ) database utilizing the OVID hunt engine. I limited the consequences to full text, English linguistic communication documents and used the cardinal words steroids, not steroidal anti inflammatory drugs, NSAIDs, Cyclooxygenase 2 inhibitors, cox-2 inhibitors and lesion healing. These single hunts brought up an unwieldy figure of hits so I so combined each drug type with lesion healing. This narrowed the figure of documents down significantly, but was still unwieldy and on upon reappraisal of the documents, a batch of them were unrelated and referred to the effects of the drug on many different tissues. I wanted my reappraisal to be more specific, so I introduced another hunt parametric quantity – collagen. An illustration of the concluding hunt is shown below ( 5 ) , taken from OVID. I so searched utilizing the same keywords as before in Google Scholar. This hunt uncovered yet more relevant stuff that the OVID hunt engine had missed. Using the documents I had found in the aforesaid hunts, I analysed the mentions they had used to bring out any farther documents I could utilize that I may hold overlooked earlier. In add-on, a relevant degree of background cognition of the pharmacological medicine of the drugs involved and their physiological effects was acquired from text editions and internet resources. Consequences The consequences brought up by my assorted hunt techniques were chiefly drug tests in rats and mice. There were besides many existing reappraisal articles related to what I intended to research. Discussion Steroids As discussed earlier, steroids have a broad scope of effects in the organic structure, due to them suppressing the enzyme responsible for the synthesis of arachidonic acid, a substance from which all eicosanoids are created. Glucocorticoids affect the healing procedure well, and if injected after hurt, dramatically lower the figure of inflammatory cells, fibroblasts, the formation of land substance and sum of new collagen. ( 5 ) It was presumed that this was because of the steroid s repressive consequence on the inflammatory response, without which mending can non happen. It has now been suggested by a survey ( 5 ) that it is besides caused by the steroid s ability to stamp down the look of TGF B ( transforming growing factor ) and IGF ( insulin like growing factor ) cytokines. The survey was performed on rats. TGF B and IGF are cytokines that are released when macrophages take portion in phagocytosis at the site of a lesion. ( 6 ) # They work by conveying about the proliferation of fibroblasts, which as discussed earlier, are built-in in the production of collagen. The graphs below ( figures 6 and 7 ) show that there was a statistically important lessening in both TGF B and IGF when the rats were admini stered with steroids. Besides determined from this survey was that there was decreased collagen synthesis caused by a lessening in steady province cellular type I procollagen messenger RNAs . Overall, this survey indicates that the decrease of TGF B and IGF in lesions as a consequence of steroid intervention causes collagen deposition to endure. This would later do the healed lesion to be weaker and have a lower breakage strength. Clinically, these consequences are really of import, as glucocorticoids are normally used in postoperative patients, which puts them at a high hazard of impaired healing and infection. ( 6 ) Timing, dosage and length of intervention besides play a cardinal function in the suppression of proper lesion fix, with patients holding more post operative jobs with lesions if they receive glucocorticoid intervention preoperatively. ( 6 ) There is a correlativity between higher doses and more hurtful wound fix effects, while patients on a long class experience well slower lesion healing. ( 6 ) Despite these obvious negative effects of steroids, they are still widely used to handle many conditions for illustration in lower doses to handle adrenal lacks and at higher doses to battle assorted inflammatory, allergic and autoimmune diseases. ( 7 ) Non Steroidal Anti Inflammatory Drugs Relatively small work has been done on researching the effects of NSAIDs on lesion healing, but there are many theories as to how it could interfere with this procedure. A survey was conducted in 1996 ( 8 ) that investigated the consequence of a specific drug, ketorolac tromethamine, on the healing of lesions in male rats. This was achieved by mensurating the breakage strength ( 8 ) , collagen content ( 9 ) and tensile strength ( 10 ) of the freshly formed tissue. It was found in this survey that the breakage strength and collagen denseness of the trial subjects was much lower than that found in the controls ; nevertheless the tensile strength was non found to be lowered significantly. The lessening in interrupting strength is likely a direct consequence of the lowered collagen content ( 8 ) as collagen gives tissue snap and the ability to stretch to defy forces without interrupting. ( 4 ) As can be seen in the graphs, it is clear that this peculiar NSAID has a definite impact on the manner in which the tissue has repaired. It is possible that NSAIDs have a direct impact on the production of prostaglandin-E ( 8 ) , a eicosanoid involved in the production of colleganase, which maps in the dislocation and formation of new collagen fibers. ( 1 ) Another survey ( 9 ) has shown a lessening in hydroxyproline in the healed lesion tissue treated with a different NSAID, isobutylphenyl propionic acid. This is a important determination as it is a constituent in collagen that is indispensable to the formation of its third construction. ( 10 ) Another consequence that is likely to be related to connective tissue fix is the lowered production of glucosaminoglycan, a substance fo und in connective tissues for illustration sinews. ( 8 ) Cyclooxygenase 2 Inhibitors As discussed earlier, cox-2 inhibitors are in consequence a more targeted version of traditional NSAIDs, for this ground, it would be a just premise that the scope of side effects is more limited. The consequences from trials from surveies refering cox-2 inhibitors show far fewer side effects and are about wholly barren of the jobs with wound fix associated with the other two drug types ( 11-13 ) . Some of the consequences are really interesting and present contradictions to informations from the surveies concerned with traditional NSAIDs ( 8 ) # . An illustration of this is shown in a survey performed to contrast the effects of NSAIDs and COX-2 inhibitors ( 11 ) . The information shows that upon disposal of Celebrex, a cox-2 inhibitor, the concentration of prostaglandin E decreases significantly ( shown below in 11 ) As discussed before, this lessening in prostaglandin E would theoretically ensue in a lessening in the collagen production at the site of the lesion. Despite this, information from the survey states that the overall healing procedure was unhampered compared to the control. It is stated that this could be attributed to the unchanged production of hydroxyproline ( shown below in 12 ) . In a different survey ( 13 ) negative effects on the healing of epithelial tissue were predicted. It states that although the drugs have negligible effects on lesion fix as a whole procedure, there is cause for concern as epithelial tissue is a peculiarly strong inducer of the Cox 2 enzyme. Despite this statement, the survey goes onto to confute this hypothesis, happening small to no difference compared to the controls ( 13 ) . Conversely, a similar survey performed in 2002 showed a slower rate of lesion healing ( although the healed lesion showed about indistinguishable features to the controls ) ( 12 ) . This trial was performed on mice. The consequences are highlighted in the graph below ( 13 ) . The dark saloon represents the cox-2 inhibitor treated mice, the white saloon traditional NSAID treated mice and the dark saloon is the controls ( i.e. untreated mice. ) If the surveies discussed here are all taken into history, it would look that cox-2 inhibitors have really small consequence on the healing procedure, simply decelerating it. Decision Remarks Steroids are really powerful drugs, and have a broad scope of perchance negative effects on a patient. The information from this reappraisal would propose that steroids are unsuitable for usage in patients with connective tissue injury, due to their impact on the healing procedure. NSAIDs are widely used in pattern for their analgetic belongingss and in higher doses to cut down redness. The information gathered to organize this reappraisal suggests that although there are negative effects on lesion healing, the usage of the drugs in a controlled environment ( i.e. as prescribed by a physician ) is warranted. A major concern would be that they are readily available over the counter , for illustration ibuprofen . As a consequence of this patients may non experience it necessary to unwrap this information to their physician, as they may non see it as of import due to the effects on lesion mending non being widely known. ( 8 ) # COX-2 inhibitors seem to hold negligible effects on lesion fix, yet exhibit about indistinguishable effects on the organic structure as a traditional NSAIDs, upon which they are based ( i.e. analgesia and decrease of redness ) . There is besides cogent evidence of the lessened hazard of developing stomachic ulcers, a complication associated with traditional NSAIDs. As identified in the debut nevertheless, cox-2 inhibitors put the patient at a much higher hazard of enduring a shot or myocardial infarction. There are obvious benefits and hazards in the usage of all the drugs discussed, and no grounds has been presented back uping the thought that the drugs are insecure if used in the right state of affairs. i.e. a patient with a predisposed hazard of myocardial infarction would non be given a cox-2 inhibitor, and a patient with a history of developing peptic ulcers would non be prescribed a traditional NSAID. In decision, after taking into history all the information gathered, despite their evident side effects, all the drugs discussed clearly have their topographic point in clinical pattern, if used carefully and the side effects are thought through with relation to the patient s status. Restrictions I believe a major restriction of this survey is the deficiency of clinical tests in worlds. I was unable to happen any research performed on worlds or human tissue, the bulk being on rats and mice. While this gives an estimate of how these drug types would interact in a human, it is executable that if the tests were performed in a existent human trial topic, the consequences would be wholly different. For this ground, it is possibly non advisable to give the consequences of this reappraisal much weight, until it is proven in worlds. Further Areas of Study Further survey would include the testing of the drugs in worlds. The proving for collagen content would affect taking a little biopsy of the lesion, but to find the mechanical features ( i.e. interrupting strength and tensile strength ) the lesion and environing tissue would hold to be removed and ripped apart. This is evidently ethically debatable, so a more realistic attack would to turn tissue civilizations and execute trials on these. This could supply another possible usage of root cells in research. 1. Ganong WF. Review of Medical Physiology. 22nd erectile dysfunction: Lange ; 2005. 2. hypertext transfer protocol: //www.elmhurst.edu/~chm/vchembook/555prostagland.html. [ cited 11th February 2009 ] . 3. Rang HP, Dale MM, Ritter JM, Flowers RJ. Pharmacology. 6th erectile dysfunction: Churchill Livingstone Elsevier ; 2008. 4. Martini FH, Nath JL. Fundamentalss of Anatomy and Physiology. 8th erectile dysfunction: Pearson ; 2009. 5. Wicke C, Halliday B, Allen D, Roche NS, Scheuenstuhl H, Spencer MM, et Al. Effectss of steroids and retinoids on lesion healing. Arch Surg. [ Comparative Study ] . 2000 Nov ; 135 ( 11 ) :1265-70. 6. Anstead GM. Steroids, retinoids, and wound mending. Adv Wound Care. [ Review ] . 1998 Oct ; 11 ( 6 ) :277-85. 7. hypertext transfer protocol: //www.uptodate.com/patients/content/topic.do? topicKey=~fpyFyamA5oQZAd. [ cited 2009 13th February ] . 8. Haws MJ, Kucan JO, Roth AC, Suchy H, Brown RE. The effects of chronic Torodal tromethamine ( ketorolac tromethamine ) on lesion healing. Annalss of plastic surgery1996 Aug ; 37 ( 2 ) :147-51. 9. Velasco M, Guaitero E. A comparative survey of some anti-inflammatory drugs in lesion healing of the rat. Experientia. [ Comparative Study ] . 1973 Oct 15 ; 29 ( 10 ) :1250-1. 10. Bansal M, Ananthanarayanan VS. The function of hydroxyproline in collagen folding: conformational energy computations on oligopeptides incorporating proline and hydroxyproline. Biopolymers. [ Research Support, Non-U.S. Govt ] . 1988 Feb ; 27 ( 2 ) :299-312. 11. Muscara MN, McKnight W, Asfaha S, Wallace JL. Wound collagen deposition in rats: effects of an NO-NSAID and a selective COX-2 inhibitor. Br J Pharmacol. [ Research Support, Non-U.S. Govt ] . 2000 Feb ; 129 ( 4 ) :681-6. 12. Futagami A, Ishizaki M, Fukuda Y, Kawana S, Yamanaka N, Futagami A, et Al. Wound mending involves initiation of cyclooxygenase-2 look in rat tegument. Lab Invest2002 Nov ; 82 ( 11 ) :1503-13. 3. Muller-Decker K, Hirschner W, Marks F, Furstenberger G, Muller-Decker K, Hirschner W, et Al. The effects of Cox isozyme suppression on incisional lesion healing in mouse tegument. J Invest Dermatol. [ Research Support, Non-U.S. Govt ] . 2002 Nov ; 119 ( 5 ) :1189-95. Steroids Essays Steroids Essay Steroids Essay There is a huge national concern over the misuse and abuse of anabolic steroids for enhancement of muscular stature and performance among competitive athletes.   Latest estimates have shown that approximately 5% of all high school students have used anabolic steroids, with almost half of the high students believing that these drugs are not harmful to their health.   Drug enforcement legislations have included anabolic steroids in its list of traffic-controlled substances (21 USC Sec. 801 1/22/02; Schedule III).   However, the bigger picture of the medical and research benefits of anabolic drugs have been overlooked due to the sensationalize media coverage of these drugs.   Current scientific researches are still inconclusive on whether anabolic steroids are extremely unsafe for administration, opposite to what has been actively claimed by anti-drug officials and government authorities.The Anabolic Steroid Control Act of 1990 (ASCA) was established to r egulate the distribution of anabolic steroids in the United States.   The Drug Enforcement Administration of the U.S. Department of Justice has been mandated to implement measures to protect the people from these dangerous drugs.   A four-part definition of anabolic steroids serves as a blueprint to identify any analogues of the chemical substance that may be uncontrollably dispensed to athletes and other youths.   The definition included substances that are chemically and pharmacologically similar to testosterone, estrogen, progesterone, as well as a very close likeness in its enhancement for muscle growth.   The Act classified anabolic steroids in the same category as barbiturates and LSD precursors and claim that these substances result in dangerous effects to the human body.   The Act declares that any individual caught in the possession of these anabolic steroids will be arrested and prosecuted.   The list of anabolic steroids in the Act is continuously being update d, as new versions of these drugs are progressively being created through the years.Anabolic androgenic steroids are testosterone derivatives that are mainly used for muscle and performance enhancement.   These drugs are frequently used by competitive athletes in order to achieve an edge or better control of their physical strength and performance during professional sports games.   Retrospective surveys indicated that anabolic steroids have been used since the 1960s to date (Duchaine, 1983), with current national user rates ranging from 3% to 9% among high school students alone.   The exact effect of anabolic steroids in the developing human body has not been fully studied, and the increase in number of reports of teenage athletes committing suicide has called the attention of the legislation to assess and review drug enforcement laws covering this specific drug.It has been reported that the prolonged use of anabolic steroids have may cause a number of adverse effects to the human body, including liver damage, gynecomastia, atherogenesis, psychiatric disorders such as aggression and violence, and even death (Balbigian, 2001; Brower, 2002; Glazer, 1991; Pope and Katz, 1990; Malone et al. 1995).   Investigations on the nationwide use of anabolic steroids have prompted Congress to establish the Anabolic Steroid Control Act of 1990, which mainly indicates that the non-medical employment of anabolic steroids is punishable by law.   Any violations will be penalized by at least 15 days to 5 years imprisonment and/or $1,000 to $1,000,000 fine, depending on the extent of the violation.   So far, the general public has supported the Anabolic Steroid Control Act, mostly due to the massive and militant media coverage of the topic.The Anabolic Steroid Control Act of 1990 classified anabolic steroids as any drug or substance related to testosterone and used for muscle growth increase.   They are Schedule III of controlled substances.   The Anabolic Steroid Control Act of 2004 amendment added hormone precursors such as androstenedione and androstenediol as controlled substances without a prescription.   Most anabolic steroids used in the United States come through the black market from other countries.   Even though sources may state the steroids are made by pharmacists and physicians, no one actually knows who produced them or how they were produced.  Ã‚   Some were produced in non-sterile environments while others may be for the use of animals but sold for human use.   Production of steroids sold illegally may have substitutions or other problems which can cause the contents to be dangerous even lethal.   Many sold via the internet are fake steroids which have contained cooking oil or toxic substances that produced methanol and/or blood poisoning.   Incorrect packaged doses and tampering of the product can also be suspected.   Since some users use more than one steroid at a time, dangers of consuming bad substances is increased.   You dont know how some of those ingredients will react together.Some research indicates anabolic steroid use may lead users to other illegal and/or legal drugs to counteract some of the side effects, especially for insomnia.   There is a limited amount of research and studies in this area.   A list of possible physical and psychological side-effects of anabolic steroid use has been reported.   These include coronary heart disease, which specifically increases the thickness and enlargement of the left ventricle.   Another side-effect is the decreased size of the user’s testicles, as well as the experience of immunodeficiencies.   The athlete who has taken anabolic steroids will also feel invincible and will actually show an aggressive behavior.   It has been reported the Hitler historically used anabolic steroids during World War II in order to increase his aggressiveness towards his troops.   In terms of damage to human health, anabolic steroids d estroy the liver as well as transform connective tissues to a condition that these are easily injured or torn.Adolescents taking anabolic steroids have been reported to show stunted growth and suffer from blood clots and insomnia or unusual sleep patterns.   In terms of the effects of anabolic steroid on an individual’s blood chemistry, there are reported that a user will experience an elevated LDL cholesterol level as well as a lowering of HDL cholesterol level.   Interestingly, adults taking anabolic steroids experience moderate to severe acne because anabolic steroids influence changes in his endocrine system.   An anabolic steroid user also faces the chance of acquiring prostate cancer at an earlier age.   Certain male anabolic steroid users observe that their breasts start developing and some users experience temporary to permanent infertility.   Other users have stimulated appetites, psychoses and mood swings.   Increasing the dosage and combining steroids a lso increases risks of possible side effects.   Some side effects can be reversed after stoppage of steroid use and other effects cannot be reversed.   It should be noted that the results of side effects may take months or years before they are apparent even after the individual has stopped using them.   Recent evidence indicates withdrawal symptoms occur in long-term users who stop using anabolic steroids.However, the actual negative effects of the use of anabolic steroidal drugs have not been comprehensively investigated to date, and that the reports that have been disclosed in the media have been isolated cases picked out from millions of cases of teenage users around the United States.   Scientifically, the adverse effects from the prolonged use of anabolic steroids remain inconclusive to date, and in actuality, anabolic steroid use has been shown to be beneficial in the treatment of medical disorders.   In one report, it has lately been determined that the effect of an anabolic steroid to the treatment of weight loss in human immunodeficiency virus (HIV)-infected patients is equivalently effective and safe as compared to the commonly administered recombinant growth hormone that has been approved by the Food and Drug Administration (Storer et al. 2005).   In another scenario, the administration of an anabolic steroid has been beneficial in prostate cancer patients by preventing further migration of prostate cancer cells to other parts of the body (Guerini et al. 2005).   The anabolic steroid oxandrolone has been successfully used in the treatment of muscle loss in patients diagnosed with Duchenne muscular dystrophy and may be a potential powerful candidate for general treatment of such types of patients (Balagopal et al. 2006).Scientific research shows that anabolic steroids provide more beneficial effects than what has been claimed by legislation as serious, adverse effects to the human body.   More so, the negative reports that have asso ciated with the use of anabolic steroids have not been investigated scientifically and have only achieved much attention through the help of media and press coverage.   Therefore, it is imperative that the legislative bodies review the restrictions associated with the Anabolic Steroid Control Act of 1990 and fully determine the actual effects of anabolic steroid intake.   It is regretful to know that there are other drugs and activities that are much more deleterious or harmful to people but are not actively controlled by the Senate, including smoking, cosmetic surgery and over-the-counter drugs such as aspirin and ibuprofen, which has caused even more cases of deaths and hospitalizations that anabolic steroids.Based on the above information on the current status, knowledge and use of anabolic steroids, several advocacy groups have proposed that anabolic steroids be legalized for use in the United States.   In turn, these groups emphasize the need for further scientific resear ch to determine the mechanisms of action of each type of anabolic drug to gain a better understanding of its indications and contraindications.   There should be a comprehensive survey on the frequency of use of anabolic steroids across the human population, with stratified categories of users such as teenage athletes, geriatric patients, cancer patients, and so on.   Any cases that report any adverse effect from use of anabolic steroids should be properly documented and analyzed.   Should there be sufficient reason that anabolic steroids be stopped from circulation in the community, these advocacy groups are willing to review these effects once significant information has been gathered from reliable reports.;