Major Issues in Bio-Science - Essay Example

Bio-science 1. Drugs which act on serotonin receptors are important for managing both migraines, mood disorders (e.g. antipsychotic) and vomiting: a. For each of these conditions name one drug (using generic drug names)which is used in Australia and acts via serotinergic receptors. b. Explain the mechanism of action of each drug (i.e. how does it work?). c. What is serotonin syndrome and why might ecstasy cause symptoms of serotonin syndrome? 1. a. The triptans act via serotinergic receptors as they are 5-HT1B/1D agonists targeting the trigeminovascular system. Sumatriptan is a triptan used in the management of migraine (Spierings & del Rio, 2002). A class of drugs used in the treatment of mood disorders, which act via the serotinergic receptors are the selective serotonin reuptake inhibitors or serotonin specific reuptake inhibitors (SSRIs). Citalopram is an SSRI used in the management of mood disorders (Rollema & Sprouse, 2005). The 5-HT3-receptor agonists are a class of drugs used in the management of vomiting, as they are capable of blocking the 5-HT-3 receptor sites efficiently. Ondansetron is a 5-HT3-receptor agonist used in the management of migraine (Husband & Worsley, 2007). 1.b. Many of the triptans that are in current use for the management of migraine have selective serotonin receptor agonist activity. This action of the triptans causes constriction in the arteriovenous anastomes. Thus it is posited that the triptans ability to control migraine is based on this constriction of the arteriovenous anastomes. Sumatriptan brings about constriction in the superficial temporal artery. In addition Triptans like sumitriptan have demonstrated the capability to inhibit the release of calcitonin gene-related peptide, which is responsible for the mediation of the vasodilation element of neurogenic inflammation (Spierings & del Rio, 2002). In essence the mode of action of the SSRIs can be taken as making more serotonin available in the extracellular environment, by inhibiting the reuptake of serotonin by the presynaptic cell. This enhanced extracellular level of serotonin makes for higher levels of serotonin to bind with the postsynaptic receptor (Rollema & Sprouse, 2005). The mechanism involved in vomiting consists of the formation of local free radicals as a result of cytotoxic agents or other substances that are potentially toxic. These free radicals bring about the release of 5-HT from the enterochromaffin cells in the GI tract. 5-HT is the stimulus for the 5-HT3 receptors present on the adjacent vagal afferent neurons to cause a vigorous vomiting response. 5-HT3- receptor agonists, like ondansetron, block the 5-HT3 receptors in the GI tract, the chemoreceptor trigger zone, and the nucleus tractus solitarius efficiently, to inhibit the vomiting response triggered by the 5-HT3 receptors. (Husband & Worsley, 2007). 1.c. Birmes et al 2003, p. 1439 define serotonin syndrome as “the result of over stimulation of 5-HT1A receptors by selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOI) or other serotonergic agents”. Serotonin syndrome can occur to any individual irrespective of age or sex triggered by an overdose of a serotonergic agent, and occurs within the time interval of twenty-four hours from the overdose event. The three features of mental, autonomic and neurological disorders characterize serotonin syndrome. Serotonin is life threatening, but normally serotonin syndrome is not fatal, when effectively managed (Birmes et al 2003). Serotonin syndrome is normally triggered when combination of serotonergic agents lead to an overdose event. Ecstasy by itself is a serotonetrgic agent, which may be taken by individuals taking serotonergic agents as medications in the management of conditions like migraine or mood disorders. Such combined use can lead to an overdose of serotonergic agents triggering serotonin syndrome. Furthermore individuals taking ecstasy as a recreational drug do not restrict it to ecstasy alone, and can combine it with methamphetamine and cocaine, which are serotenergic agents themselves, thus leading to an overdose situation (Silins, Copeland & Dillon, 2007). 2. Two men are brought to the emergency department following a car accident. One has a spinal cord injury at the C2-C3 level while the other has an injury at T12. Explain the effects that these injuries will have on the autonomic, motor and sensory function in these individuals. The spinal cord may be taken as consisting of a set of neuropathways that transmit descending motor information and ascending sensory information. From an anatomical perspective the cortico-spinal tracts make up the descending motor pathways, which are located anteriorly within the spinal cord. Axons stretch from the cerebral cortex of the brain to the corresponding segment, and then go on to form synapses with the motor neurons present in the anterior or ventral horn. Prior to entry into the spinal column, they cross over into the medulla. In comparison the dorsal columns make up the ascending sensory tracts that execute the functions of relaying, light touch, propioception, and vibratory information to the sensory regions of the cortex. They do not cross over, till the medulla is reached. It is the lateral spinothalamic tracts that are responsible for the transmission of the sensations of pain and temperature. The normal pattern is for these ascending sensory tracts to cross over within three segments of their origin. The anterior spinothalmic tract is responsible for relaying information of light touch. Autonomic function is found to traverse within the anterior interomedial tract of the spinal cord. Exiting of the sympathetic nervous system fibers from the spinal cord are found to occur between C7 and L1, while fibers of the parasympathetic system exit the spinal cord between S2 and S4. Since autonomic function is relayed in the anterior interomedial tract and the sympathetic system fibers make their exit from the spinal cord between C7 and L1 and the parasympathetic system fibers exit the spinal cord between S2 and S4, progressively higher spinal cord injuries lead to increasing levels of autonomic dysfunction. The anatomy of the spinal cord shows that the position of the injury and the level of the injury are critical to the loss of autonomic, motor and sensory functions of the individual. The C2 and C3 level of the spinal cord has close proximity to the brain. This proximity to the brain makes for injury at this level having severe impact on the autonomic, motor and sensory functions of the individual. The consequences of injury to at the C2 and C3 level of the spinal cord on the autonomic function are severe autonomic dysfunction that can lead to hypotension, bradychardia, peripheral vasodilation and hypothermia. The severe consequences to motor function due to injury at the C2 and C3 level of the spinal cord include paralysis below the neck, impaired respiratory function that requires the use of a ventilator, bowel and bladder incontinence and sexual dysfunction. The severe consequence to sensory function due to injury at the C2 and C3 level of the spinal cord is that there is no sensation below the neck. The T12 injury on the spinal cord is at a distance from the brain and many nerve fibers enter and exit above the site of injury reducing the severity in the consequences of the injury. The severe autonomic dysfunction seen in the case of injury at the C2 and C3 level are absent and the individual demonstrates some degree of trunk and abdominal control, though paralysis of the lower limb muscles are demonstrated in the case of motor functions. The effect on the sensory function is also less severe, with the individual demonstrating a small degree of sensation even below the waist (Timby & Smith, 2007). 3. Oral contraceptives are widely used as contraceptives and in the management of a range of gynaecological conditions. Explain how oral contraceptives work to prevent pregnancy and explain the physiological basis of the most common side effects of oral contraceptives. There are essentially three ways in which oral contraceptives work. In the first place oral contraceptives inhibit ovulation. Estrogen or progesterone either or both of which are present in oral contraceptives can prevent ovulation through the inhibition of follicle stimulating hormone (FSH) or luteinizing hormone (LH). Thus eggs are not released into the ovary, and so even though sperms move up the reproductive tract there are no eggs present for fertilization. Eggs after fertilization attach themselves to the lining of the uterus. In its second mode of action oral contraceptives alter the lining of the uterus making it difficult for the fertilized eggs to attach themselves to the lining of the uterus, which is essential for their development. In its third mode of action, oral contraceptives create hurdles for the sperm itself to reach the upper reproductive tract for fertilization. This is done through increasing the thickness of the cervical mucus, and thus hampering the movement of sperm (Youngson & Jacoby, 2005). Nausea, mood changes, breast tenderness, lowered sex drive and weight gain are among the common side effects of oral contraceptives. Oral contraceptives contain estrogen and progestin (synthetic replacement for the female hormone progesterone), which are essentially hormones connected to sex and fertilization. By increasing the levels of estrogen in the body fertilization is inhibited, but at the cost of unwanted side effects due to the excess presence of these hormones in the body. For example progestin is known to reduce the levels of serotonin in the brain, through enhancing the presence of the brain enzyme responsible for reducing serotonin. This lowering of serotonin levels in the brain can bring about mood changes through depression in these otherwise healthy women (Guillebaud, 2005). Both progestin and estrogen are responsible for the possible weight gain in women taking oral contraceptives. Progestin is known to stimulate appetite in high doses and cause a reduction in insulin sensitivity and through that effect carbohydrate metabolism. Oral intake of estrogen is found to cause a reduction in postprandial lipid oxidation and cause an increase in fat mass (Rickenlund et al, 2004). 4. The presence of intestinal pathogens can result in both large volume and small volume diarrhoea. Differentiate between large and small volume diarrhoea and explain using specific examples how intestinal pathogens can cause diarrhoea. Large volume diarrhoea is characteristic of infection in the small intestine. The diarrhoea leads to watery stools. The increase in the number of stools is limited as the reservoir in the large intestine remains unaffected. In large volume diarrhoea there is no inflammation of the small intestine and hence no presence of leukocytes in the feces. Large volume diarrhoea is essentially caused by bacterial enterotoxins that are responsible for the changes in the fluid and electrolyte absorption and transport from the GI tract. Bacteria normally associated with large volume diarrhoea include Vibrio cholerae, enterotoxigenic E. coli, enteropathogenic E. coli, Salmonella spp., Cryptosporidium, Clostridium perfringens, and Bacillus cereus. Viruses that may cause large volume diarrhea include Rotavirus, and Norovirus. The parasite Giardia lamblia is also a causative agent for large volume diarrhea. On the other hand small volume diarrhea has bloody stools and is characteristic of infection of the large intestine. Inflammation of the large intestine is likely to be present leading to cramps in the lower abdomen. Leukocytes are present in the feces (Duncombe, 2006). The mechanisms through which the enteropathogens of viruses and bacteria cause diarrhoea vary and are dependant on very specific virulence factors of that interface with the host by means of receptor-ligand interactions. The essential factors of such virulence are adhesions through which adherence to the intestinal epithelium is achieved, enterotoxins that are responsible for secretions of the intestine, cytotoxins that are directly responsible for injury to the epithelial cells, and invasions that are responsible for mediating the invasion by bacterial enteropathogens. Vibrio cholerae is responsible for Cholera, which brings on diarrhea through the production of enterotoxins. Some of the other Vibrio species can cause a more invasive enteric infection. The parasite Giardia lamblia causes diarrhea when a large number of the parasites attach themselves to the duodenal mucosal cells and lead to severe secretory diarrhea. The Cryptosporidium species also cause a secretory form of diarrhea, but the invasion is limited to the cells of the intestinal epithelium. Salmonella and the Campylobacter species of bacteria are organisms that invade the mucosa of the intestines and secrete toxins that are responsible for the diarrhea caused by these pathogens (Inglis, 2003). . Literary References Birmes, P., Coppin, D., Schmitt, L. & Lauque, D. (2003). Serotonin syndrome: a brief review. Canadian Medical Association Journal, 168(11), 1439-1442. Duncombe, V. (2006). Chronic Diarrhoea. In Nicholas Joseph Talley & Christopher Martin (Eds.), Clinical Gastroenterology. Second Edition (pp.223-252) Australia: Elsevier Guillebaud, J. (2005). Contraception: Your Questions Answered. Fourth Edition. Elsevier Health Sciences, Amsterdam, pp.229-278. Husband, A. & Worsley, A. (2007). Nausea and Vomiting – pharmaceutical management. Hospital Pharmacist, 14,189-192. Inglis, T. J. J. (2003). Microbiology and Infection. Second Edition. Elsevier Health Sciences. Amsterdam. Rickenlund, A., Carlstrom, K., Ekblom, B., Brismar, T. B., von Schoultz, B. & Hirschberg, A. L. (2004). Effects of Oral Contraceptives on Body Composition and Physical Performance in Female Athletes. The Journal of Clinical Endocrinology & Metabolism, 89(9), 4364-4370. Rollema, H. M. & Sprouse, J. (2005). Potential Targets for the Treatment of Depressive Disorders. In E. J. L. Griez (Ed.), Mood Disorders: Clinical Management and Research Issues. (pp.429-448). New Jersey: John Willey and Sons. Silins, E. Copeland, J. & Dillon, P. (2007). Qualitative review of serotonin syndrome, ecstasy (MDMA) and the use of other serotonergic substances: hierarchy of risk. Australia NewZealand Journal of Psychiatry, 41(8), 649-655. Spierings, E. L. H. & del Rio, M. S. (2002). Inflammation in migraine pathogenesis: when, where, and how. In Egilius L. H. Spierings (Ed.), (pp.17-19.). Basel, Switzerland: Birkhauser. Timby, B. K. & Smith, N. E. (2007). Introductory Medical-Surgical Nursing. Ninth Edition. Lippincott Williams & Wilkins, Philadelphia, PP.730-736. Youngson, R. M. & Jacoby, B. J. (2005). Encyclopedia of Family Health. Marshall Cavendish, London, pp.1414-1417. Read More