pharmacology assignment with questions and answers PDF

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medication for disease and disorders...

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STEVEN SSEMWOGERERE 10433725

Part A (Total 15 marks) Mr BT is 47-year-old man admitted to hospital with prostate hypertrophy requiring a transurethral resection of the prostate (TURP). The procedure is completed without complication and Mr BT returns to the ward with an indwelling catheter in place, it remains in situ for three days. After the catheter is removed, Mr BT experiences urinary frequency and a burning sensation during micturition. A urine sample is taken and sent to the microbiology laboratory for analysis. The microbiology report shows the following:   

Microscopy: white blood cells ++, Gram-negative rods Culture: Pseudomonas aeruginosa Sensitivity: amoxicillin-resistant, cephalexin-sensitive, gentamicin-sensitive

trimethoprim-resistant,

His medical history indicates hypersensitivity to penicillin.

1. Which antibacterial agent(s) would be effective in the therapy of Mr BT’s urinary tract infection? (4 marks) In a study carried out within an Indian tertiary hospital to check the anti-biotic patterns with Pseudomonas aeruginosa. Had results showing pseudomonad urinary infections that tend to be resistant during therapy. Therefore, combined treatment using beta lactamase inhibitors like cephalosporin (cephalexin) with an amino glycoside (Gentamicin) creates a more effective therapy. This is due to the fact that the bacterial strain identified in the urine sample of Mr. BT (Pseudomonas aeruginosa) is sensitive to these two antibiotic drugs. Thus, the two drug combination would kill the bacteria (Javiya, Ghatak, Patel, & Patel, 2008). 2. State the mechanisms of action of each of these agents. (4 marks) The mode of action for Cephalosporin’s includes disruption of synthesis of bacterial cell wall component known as peptidoglycan. The peptidoglycan is the strongest structural molecule which is present only in the cell wall of the bacteria which helps the bacteria to

survive harsh and unfavourable conditions. As the peptidoglycan layer of the bacterial cell wall is damaged the cell wall gets compromised thus resulting into entry of bactericidal molecules inside the bacteria and ultimately bacterial death. Since human cells do not have peptidoglycan layer therefore the beta-lactam antibiotics which are specific to that layer do not attack the human cells and only kill bacterial cells. On the other hand the Gentamicin kills bacteria through disrupting synthesis of bacterial protein and bacterial cell wall damage. The aminoglycosides bind with the 30S ribosomal subunit of the bacteria. Ribosomes are also known as the protein factory of the cells and it consist of two subunits namely 30S and 50S. Upon binding with the ribosome the translocation of the tRNA is inhibited by the aminoglycosides during the event of translation. Therefore it does not allow the bacterium to synthesize the necessary growth proteins. Although the human cells also do have ribosomes but the size and structure differs from that of the bacterial ribosomes. Therefore the aminoglycosides do not interfere with the human cells protein synthesis (Kapoor, Saigal, & Elongavan, 2017). Inhibition of protein synthesis is not the only mechanism for bacterial cell death rather the aminoglycosides also damages the bacterial cell wall by displacing the cations in the biofilm produced by the bacteria. These biofilm are responsible for linking the lipopolysaccharides (LPS) molecules to the cell walls. With the displacement of the cations there is creation of holes in the cell wall of the bacteria thus exposure for easy penetration of anti-biotic substances and allowing the aminoglycosides to reach to the ribosomes. Since the human cells do not have cell walls therefore the human cells are not susceptible to destructive actions of the aminoglycosides (Kapoor, Saigal, & Elongavan, 2017).

3. Outline the pathophysiology underlying Mr BT’s hypersensitivity to penicillin (4 marks) The hypersensitivity reactions associated with any drug are the immunological responses towards that drug. The Penicillin drug is the most common drug to which people develop allergies. All types of penicillins have a common core structure consisting of beta-lactam and thiazolidine rings but the side chain differs. When subjected to specific physiological conditions the core ring structure of penicillin metabolises into one penicilloyl and penicilloate, penicillin and penilloate. These are the antigenic determinants that trigger the IgE responses immediately. These immediate reactions generally occur within first hour of first dose of the drug, sometime the allergic reactions may also appear after two hours of drug administration. The symptoms of allergic reaction consist of wheezing, shortness of breath, pruritus, vomiting, and cardiorespiratory collapse. The non-IgE mediated reaction which includes development of allergic reaction through IgG response show delayed reactions which consist of serum sickness, rashes appear at the surface of the skin, anaemia, eosinophilia, intestinal nephritis and systemic symptoms (Bhattacharya, 2010).

4. Given the fact that Mr BT is allergic to penicillins, is cephalexin therapy contraindicated here? (3 marks) The incidences of correlation between cross-reactivity of penicillin and cephalosporin family antibiotics is very limited. Although both penicillin and cephalosporin’s belong to beta-lactam group but most of the cross-reactivity between the cephalosporin family drugs and the penicillins are based upon the fact whether the side chains are similar in structure (Dickson & Salazar, 2013). Often there is cross-reactivity between penicillin

with the first and second generation drugs of cephalosporin family having similar R 1 side chain like efadroxil, cefatrizine, cefprozil, cephalexin, and cephradine (Campagna, Bond, & Schabelman, 2012). Therefore, high chances of cross-reactivity among the two drugs and it is not safe to give Mr. BT to treat urinary tract infection as he is sensitive to penicillin.

Part B (Total 30 marks) KY is a 12-year-old boy who has been diagnosed recently with acute lymphoblastic leukaemia (ALL). He has been admitted to hospital for treatment. KY’s initial therapy will comprise the corticosteroid dexamethasone, as well as the cytotoxic agent’s vincristine, L-asparaginase, daunorubicin, methotrexate and cytarabine. He experiences gastrointestinal upset but responds well to therapy; however, he does require close monitoring of his condition. KY receives adjunct therapy with the colony stimulating factor filgrastim. KY’s four siblings are tissue-typed for bone marrow transplant. One of the children is considered a good match. While awaiting transplantation, KY develops a fever. He receives intravenous therapy with doxycycline to reduce the risk of sepsis. This crisis passes. After bone marrow transplant, KY makes good progress and moves into remission.

1. Describe the mechanism of action of the corticosteroids and indicate the adverse effects that require monitoring during treatment with these drugs. (6 marks)

The mechanism of action of different corticosteroids produced in the adrenal cortex is different (Becker, 2013). However in the common mode of action the corticosteroids once enter the cells quickly combines with the steroid receptors present in the cytoplasm. The combination formed then enters the nucleus where it controls the protein synthesis that includes the enzymes which regulates the vital activities of the cells and wide range of the metabolic functions including the different aspects of inflammation. There is formation of protein which inhibits the phospholipase enzyme A2 which is important for

the supply of arachidonic acids. The arachidonic acid is important for the initiation of the inflammatory mediators. The corticosteroids also act upon the cell membranes altering the permeability of ions and it also modifies the neurohormone production (Inaba & Pui, 2010). The circulating corticosteroids namely the cortisol and the aldosterone differ in their rate of secretion, concentration in the plasma as well as the extent to which they binds with the protein present in plasma. Approximately the half of the aldosterone circulating are loosely bound with albumin and rest half is free. On the other hand the cortisol is limitedly available although it depends upon concentration of the steroid. The major percentage of cortisol has high affinity for transcortin. It has been observed that the synthetic corticosteroids have relatively less affinity for transcortin compared to physiological corticosteroids. The steroid concentration present within the cell to activate the receptors demonstrates its free concentration in plasma. In liver and spleen tissues the transit time is enough for dislocation of the steroid from the albumin. This makes the steroid concentration available for binding with the receptors. The transcortin binding is different from that of albumin binding as there are various physiological roles of transcortin. The transcortin act as the reservoir of steroids and that transcortin bound corticoids do not get metabolized. Secondly binding with the transcortin is temperature dependent that is at high temperature binding affinity between transcortin and corticosteroid is very low. Thirdly the neutrophil elastase cleaves specifically the transortin that releases the bound steroids that initiates the inflammatory responses. The classical steroid receptors in contrast to the neurotransmitters and protein hormones are present within the cells instead of on the surface of the cells. Both

mineralocorticoids and glucocorticoids in the absence of the hormone are present primarily in the cytoplasm of the cell. Various other proteins such as heat shock proteins help in maintaining the receptors to form high affinity for the steroids. Such proteins also inhibit the receptors to interact with the DNA in absence of hormone. Upon binding with the steroid the receptors sheds all the associated proteins and Trans locates into the nucleus to bind as a dimer to a specific nucleotide sequence of the target gene and this is known as the response elements. The receptor then initiates the mRNA transcription to encode the proteins that are responsive to corticosteroid in the specific target tissue. The mineralocorticoid steroid and aldosterone is produced in the outer zona glomerulosa of the adrenal cortex with the help of different enzymatic modifications of the cholesterol. The aldosterone gets secreted in the response to the increased concentrations of the angiotensin II or the plasma potassium due to deficiency of sodium. The normal rate of secretion and concentrations of circulating aldosterone are lower than the glucocorticoids. Cortisol is the naturally produced glucocorticoid in most of the species (McKay & Cidlowski, 2010: Liu, et al., 2013). Most of the corticosteroid side effects are related to the type of corticosteroids. It is suggested that if one have been taking steroids for long time should not stop it abruptly as the withdrawal symptoms may become severe (Miller, 2016). Therefore one has to take steroids with caution. Following are some of the side effects of corticosteroids and the recommended management of these side effects:  Weight gain: The steroids are known to affect the body metabolism and the way body stores the fat. Due to steroids the water retention capacity of the body increases which results into weight gain, however over the time period the body fat starts increasing. The

corticosteroids also increase the appetite that makes one to eat more than required. Fat accumulation on the face, abdomen and neck area also becomes very significant. In order to manage the weight gain one should be involved in regular physical activities such as exercise and watch food intake (Dr. Theodore, 2017).  Mood swings: The corticosteroids result into mood swings that is an individual may feel sad, nervous, and anxious at one moment and next moment he will be happy and positive. In general the mood swing subsides in first few days of the treatment but it may also accompany the sleep disorders thus stress reliving exercises should be encouraged along with proper medications that will help in stabilizing the moods (Dr. Theodore, 2017).  Increased susceptibility to infections: The corticosteroids suppress the immune system of the body and increase the inflammation. Due to this the body becomes susceptible to infections as the immune system fails to respond appropriately against infectious agents. This is one of the most important side effects to be managed among the individuals given corticosteroids. Proper hygiene should be maintained while treating the patients, crowded places should be avoided and if any symptoms of dry cough or fever are identified then it should be immediately attended (Dr. Theodore, 2017).  Eye problems: there is increased risk of various eye problems when a person uses corticosteroids for longer period of time. This includes cataracts and glaucoma. This can be managed by avoiding direct sunlight and applying lower doses of eye medicines.  Loss of bone density: This is one of the most common side effects of corticosteroids which results into osteoporosis. The density of the bone reduces that causes thinning of bones and leads to fractures or painful experiences. Therefore in order to manage this condition it is important that one has to take enough amount of calcium while undergoing

corticosteroid medications. Along with calcium, vitamin D is also recommended as well as undertaking mild physical exercises and walking (Dr. Theodore, 2017).  Changes in blood sugar level: The corticosteroids are also known as glucocorticoids as they have effect upon the metabolism of glucose. People undertaking corticosteroid medications are often detected with altered level of sugar in their blood and some even develops steroid-induced diabetes. The solution for this is a constant monitoring of the blood sugar level has to be done. Along with this diet plan has to be designed so that excessive intake of sugar is avoided that can become of the additional factors for development of blood sugar. The issue of altered sugar level in blood is often resolved when the intake of steroids are either reduced or discontinued (Dr. Theodore, 2017).  Altered Response to Physical Stress: If steroids were taken for over two weeks, even though you then stop, your body could have a diminished ability to retort to physical stress - as a result of your adrenal glands which might not react as they must usually. This result will last as long as a year once steroid discontinuance. If one got a surgery, develop a brand new serious sickness, or experience serious trauma (such as an automotive accident), your body might not be ready to answer the physical stress. Your pressure level may drop, and alternative physical effects will occur, that sometimes is terribly serious. This condition, referred to as adrenal insufficiency, is avoided by taking "stress dose steroids" ought to such sickness or injury occur whereas taking steroids or throughout the year once you've not been on them. The strain dose makes up for the sluggishness of your adrenal glands and provides your body with the steroid it must handle the physical stress. Once a year off steroids, basically all patients are shown to possess recovery of adrenal function and are ready to respond properly to the physical stress of surgery or major

sickness. Self-care tips involve, informing medical personnel if you were a former steroid user before receiving any medication (Dr. Theodore, 2017).  Insomnia: Steroids might impair your ability to go to sleep, particularly once they square measure taken within the evening. Self-care tips, enquire from medical personnel if you’re able to take entire daily dose within the morning and try to establish an everyday hour for moving into bed and tiny rituals that assist you harden sleep (Dr. Theodore, 2017).  Atherosclerosis (Hardening of the Arteries): Steroids might increase the speed of development of induration of the arteries that may increase your risk of cardiovascular disease. This risk is maybe way more vital if steroids square measure taken for quite a year, and if taken in high dose. Self-care tips, Follow a wholesome mode - a lowcholesterol and diet, regular exercise, and stress management. If you develop signs suggesting a heart drawback, like hurting, get medical attention quickly. Check that that your sterol and pressure level are checked and treated if necessary (Dr. Theodore, 2017).

2. To which cytotoxic drug groups do each of the drugs in the case study belong? (5 marks)

Vincristine belongs to drug group known as vinca alkaloids (Moudi, 2013). Both Lasparaginase and daunorubicin belong to drug class known as antineoplastic (Connor, MacKenzie, DeBord, Trout, & O’Callaghan, 2016). Methotrexate belongs to drug class known as antimetabolite (U.S. National Library of Medicine, 2018). Also cytarabine belongs to the above same drug class (MedlinePlus, 2012). The mechanism of action of each drug given to KY is below as follows:

3.

Describe the mechanism of action of each of the drug groups identified in question two (5 marks)

Vinca alkaloids: these medicines are cytotoxic, they should be strictly received for the conditions mentioned by physicians and not for any other use. These drugs are classified as anti-microtubule drugs as they works as anti-cancer drugs. They cause development of abnormalities in the formation of microtubule in the cells. Vinca alkaloids bind to micro tubules and spindle proteins in S part of the cell cycle and interfere with the formation of the mitotic spindle, thereby stunning tumour cells in metaphase. These agents conjointly depolymerize microtubules and will conjointly interfere with organic compounds like cyclic AMP, and glutathione metabolism. And the calmodulin-dependent Ca++ -transport ATPase activity; cellular respiration; and super molecule and lipoid bio genesis. The microtubules are the cell components that give the structural framework to the cell to divide and grow further. The formation of abnormal microtubule due to the effect of vinca alkaloids, thus inhibiting the cell replication leading to cell death finally (Moudi, 2013). Antineoplastic: this is an anthracyclines chemotherapy drug group for treating cancer cells. Uses multiple mechanisms like inhibiting replication and damaging cells in ways that promote necrobiosis. They work primarily by deoxyribonucleic acid intercalation so as for cells to divide. The deoxyribonucleic acid within the cell's nucleus should be unravelled and so duplicated (a method referred to as transcription). Anthracyclines bind to parts of the straight strand of nuclear deoxyribonucleic acid, halting the transcription method that successively prevents cell replication. Deoxyribonucleic acid additionally

happens in different elements of the cell, significantly the cell's mitochondria, and the cell's energy-generating structures, wherever it's used as a templet for producing proteins required for cell performance and survival. Anthracyclines additionally bind to mitochondrial deoxyribonucleic acid, inhibiting these most simple cellular functions (Toxipedia, 2011). Antimetabolites: this drug group was among the primary powerful chemotherapeutic specialists found, and are folic corrosive, pyrimidine or purine analogs. They have comparative structures to atoms of the body that utilizes as a part of nucleic corrosive (DNA and RNA) amalgamation. Antimetabolites are like chemicals required for ordinary biochemical action, however vary enough that they meddle with typical cell work. For the most part, antimetabolites actuate cell passing amid the S period of cell development when consolidated into RNA and DNA or repress catalysts required for nucleic corrosive creation. These operators are utilized for an assortment of growth treatments, including leukaemia, bosom, pancreatic, ovarian, and gastro-intestinal diseases (Mihlon, Ray, & Messersmith, 2010).

4. What are the common immediate and delayed adverse reactions associated with cytotoxic d...