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UNIT SCH3236 PAHRMACOLOGY NAME OF STUDENT Chantara Sofair STUDENT ID NO. 10183854 DRAGANA KLINAC DUE DATE 25/10/2012 Campus JO OFFICE USE ONLY

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Course E70

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PHARMACOLOGY SCH3236 SEMESTER TWO 2012 ASSIGNMENT THREE DUE DATE: 25th Oct 2012 (Thursday) Before 6pm SECTION ONE: Multiple Choice (total 10 marks) Select the best answer for the following: 1. a. b. c. d. 2. a. b. c. d. Adrenocortical agents are widely used: To cure chronic inflammatory disorders For short-term treatment to relieve inflammation For long-term treatment of chronic disorders To relieve minor aches and pains and to improve quality of care for patients When asked to explain the adrenal medulla, it would be appropriate to say: Is the outer core of the adrenal gland Is the site of production of aldosterone and corticosteroids Is a neural ganglion of the sympathetic nervous system Consists of three layers of tissue which contain cells that produce hormones

3. Glucocorticoids are hormones that: a. Are enzymes that are released in response to increased glucose levels b. Aid in the regulation of hydrostatic electrolyte levels c. Aid in the regulation of electrolyte balance in the body d. Promote the preservation of energy through increased glucose levels, protein catabolism and fat formation 4. a. b. c. d. Dirunal rhythm in a person with regular sleep cycle would show: High levels of ACTH during the night while sleeping Rising levels of corticosteroids throughout the day Peak levels of ACTH and corticosteroids early in the morning Hypothalamic stimulation to release CRH around noon

5. People who have been receiving corticosteroid therapy for a prolonged period and suddenly stop the drug will experience and adrenal crisis due to their adrenal glands no longer producing any adrenal hormones. Your assessment of a person for the possibility of adrenal crisis may include: a. Physiological exhaustion, shock and fluid shift b. Acne development and hypertension c. Water retention and increased speed of healing d. Water retention and Hyperglycaemia

6. A person is started on a regimen of prednisone due to a crisis in her ulcerative colitis. Care of this person would need to include: a. Immunisation to prevent infections b. Increased calories to deal with metabolic changes c. Administration of the drug around 8 or 9 am to mimic normal diurnal rhythm d. Fluid restriction to decrease water retention 7. Mineralocorticoids are used to maintain electrolyte balance in situations of adrenal insufficiency. Mineralocorticoids: a. Are usually given alone b. Can be given only intravenously c. Are always given in conjunction with appropriate glucocorticoids d. Are separate in their function from the glucocorticoids 8. a. b. c. d. 9. a. b. c. d. 10. a. b. c. d. The fluoroquinolones: Are broad-spectrum antibiotics with few associated adverse effects Are associated with severe adverse reactions Are widely used to treat gram-positive infections Are widely used to treat gram-negative infections Which of the following is not a caution for the use of cephalosporins? Allergy to penicillin Renal failure Allergy to aspirin Concurrent treatment with aminoglycosides Ciprol, a widely used antibiotic, is an example of: A penicillin A fluoroquinolone An aminoglycoside A macrolide antibiotic

SECTION TWO: Case Study Answer the following questions: 1. Patients with penicillin hypersensitivity should NOT take antibiotics, or any medication that contains penicillin, this includes all antibiotics that have the suffix cillin at the end such a: piperacillin, and mezlocillin. Furthermore, drugs such as cephalosporins, monobactams, cephalexins and carbapenems should not be used in patients with penicillin allergies as they have shown to cause a possible negative reaction (Aschenbrenner & Venable, 2008). Infections of this nature are often immune to many of the available antibiotic treatments (Asperheim, 2005). Aminoglycosides and polymyxins are two different groups of antibiotics that do not contain penicillin. Polymyxins such as Colistin and polymyxin B have both shown to be effective in treating this infection, and the bacteria are not resistant to them. Some aminoglycosides such as amikacin, gentamicin and tobramycin would be effective in treating this infection by killing or slowing down the growth of the bacteria. However, not all aminoglycosides would be effective, for example, bacteria are resistant to the aminoglycoside kanamycin (Aschenbrenner & Venable, 2008).

2.

Aminoglycosides
Aminoglycosides can cause damage to the cell membrane of bacteria and are referred to as bactericidal or bacteriostatic. The general mechanism of action for aminoglycosides is to inhibit protein synthesis which can interfere with proofreading processes (Bullock & Manias, 2010). This can increase the chance of error in synthesis of bacteria, resulting in an increased likelihood of termination as well as decrease the chance of the bacteria growing again. The binding site for aminoglycosides is the 30s ribosomal subunit (Arcangelo & Peterson, 2005).

Gentamicin
Gentamicin works by inhibiting the protein synthesis in bacteria. Furthermore, when protein synthesis does occur, gentamicin will inhibit the growth of bacteria (Bullock & Manias, 2010).

Polymyxins
Polymyxins cause membrane damage to bacteria, by decreasing the integrity of bacteria cell membranes (both inner and outer). Specifically, Polymyxin B causes the membrane of bacteria to be unstable by binding to the bacteria and reducing cell permeability, this inhibits cellular respiration, and results in leakage of the cellular molecule and kills the bacteria (Bullock & Manias, 2010).

Colisitin
Penetrates the cell wall of bacteria and disrupts the membrane, and, similar to polymyxin B, changes the permeability of the bacteria membrane (Asperheim, 2005).

Tobramycin
Binds to ribosomes on the bacteria and prevents bacteria from forming a complex, this causes the cessation of protein synthesis and death to the cell (Asperheim, 2005).

3. A hypersensitivity or allergy is when the body produces a damaging immune response to a substance (Whitney & Rolfes, 2011). Hypersensitivity is considered a type 1 allergy and means an allergic response occurs immediately. Penicillin hypersensitivity, however, usually occurs as a type 2 hypersensitivity as a reaction to penicillin often happens after the drug is absorbed into the body (Bullock & Manias, 2010). Upon the binding of penicillin and macromolecules, a complex called haptencarrier complex is formed (Arthur J. Atkinson, Huang, Lertora, & Markey, 2012). Hapten, when attached to a carrier, such as protein, can cause an immune response

in the body as immunoglobulin E on mast cells and basophils recognizes these hapten-carrier complexes as antigens (Asperheim, 2005). Haptenation can cause an increase in epitopes (antigenic determinants) resulting in an immune response. Once penicillin is absorbed it can bind to cells forming an antibody-drug complex, once this has occurred the antibody-drug complex causes the breakdown of blood cells, resulting in low blood cell count, in both white and red blood cells i.e. anaemia, thrombocytopenia (Bullock & Manias, 2010). The beta lactam ring of penicillin is unstable and as it binds to a protein it acrylates residue of lysine which results in a penicilloyl epitope which is called benzylpenicilloyl (Asperheim, 2005).

4. Cephalexin should not be used to treat patients with penicillin allergies, as there can be adverse affects (Aschenbrenner & Venable, 2008). Although an adverse reaction to cephalexin will not definitely occur in patients with a hypersensitivity to penicillin, it has been shown to show adverse affects in some patients with penicillin hypersensitivity (Asperheim, 2005). Therefore, another antibiotic that can affectively treat a urinary tract infection without risking adverse affects to MR BTs health would be more appropriate.

SECTION THREE: Case Study Answer the following questions: 1, a. Corticosteroids mechanism of action Corticosteroids are used as an anti-inflammatory agent and immune system suppressor (Hong et al, 2009). These drugs enter cells from the bloodstream, and bind with cytoplasmic glucocorticoid receptors, forming a receptor steroid complex (Bullock & Manias, 2011). This complex enters into the cell nucleus where it interacts with the cells DNA, causing modification of transcription, and resulting in the alteration of protein synthesis (Perry, 2008). Through alteration of protein synthesis, corticosteroids can cause the suppression of leukocytes at the site of inflammation, interfere with inflammatory mediators, and suppress overall immune system

responses to inflammatory agents (Hong et al, 2009). Corticosteroids such as Dexamithasone specifically result in the development of proteins that inhibit phospholipase A2, a protein involved in the development of inflammatory mediators such as prostaglandins and leukotrienes (Hong et al, 2009). Corticosteroids can also alter the ionic permeability of cellular membranes, resulting in a disruption of cellular function (Bullock & Manias, 2011). Secondary effects of Corticosteroids include: lowered levels of antibodies in the blood stream, the suppression of the responsiveness of macrophages, and enhanced tissue responsiveness to noradrenaline and adrenaline resulting in an increase in sympathetic nervous system activity (Hong et al, 2009). Corticosteroids have also been demonstrated to reduce the size of lymph nodes without suppressing bone marrow cells (Bullock & Manias, 2011). 1, b. Adverse effects requiring monitoring The widespread effects of corticosteroids within the body can result in a number of adverse consequences that may require monitoring during treatment (Bullock & Manias, 2011). Extended use of corticosteroids can result in hypertension, redistribution of subcutaneous fat. Alopecia, impaired wound healing, and oral candidiasis (Perry, 2008). Further, the lowering of the immune system for an extended period of time can leave the patient susceptible to invasive diseases and infections (Hong et al, 2009). At high doses corticosteroids may cause joint discomfort, headaches, and flushing. Oral doses of corticosteroids can result in imbalanced fluid and electrolytes, while the administration via eye drops can result in an increase in intraocular pressure (Bullock & Manias, 2011). Adverse reactions specially linked to Dexamethasone include: Insomnia, retention of fluid, chest discomfort and heartburn, increases in appetite, and muscle weakness. More rare reactions can include mood swings, shortness of breath, general tiredness and fatigue, and bone thinning (Allen, 2007). Allergic reactions to the drug can result in itching and skin rashes, tightening of the chest and breathing complications, fever, and nausea and vomiting (Allen, 2007).

2. The drugs used in the case study belong to the following cytotoxic groups. 1. 2. 3. 4. 5. 3. Vincristine: Mitotic inhibitors L-asparaginase: Antineoplastic Daunorubicin: Anthracycline Methotrexate: Antimetabolite Cytarabine: Antimetabolite

Mitotic inhibitors (Vincristine)

Mitotic inhibitors are a class of cytotoxic drugs that disrupt mitosis, or cell division, resulting in the inhibition of cellular replication (Bullock & Manias, 2011). The predominant method of action for this class of drugs is the disruption of mitosis through the prevention of the formation of mitotic spindles, necessary for mitosis (Bullock & Manias, 2011). The drug also disrupts the organisation of the cell during preparation for division (Hong et al, 2009).

Antineoplastic (L-asparaginase)
L-asparaginase does not fit specifically into one of the cytotoxic drug subcategories and is labelled as a general antineoplastic drug (Bullock & Manias, 2011). Specifically L-asparaginase inhibits the synthesis of proteins containing the amino acid asparagine, resulting in cellular disruption (Perry, 2008).

Anthracycline (Daunorubicin)
Antgracyclines disrupt enzymes employed in DNA replication (Bullock & Manias, 2011). Drugs from this class bind to DNA, preventing both replication, and subsequent development of RNA, thus resulting in the disruption of protein

transcription (Hong et al, 2009). This class of drug can also cause breaks in DNA strands, and increase free radicals in the system (Perry, 2008).

Methotrexate: Antimetabolite (Methotrexate and Cytarabine)

Antimetabolites prevent cell growth by disrupting both DNA and RNA molecules (Hong et al, 2009). One prominent class of antimetabolites exist as structural analogues of DNA nucleotides. Upon administration, this class of drug substitutes itself into the chemical make up of both DNA and RNA, resulting in a disruption in both replication and subsequent protein development (Bullock & Manias, 2011). Other classes of antimetabolites interfere with enzyme metabolism, disrupting the breakdown of specific enzymes, resulting in a disruption of cellular function (Hong et al, 2009). 4. Cytotoxic drugs are designed to target cancerous cells. However, as they often also act on healthy cells, specifically cells with fast replication, therefore administration of these drugs can cause a number of adverse reactions (Hong et al, 2009). Immediate effects of these drugs can include: mouth ulcers and inflammation of oral areas, blistering and necrosis of the skin, nausea, vomiting, and cause general feelings of being unwell (Bullock & Manias, 2011). Delayed effects include: low platelet counts, anaemia, and leukopenia, a reduction in the immune system, resulting in a greater susceptibility to infections, and may influence the function of the heart kidneys and liver (Hong et al, 2009). 5. Chemotherapy leaves the patient with a greater susceptibility to infection largely due to the drugs causing a reduction in the immune system, resulting in a reduced resistance to bacteria and foreign bodies (Bullock & Manias, 2011). Clients undergoing this treatment should be carefully monitored to ensure that infections are detected and treated as soon as possible (Perry, 2008). Specifically, monitoring of the patient can involve carful examination of temperature and fluid balance, and

constant monitoring and check ups. To decrease the likelihood of infections patients should be informed to keep a healthy diet and sleeping patterns, to avoid strenuous activity, and anyone who may pass on infections, and to be careful to treat, and sanitise any small wounds as soon as they appear. The patient should be informed to seek medical treatment immediately when infection is suspected (Perry, 2008).

6. Doxycycline belongs to the tetracycline class and is a bacteriostatic agent (Hong et al, 2009). Bacteriostatic agents refer to drugs that limit bacterial growth by inhibiting their reproduction, often by preventing the synthesis of proteins or nucleic acids. In contrast, bactericidal agents control bacteria by directly killing them (Hong et al, 2009). For example, penicillin disrupts normal cell wall development, causing bacteria to continue to grow without dividing, resulting in lyses, and eventually killing the cell. As bacteriostatic agents, Tetracycline antibiotics, therefore, inhibit the development of bacteria by interfering with bacterial reproduction without directly killing the bacteria itself (Bullock & Manias, 2011). The predominant mechanism of action specific to tetracycline involves the binding of the drug to bacterial ribosomes, subsequently preventing the development of proteins by inhibiting the addition of new amino acids. This causes cellular disruption and limits reproduction of the cell (Hong et al, 2009). 7. Antimicrobial drug spectrum of activity can be defined as the range of microorganisms that can be inhibited by a specific antibiotic drug (Hong et al, 2009). A wider spectrum of activity indicates a larger number of different microorganisms inhibited by the drug (Parija, 2009). Doxycycline is labelled as a broad-spectrum antibiotic, as it inhibits a wide range of both Gram-positive and Gram-negative bacteria (Parija, 2009). Broadspectrum antibiotics allow treatment of a wide range of bacterial infections (Hong et al, 2009). When KY presented with fever during treatment, a broad-spectrum

approach allowed a number of different possible bacterial infections to be treated without the need for identification of the specific bacterial infection. This allowed fast response to the infection, which was particularly critical for KY, as his immune system had been previously reduced during cytotoxic drug treatment. Broad-spectrum antibiotics can also be used in the presence of multi bacterial infections (Parija, 2009). However, care must be taken in the administration of broad spectrum antibiotics as they may not be as effective on one particular type of bacteria as narrow range antibiotics, and may fail to inhibit it, which can lead to the development of antibiotic resistant bacterial infection (Hong et al, 2009).

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