Impact of Life Stages and Disease States on Drug Therapy, and Drug Dependence, Misuse and Abuse Read the assignment details below carefully. Part 2 drug (( perindopril )) Part 3 drug ((atorvastatin )) 1. Be awarethat there are a lot of my friends dealing with your company. They have same assignment. So, please as I trust that your are professional writer, I expected that you will provide me by a original papers. I’m sorry for saying that but just to avoid plagiarism & this happened many times then they got fail the topic. So, please I trust you. 2. all assignments we will be passing through (Turnitin) text matching software, this software is part of the University Academic Integrity policy. please note that all references have to be after 2006 and they should be peer reviewed journals. It prefers to get new journals “ date 2012& 2011- peer reviewed journals articles.You can get information from text book, but no more 2 or 3 books , you should provide chapter and page numbers please. The rest of references list have to be peer reviewed journals articles only. 3. Please be specific with (in text reference) & (reference list).As Harvard guide lines. I want you to write page number with every in text reference. It’s important to do that. Please, 4. The major assignment for this topic will take the form of an Intergrated Clinical Case. This assignment will require you to address questions relating to drugs used in paramedic practice, and also questions relating to drugs used in the community. This assignment will be broken into three (3) parts; the Patient Background (Part 1), the Scenario (Part 2) and the Follow-up (Part 3). While the questions that relate to the use of paramedic drugs will be answered by everyone, you will be allocated two drug from the patients medication lists to complete certain questions in Parts 2 and 3. The drug you are allocated for œPart 2³ should be used to addressquestions 4 and 5, while the drug you are allocated for œPart 3³ should be used to address questions 11 to 18. Use this book for 2 “ 4 references Bryant B & Knights K 2011, Pharmacology for Health Professionals, 3rd Edition, Mosby Elsevier, Sydney) If you need any questions please ask . PARA3006: Applied Pharmacology: Integrated Clinical Case Patient Background (Part 1) For much of his life Howard Bloom rarely saw his GP, however in the last 5 years he has needed to visit his GP with increasing frequency to address a number of ongoing medical conditions. The following baseline characteristics were recorded at his last GP visit, which was one week ago: Age 63years Height 178cm Weight 98kg Blood Pressure 146/87mmHg Occupation Chief Information Officer (CIO) at KPMG Pulse 67bpm Smoking status Non-smoker Alcohol status Social drinker (8-12 std drinks / week) with history of heavy drinking (20-40 std drinks / week) until 5 years ago Blood analysis Fasting blood glucose 14.2mmol/L (healthy 3 “ 5.4mmol/L) HbA1c 7.8 (healthy < 4.8) GFR (measured as creatinine clearance) 78mL/min (healthy > 90mL/min) Child-Pugh score 5 (healthy < 5) Cholesterol 6.4mmol/L (healthy < 5.5mmol/L) Plasma albumin 39g/dL (healthy 32 to 54 g/L) Prescription medication history Probitor (20mg OD), Cardipirin (100mg OD), Zocor (40mg OD), Endone (5mg PRN), Coversyl (5mg OD), Lasix (40mg OD), Noten (50mg OD) and Diaformin (850mg BD). Medical history History of ischaemic heart disease, type-2 diabetes, congestive cardiac failure, gastro-oesophageal reflux, and recent surgery to repair a partial torn ligament in left shoulder (3 weeks ago). 1. For each prescription medications listed in the patients prescription medication history determine the: a. Generic name b. Drug class c. Approved indications d. Regulatory schedule Scenario (Part 2) At 6:15am on a Wednesday morning, Howard has called 000 after experiencing a sudden onset of shortness of breath and chest pain while lying in bed shortly after waking up.You attend the call and perform an initial assessment which reveals: Primary complaint Feeling of pressure on chest, uncomfortable (nauseous) feeling in stomach. Level of consciousness Alert and conscious, can recall the time, identity and location. Airway and breathing Airway is clear however patient is visibly short of breath. Circulation Radial pulse is ~84beats/min, strong and regular. While sitting with Howard, he tells you that in addition tohis prescription medications he is also currently taking Blackmores Joint Formula (OD), Nature’s Way Brain and Memory supplement (OD) and Blackmores Mood Support St Johns Wort supplement (OD). 2. For each of the complementary alternative medicines (CAMs) listed above determine the: a. Active ingredients b. Dose of active ingredient in each preparation 3. Using ONLY primary literature sources: a. Discuss the evidence for any CLINICALLY RELEVANT interactions that may occur between the prescription medicines and the active ingredients in the complementary alternative medicines that the patient has identified in his medication history. Describe the: ? Type of interaction (i.e. pharmacokinetic or pharmacodynamic) ? Mechanism of interaction (e.g. reduced clearance by inhibition of drug metabolising enzyme x) ? Clinical consequences of the interaction b. List the sources of information and indicate the strength of the evidence (e.g. anecdotal report, clinical case, clinical trial, etc) for each of the interactions that you have identified. 4. For your ˜allocated part 2 drug’ from the patients current medications list (see FLO site for allocation) describe the therapeutic mechanism of action of the drug relevant to the context of this scenario: a. Identify which of the patients pre-existing conditions (indications) it may be used to treat. b. Explain how the interaction of this drug with its molecular target(s) at the cellular level leads to a change in body function, and eventually accounts for the therapeutic effect when used to treat the condition identified in part a. 5. Considering the same drug and indication identified in Question 4, critically review 2 ORIGINAL RESEARCH journal articles that provide evidence for the clinical effectiveness of this drug in HUMANS. a. Individually for each article CRITIQUE the appropriateness of the: ? Type of study (e.g. randomised control trial, anecdotal report). ? Comparator agent (e.g. placebo, current gold standard therapy). ? Sample size (i.e. the number of study participants). ? Measures of effectiveness (i.e. how was the effectiveness of your drug assessed). b. On the basis of these critiques, briefly summariseYOUR interpretation of the evidence for the clinical effectiveness of this drug. During your initial treatment you administer oxygen and set up a 3 lead cardiac monitor, which shows that the patient has a normal sinus rhythm of 83beats/min. You then perform a thorough history and physical examination, which reveals: Symptoms Chest pain, nausea, diaphoresis, pale, cool skin. Onset œThe pain began really suddenly just after I woke up, about an hour ago. I was about to get out of bed when the pain began Provocation œNo matter what I try to do, the pain won’t go away Quality œIt feels like someone is pressing really hard on my chest Radiation The pain appears to be localised to the patient’s chest Severity 8 on a scale of 1 to 10 Chest examination No signs of trauma, expansion is normal and symmetrical Breathing sounds Nil adventitious sounds Jugular veins Not elevated Blood pressure 158/91mmHg Pulse 83 beats/min, strong and regular Respiration 22 breaths/min Oxygen saturation 98% (on 100% oxygen) Allergies œI am allergic to penicillin Last oral intake œI had a cup of tea and two biscuits before I went to bed last night After consulting with your partner, you prepare to administerglyceryl trinitrate (GTN) to the patient in the form of a sublingual spray. 6. Critically review 2 ORIGINAL RESEARCH peer reviewed journal articles that consider the mortality benefit obtained by administering GTN in this scenario. a. Individually for each article CRITIQUE the appropriateness of the: ? Type of study (e.g. longitudinal study, cross-sectional study, anecdotal report, etc). ? Study duration (i.e. how long did the study continue to monitor participants for following the intervention) ? Sample size (i.e. the number of study participants). ? Outcome measures (e.g. 3-month survival, 5-year survival, etc). b. On the basis of these critical reviews, briefly summarise YOUR interpretation of the evidence for the mortality benefit of administering GTN to a patient in this scenario. 7. Discuss the relevant factors regarding patient’s vital signs and medical history that should be considered prior to administering GTN. a. Identify any factors (e.g. pre-existing medical condition, current medication, etc) b. Discuss the consequences/risks of not addressing each factor. c. Discuss the risk benefit relationship that must be considered for each factor. d. Identify a strategy for addressing each factor. Once you have administered the GTN to the patient, you perform a 12-lead ECG which differs from your initial 3-lead ECG and presents a clinical picture consistent with the sample ECG shown in Figure 1: Figure 1 “ Example of a 12-lead ECG obtained from an individual experiencing the patient’s condition (not the patient’s ECG) On the basis of this 12-lead ECG, you diagnose that the patient is having an ST elevation myocardial infarction (STEMI). Shortly after commencing GTN, the patient describes his pain as a 5 (previously an 8). After rechecking the patient’s blood pressure again (138/84mmHg), you load the patient into the ambulance to drive him to Flinders Medical Centre, undertaking an on-going assessment and treatment en-route: Level of consciousness Alert and conscious; can recall the time, identity and location. Respiration 18 breaths/min, unlaboured. Oxygen saturation 98% (on 100% oxygen). Blood pressure 138/84mmHg Pulse 78 beats/min, strong and regular. Chest pain 4 on a scale of 1 to 10 While obtaining this history from the patient, you hand him a 300mg aspirin chewable tablet and tell him to chew and swallow it. 8. Critically review 2 ORIGINAL RESEARCH peer reviewed journal articles that consider the mortality benefit obtained by administering aspirin to a patient that has recently suffered a STEMI. a. Individually for each article CRITIQUE the appropriateness of the: ? Type of study (e.g. longitudinal study, cross-sectional study, anecdotal report, etc). ? Study duration (i.e. how long did the study continue to monitor participants for following the intervention) ? Sample size (i.e. the number of study participants). ? Outcome measures (e.g. 3-month survival, 5-year survival, etc). b. On the basis of these critical reviews, briefly summarise YOUR interpretation of the evidence for the mortality benefit of administering aspirin to a patient in this scenario. Upon arrival at the emergency department at Flinders Medical Centre, you give a verbal report to the ED physician and present them with the 12-lead ECG obtained in the field. The ED physician immediately alerts the cardiology registrar who orders a repeat ECG, which confirms your findings. The cardiology registrar then administers 300mg of clopidogrel to the patient and organises for him to be moved to the Cath Lab for coronary angiography and possible stenting. 9. Discuss the therapeutic mechanism of action of clopidogrel relevant to the context of this scenario: a. Describe, with the aid of a diagram, the metabolicprocess that must occur in the body before clopidogrel can elicit a therapeutic effect b. Identify how the interaction of clopidogrel (once it has undergone the metabolic process identified in part a) with its molecular target accounts for the therapeutic effect of this drug. 10. Using ONLY primary literature sources, identify and discuss any potential interactions with the patient’s current medications that may alter the clinical effectiveness of clopidogrel. a. Describe the: ? Type of interaction ? Mechanism of interaction ? Clinical consequences of the interaction b. List the sources of information and indicate the strength of the evidence (e.g. anecdotal report, clinical case, clinical trial, etc) for each of the interactions that you have identified. Follow-up (Part 3) Howard remains in hospital for seven days following the successful insertion of a stent into the occluded coronary artery, during this time he contracts a bacterial infection, which following the failure of various other antibacterial agents is eventually treated with long term use of Ciproxin (500mg TID). One month after his release from hospital, Howard visits his GP for a routine follow-up. During this consultation, Howard identifies to his GP that lately he has been having a lot of trouble sleeping at night, and that for the last two weeks he has been feeling very nauseous every time he takes the Ciproxin tablets. Howard’s GP undertakes a physical examination, orders some blood tests and makes some modifications to his medications to address these ongoing medical conditions. The physical examination and blood tests reveal the following changes from Howard’s baseline characteristics: Weight 101kg Baseline Blood Pressure 151/89mmHg Baseline Pulse 71bpm Blood analysis Fasting blood glucose 13.8mmol/L (healthy 3 “ 5.4mmol/L) HbA1c 8.1 (healthy < 4.8) GFR (as creatinine) 61mL/min (healthy > 90mL/min) Child-Pugh score 6 (health < 5) Cholesterol 6.2mmol/L (healthy < 5.5mmol/L) Plasma albumin 22g/L (healthy 32 to 54 g/L) New prescription medications list Somac (40mg OD), Plavix (75mg OD), Cardiprin (100mg OD), Avapro (300 OD), Lasix (40mg OD), Noten (25mg OD), Lipitor (20mg OD), Diaformin (1500mg BD), Maxalon (10mg BD), Ciproxin (500mg TID) and Temaze (10mg OD). When Howard’s GP receives the results of the blood tests that he has ordered he is a little concerned that Howard’s renal function and liver function appear tohave declined. Worried that these reductions in renal and hepatic function may impair the elimination of one or more of Howard’s medications, he checks over the pharmacokinetics of these drugs to see whether he needs to make any dose adjustments. For your ˜allocated part 3 drug’ from the patients ˜new prescription medication list’ (see FLO site for allocation), examine the pharmacokinetics of the drug in NORMAL/HEALTHY HUMANS by answering the following questions: 11. Determine the extent of binding of the drug to plasma proteins: a. State the percent bound (answer must be as a percentage). b. Calculate the unbound fraction. c. Comment on whether the change in plasma albumin concentration is likely toalter protein binding of this drug, and what effect this may have on clearance. 12. Examine the distribution of the drug within the body: a. State the volume of distribution (Vd) in either L/kg or L. b. Describe whether this is this small or large relative to blood volume. c. Comment on what the volume of distribution tells you about your drug (think in terms of binding to plasma proteins and tissue distribution). 13. Determine the primary route of elimination for the drug: a. Determine the fraction excreted unchanged in urine (fe). b. Percentage excreted as metabolites. 14. Use a diagram to depict the major route of elimination for the drug, identifying the: a. Organs that are involved (i.e. liver or kidneys). b. Processes (e.g. metabolism, secretion, etc) and types of reactions (e.g. functionalization or conjugation). c. Enzymes and/or transporters that are involved in these processes (e.g. CYP, UGT, PgP, OATP). 15. Determine the systemic clearance: a. Individually calculate the hepatic and renal clearances. b. Determine the classification of the clearance of the drug (e.g. low hepatic clearance). c. Referring to the equations used to calculate clearance and based on the classification of the clearance of the drug in part b, discuss which of the determinants of clearance (i.e. enzyme activity, unbound fraction, organ perfusion, filtration, secretion, reabsorption) are important for this drug. 16. Examine the bioavailability of the drug: a. State the oral bioavailability (as a percentage). b. Discuss whether the bioavailability is influenced bygastrointestinal absorption, first pass hepatic extraction or both. c. Comment on whether bioavailability is likely to be increased, decreased or remain constant in this scenario. 17. Discuss the influence of host (e.g. disease states) and environmental (e.g. alcohol, diet, smoking) factors that may alter the rate of clearance of this drug. 18. On the basis of your investigation of the pharmacokinetics of this drug discuss WITH REASONS whether YOU feel it would be appropriate to (1) continue using the drug without dose adjustment, (2) continue using the drug but adjust the dose, or (3) switch the patient to a more appropriate drug (need to provide an alternative with reasoning).