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.
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 “Part 2″ should be used to addressquestions 4 and 5, while the drug you are allocated for “Part 3″ should be used to address questions 11 to 18.
Use this book for 2 – 4 references
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 “Part 2″ should be used to addressquestions 4 and 5, while the drug you are allocated for “Part 3″ 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).
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).
CLICK HERE TO GET MORE ON THIS PAPER.....
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).
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).
CLICK HERE TO GET MORE ON THIS PAPER.....
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
“The 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 “No matter what I try to do, the pain won’t go away”
Quality “It 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 “I am allergic to penicillin”
Last oral intake
“I 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).
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
“The 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 “No matter what I try to do, the pain won’t go away”
Quality “It 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 “I am allergic to penicillin”
Last oral intake
“I 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).
