COMPARISON OF ACUTE AND DELAYED ANTIEMETIC EFFECT AND THE.pdf. COMPARISON OF ACUTE AND DELAYED ANTIEMETIC EFFECT AND THE
Republic of Iraq Kurdistan Regional Government Ministry of Higher Education & Scientific Research University of Sulaimani College of Pharmacy
COMPARISON OF ACUTE AND DELAYED ANTIEMETIC EFFECT AND THE CHANGE IN QUALITY OF LIFE BY (APREPITANT,ONDANSETRON AND DEXAMETHASON) AND (ONDANSETRON, DEXAMETHASON) IN HODGKINS LYMPHOMA PAYIENTS RECEIVING HIGHLY EMETOGENIC CHEMOTHERAPY IN HIWA HOSPITAL A Thesis submitted to the council of the college of Pharmacy at University of Sulaimani in Partial Fulfillment of the Requirements for the Degree of Master of Science in Pharmacy Practice-Hospital Setting
Dara Abdulla Mohammed
B.Sc. Pharmacy 2011-2012 Supervisor
Dr. May Taha Sdiq Assistant Professor-College of Pharmacy/University of Baghdad
Sulaimani 2016 A.D
1438 A.H
Kurdi2716
صدق هللا العظيم سورة المجادلة آيە ()11
Supervisor certification I certify that this thesis was carried out under my supervision by student Dara Abdulla Mohammed entitled (Comparison of acute and delayed antiemetic effect and the change in the quality of life by (Aprepitant,Odansetron and Dexamethason) and (Odansetron, Dexamethason) in Hodgkin's Lymphoma patients receiving highly emetogenic chemotherapy in Hiwa Hospital) and do herby recommend that it is accepted as a partial fulfillment of the requirement for degree of Master of Science in Pharmacy Practice-Hospital Setting
Signature Supervisor
Assistant Professor Dr.May Al-Sabbagh
EXAMINATION COMMITTEE CERTIFICATION We, the examining committee, certify that we have read this thesis entitled {Comparison of acute and delayed antiemetic effect and the change in the quality of life by (Aprepitant,Odansetron and Dexamethason) and (Odansetron, Dexamethason) in Hodgkin's Lymphoma patients receiving highly emetogenic chemotherapy in Hiwa Hospital} and have examined the candidate pharmacist Dara Abdulla Mohammed in its contents and it meets the standard requirements for the degree of Master of Science in Pharmacy Practice-Hospital Setting. Signature:
Signature:
Name: Dr. Mohammed Omer Mohammed
Name: Dr. May taha sdiq
Title: Professor
Title: Assistant Professor
Date: 24/12/2016
Date: 24/16/2016
( Chairman )
( Supervisor-Member )
Signature:
Signature:
Name: Dr. Hiwa Khdir saaed
Name: Dr.Niazi Burhanaldin Husamaldin
Title: Lecturer
Title: Lecturer
Date: 24/12/2016
Date: 24/12/2016
( Member )
( Member )
Approved by the Head of Clinical Pharmacy Department Signature: Name: Hiwa Khdir saaed Title: Lecturer Date: 24/12/2016
Dedication
To my father To my mother To my Wife To my brother & sister To my son & daughter
Acknowledgement Thanks for Great God for helping me to accomplish this work. I would like to express my deep gratitude and endless appreciation to my teacher and supervisor, Dr.MayAl-Sabbagh, for her continuous support, guidance, and encouragement through providing me valuable advice during the entire period of conducting this thesis. I am indebted to Dean of School of Pharmacy-Sulaimani University. Dr. Hiwa K. Saaed for his guidance and real support from beginning and throughout the study. I am very much thankful to my teacher Dr. Zheen Aorahman/ Head of Clinical Pharmacy department for his continuous help and guidance. My sincere appreciation to Dr. Najmaddin Khoshnaw, who provided me with valid notes and advice. Great thanks to Dr. Ahang Esmail Amin; who support me during my study. Also special thanks to Dr. Osama F. Al-Qaisi for his efforts in statistical analysis.
Finally, I shouldn’t forget all my colleagues
Pharmacy College who helped and supported me during the study.
contents Subject
Page no.
List of contents
I
List of tables
II
List of graphs
III
List of abbreviations
IV
Abstract
V
Chapter one Introduction
2
General objectives
6
Literatures review
7
1.1. Background
7
1.2. Definitions of nausea, vomiting and retching
9
1.3. Chemotherapy- induced nausea and vomiting
10
1.4. Mechanisms of CINV
11
1.5. Incidence and Impact CINV
13
1.6. Classification
15
1.7. Risk Factors
17
1.8. Prophylaxis and treatment options
18
1.9. Chemotherapy drug emetogenicity
21
1.10. Poor control of emesis
50
1.11. Cannabinoids and medical marijuana
51
1.12. Complementary therapies
53
Chapter two Patients & Methods
57
2.1. Study design & settings
57
2.2. Population of the study
57
2.3. Medication
57
2.4. Sampling & randomization
58 I
2.5. Treatment protocol
59
2.6. Assessment
61
2.7. Ethical protocol
62
Chapter three Results
65
Chapter four Discussion
81
Chapter five Conclusions & Recommendations
91
References
93
II
List of tables Title
Page no.
Table 1.1: Classification of the emetogenic potential antineoplastic agents. Table 1.2: Roles of 5HT and substance P in CINV. Table 1.3: Agents used for prophylaxis and treatment of CINV.
of
Table 2.1: Treatment protocol Table 3.1: Demographic characteristics of study participants. Table 3.2: Nausea scores and emetic effect of study participants. Table 3.3: Vomiting scores and emetic effect of study participants. Table 3.4: Distribution of demographic characteristics and rescue medications of study participants according to study groups. Table 3.5: Distribution of nausea scores and emetic effect of study participants according to study groups. Table 3.6: Distribution of vomiting scores and emetic effect of study participants according to study groups. Table 3.7: Distribution of nausea scores of study participants according to study groups. Table 3.8: Distribution of vomiting scores of study participants according to study groups. Table 3.9: Distribution of nausea and vomiting scores of treatment group according to administration days. Table 3.10: Distribution of total nausea and vomiting scores of study participants aging less than 40 years according to study groups. Table 3.11: Distribution of total nausea and vomiting scores of study participants aging 40 years and more according to study groups. Table 3.12: Distribution of total nausea and vomiting scores of male study participants according to study groups. Table 3.13: Distribution of total nausea and vomiting scores of female study participants according to study groups.
III
16 18 20 61 65 67 68 70 72 73 74 75 76 77
78
78 79
List of figures Subtitle
Page no.
Figure 1.1: The main inputs into the vomiting center that lead to the vomiting.
13
Figure 2.1: Sampling and randomization schedule
62
Figure 3.1: Age distribution of study participants.
66
Figure 3.2: Gender distribution of study participants.
66
Figure 3.3: Total emesis effect of all study patients.
69
Figure 3.4: Distribution of rescue medications.
69
Figure
medications
71
Figure 3.6: Distribution of nausea score emesis effect
72
3.5:
Distribution
of
rescue
according to study groups.
according to study groups. Figure 3.7: Distribution of vomiting score emesis effect
74
according to study groups. Figure 3.8: Distribution of nausea scores according to
75
study groups. Figure 3.9: Distribution of vomiting scores according to
76
study groups. Figure 3.10: Distribution of total nausea and vomiting scores according to days of administration.
IV
77
List of abbreviations Abbreviations 5-HT3 AC ANV APR ASCO CINV DNA FDA FILE HEC IV LEC MASCC/ESMO
Meanings Serotonin receptor The Doxorubicin plus Cyclophosphamide Anticipatory Nausea and Vomiting Aprepitant American Society of Clinical Oncology Chemotherapy-Induced Nausea and Vomiting Deoxyribo Nucleic Acid US Food and Drug Administration Functional living index- Emesis Highly Emetogenic Chemotherapy Intravenous Low Emetogenic Chemotherapy Multinational Association of Supportive Care in
MEC
Cancer/Economic Society for Medical Oncology Moderately EmetogenicChemotherapy
MinEC NCCN NIDL NEPA NK-1 NK1R QoL RNA RR SD SPSS UK USA WHO
Minimal EmetogenicChemotherapy National Comprehensive Cancer Network No effect on daily life NetupitantPlus Palonosetron Neurokinin-1 NK1 Receptor Quality of Life Ribo Nucleic Acid Risk Ratio Standard Deviation Statistical Package for Social Sciences United Kingdom United States of America World Health Organization V
Abstract Introduction: Chemotherapy-induced nausea and vomiting will be around as long as cytotoxic chemotherapy is used to treat cancer. Nausea and vomiting are common and feared symptoms among cancer patients, and up to 80% of patients will
experience
chemotherapy-induced
nausea
and
vomiting
without
prophylactic therapy. Aim of Study: To compare the acute and delayed antiemetic effect and the change in the quality of life by (Aprepitant, Ondansitron and Dexamethason) and (Ondansitron, Dexamethason) in Hodgkin's Lymphoma patients receiving highly emetogenic chemotherapy in Hiwa Hospital Patients & Methods: A randomized single blind controlled clinical trial conducted in Hiwa Teaching Hospital in Sulaimani city for period from 1st of January to the end of December, 2015 on convenient sample of 70 Hodgkin's lymphoma patients. Patients received either the treatment (Aprepitant, Ondansitron and Dexamethason) or the standard regimen (Ondansitron, Dexamethason) in a 1:1 ratio according to a computer-generated, random allocation schedule. Results: There was no significant difference between two study groups in mean nausea scores at first day (p=0.3). A significant higher mean nausea and vomiting anti-effect scores was observed for treatment groups patients at 2nd , 3rd and 4th days than standard group patients (p90% risk of inducing vomiting after chemotherapy administration), moderate emetogenic potential (>30–90% risk), low emetogenic potential (10– 30% risk), and minimal emetogenic potential (
