Marcellus Simadibrata Kolopaking MD PhD
Department of Medical Education
Division Gastroenterology Department of Internal Medicine
Faculty of Medicine University Indonesia
Dr.Cipto Mangunkusumo Hospital Jakarta
Imeglimin, What is new?
By Dr. Usama Ragab Youssif
Lecturer of Medicine - Zagazig University
Agenda
Mitochondrial function and dysfunction
Mitochondrial (dys)function in diabetes
Diabetes core defects and Imeglimin
Imeglimin drug development and approval
Imeglimin and Heart
Imeglimin, What is new?
By Dr. Usama Ragab Youssif
Lecturer of Medicine - Zagazig University
Agenda
Mitochondrial function and dysfunction
Mitochondrial (dys)function in diabetes
Diabetes core defects and Imeglimin
Imeglimin drug development and approval
Imeglimin and Heart
Cefdinir and its role in otitis media, clinical study, indications, dosages, advantage, role of clavunalic acid, hepatotoxicity role all the research features are includes here to be prepared for Rajshahi Medical College, Focusing ENT specialist
Montelukast is a selective and orally active leukotriene receptor antagonist that inhibits the Cysteinyl leukotriene CysLT1 receptor. Each 10 mg film-coated Loctril tablet contains 10.4 mg Montelukast sodium, which is equivalent to 10 mg of Montelukast.
Dr. Swamy Venuturupalli talks about Rheumatoid Arthritis, Early Diagnosis and Treatment at the James R. Klinenberg symposium on Rheumatic diseases in Pasadena, CA.
Review of new alerts on PROTON PUMP INHIBITORS (PPI) adverse effects 2016 UPD...PAWAN V. KULKARNI
Last Updated: 15th MAY: ALL NEW STUDIES INCLUDED. After more than 2 decades of USE, ABUSE, OVERUSE.... PPIs are under scanner. Not just Osteoporosis, other complications but Proton pump inhibitors have been confirmed to cause insistent Kidney failure/disease, heart attacks to name a few. This new revelations should open the eyes of so many consumers and several doctors.
Cefdinir and its role in otitis media, clinical study, indications, dosages, advantage, role of clavunalic acid, hepatotoxicity role all the research features are includes here to be prepared for Rajshahi Medical College, Focusing ENT specialist
Montelukast is a selective and orally active leukotriene receptor antagonist that inhibits the Cysteinyl leukotriene CysLT1 receptor. Each 10 mg film-coated Loctril tablet contains 10.4 mg Montelukast sodium, which is equivalent to 10 mg of Montelukast.
Dr. Swamy Venuturupalli talks about Rheumatoid Arthritis, Early Diagnosis and Treatment at the James R. Klinenberg symposium on Rheumatic diseases in Pasadena, CA.
Review of new alerts on PROTON PUMP INHIBITORS (PPI) adverse effects 2016 UPD...PAWAN V. KULKARNI
Last Updated: 15th MAY: ALL NEW STUDIES INCLUDED. After more than 2 decades of USE, ABUSE, OVERUSE.... PPIs are under scanner. Not just Osteoporosis, other complications but Proton pump inhibitors have been confirmed to cause insistent Kidney failure/disease, heart attacks to name a few. This new revelations should open the eyes of so many consumers and several doctors.
Peptic ulcer disease a brief insight- by rxvichu!!!!RxVichuZ
Hello friends...............its me Vishnu................with my 14th ppt............................
This ppt is on PEPTIC ULCER DISEASE.................Based on therapeutic, pharmacological, and patient counselling point of view...........................
Done with great detail and incorporation of maximum information as possible....hope it helps the readers n viewers!!
Do post ur comments! and reviews!!!
Thank you!!!!
@rxvichu-alwz4uh!!
NON-STEROIDAL ANTI INFLAMMATORY DRUGS AND GASTROINTESTINAL TOXICITYApollo Hospitals
Non-steroidal anti inflammatory drugs (NSAIDs) because of their high efficacy as both anti-inflammatory and analgesic agents, are one of the most commonly prescribed drugs world-wide. They are used in treatment of many commonly occurring disorders such as chronic arthropathies, headache and low back pain. Their widespread and uncontrolled use is promoted by their over the counter availability. This acts as a double edge sword. One of the most common adverse effects that add largely to its morbidity and mortality
is the gastrointestinal tract damage.
Gastroenterology is the branch of medicine focused on the digestive system and its disorders. Diseases affecting the gastrointestinal tract, which include the organs from mouth into anus, along the alimentary canal, are the focus of this speciality
Context—Proton pump inhibitors (PPIs) are among the most commonly used drugs worldwide, and have been linked to acute interstitial nephritis. Less is known about the relationship between PPI use and chronic kidney disease (CKD).
Objective—To quantify the association between PPI use and incident CKD in a population based cohort.
In total, 144,032 participants in Communities study with an estimated glomerular filtration rate of at least 60 mL/min/1.73 m2 were followed from a baseline visit between February 1, 1996, and January 30, 1999, to December 31, 2011. The data was analysed from May 2015 to October 2015.
Introduction: Progress in management of Nonsteroidal anti-inflammatory drug (NSAID) induced gastrointestinal toxicity requires the availability of appropriate experimental animal models that are as close to humans as feasible. Our objective was to develop a rat model for NSAID-induced gastroenteropathy and also to simulate the common clinical scenario of co-administration of NSAID and proton pump inhibitor (PPI) to explore if PPI contribute to exacerbation of NSAID-enteropathy. Methods: Rats were treated twice daily with pantoprazole sodium (PTZ; 10 mg/kg peroral) or vehicle for a total of 10 days. In some experiments, Diclofenac sodium (DCF; 9 mg/kg) or vehicle was administered orally twice daily for the final 5 days of PTZ/vehicle administration. After the last dose on 9th day, rats in all the groups were fasted but water was provided ad libitum. 12 hours after the last dose on 10th day, rats in all the groups were euthanized and their gastrointestinal tracts were assessed for haemorrhagic lesions, lipid peroxidation, intestinal permeability and gastrointestinal luminal pH alterations. Changes in haemoglobin, haematocrit and serum levels of albumin, total protein, ALT and bilirubin were calculated. Results: The macroscopic and histological evidence suggested that administration of DCF resulted in significant gastroenteropathic damage and co-administration of PTZ resulted in significant exacerbation of NSAID enteropathy, while attenuation of NSAID induced gastropathy was observed. Our results were further supported by the significant decrease in haemoglobin and haematocrit levels and serum levels of albumin and total proteins, an increase in oxidative stress and intestinal permeability with the use of DCF either alone or in combination with PTZ. Conclusions: This model was developed to simulate the human clinical situation during NSAID therapy and indeed the present DCF regimen caused both gastric and small bowel alterations, such as multiple erosive lesions, together with a decrease in haemoglobin, haematocrit, serum albumin, serum total protein levels and IP alteration, known to occur in patients receiving NSAIDs. Additionally, this paper provides yet another evidence for PPI induced exacerbation of NSAID enteropathy.
Controversy: the role of immunomodulator in allergic caseSuharti Wairagya
dipresentasikan oleh Erwanto BW Teguh HK
Divisi Alergi Imunologi Klinik Departemen 1. Penyakit Dalam FKUI/RSCM Bagian Penyakit Dalam SMF non Bedah RS. dr. H. Marzoeki Mahdi Bogor
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
Follow us on: Pinterest
Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
1. MANAGEMENT OF NSAID
GASTROPATHY
Marcellus Simadibrata Kolopaking MD PhD
Department of Medical Education
Division Gastroenterology Department of Internal Medicine
Faculty of Medicine University Indonesia
Dr.Cipto Mangunkusumo Hospital Jakarta
2. Introduction
NSAIDs are used throughout the world.
NSAIDs are associated with significant upper
GI side-effects NSAID gastropathy
3. Epidemiology
United States:
+ 15 – 20 million people long-term NSAID
users.
Incidence serious GI complications with NSAID
use :1 - 3 % per year.
Exposure of 10 million patients 100,000 -
300,000 potentially fatal GI complications
annually.
4. Epidemiology
Indonesia hospital base data of NSAID
adverse effect :
Makassar 71%
Jakarta 62.7%
Surabaya 61%
Malang 21% (NSAID 22.6%, Jamu 65.3%, NSAID +
Jamu 12.1%)
No population data
5. Arachidonic acid
COX-1
(constitutive)
COX-2
(induced by inflammatory stimuli)
Non-selective NSAIDs
• Gastrointestinal cytoprotection
• Platelet activity
• Inflammation
• Pain
• Fever
Prostaglandins Prostaglandins
COX-2 selective NSAIDs
Vane & Botting 1995
NSAIDs inhibit enzim COX (siklooksigenase) enzyme which has
the role in prostaglandinproduction
6.
7. NSAIDs are associated with
significant upper GI side-effects
Classical NSAIDs account for approximately 20-
25% of all reported drug adverse events.
It has been estimated that 15-40% of patients
taking NSAIDs experience upper GI symptoms.
The majority(50%) of patients develop some gastric
erosions after each dose of a classical NSAID, up to
100% patients will demonstrate subepithelial
hemorrhage, and 10-25% of chronic users will
develop a peptic ulcer.
Hazleman 1989; Wolfe et.al. 1986
Hirschowitz 1994; Langman et.al. 1999; Silverstein et.al. 2000; Singh et.al. 1996
Brown & Yeomans 1999; Eliott et.al. 1994; Laine 1996
8. NSAIDs are associated with the risk of serious
upper GI complications, hospitalisation and
mortality
80% of peptic ulcer-related deaths occur in classical NSAID
users.
50-60% of NSAID-associated peptic ulcers, presenting for
the first time as a complication, have been silent previously.
Potentially life-threatening upper GI complications occur in
1-4% of classical NSAID users each year.
In the USA, NSAID use has accounted for approximately
107.000 hospitalisations and 16.500 deaths per year
Armstrong & Blower 1987
Singh 1998
Wolfe et.al. 1999
9.
10. Table 1. Risk For Serious Gastrointestinal Complications
Related To Use Of Nonsteroidal Antiinflammatory Drugs
NUMBER 95%
OF ODDS CONFIDENCE
CATEGORY STUDIES* RATIO INTERVAL
Overall 16 2.74 2.54–2.97
Patient > 60 years old 8 5.52 4.63–6.60
Patient < 60 years old 3 1.65 1.08–2.53
Gastrointestinal bleeding 9 2.39 2.11–2.70
Gastrointestinal surgery 3 7.75 5.83–10.31
Gastrointestinal cause of death 4 4.79 3.64–6.22
*Data derived from metaanalysis of 16 casecontrol and cohort studies.
Modified from Gabriel S. Jaakkimainen L. Bombardier C. Risk for serious gastrointestinal
complications related to use of nonsteroidal antiinflammatory drugs. A metaanalysis. Ann
intern Med 1991; 115: 787.
11. Patient’s Risk Factor for GI complications
High risk:
- History of peptic ulcer with complication
- Multiple(>2) risk factors
Moderate risk:
- Age > 65 yo
- High dose NSAID therapy
- History of ulcer without complication
- Uses of aspirin, corticosteroid or anticoagulat
Low risk:
- Without risk factor
Konsensus Gastropati OAINS 2010
12. Patient’s Risk Factor for GI complications
High risk:
- History of peptic ulcer with complication
- Multiple(>2) risk factors
Moderate risk:
- Age > 65 yo
- High dose NSAID therapy
- History of ulcer without complication
- Uses of aspirin, corticosteroid or anticoagulat
Low risk:
- Without risk factor
Konsensus Gastropati OAINS 2010
13.
14.
15.
16.
17.
18. Long-term Risks of Peptic Ulcers
Associated With Helicobacter pylori
Infection and NSAIDs
Study design/methods.
183 cases with peptic ulcers and 730 controls (1:4)
Results.
H pylori infection is associated with an elevated risk of peptic ulcers (OR:
1.95, 95% CI: 1.38-2.74).
Compared to no NSAIDs, any NSAID use (OR: 1.54, 95% CI: 1.06-2.23)
increases the risk of peptic ulcers.
There is also a significant interaction between NSAIDs and H pylori (P =
.047 for interaction of H pylori and increasing quartiles of NSAID use).
Conclusion.
H pylori infection and NSAID use increase the risks of peptic ulcers.The
ulcer risk associated with NSAID use among H pylori-negative subjects is
greater than that for those with H pylori infection.
Lew et.al. http://cme.medscape.com/viewarticle/490253_12
19. Definition of NSAID
Gastropathy
NSAID gastroduodenopathy: acute mucosal
lesion of the gaster & duodenum due to
Nonsteroidal antiinflammatory
drugs(NSAID): hyperemia, erosions & ulcer
Peptic ulcer: ulceration of the gaster &
duodenum related to acid – pepsin & other
agresive factors
21. ETIOLOGY OF NSAID GASTROPATHY
Etiology : NSAID agresive factor
Imbalance of agresive factor and defensive
factor
22. Agressive factors Defensive factors
-Gastric acid -Mucosal blood flow
-Pepsin -Surface epithelial cell
-Bile reflux -Prostaglandin
-Niotine -Phospholipid/surfactan
-NSAID -Mucus
-Corticosteroid -Bicarbonat
-Helicobacter pylori -Motility
-Stress -Mucosal impermeability to H+
-Chemical -Intracell pH regulation
Normal balance of aggressive factors & defensive factors in normal stomach
23.
24. Hiraishi H et al., Mebio 1994;11(19):86 (Japanese)
Phospholipase
LipoxygenaseCyclooxygenase
NSAIDs
Phospholipid
Arachidonic acid
Decrease of PGs
Decrease mucosal
defense
Mucus reduction
Decrease of HCO3
- secretion
Microcirculation injury
Gastric mucosal injury
Increase of LTs
Increase free radicals
Ischemia-reperfusion
Neutrophil activation
H+ dependent pathway
Accumulation in cells
Directly damage cells
Vasospasm
LTC4
LTD4
LTB4
Liposoluble
Inhibition
Free radicals play an important role in
NSAIDs-induced gastric mucosal injuries
25. Aspirin
and other
NSAIDs
PROTECTIVE
FACTORS
Mucus layer
Ionic gradient
Bicarbonate layer
Prostaglandins
Surface epithelial
cells
Mucosal blood
supply
H. pylori
PepsinGastric
acid
AGGRESSIVE FACTORS
Aspirin and
other NSAIDs
Prostaglandin
production
Bicarbonate
production
Mucus
production
Acidic
environment
Neutral environment
Gastric acid plays a central role in
NSAID-associated gastroduodenal damage
26. CLINICAL MANIFESTATION OF NSAID
GASTROPATHY
No symptom
Dyspepsia: epigastric pain, epigastric
discomfort, bloating, early satiety, vomitus,
nausea, belching etc
Fatigue
Upper GI bleeding
Stricture/stenosis
Acute abdomen: perforation
27. SUPPORTING EXAMINATION
Pheripheral blood examination, liver function
test, kidney function test, fecal occult blood test.
H.pylori infection: serology, biopsy culture of the
gastric mukosa, histopathology, CLO test, 14 C
urea breath test, stool antigen
Esophago-gastroduodenoscopy
Barium meal X-ray(OMD)
28. Diagnosis of NSAID
Gastropathy
History of NSAID consumption & dyspepsia
Physical examination
Supporting examinations: laboratory,
esophagogastroduodenoskopy examination,
Barium meal(OMD)
33. INDONESIAN CONSENSUS RECOMMENDATIONS
1. GI complications of NSAID (ASA and Non
ASA NSAID)
As the use of NSAID (Including COX-2 selective and
OTC traditional NSAID) in conjunction with cardiac-
dose ASA increase the risk of ulcer complications
gastroprotective therapy should be prescribed for
at risk patients
34. 2. GI Effects of ASA
The use of low-dose ASA for cardioprophylaxis is
associated with a two-to four fold increase in in UGI
effects
Enteric coated or buffered preparation do not
reduce the risk of bleeding
The risk of UGI effects increases with ASA dose
escalation for chronic phase of therapy, doses
>81 mg should not be routinely prescribed
For patients at risk of adverse effects gastro
protective therapy should be prescribed
35. 3. Gastrointestinal Effect of Combined
ASA and Anticoagulant Therapy
The combination between ASA & anticoagulant
therapy (including unfractionated heparin,
LMWH,Warfarin) is associated with extracranial
bleeding, and the large proportion is UGI
bleeding
Patient should receive concomitant PPI as well
36. In the long term management of ACS, multiple
RCTs show that combination between
anticoagulant therapy and antiplatelet is superior to
anti platelet alone, but it also increase the risk of GI
effect
A meta analysis of 4 RCTs unfractionnated
heparin + ASA vs ASA alone for ACS 50%
increase of major bleeding
37. 4. GI Effects of Clopidogrel
Substitution of clopidogrel (thienopyridine) is
not a recommended strategy to reduce the risk
of recurrent ulcer bleeding in high risk patients
and is inferior to the combination of ASA plus
PPI
Many studies show that combination between
PPI and clopidogrel decrease the risk of UGI
bleeding compared with clopidogrel alone
38. Conlicting data exist as to wether PPI diminish the efficacy
of clopidogrel
The current trials: PRINCIPLES-TIMI 44 (Prasugrel in
comparison to clopidogrel for inhibition of platelet activation
and aggregation thrombolysis in myocardial infarction) and
TRITON-TIMI 38 (Trial to Assess Improvement inTherapeutic
Outcomes by optimizing Platelet Inhibition with Prasugrel-
Thrombolysis in Myocardial Infarction)
Assessed the association between PPI use, platelet function
and clinical outcomes for patient treated with clopidogrel or
prasugrel PPIs do not diminish antiplatelet effect of
clopidogrel or prasugrel
39. 5. GI Effects of Combination Between
Clopidogrel and Anticoagulant Therapy
The combination of clopidogrel and warfarin
therapy greater risk of bleeding, compared
with monotherapy alone
use of combination antiplatelet and
anticoagulant therapy should be considered only
in cases which the benefits are likely to outweigh
the risk
40. 6. Treatment and Prevention of
NSAID Gastropathy
PPI are the preferred agents for the therapy and
prophylaxis of NSAID (including ASA) GI-injury
Goal of treatment :
To relief the symptoms
To heal the lession
To prevent ulcer and complication
To prevent ulcer reccurence
41. Prevention
NSAID + PPI/Misoprostol
Less side effect NSAID
Misoprostol (synthetic prostaglandin
analogue)
effective in the prevention of NSAID
Gastropathy, but it has more side effects
as abdominal cramp and diarrhea
42. Patient with NSAID or antiplatelet (ASA or clopidogrel) consumption
Evaluate gastrointestinal risk factors
Gastrointestinal bleeding
Dual antiplatelet therapy
Anticoagulant therapy
History of complicated ulcer
History of ulcer without bleeding
Upper and/or Low GI Endoscopy
(if facility available)
More than 1 risk factor:
Age ≥ 65 yo
Corticosteroid consumption
Dyspepsia or GERD
PPI+rebamipide/misoprostol*** PPI/rebamipide/misoprostol***
UpperGI Ulcer
H. Pylori test
(UBT, HpSA)
If (+) therapy
PPI/rebamipide/misoprostol***
TREATMENT AND PREVENTIONOF NSAID GASTROENTEROPATHY
Yes
Yes
Yes
Yes No
No
43. PATIENT RISKS FOR GASTROINTESTINAL
COMPLICATIONS
• High risk:
1. History of complicated ulcer
2. Multiple of risks(>2)
• Moderate risk:
1. Age > 65 yo
2. High dose NSAID treatment
3. History of non complicated ulcer
4. Consumption: Aspirin, corticosteroid, anticoagulan
• Low risk:
1.Without risk factor
National consensus 2011 on the management of NSAID
Gastroenteropathy in Indonesia. Jakarta
44. SUMMARY OF THE RECOMMENDATION PREVENTION OF NSAID GASTROENTEROPATHY
Gastrointestinal Risks
Mild Moderate Severe
CV Risks
low*
NSAID +
rebamipide/
misoprostol***
NSAID + PPI/
rebamipide /
misoprostol***
Alternative
therapy or COX2
inhibitor +PPI /
rebamipide /
misoprostol***
CV Risks
high**
Naproxen +
PPI/rebamipide/
misoprostol***
Naproxen +
PPI/rebamipide/
misoprostol***
Avoid NSAID or
COX2 inhibitor,
Alternative therapy
*Cardiovascular Risks (CV) low: do not need low dose aspirin / clopidogrel
** Cardiovascular Risks(CV) high: need low dose aspirin / clopidogrel
*** Misoprostol frequently caused side effects diarrhea and abdominal cramp.
45. Many RCTs showed:
Lansoprazole is more effective than ranitidine
Lansoprazole is more effective than omperazole
in the prevention and treatment of NSAID
gastropathy and in the prevention of ulcer
reccurency
Effectivity of other PPI in the management of
NSAID gastropathy required further data
48. Figure. Cumulative rates of healing at 4 and 8 weeks during
treatment with ranitidine hydrochloride, 150 mg twice daily;
15 mg once daily; or lansoprazole, 30 mg once daily, among
intent-to-treat patients
Naurang. et al. 2000. Arch Intern Med
4 8
50
100
(%)Healed
Week
: Ranitidine Hydrochloride
: Lansoprazole, 15 mg
: Lansoprazole, 30 mg
(%)
40
90
30
80
20
70
10
60
Gastric ulcers
49. Pharmacokinetic and acid inhibition
profiles
Efficacy
Indications and formulations
Potential for drug interactions
Tolerability/safety
Choosing a PPI to manage acid related diseases:
factors to be considered
50. Tolman et al,J Clin Gastroenterol 1997; 24: 65–70.
Howden et al, Clin Pharmacokinet 1991; 20: 38–49.
Hassan-Alin et al, Eur J Clin Pharmacol 2000; 56: 665–70.
Omeprazole has up to 40% bioavailability after
first dose
l Progressive increase in bioavailability (to
about 60%) and antisecretory effect to
day 5
Lansoprazole bioavailability is 85% after first
dose
Esomeprazole bioavailability is 64% after first
dose; half-life similar to omeprazole
Bioavailability of PPIs
51. Bioavailability(%)
Tolman et al,J Clin Gastroenterol 1997; 24: 65–70.
Fitton &Wiseman, Drugs 1996; 51: 460–82.
Hassan-Alin et al,Gastroenterology 2000; 118:A16.
Swan et al., Aliment PharmacolTher 1999; 13(Suppl 3): 11–7.
Howden, Clin Pharmacokinet 1991; 20: 38–49.
PPI bioavailability after the first dose
80
90
80
70
60
50
40
30
20
10
0
Lansoprazole Pantoprazole Esomeprazole Rabeprazole Omeprazole
77
64
52
40
52.
53. Tolman et al., J Clin Gastroenterol 1997; 24: 65–70.
Mean24-hgastricpH
5
Pre-regimen Day 1 Day 5
4
2
0
**
**
Lansoprazole 30 mg once daily
Omeprazole 20 mg once daily
Double-blind crossover study in 14
healthy volunteers
**p<0.002 after first and fifth doses
Speed of onset of PPI-induced
acid suppression
3
1
54. Thoring et al., Scand J Gastroenterol 1999; 34: 341–5.
n=15, crossover
study healthy
volunteers
300
200
0
TimetoreachpH>4(minutes)
130
250
Lansoprazole
30 mg
100
Omeprazole
20 mg
Time to acid suppression:
lansoprazole vs omeprazole
55. Mean time
to pH 4
(hours:minutes)
Difference (minutes) p-value
Lansoprazole 30 mg 1:29
-7 0.70
Esomeprazole 40 mg 1:22
Lansoprazole 15 mg 1:50
16 0.48
Esomeprazole 20 mg 2:06
Eriksson et al., Scand J Gastroenterol 2001; 36(Suppl 233): 49.
Equivalent speed of onset of acid
suppression: lansoprazole and esomeprazole
56. Esomeprazole 40 mg IV satu kali sehari lebih cepat dan lebih efektif mengontrol
keasaman lambung dibandingkan pantoprazole 40 mg IV
57. Drug tested Lansoprazole Omeprazole Esomeprazole Pantoprazole Rabeprazole
Phenytoin No Yes No No No
Warfarin No Yes No No No
Diazepam No Yes Yes No No
Prednisone No No NT NT NT
Oral contraceptive No No NT No NT
Propranolol No No NT NT NT
Metoprolol NT NT NT No NT
Theophylline No No NT No No
Parsons et al., Eur Gastro Hepatol 1996; 8(Suppl 1): S15–20; Fitton &Wiseman, Drugs 1996; 51: 460–82. Freston, AmJ
Gastroenterol 1997; 92(Suppl 4): S51–5; Humphries et al., Gut 1996; 39(Suppl 3): 297.
Pan et al., Gastroenterology 1999; 116:A276; Nexium Prescribing Information, 2001.
Henry et al., Eur J Clin Pharmacol 1987; 33: 369–73; Karol et al., J Clin Pharmacol 2000; 40: 301–8.
NT = not tested
Interactions between PPIs
and other drugs
58.
59. 7. Role of H. pylori
Testing for and eradicating H. pylori in patient
with history of ulcer disease is recommended
before starting NSAID/Antiplatelet therapy
60. Both H. pylori infection and NSAID use
independently and significantly increase
the risk of peptic ulcer and ulcer bleeding
H. pylori infection and NSAID use are
synergistic for peptic ulcer development
and ulcer bleeding
Huang et al., Lancet 2002; 359: 14–22.
61.
62.
63.
64. Intragastric pH with high-dose
iv PPI therapy
Clinical pharmacology studies
H. pylori-negative healthy volunteers
24 hour iv infusion
1Röhss K, et al. Intl J Clin PharmTher 2007;45:345–54; 2Metz DC, et al. Aliment PharmacolTher 2006;23:985–95
n Median/mean Time pH>6
24-hour pH (0–24 hours)
Esomeprazole
80 mg + 8 mg/hour1 25 5.8 12.6
Pantoprazole
80 mg + 8 mg/hour2 36 5.0 5.5–6.7
*This is not “ a head to head” study
65. 8. Discontinuation of Antiplatelet
Therapy Because of Bleeding
decision for discontinuation of ASA in the
setting of acute ulcer bleeding must be made on
an individual basis, based upon cardiac risk and
GI risk assessment to discern potential
thrombotic and hemorraghic complication
There is no evidence that non-ASA anti
platelet drug such as clopidogrel will reduce
bleeding risk in the presence of active ulcers
66. 9. Endoscopy in patients on mono
or dual antiplatelet therapy
Endoscopic therapy may be performed in
high risk cardiovascular patients on dual
antiplatelet therapy, and collaboration between
the cardiologist and endoscopist should be
balance the risk of bleeding with thrombosis,
with regard to the timing of cessation of
antiplatelet therapy
67.
68.
69.
70. Conclusion
NSAID Gastroduodenopathy is one of
important problems in daily clinical practice.
There are some risk factors which correlated
to NSAID ulcers complications.
The treatment and prevention of NSAID
gastropathy Proton Pump Inhibitor.
The most effective and safe PPI for the
treatment and prevention of NSAID
gastropathy is Esomeprazole.