This document summarizes guidelines for diagnosing hypertension, mechanisms of action for antihypertensive drug classes, and clinical trials of new antihypertensive drugs. The JNC 7 criteria classify blood pressure and define thresholds for normal, prehypertension, and stages 1 and 2 of hypertension. Drugs that inhibit the renin-angiotensin-aldosterone system lower blood pressure by blocking counter-regulatory mechanisms. New direct renin inhibitors and their mechanisms of action are discussed along with clinical trial results comparing their efficacy to ACE inhibitors and ARBs. Calcium channel blockers mechanisms and advantages are also summarized, along with current uses and new drugs in clinical trials.
This prsentation explains the use of biomarker with reference to an article: Accelerating Drug Develeopment using Biomarkers-Sitagliptin.
It was presented my my 2 friends and me. Hope it helps you guys.
This presentation consists of various approaches to treat hypertension depending on severity. It also include treatment according to international guidelines. Classification and brief description of each antihypertensive agent has been mentioned.
Teneligliptin the next generation gliptinAKSHATA RAO
Teneligliptin , one of the emerging gliptins have established its prowess among the gliptin giants like Sitagliptin Vildagliptin and Linagliptin. Proven to be safe in renally compromised patients, this one is to watch out for.
ARBs (Angiotensin receptor blockers) are the most widely used anti hypertensive throughout the world. A solid knowledge related to ARB will make our practice more patients friendly & benefit will be maximum.
VILDAGLIPTIN: DPP-IV INHIBITOR
Generic name: Vildagliptin
Brand name: Galvus
Treatment for: type 2 diabetes
selective inhibitor of dipeptidyl-
peptidase IV (DPP-IV)
- the first in a new class of oral antidiabetic agents
- known as dipeptidyl peptidase IV inhibitors
(DPP-IV) inhibitors
SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:Naina Mohamed, PhD
Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors such as Dapagliflozin (Farxiga), Canagliflozin (Invokana) and Empagliflozin (Jardiance) are a new class of oral drugs available to treat type 2 diabetes mellitus (Type 2 DM).
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,...Dr. Ravi Sankar
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
BY P. RAVISANKAR, VIGNAN PHARMACY COLLEGE, VADLAMUDI, GUNTUR,A.P, INDIA.
This prsentation explains the use of biomarker with reference to an article: Accelerating Drug Develeopment using Biomarkers-Sitagliptin.
It was presented my my 2 friends and me. Hope it helps you guys.
This presentation consists of various approaches to treat hypertension depending on severity. It also include treatment according to international guidelines. Classification and brief description of each antihypertensive agent has been mentioned.
Teneligliptin the next generation gliptinAKSHATA RAO
Teneligliptin , one of the emerging gliptins have established its prowess among the gliptin giants like Sitagliptin Vildagliptin and Linagliptin. Proven to be safe in renally compromised patients, this one is to watch out for.
ARBs (Angiotensin receptor blockers) are the most widely used anti hypertensive throughout the world. A solid knowledge related to ARB will make our practice more patients friendly & benefit will be maximum.
VILDAGLIPTIN: DPP-IV INHIBITOR
Generic name: Vildagliptin
Brand name: Galvus
Treatment for: type 2 diabetes
selective inhibitor of dipeptidyl-
peptidase IV (DPP-IV)
- the first in a new class of oral antidiabetic agents
- known as dipeptidyl peptidase IV inhibitors
(DPP-IV) inhibitors
SGLT2 Inhibitors (Gliflozins): A New Class of Drugs to treat Type 2 Diabetes:Naina Mohamed, PhD
Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors such as Dapagliflozin (Farxiga), Canagliflozin (Invokana) and Empagliflozin (Jardiance) are a new class of oral drugs available to treat type 2 diabetes mellitus (Type 2 DM).
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,...Dr. Ravi Sankar
ANTI HYPERTENSIVE AGENTS [MEDICINAL CHEMISTRY] BY P.RAVISANKAR, HYPERTENSION,TYPES,CAUSES OF HYPERTENSION, CLASSIFICATION, MECHANISM OF ACTION, SAR, ACE INHIBITORS, ARB , DIURETICS(WATER PILLS), TIPS TO STOP SILENT KILLER.
BY P. RAVISANKAR, VIGNAN PHARMACY COLLEGE, VADLAMUDI, GUNTUR,A.P, INDIA.
Hypertension is a major concern & dreaded complication. It is known as the silent killer and responsible for a large number of cardiovascular morbidity and mortality. There are many antihypertensive drugs . Calcium channel blockers were the oldest one and widely used in the management. Azeldipine is the recent addition to this.
The natriuretic peptide system works antagonistically to the RAAS and has favorable effects on the pathogenesis of heart failure
Natriuretic peptides are broken down by an enzyme called neprilysin
Neprilysin is also responsible for the breakdown of other substances, including bradykinin and angiotensin II
Sacubitril/valsartan is a combination product
Sacubitril is a pro-drug that, upon activation, acts as a neprilysin inhibitor
It works by blocking the action of neprilysin, thus preventing the breakdown of natriuretic peptides
This leads to a prolonged duration of the favorable effects of these peptides
- Describe the basic characteristics of new oral anticoagulants (OACs)
- Recognize potential candidates for new anticoagulants for atrial fibrillation and treatment of venous thrombosis
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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
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.
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
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Recent advances in treatment of Hypertension -- Drugs inhibiting RAAS, Diuretics, Calcium channel blockers, Vasodilators
1. Dr Deepthi S VaggeDr Deepthi S Vagge
MD PharmacologyMD Pharmacology
BMCRIBMCRI
2. JNC 7 criteria for diagnosis of
HTN
BP classification Blood pressure levels
SBP mmHg DBP mmHg
Normal <120 and <80
Pre-hypertension 120-139 Or 80-89
Hypertension -I 140-159 Or 90-99
Hypertension -II >/= 160 Or >/= 100
3. Targets of drug action
Counter-regulatory mechanisms –fall in BP
7. vasoconstriction, cell growth in heart and
arteries
Aldosterone secretion
Reabsorption of Na
Enhances sympathetic activity
Vasodilation
Antiproliferative
promotes apoptosis
fetal tissue development
12. Comment Strength
of evidence
Conclusion
Aliskiren is
more
effective
than
ramipril
Low 1 RCT–842 pt. 26 weeks duration. Aliskiren 150mg /ramipril 5mg.
Mean reductions in BP: Aliskiren 150mg -17.9/13.3
ramipril 5mg. -15.2/12.
P<0.0001
Plasma renin concentration was increased in both groups , PRA was reduced in
aliskiren .
No SAE
Aliskiren is
as effective
as ARB
Low 2 RCTs compared aliskiren to ARB
1.aliskiren Vs losartan. 4 weeks, n=226. Randomized to
losartan 100mg. aliskiren 150mg, aliskiren 300mg
p=0.0002
Mean reduction in BP were losartan 100mg -11.4/-5.5;
aliskiren 150mg --10/-5.7; aliskiren 300mg -11.8/-5.7
Efficacy and evidence
13. Comment Strength of
evidence
Conclusion
2.aliskiren Vs irbesartan. 8week. n=652 randomised to receive
aliskiren 150mg /irbesartan 150mg
Mean reduction in BP: aliskiren 150mg:-10.9/-9.4
irbesartan 150mg: -12.5/-9.1
p<0.0001
BP control rate was similar in all groups
Aliskiren + valsartan
more effective than
either monotherapy
Low 1 RCT
Aliskiren +valsartan Vs aliskiren Vs valsartan
8week, n=1,797, randomized to either of the three groups
Mean reduction in BP
Aliskiren 300mg -13/9mmhg
Valsartan 320mg: -12.9/-9.7 mmhg
Aliskiren + valsartan: -17.2/ -12.2 mmhg
P<0.0001
14.
ADVANTAGES:
Efficacy greater than ACE inhi/ ARB, safety equal
The long t1/2
Most comprehensive inhibition of the RAAS, reducing PRA,
Ang I, Ang II, and aldosterone
No dose adjustment in elderly, liver or moderate renal
impairement
16. DIRECT RENIN INHIBITORS UNDER TRIAL:
DRUG TRIAL NO. of Pt INTERVENTIO
N
END POINTS RESULTS
SPP635
SPP1148
SPP800
A Phase IIa,
Double-Blind,
Placebo-
Controlled trial
-SPP635 in Mild
to Moderate
Hypertension
Phase I
Preclinical trial
n:35
mild to
moderate
HTN
SPP635 OD
(20)
Placebo(15)
For 4 weeks
Mean reduction in
sitting SBP
Mean reduction in
sitting DBP
SPP635
-17.9
-9.8
NO SAE
PLA
-3.1
-2.4
p<0.001
SPP635 Presently Phase IIa Study to Investigate the Efficacy and Safety
of SPP635 in Diabetic and Hypertensive Patients With Albuminuria
19.
lack of postural hypotension
No tachycardia
Safe in asthamatics, diabetes, PVD
Reduce the incidence of T2DM in high risk individuals
Renal blood flow is well maintained
ADVANTAGES
20. No deleterious effect on plasma lipid profile, no hyperuricemia
Delay development of diabetic glomerulopathy
Reverse left ventricular hypertrophy and increased wall:lumen ratio
No rebound hypertension on withdrawal
Reduce cardiovascular morbidity and increase life expectancy of
hypertensives
21.
Stage I HTN :first choice if thiazides are not being used
Stage II HTN: in combination with thiazides
Drug of choice: in HTN associated with diabetics, LVH, CHF,
post MI, renovascular HTN
CURRENT STATUS
22.
MC-4232 is a combination of MC-1 and lisinopril.
MC-1 is a naturally occurring small molecule, a metabolite of
vitamin B6
Presently under Phase II MATCHED study (MC-1 and ACE
Therapeutic Combination for Hypertensive Diabetics),
evaluating the effects of MC-4232 in patients with coexisting
diabetes and hypertension.
DRUG UNDER TRIAL
25.
Similar to ACE , but with better tolerability profile
Complete inhibition of AII actions
Result in indirect AT 2 receptor activation
Advantages
26.
Intolerance to ACEI therapy and as an important option in the
treatment of patients with concurrent disorders such as heart
failure and type 2 diabetes
CURRENT STATUS:
27.
Azilsartan medoxomil is an angiotensin receptor
blocker, approved in 2011the US Food and Drug
Prodrug
Azilsartan - active moiety
Newer drugs
28.
Trial No.of pt Intervention End points Results
Phase III
Double-blind,
randomized,
placebo-
controlled
trial-
azilsartan,
olmesartan,
valsartan, and
placebo.
1285
SBP 150–180
mm Hg
Placebo
Azilsartan
20 mg
( titr 40 mg)
Azilsartan
40mg
(titr 80mg )
olmesartan 20
mg
( titr 40 mg)
valsartan 160
mg
(titr 320mg)
for 6 weeks
reductions in
24-hour mean
SBP at 6weeks
azilsartan
40mg
–14.3 mm Hg
valsartan 320
mg
–10.0 mmHg;
P 0.001
olmesartan 40
mg
–11.7 mm Hg
P 0.009
29.
Trial No pt Intervention End points Results
Phase III
Double-blind,
randomized
trial -azilsartan
Vs valsartan
984
SBP
150-180mm
Hg
Placebo
Azilsartan 20mg
(titr 40 mg)
Azilsartan 40mg
(titr 80 mg)
Valsartan 160 mg
(titr 320 mg)
24 weeks.
reductions
in 24-hour
mean SBP at
study
end
Azilsartan 40 mg
–14.9 mm Hg
Azilsartan 80mg
-15.3 mm Hg
valsartan 320 mg
–11.3mmHg
30.
Drugs under trial: LCZ696 (valsartan + AHU337 neprolysin
inhibitor)
Trial Pt Efficacy end
point
Intervention Result
Phase II
Randomized,
Double Blind,
active comparator
trial
1328 More than
20mmhg
reduction in the
SBP
LCZ696
100mg (156)
200mg (169)
400mg (172)
Valsartan
80mg (163)
160mg (166)
320mg (164)
47 (31%)
76 (45%)
87 (51%)
51 (31%)
49 (30%)
53 (33%
31.
Trial Particip
ants
Interventions and
duration
Primary end
point
Results
Irbe PS
200
400 800 Place
bo
A phase II
Randomized,
Double-Blind,
Placebo And
Active-
Controlled-
PS433540 In
Hypertension
261 Drug:
irbesartan
300 mg OD (58)
PS433540
200 mg OD (58)
400 mg OD (58)
800 mg OD (28)
Placebo (59)
The duration
12weeks
Primary :
Chage from
baseline in
mean SBP.
Secondary:
Chage from
baseline in
mean DBP.
Percentage of
patients
achieving BP
<140/90mmhg
-10.7 -13.2 -14.2 -23.4 1.8
-7.1 -7.2 -9.2 -14.3 0.2
17% 21% 16% 28% 5%
PS433540 : a dual acting angiotensin and endothelin receptor antagonist
32.
Drug combinations Rationale
RAAS Inhibitor + a low-dose, thiazide Improves efficacy and side
effect profile
RAAS Inhibitor + CCB improves the tolerability
profile of the CCB
Renin inhibitor with an ARB More complete inhibition of
RAAS
RAAS Inhibitors + beta Blocker Combination may result in
severe bradycardia.
ACE Inhibitors + ARB More SE
Combination therapy with RAAS
inhibitors:
33.
ACEIs, ARBs, and Direct Renin Inhibitors
for Treating Essential Hypertension ?
Evidence on the comparative long-term benefits and harms of
ACEIs, ARBs, and direct renin inhibitors, focusing on their use
for treating essential hypertension in adults*
* Advancing excellence I n health care ahrq.gov/reports/final.cfm 2011
34. Efficacy Strength of evidence Evidence
ACE in & ARBs
have similar long
term effects on BP
control
Aliskiren more
effective than
ramipril and as
effective as ARB
High (ACEI vs.
ACEIs )
Low
(DRI vs.
ACEI,ARB )
77 studies (70 RCTs, 5 nonrandomized
controlled clinical trials, 1 retrospective
cohort study, and 1 case-control study)
1,26,170 patients receiving an ACEI or an
ARB were followed for periods from 12
weeks to 5 years (median 24 weeks).
Based on 3 RCT
These studies found the direct renin
inhibitor to
have a greater reduction in blood pressure
compared to the ACEI ramipril (1 study )
and no significant difference compared to
the ARB losartan (2 study).
35. Reducing
mortality and
major
cardiovascular
events:
Strength of
evidence
Evidence
ACE inhi = ARBs
??
Low (ACEI vs.
ARBs )
Insufficient
(DRI vs. ACEI,ARB
)
In 21 studies that reported mortality, MI, or
clinical stroke as outcomes
among 38,589 subjects, 38 deaths and 13
strokes were
reported.
3 of these 21 studies (including 1 death)
evaluated
36. Safety profile Strength of evidence Evidence
Incidence of cough is more
with ACE inhi compared to
ARBs
High
(ACEI vs. ARBs )
Insufficient
(DRI vs. ACEI,ARB )
difference rates of cough
7.8 percent
4% higher in ACE
inhibitors
Withdrawals due to AE
were more in ARB
High (ACEI vs. ARBs )
Low
(DRI vs. ACEI,ARB )
Withdrawals were 2.3%
more with ARBs (5.4%
vs. 3.1%).
No statistically
significant difference in
the withdrawal rate
39. Advantages
More beneficial in elderly
Safe in asthama, PVD
Lipid profile, uric acid levels or glucose metabolism not effected
No renin release
No postural hypotension , rebound phenomenon
No tolerance
Renal or cerebral perfusion, male sexual activity, physical work capacity
not impaired
Used in pregnancy
40.
Preferred in elderly hypertensives
They have stroke prevention potential
Next to ACE inhi in reducing albuminuria and slowing disease
progression in hypertensive / diabetic nephropathy
cyclosporin induced hypertension in renal transplant
Current Status :
41. Clevidipine
Newer drugs
Trial No pt Intervention End points Results
ESCAPE-1
Phase III,
double-
blind,
randomized,
placebo-
controlled
study
-clevidipine
in
preoperative
hypertensio
n
105
hypertensive
scheduled for
cardiac
surgery with
hypertension
Clevidipine
(53)
placebo (52)
Preoperative
ly
incidence of
treatment
failure (to
decrease SBP
by >15% from
baseline at
any time
within the 30-
minute
BP target
levels
reached
Clevidipine :
92.5% (49 of
53 patients
placebo
(7.5%)
P<0.0001).
42.
Trial No pt Intervention End points Results
ESCAPE-2
Phase III,
double-blind,
randomized,
placebo-
controlled,
multi-center
study
-clevidipine
in
postoperativ
e
hypertension
after cardiac
surgery
110 patients
with
SBP>140
mm Hg
within 4
hours of
admission to
a
postoperativ
e setting,.
clevidipine
(61)
placebo (49)
the
incidence of
treatment
failure (the
inability to
decrease
SBP by
>15% from
baseline).
Target BP
reached
Clevidipine :
91.8%
Placebo:
20.4%
43.
Trial No pt Intervention End point results
VELOCITY
The phase III
prospective,
open-label,
single-arm
study -
clevidipine in
Treatment
Acute Severe
Hypertension
117 patients
the ER or ICU
with SBP>180
and/or
DBP>115 mm
Hg
The initial
dose of
clevidipine
was 2 mg/hr
for 3 minutes
the dose was
doubled every
3 minutes as
needed to a
maximum
dose of 32
mg/hr, which
was then
continued for
18-96 hours
Achieving of
a patient-
specific
systolic blood
pressure
range the first
30 minutes of
infusion;
88.9% of
patients
(104/117)
receiving
clevidipine
achieved their
target SBP
range within
30 minutes of
treatment
initiation,
with a median
time-to-target
of 10.9
minutes
46.
Current status:
Thiazides Loop K+ sparing
First choice in
treatment of
essential HTN esp.
in elderly.
Overcoming
resistance to other
antihypertensives
Severe HTN
associated with
CRF, CHF
Used with thiazides
to prevent K loss
Current Status
47. COMBINATION RATIONALE
Diuretic and a CCB results Side effect profile improved.
b-Blockers+ Diuretics Efficacy improved
Thiazide Diuretics + Potassium-
sparing
Diuretics
Side effect profile improved.
Combination therapy
49.
Drugs MOA Role in HTN AE
Hydralazine Activate K channels
Generate NO &
stimulate cGMP
Moderate HTN not
controlled by beta
blocker /diuretic
Headache, nausea,
nasal congestion,
angina attack (due to
tachycardia
: reversible
dessiminated lupus
erythematosus
Minoxidil Converted to active
metabolite minoxidil
sulfate which activates
K channels
Severe HTN, life
threatening HTN,
resistant HTN
Hirsutism
Diazoxide activates K channels HTN emergencies Na, water retention
50.
Drugs MOA Role in HTN AE
Fenoldopam D1 receptor agonist—
dilation of peripheral
arteries and natriuresis
Hypertensive
emergencies esp in
those with renal
impairement
Tachycardia,
headache, flushing
Increase intraocular
pressure
Hypokelemia,
electrolyte
disturbances
Sodium nitroprusside Activates guanylyl
cyclase either directly
or through the release
of NO---increase in
intracellular cGMP---
vascular smooth
muscle relaxation
Hypertensive
emergencies
Tachycardia,
headache, flushing
Toxicity due to
accumulation of
cyanide/ thiocyanate
Disadvantage: long term efficacy and safety studies not available, safety in childreen and early pregnanacy not available CI in pt allergic to it
Recommended dose for starting, ot included in any guideline as it a new drug, as an added om drug rather than a substitution for well esstablished drug
No potural hypo, as it does not interfere with cardiac reflexes . No reflex stimulation sympathtic---used in IHD
do not interfere with degradation of bradykinin or other ACE substrates
Dis ad with ACE and ARB aldosterone escape. Indirect activation of AT2 may have antigrowth & antiproliferative ctions
See if OD dose , phase of study
vAlsartan 80 mg ??????????? Phase
interchange column 3 and 4 phase mst common AE diarrhoea, back pain
Useful in pt of low renin levels, as its efficacy not depended on it as RAAS inhibitore. PRC is ususally low in elderly
CI in heart failure, angina
Write when approved clevidipine 0.5 mg/mL in 20% lipid or 20% lipid emulsion (placebo) by infusion over a minimum 30 minutes immediately before anesthesia induction for cardiac surgery (Efficacy Study of Clevidipine Assessing its Preoperative
Antihypertensive Effect in Cardiac Surgery
TY (Evaluation of the Ultra-ShortActing
Clevidipine in the treatment of patients with
severe hypertension) tr