Discovery And Development Of Renin Inhibitors
Renin inhibitors are pharmaceutical drugs inhibiting the activity of renin that is responsible for hydrolyzing angiotensinogen to angiotensin I, which in turn reduces the formation of angiotensin II that facilitates blood pressure. Renin inhibitor is often preceded by ''direct'', called ''direct'' renin inhibitor in order to distinguish its mechanism from other renin–angiotensin–aldosterone system-interfering drugs such as angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) and aldosterone receptor antagonists. These drugs Enzyme inhibitor, inhibit the first and rate-limiting step of the renin–angiotensin–aldosterone system (RAAS), namely the conversion of angiotensinogen to angiotensin I. This leads to a totality in absence of angiotensin II based on the rationale that renin only acts to inhibit this step unlike Angiotensin Converting Enzyme which is also involved in other biochemical reactions. Since the 1970s, scientists have been tr ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
|
Aliskiren
Aliskiren (brand names Tekturna and Rasilez) is the first in a class of drugs called direct renin inhibitors. It is used for essential (primary) hypertension. While used for high blood pressure, other better studied medications are typically recommended due to concerns of higher side effects and less evidence of benefit. In December 2011, Novartis halted a trial of the drug after discovering increased nonfatal stroke, kidney complications, high blood potassium, and low blood pressure in people with diabetes and kidney problems. As a result, in 2012: * A new contraindication was added to the product label concerning the use of aliskiren with angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) in patients with diabetes because of the risk of kidney impairment, low blood pressure, and high levels of potassium in the blood. * A warning to avoid use of aliskiren with ARBs or ACEIs was also added for patients with moderate to severe kidney impairme ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
|
Chemical Compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element is therefore not a compound. A compound can be transformed into a different substance by a chemical reaction, which may involve interactions with other substances. In this process, bonds between atoms may be broken and/or new bonds formed. There are four major types of compounds, distinguished by how the constituent atoms are bonded together. Molecular compounds are held together by covalent bonds; ionic compounds are held together by ionic bonds; intermetallic compounds are held together by metallic bonds; coordination complexes are held together by coordinate covalent bonds. Non-stoichiometric compounds form a disputed marginal case. A chemical formula specifies the number of atoms of each element in a compound molecule, using the s ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
|
Pharmacokinetic
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models. Overview Pharmacokinetics describes how the body affects a specific xenobiotic/chemical after administration through the mechanisms of absorption and distribution, ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
|
Pepstatin
Pepstatin is a potent inhibitor of aspartyl proteases. It is a hexa-peptide containing the unusual amino acid statine (Sta, (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid), having the sequence Isovaleryl-Val-Val-Sta-Ala-Sta (Iva-Val-Val-Sta-Ala-Sta). It was originally isolated from cultures of various species of Actinomyces due to its ability to inhibit pepsin at picomolar concentrations. Pepstatin A is well known to be an inhibitor of aspartic proteases such as pepsin, cathepsins D and E. Except for its role as a protease inhibitor, however, the pharmacological action of pepstatin A upon cells remain unclear. Pepstatin A suppresses receptor activator of NF-κB ligand (RANKL)–induced osteoclast differentiation. Pepstatin A suppresses the formation of multinuclear osteoclasts dose-dependently. This inhibition of the formation only affected osteoclast cells, i.e., not osteoblast-like cells. Furthermore, pepstatin A also suppresses differentiation from pre-osteoclast cells to mo ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
|
Clinical Trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small pilot studies, and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary i ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
|
Cardiovascular Disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, abnormal heart rhythms, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, thromboembolic disease, and venous thrombosis. The underlying mechanisms vary depending on the disease. It is estimated that dietary risk factors are associated with 53% of CVD deaths. Coronary artery disease, stroke, and peripheral artery disease involve atherosclerosis. This may be caused by high blood pressure, smoking, diabetes mellitus, lack of exercise, obesity, high blood cholesterol, poor diet, excessive alcohol consumption, and poor sleep, among other things. High blood pressure is estimated to account for approximat ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
|
Pathogenesis
Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pathos'' 'suffering, disease' and γένεσις ''genesis'' 'creation'. Description Types of pathogenesis include microbial infection, inflammation, malignancy and tissue breakdown. For example, bacterial pathogenesis is the process by which bacteria cause infectious illness. Most diseases are caused by multiple processes. For example, certain cancers arise from dysfunction of the immune system (skin tumors and lymphoma after a renal transplant, which requires immunosuppression), Streptococcus pneumoniae is spread through contact with respiratory secretions, such as saliva, mucus, or cough droplets from an infected person and colonizes the upper respiratory tract and begins to multiply. The pathogenic mechanisms of a disease (or cond ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
|
Renal Ischaemia
Renal ischemia also known as ''nephric ischaemia'', is the deficiency of blood in one or both kidneys or nephrons, usually due to functional constriction or actual obstruction of a blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away .... References Kidney diseases Ischemia {{genitourinary-disease-stub ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
|
Renal Cortex
The renal cortex is the outer portion of the kidney between the renal capsule and the renal medulla. In the adult, it forms a continuous smooth outer zone with a number of projections ( cortical columns) that extend down between the pyramids. It contains the renal corpuscles and the renal tubules except for parts of the loop of Henle which descend into the renal medulla. It also contains blood vessels and cortical collecting ducts. The renal cortex is the part of the kidney where ultrafiltration occurs. Erythropoietin is produced in the renal cortex. Additional images File:Njuren.gif, Kidney File:Kidney-Cortex.JPG, Microscopic cross section of the renal cortex File:Kidney_cd10_ihc.jpg, CD10 immunohistochemical staining of normal kidney. CD10 stains the proximal convoluted tubules and glomeruli ''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', me ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
|
Jugular Vein
The jugular veins are veins that take deoxygenated blood from the head back to the heart via the superior vena cava. The internal jugular vein descends next to the internal carotid artery and continues posteriorly to the sternocleidomastoid muscle. Structure and Function There are two sets of jugular veins: external and internal. The left and right external jugular veins drain into the subclavian veins. The internal jugular veins join with the subclavian veins more medially to form the brachiocephalic veins. Finally, the left and right brachiocephalic veins join to form the superior vena cava, which delivers deoxygenated blood to the right atrium of the heart. The Jugular veins help carry blood from the heart to and from the brain. An average human brain weighs about 3 pounds, and gets about 15%-20% of the blood that the heart pumps out. It is important for the brain to get enough blood for many reasons. The jugu ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
|
Extract
An extract is a substance made by extracting a part of a raw material, often by using a solvent such as ethanol, oil or water. Extracts may be sold as tinctures, absolutes or in powder form. The aromatic principles of many spices, nuts, herbs, fruits, etc., and some flowers, are marketed as extracts, among the best known of true extracts being almond, cinnamon, cloves, ginger, lemon, nutmeg, orange, peppermint, pistachio, rose, spearmint, vanilla, violet, rum, and wintergreen. Extraction techniques Most natural essences are obtained by extracting the essential oil from the feedstock, such as blossoms, fruit, and roots, or from intact plants through multiple techniques and methods: * Expression (juicing, pressing) involves physical extraction material from feedstock, used when the oil is plentiful and easily obtained from materials such as citrus peels, olives, and grapes. * Absorption (steeping, decoction). Extraction is done by soaking material in a solvent, as ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
|
Circulatory System
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, that consists of the heart and blood vessels (from Greek ''kardia'' meaning ''heart'', and from Latin ''vascula'' meaning ''vessels''). The circulatory system has two divisions, a systemic circulation or circuit, and a pulmonary circulation or circuit. Some sources use the terms ''cardiovascular system'' and ''vascular system'' interchangeably with the ''circulatory system''. The network of blood vessels are the great vessels of the heart including large elastic arteries, and large veins; other arteries, smaller arterioles, capillaries that join with venules (small veins), and other veins. The Closed circulatory system, circulatory system is closed in vertebrates, which means that the blood never leaves the network of blood vessels. Some in ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |