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Describe and explain the effect(s) of competitive and non- competitive antagonists on the dose- response curve for an agonist. Describe the characteristics of a quantal dose- response curve. Strength training is a vital part of a balanced exercise routine that includes aerobic activity and flexibility exercises. Regular aerobic exercise, such as running. Buy Ephedra Diet Pills to promote weight-loss & burn unwanted fat online at i-Supplements.com for low prices. Select from the Ephedra Diet Pills that are available. Explain what is meant by additive and synergistic drug effects. Define the terms ED5. LD5. 0, TD5. 0 and Therapeutic Index. You are expected to have read this handout and completed the online Canvas Med Pharm quiz by 3 AM before the day of this class session. Bring your “clickers” with you to class. DEFINITIONSPharmacology - is the science of the interaction of chemical agents (drugs) with living systems. Drug - a substance (chemical agent) that affects a biological system in a potentially useful way. EC5. 0: the drug concentration producing 5. ED - Effective Dose (e. ED5. 0: the drug dose producing 5. Which definition is appropriate depends on the context in which the abbreviation is being applied; i. TD5. 0: the dose producing a toxic effect in 5. LD - Lethal Dose (e. LD5. 0: the dose producing a lethal effect in 5. LD values almost always refer to animal studies, since lethal doses in humans are rarely known with any accuracy. Two Primary Branches of Pharmacology. The two major branches of pharmacology are: pharmacodynamics and pharmacokinetics. The mechanism of action can typically be described in biochemical or molecular terms. Clinical Pharmacology and Therapeutics. This discipline is interested in characterizing the Indications and therapeutic uses of drugs- Emphasis is placed on the therapeutic use of drugs for the treatment of disease in the clinical years with clinical pharmacology, internal medicine and therapeutics. Toxicology. The aspect of pharmacology that deals with the adverse effects of drugs. S (- ) Carvedilol binds to both . Differences in drug potency are evaluated by comparing EC5. The two major branches of pharmacology are: pharmacodynamics and pharmacokinetics. Pharmacodynamics - The study of the relationship between concentrations of drug and. ED5. 0) values. Differences in drug efficacy are evaluated by comparing differences in maximal response at high drug doses or concentrations. In contrast, full agonists produce a full or maximal response. In figure 3, Drug A is a full agonist, and Drugs B, C & D are partial agonists. The drug which can produce an effect at lower drug concentrations is “more potent” (in Figure 2, Drug A is the most potent, and Drug D is the least potent). Drugs B, C & D) are referred to as partial agonists. Drug A has a relative efficacy that is 2 times than Drug C, and ~1. Drug D. Clinical Examples of Partial Agonists. Clinically used examples of partial agonists include. Aripiprazole (Abilify . Schizophrenia is a condition associated with both excess dopamine activity in one area of the brain (resulting in hallucinations and delusions), as well as a co- existing reduced dopamine activity in another area (causing cognitive impairment). Aripiprazole is thought to produce beneficial effects in schizophrenia by exerting agonist effects in areas of dopamine deficit, while exerting sufficient antagonist effects in areas of dopamine hyperactivity. Buprenorphine (Suboxone . Acebutolol, penbutolol & pindolol are “beta blockers” that have additional “intrinsic sympathomimetic activity” (ISA), which is a different way of saying they behave as partial agonists at . The presence of ISA results in a neutral effect on heart rate and cardiac output when the sympathetic nervous system is not activated (e. These drugs have been shown to be effective and relatively safe, but the issue of whether their “ISA” constitutes a therapeutically significant advantage over pure receptor antagonism is still being debated (Frishman & Saunders, 2. They may be an appropriate choice for patients who require a beta blocker (e. They are generally considered undesirable for use in patients who have previously had an myocardial infarction, since this may interfere with their otherwise anti- ischemic properties on the heart. Signal Transduction Mechanisms for Agonists. Once an agonist has bound to its receptor, its effects are transduced into a cellular response by one of several different mechanisms. Examples of these mechanisms are shown below. Binding of the drug to the receptor site(s) results in a conformational change in the receptor/channel complex that typically causes the ion channel to open. Na and K for nicotinic receptors) down their electrochemical gradient with a resultant change in membrane potential (Figure 4). Binding of 2 molecules of acetylcholine to the nicotinic receptor/channel complex causes the channel to open. Either the alpha or beta/gamma subunits stimulate the channel to open. Binding of an agonist to the m. G- protein (Gi) which in turn stimulates a K- selective channel to open. One involves the G- protein (Gs) mediated activation of adenylyl cyclase, with subsequent formation of camp and activation of protein kinase A (PK- A) (Figure 6). Norepinephrine binding to beta. AC), which converts ATP to c. AMP. Angiotensin II binding to AT1 receptors activates phospholipase C (PLC). Tyrosine Kinases). This class of receptors mediates the first steps in the transduction of signals carried by insulin and a wide variety of growth factors such as epidermal growth factor (EGF), atrial natriuretic factor (ANF) and transforming growth factor beta (TGF- . The interaction between receptors causes the tyrosine kinases to become active, resulting in auto- phosphorylation of the enzyme domains, and phosphorylation of tyrosine residues on different downstream signaling proteins (S. Noncompetitive Antagonists. Antagonists are drugs that bind to receptors (have affinity), but do not produce a substantial degree of receptor stimulation (they have very low efficacy). The vast majority of clinically used drugs that act as receptor antagonists are competitive antagonists. Noncompetitive antagonists either bind irreversibly (e. Competitive Antagonism, where both the agonist (Isoproterenol) and the antagonist (Propranolol) bind reversibly to the same receptor subtype (. Non- competitive antagonism. This results in a tonic level of stimulation of downstream events, such as stimulation of adenylate cyclase. However, in addition, the binding of the reverse agonist to the receptor alters the receptor conformation in such a way as to decrease its interaction with G- proteins, resulting in a decrease in basal stimulation of G- proteins and a reduction in the activity of adenylate cyclase. Acetylcholine and norepinephrine exert their effects through different receptors and signal transduction pathways, which when activated produced opposing effects (e. They therefore “physiologically” antagonize each others effects without interacting with the same receptors. Chemical antagonism occurs when a drug reduces the concentration of an agonist by forming a chemical complex (e. Example: protamine sulfate is a positively charged substance that when given i. As a result, protamine sulfate administration is a type of “antidote” for heparin overdose, because once heparin binds to protamine sulfate, it cannot exert its anticoagulant effects. Pharmacokinetic antagonism occurs when one drug accelerates the metabolism or elimination of another (e. Drugs often work on multiple receptors. Drugs often work on more than one receptor, and as a result produce more than one kind of biological response (Figure 1. Each receptor subtype selectively interacts with different G proteins & thus activate different intracellular messenger pathways, resulting in different biological responses. Selectivity, and the Therapeutic Window. If a drug has one effect, and only one effect on all biological systems it possesses the property of specificity. Hence when studying drug effects in vitro, one can most commonly compare drug effects to drug concentrations and a concentration producing 5. EC5. 0) can be defined. An example of an exception to this rule is when one is using an impure source of a drug (e. John’s wort – a herbal medication containing a mixture of active ingredients, with varying purity between preparations). In this case the total dose (gram weight) of St. John's wort used would be more easily defined vs the concentration of the active ingredient(s), which may be unknown. The concentration of drug achieved in the bloodstream (e. As a result, in whole animal experiments, we talk of doses that produce a given magnitude of therapeutic effect, e. ED5. 0 (and not EC5. These studies typically involve giving a range of doses to a large population of animals/patients and measuring an all- or- none type of “quantal” response (such as – does this dose produce vomiting, or prevent hiccups within a 1 hour time period). In this situation, one can define the minimum dose needed to produce the desired effect in each animal or patient. The results of this type of study can be plotted in the form of a quantal dose response curve (Figure 1. In a population study, the dose that produces the desired effect in 5. ED5. 0 or ED5. 0. To summarize, ED5. The key to understanding the meaning of the term “ED5. If ED5. 0 is being used to describe drug effects in an individual subject, ED5. In contrast, if the discussion concerns drug responses in a population, ED5. Compare what is represented on the y- axis of Figure 1. Figures 2 & 3. The results have been plotted as a histogram, and fit with a gaussian curve. The reason this index is less commonly used is because the LD1 value, at least for human populations, is typically unknown or poorly defined, for ethical reasons! Figure 1. 3. The relationship between the dose- response relationships for producing therapeutic and toxic side effects. Examples of physiological, chemical and pharmacokinetic antagonism were discussed above (page 8). Two common types of “agonistic” drug interactions are additive or synergistic interactions. An additional (graphical illustration) of additive and synergistic effects is shown in Figure 1. Synergistic effects. Following an initial response (such as cellular accumulation of c. Chronic Pancreatitis Online Medical Reference - from diagnosis through treatment. Co-authored by Tyler Stevens and Peter Lee of the Cleveland Clinic. Dog Kidney Failure Symptoms . And while dogs of any age can be diagnosed with the kidney disease, it is more commonly seen in older dogs. Failure of the kidney - - which among other things regulates blood pressure, blood sugar, blood volume, water composition in the blood, and p. H levels, and produces red blood cells and certain hormones - - can take so place so slowly, that by the time the symptoms have become obvious, it may be too late to treat the condition effectively. Often, the kidney will find ways to compensate as it loses functionality over the course of months, or even years. A diet for CKD. Kidney failure, also known as renal failure or renal insufficiency, is a medical condition of impaired kidney function in which the kidneys fail to adequately filter.
While chronic renal failure cannot be reversed or cured, treatment and management aimed at reducing the contributing factors and symptoms can slow its progression. Chronic renal failure can affect both dogs and cats. If you would like to learn more about how this disease affects cats, please visit this page in the Pet. MD health library. Symptoms and Types of Kidney Failure in Dogs. Symptoms often occur gradually over an extended petriod of time. When you have chronic kidney disease,your kidneys are no longer working as well as they need to. Changing your diet can help protect your kidneys. It can also help. Reception Desk. Hello and welcome to the Feline Chronic Renal Failure Information Center. If your cat has been diagnosed with chronic renal failure (kidney failure. In addition, symptoms may vary and not all of those listed below will be seen in every dog: Causes of Kidney Failure in Dogs. Causes of kidney failure can include kidney disease, urinary blockage (obstruction of the urinary tract or of the ureters), certain prescription medications, lymphoma, diabetes mellitus, and genetic (hereditary) factors. The following breeds are prone to chronic renal failure: Diagnosis of Kidney Failure in Dogs. Your dog will undergo a complete blood profile, including a chemical blood profile, a complete blood count, and a urinalysis. Dogs with chronic renal failure may have anemia, abnormal electrolyte levels, and elevated blood pressure. The levels of certain protein enzymes and chemicals such as creatinine and blood urea nitrogen (BUN) will also be high. Another good indicator of chronic renal failure is urine that is either concentrated or dilute, thus indicating the kidney's inability to process the urine correctly. X- ray or ultrasound imaging may also be used to observe the size and shape of the dog's kidney(s) to see if there are any visibly noticeable abnormalities. Often, chronic renal failure causes kidneys to become abnormally small. The prediction of a disease’s outcome in advancelymphoma. A term for a type of neoplasm that is made up of lymphoid tissue; these masses are usually malignant in naturerenal failure. The failure of the kidneys to perform their proper functionsurea. The product of protein being metabolized; can be found in blood or urine. An in- depth examination of the properties of urine; used to determine the presence or absence of illnesshematuria. Blood in the urinegastritis. A medical condition in which the stomach becomes inflamedblood pressure. The amount of pressure applied by the blood on the arteries. A medical condition in which the body has lost fluid or water in excessive amountselevator. A type of tool used to separate tissue from bonegastric. Anything having to do with the stomachanemia. A condition of the blood in which normal red blood cell counts or hemoglobin are lacking. Fat Loss via Better Science and Simplicity. It is possible to lose 20 lbs. WELCOME The Science of Raw Food. A raw food diet is not just good for you - it’s. Being in private practice for almost a decade will do that to you. Raw Till 4 . Men should strive for at least 3. I’ve decided to kick off 2008 with a 30-day trial of eating a 100% raw vegan diet. I’ve done a couple 30-day trials as well as a 45-day trial of raw foodism. Whole Food Mommies is a best Cooking Blog where you can find Whole Food Recipes, Healthy Dishes and Whole Food Nutrition for your kids and family. The Garden Diet 28 Days Raw Program Philosophy. Food: Our Delicious, nutritious, and affordable Raw Vegan Cuisine: Patées, Wraps, Soups, Salads, Dressings. If you think that eating more fresh, natural raw food in your diet is too expensive, then this recipe is definitely for you! Making fermented foods at home is one of.What to Eat and What to Avoid. In short, you should eat REAL food (meat, eggs, nuts, yogurt, vegetables and occasionally some fruits). Apart from the obvious. |
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