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Schedule Deals with C and C1 Biological and special products F and F1 Bacterial vaccines G Drugs to be labelled with the word “Caution”-It is dangerous to take this preparationexcept under medical supervision H Drugs that must be sold by retail only when a preseription by RMP is produced M. Good manufacturing practices (GMP) P Expiry period of drug formulations W. Drugs that shall be marketed under generic names only X Psychotropic drugs requiring special licence for manufacture and sale Y Requirements and guidelines on clinical trials, import and manufacture of new drugs

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ANTIDIURETICS The drugs that decrease urine volume are called antidiuretics. Primary indication of antidiuretics is the treatment of diabetes insipidus (DI). ● Anti-Diuretic Hormone (ADH) Physiological antidiuretic is vasopressin (antidiuretic hormone or ADH) that is synthesized in the hypothalamus and secreted by the posterior pituitary. It is secreted in response to increased plasma osmolality or decreased volume of extracellular fluid (ECF). ADH acts via 3 receptors V1; V2 and V3 ◆ Actions of ADH • In the absence of ADH, collecting ducts (CD) of the nephron are impermeable to water. ADH increases the permeability of CD by its action on V2 receptors. Stimulation of these receptors elevates cAMP levels that increase aquaporins on the apical membrane of CD (by decreasing endocytosis and increasing exocytosis).V2 receptor activation also increases permeability of CD to urea by stimulating the urea transporter. • Vasopressin (ADH) as the name suggests is a potent pressor of blood vessels. Vasoconstrictor action is mediated by the activation of V1 (also called V1a) receptors. This action requires much higher concentration than V2 receptor activation. V2 receptor mediated vasodilatory action (due to the release of NO) has also been demonstrated. • ADH is also involved in the release of vWF and factor VIII from the endothelium. This action is also mediated by V2 receptors. • V3 receptors (previously known as V1b receptors) are involved in the release of ACTH. ●Thiazides These drugs are used as diuretics but, exert paradoxical effect (decrease urine formation) in DI. This paradoxical effect is believed to be due to increased formation of cAMP in the distal tubules. Another proposed mechanism is that thiazides cause dehydration that result in compensatory increase in reabsoprption of Na+ and water from the proximal portions of nephron. These are low efficacy antidiuretics but are beneficial in both central as well as nephrogenic DI. e.g. Chlorpropamide, Clofibrate and Carbamazepine ● Amiloride It is the agent of choice for the treatment of Lithium induced DI. ● VASOPRESSIN RECEPTOR ANTAGONISTS • V1receptor antagonists may be useful when total peripheral resistance is increased (e.g. CHF and hypertension) whereas V2 antagonists may be useful for the treatment of SIADH • Relcovaptan is selective V1 antagonist whereas lixivaptan, mozavaptan and tolvaptan are V2 selective antagonists. • Conivaptan is V1a/V2 receptor antagonist used as an aquaretic (increase water excretion without affecting electrolytes like sodium) in CHF.

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Diuretics (Part -2) 3. Diuretics Acting on the Distal Tubules and Collecting Ducts ● Thiazides Drugs in this group include bendroflumethiazide, chlorthiazide, hydrochlorthiazide, methiclothiazide, polythiazide, trichlormethiazide, benzthiazide, hydroflumethiazide, chlorthalidone, metolazone, quinethazone and indapamide. These drugs act by inhibiting Na+-Cl– symporter at the luminal membrane of early DT. ● Potassium Sparing Diuretics These diuretics act in the late DT and CD cells to preserve K+. (a) Epithelial Na+ channel inhibitors These drugs are basic in nature and reach the lumen of PT by secretion through organic base secretory system. By travelling through the lumen, these drugs reach its site of action i.e. late DT and CD. Members of this group are amiloride and triamterene (b) Aldosterone antagonists Spironolactone, canrenone, potassium canreonate and epleronone antagonize the action of aldosterone and produce effects similar to amiloride. These drugs act from the interstitial site of tubular cel

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Diuretics mainly exert their effect by the inhibition of renal tubular reabsorption of sodium and water. These may be classified according to ◆ their efficacy as ● high ceiling (loop and osmotic diuretics), ● medium ceiling (thiazides) and ● low ceiling (carbonic anhydrase inhibitors ● potassium sparing) diuretics. ◆ based on their site of action 1. Diuretics Acting on the Proximal Tubule (Pt) These are non-competitive but reversible inhibitors of carbonic anhydrase and act by inhibiting the reabsorption of sodium in the proximal tubular portion of the nephron. ● Carbonic Anhydrase (CA) Inhibitors net effect of carbonic anhydrase is to cause the absorption of sodium and bicarbonate. (acetazolamide, dichlorphenamide and methazolamide) 2. Diuretics Acting on the Loop of Henle ● Inhibitors of Na+-K+-ATPase loop diuretics and act by causing inhibition of Na+ K+ 2Cl–symporter present at the luminal membrane of the ascending limb of loop of Henle. (Furosemide, torsemide, bumetanide, ethacrynic acid, axosemide, piretanide, tripamide and mersaly) ● Osmotic Diuretics Mannitol, glycerol, urea and isosorbide are inert drugs that can cause osmotic diuresis. these drugs act both in PT as well as loop of Henle,

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Vasopressin receptors V1 (V1a) • Vascular smooth muscle - Vasoconstriction • Platelets – Aggregation • Hepatocytes – Glycogenolysis • Uterus – contraction V2 • Collecting tubules – Insersionof AQP2 water. channels • Endothelium – Release of vWF and factor 8 • Vascular smooth muscle –Vasodilation V3 (V1b) • Ant pituitary – ACTH release

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CAD What Is Coronary Artery Disease? Coronary artery disease (CAD) causes impaired blood flow in the arteries that supply blood to the heart. Also called coronary heart disease (CHD), CAD is the most common form of heart disease and affects approximately 16.5 million Americans over the age of 20. It’s also the leading cause of death for both men and women in the United States. It’s estimated that every 40 seconds, someone in the United States has a heart attack. A heart attack can come from uncontrolled CAD. Causes of coronary artery disease The most common cause of CAD is vascular injury with cholesterol plaque buildup in the arteries, known as atherosclerosis. Reduced blood flow occurs when one or more of these arteries becomes partially or completely blocked. The four primary coronary arteries are located on the surface of the heart: right main coronary artery left main coronary artery left circumflex artery left anterior descending artery These arteries bring oxygen and nutrient-rich blood to your heart. Your heart is a muscle that’s responsible for pumping blood throughout your body. According to the Cleveland Clinic, a healthy heart moves approximately 3,000 gallons of blood through your body every day. Like any other organ or muscle, your heart must receive an adequate, dependable supply of blood in order to carry out its work. Reduced blood flow to your heart can cause symptoms of CAD. Other rare causes of damage or blockage to a coronary artery also limit blood flow to the heart. Symptoms of CAD When your heart doesn’t get enough arterial blood, you may experience a variety of symptoms. Angina (chest discomfort) is the most common symptom of CAD. Some people describe this discomfort as: chest pain heaviness tightness burning squeezing These symptoms can also be mistaken for heartburn or indigestion. Other symptoms of CAD include: pain in the arms or shoulders shortness of breath sweating dizziness You may experience more symptoms when your blood flow is more restricted. If a blockage cuts off blood flow completely or almost completely, your heart muscle will start to die if not restored. This is a heart attack. Don’t ignore any of these symptoms, especially if they are excruciating or last longer than five minutes. Immediate medical treatment is necessary. Symptoms of CAD for women Women may also experience the above symptoms, but they’re also more likely to have: nausea vomiting back pain jaw pain shortness of breath without feeling chest pain Men have a higher risk of developing heart disease than premenopausal women. Postmenopausal women by age 70 have the same risk as men. Due to decreased blood flow, your heart may also: become weak develop abnormal heart rhythms (arrhythmia) or rates fail to pump as much blood as your body needs Your doctor will detect these heart abnormalities during diagnosis. Risk factors for CAD Understanding the risk factors for CAD can help with your plan to prevent or decrease the likelihood of developing the disease. Risk factors include: high blood pressure high blood cholesterol levels tobacco smoking insulin resistance/hyperglycemia/diabetes mellitus obesity inactivity unhealthy eating habits obstructive sleep apnea emotional stress excessive alcohol consumption history of preeclampsia during pregnancy The risk for CAD also increases with age. Based on age alone as a risk factor, men have a greater risk for the disease beginning at age 45 and women have a greater risk beginning at age 55. The risk for coronary artery disease is also higher if you have a family history of the disease. Diagnosing CAD Diagnosing CAD requires a review of your medical history, a physical examination, and other medical testing. These tests include: Electrocardiogram: This test monitors electrical signals that travel through your heart. It may help your doctor determine whether you’ve had a heart attack. Echocardiogram: This imaging test uses ultrasound waves to create a picture of your heart. The results of this test reveal whether certain things in your heart are functioning properly. Stress test: This particular test measures the stress on your heart during physical activity and while at rest. The test monitors your heart’s electrical activity while you walk on a treadmill or ride a stationary bike. Nuclear imaging may also be performed for a portion of this test. For those unable to perform physical exercise, certain medications can be used instead for stress testing. Cardiac catheterization (left heart catheterization): During this procedure, your doctor injects a special dye into your coronary arteries through a catheter inserted through an artery in your groin or forearm. The dye helps enhance the radiographic image of your coronary arteries to identify any blockages. Heart CT scan: Your doctor may use this imaging test to check for calcium deposits in your arteries. What is the treatment for CAD? It’s important to reduce or control your risk factors and seek treatment to lower the chance of a heart attack or stroke, if you’re diagnosed with CAD. Treatment also depends on your current health condition, risk factors, and overall wellbeing. For example, your doctor may prescribe medication therapy to treat high cholesterol or high blood pressure, or you may receive medication to control blood sugar if you have diabetes. Lifestyle changes can also reduce your risk of heart disease and stroke. For example: quit smoking tobacco reduce or stop your consumption of alcohol exercise regularly lose weight to a healthy level eat a healthy diet (low in fat, low in sodium) If your condition doesn’t improve with lifestyle changes and medication, your doctor may recommend a procedure to increase blood flow to your heart. These procedures may be: balloon angioplasty to widen blocked arteries and smoosh down the plaque buildup, usually performed with insertion of a stent to help keep the lumen open after the procedure coronary artery bypass graft surgery: to restore blood flow to the heart in open chest surgery enhanced external counterpulsation: to stimulate the formation of new small blood vessels to naturally bypass clogged arteries in a noninvasive procedure What is the outlook for CAD? Everyone’s outlook for CAD is different. You have better chances of preventing extensive damage to your heart the earlier you can start your treatment or implement lifestyle changes. It is important to follow your doctor’s instructions. Take medications as directed and make the recommended lifestyle changes. If you have a higher risk for CAD, you can help to prevent the disease by reducing your risk factors.

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