This document discusses coagulants and anticoagulants. It describes how coagulants promote coagulation and control bleeding, including systemic coagulants like vitamin K, tranexamic acid, and fibrinogen. Local coagulants called styptics are also discussed. Anticoagulants prevent coagulation and control conditions involving excessive clotting. Common anticoagulants described are heparin, low molecular weight heparin, warfarin and newer oral anticoagulants. Warfarin is a vitamin K antagonist that inhibits vitamin K-dependent clotting factors. Its mechanism of action and factors affecting dosing are summarized.
Coagulants and anticoagulants work in opposing ways to regulate blood coagulation. Coagulants such as vitamin K and plasma fractions help promote coagulation by activating clotting factors. Anticoagulants like heparin and warfarin inhibit coagulation factors or their production. Thrombolytics such as streptokinase and tissue plasminogen activator dissolve clots by activating plasmin. Platelet aggregation inhibitors including aspirin and clopidogrel prevent platelet activation and aggregation, which are key steps in clot formation. These drugs are used to treat and prevent thrombotic conditions.
This document summarizes different types of plasma expanders used to treat conditions involving fluid loss such as hemorrhage and shock. There are two main types of volume expanders: crystalloids like saline and colloids made from large insoluble molecules such as dextran, albumin, and gelatin. Common colloid plasma expanders discussed include albumin from human plasma, gelatins produced from collagen, hydroxyethyl starches, dextrans made by bacteria, and hypertonic saline solutions. The document compares the characteristics, mechanisms, and side effects of these different plasma expander options.
This document discusses drugs used for treating shock. It describes different types of shock including hypovolemic, septic, cardiogenic, and anaphylactic shock. It then discusses three categories of drugs used to treat shock: vasoconstrictors like epinephrine and norepinephrine which increase blood pressure, cardio tonic drugs like digoxin, dobutamine, and dopamine which increase heart function, and fluid replacement agents like blood, colloids, and crystalloids which replace lost fluids. Epinephrine causes vasoconstriction, increases heart rate and output, and dilates airways. Norepinephrine also causes vasoconstriction. Digoxin increases heart contraction force while
This document summarizes fibrinolytics and antiplatelet drugs. It describes the fibrinolytic system and how fibrinolytics like streptokinase, urokinase, alteplase work to activate plasminogen and lyse clots. Newer fibrinolytics like reteplase and tenecteplase are discussed. Antiplatelet drugs discussed include aspirin, dipyridamole, clopidogrel, abciximab and how they inhibit platelet aggregation by blocking TXA2 synthesis, increasing cAMP, or blocking ADP/GP-IIb-IIIa receptors. Their uses for coronary artery disease and procedures are highlighted.
This document discusses drugs used for congestive heart failure (CHF). It begins by defining heart failure as the heart's inability to pump enough blood to the body. It then classifies CHF drugs into those with positive inotropic effects, like cardiac glycosides and phosphodiesterase inhibitors, and those without, like diuretics and ACE inhibitors. The document provides detailed mechanisms of action, therapeutic uses, benefits, and adverse effects of various drug classes. It emphasizes that diuretics, ACE inhibitors, beta blockers, and spironolactone have been shown to reduce mortality and hospitalizations in CHF patients.
This document discusses different types of shock and their management. It outlines four main types of shock: hypovolemic, cardiogenic, septic, and anaphylactic. For each type, it describes the causes and pathophysiology. It then provides details on treatment approaches for each shock type, including use of specific drugs to increase blood pressure and cardiac output. The management sections emphasize fluid resuscitation, vasopressors, inotropes, antibiotics for infection, and corticosteroids depending on the shock etiology.
The document discusses pancreatic hormones and insulin. It describes the four main cell types in the islets of Langerhans and the hormones they secrete, including insulin secreted by beta cells. Insulin was discovered in 1921 and contains two polypeptide chains connected by disulfide bonds. Insulin regulates glucose levels by facilitating glucose transport and storage and inhibiting gluconeogenesis. Various insulin preparations are discussed, from conventional insulin to highly purified pork insulin to human insulin produced through recombinant DNA technology to analogues like insulin lispro and glargine which have altered pharmacokinetic properties.
Coagulants and anticoagulants work in opposing ways to regulate blood coagulation. Coagulants such as vitamin K and plasma fractions help promote coagulation by activating clotting factors. Anticoagulants like heparin and warfarin inhibit coagulation factors or their production. Thrombolytics such as streptokinase and tissue plasminogen activator dissolve clots by activating plasmin. Platelet aggregation inhibitors including aspirin and clopidogrel prevent platelet activation and aggregation, which are key steps in clot formation. These drugs are used to treat and prevent thrombotic conditions.
This document summarizes different types of plasma expanders used to treat conditions involving fluid loss such as hemorrhage and shock. There are two main types of volume expanders: crystalloids like saline and colloids made from large insoluble molecules such as dextran, albumin, and gelatin. Common colloid plasma expanders discussed include albumin from human plasma, gelatins produced from collagen, hydroxyethyl starches, dextrans made by bacteria, and hypertonic saline solutions. The document compares the characteristics, mechanisms, and side effects of these different plasma expander options.
This document discusses drugs used for treating shock. It describes different types of shock including hypovolemic, septic, cardiogenic, and anaphylactic shock. It then discusses three categories of drugs used to treat shock: vasoconstrictors like epinephrine and norepinephrine which increase blood pressure, cardio tonic drugs like digoxin, dobutamine, and dopamine which increase heart function, and fluid replacement agents like blood, colloids, and crystalloids which replace lost fluids. Epinephrine causes vasoconstriction, increases heart rate and output, and dilates airways. Norepinephrine also causes vasoconstriction. Digoxin increases heart contraction force while
This document summarizes fibrinolytics and antiplatelet drugs. It describes the fibrinolytic system and how fibrinolytics like streptokinase, urokinase, alteplase work to activate plasminogen and lyse clots. Newer fibrinolytics like reteplase and tenecteplase are discussed. Antiplatelet drugs discussed include aspirin, dipyridamole, clopidogrel, abciximab and how they inhibit platelet aggregation by blocking TXA2 synthesis, increasing cAMP, or blocking ADP/GP-IIb-IIIa receptors. Their uses for coronary artery disease and procedures are highlighted.
This document discusses drugs used for congestive heart failure (CHF). It begins by defining heart failure as the heart's inability to pump enough blood to the body. It then classifies CHF drugs into those with positive inotropic effects, like cardiac glycosides and phosphodiesterase inhibitors, and those without, like diuretics and ACE inhibitors. The document provides detailed mechanisms of action, therapeutic uses, benefits, and adverse effects of various drug classes. It emphasizes that diuretics, ACE inhibitors, beta blockers, and spironolactone have been shown to reduce mortality and hospitalizations in CHF patients.
This document discusses different types of shock and their management. It outlines four main types of shock: hypovolemic, cardiogenic, septic, and anaphylactic. For each type, it describes the causes and pathophysiology. It then provides details on treatment approaches for each shock type, including use of specific drugs to increase blood pressure and cardiac output. The management sections emphasize fluid resuscitation, vasopressors, inotropes, antibiotics for infection, and corticosteroids depending on the shock etiology.
The document discusses pancreatic hormones and insulin. It describes the four main cell types in the islets of Langerhans and the hormones they secrete, including insulin secreted by beta cells. Insulin was discovered in 1921 and contains two polypeptide chains connected by disulfide bonds. Insulin regulates glucose levels by facilitating glucose transport and storage and inhibiting gluconeogenesis. Various insulin preparations are discussed, from conventional insulin to highly purified pork insulin to human insulin produced through recombinant DNA technology to analogues like insulin lispro and glargine which have altered pharmacokinetic properties.
The document is a student submission on the topic of haemostasis and coagulation to their pharmacology department. It provides an overview of haemostasis and the three stages of coagulation, describes various coagulants, anticoagulants, vitamin K, heparin and other agents used to control bleeding and clotting. The submission also reviews the mechanisms, uses and adverse effects of different coagulation and anticoagulation drugs.
Drugs used in Congestive heart failure shoaib241087
This document provides an overview of drugs used to treat congestive heart failure (CHF). It begins with definitions and classifications of CHF, then describes diagnostic methods. The main treatment strategies and drugs are discussed, including inotropic drugs like digoxin, dobutamine, and dopamine. Renin-angiotensin system inhibitors like ACE inhibitors are also covered. The document provides details on mechanisms of action, pharmacokinetics, uses, interactions, and side effects of common CHF drugs.
This document provides information about antianginal drugs used to treat angina pectoris. It discusses the three main types of angina and describes the mechanisms of action and uses of various antianginal drug classes including nitrates, beta-blockers, calcium channel blockers, and potassium channel openers. Specific drugs discussed include nitroglycerin, isosorbide mononitrate, atenolol, metoprolol, nifedipine, and nicorandil. Nursing responsibilities related to administration and patient education for these antianginal medications are also reviewed.
This document discusses antihyperlipidemic agents used to treat hyperlipidemia, a condition of high lipid levels in the blood. It begins by defining hyperlipidemia and describing its causes such as diet, genetics, and medical conditions. It then covers the main classes of antihyperlipidemic drugs like HMG CoA inhibitors, fibrates, bile acid sequesterants, and their mechanisms and examples like lovastatin, atorvastatin, clofibrate, and cholestyramine. The document concludes by explaining how these drugs work to lower lipid levels through inhibiting cholesterol synthesis and absorption or increasing lipid catabolism.
Calcium channel blockers are used to treat angina and hypertension by blocking L-type calcium channels. This prevents calcium entry into cardiac and smooth muscle cells, causing vasodilation, decreased heart rate and blood pressure. Nitrates are commonly used to treat angina via conversion to nitric oxide which causes smooth muscle relaxation and vasodilation, reducing workload on the heart. Verapamil and diltiazem have more prominent cardiac effects while dihydropyridines like nifedipine are potent vasodilators. Calcium channel blockers are effective for various types of angina, hypertension, arrhythmias and other uses.
This document discusses different classes of hypoglycemic agents used to treat type 2 diabetes. It describes 5 classes: sulfonyl ureas, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, and meglitinides/phenylalanine analogues. Sulfonyl ureas work by stimulating insulin secretion from pancreatic beta cells. Biguanides like metformin increase insulin sensitivity. Thiazolidinediones are insulin sensitizers that enhance insulin action in target tissues like liver and muscle. Alpha-glucosidase inhibitors prevent glucose absorption from the gut. Meglitinides stimulate acute insulin release. The document provides examples of drugs in each class and briefly summarizes their mechanisms of action and
Digitalis is obtained from the leaves of Digitalis purpurea. It has positive inotropic effects on the heart by enhancing myocardial activity and contractility. This increases cardiac output and shifts the stroke volume-preload curve towards normal in patients with congestive heart failure (CHF), improving cardiac function and relieving symptoms. Digitalis is used to treat CHF and cardiac arrhythmias, but it has contraindications like tachycardia, hypokalemia, and myocardial infarction.
1. Shock is defined as inadequate tissue perfusion resulting in cellular dysfunction. It can occur with normal or low blood pressure and results from various causes like sepsis, hemorrhage, cardiac failure, etc.
2. Early goal-directed therapy for septic shock involves rapid fluid resuscitation, antibiotics, and vasopressors to maintain adequate perfusion. Dopamine, norepinephrine, and epinephrine are commonly used vasopressors.
3. Cardiogenic shock results from inadequate cardiac output, usually from acute myocardial infarction or myocarditis. It requires fluids, inotropes like dobutamine, and revascularization when possible.
Seretonin (5HT) and Its Antagonists PharmacologyPranatiChavan
Serotonin is a chemical that has a wide variety of functions in the human body. It is sometimes called the happy chemical, because it contributes to wellbeing and happiness.
The scientific name for serotonin is 5-hydroxytryptamine, or 5-HT. It is mainly found in the brain, bowels, and blood platelets.
Serotonin is used to transmit messages between nerve cells, it is thought to be active in constricting smooth muscles, and it contributes to wellbeing and happiness, among other things. As the precursor for melatonin, it helps regulate the body’s sleep-wake cycles and the internal clock.
It is thought to play a role in appetite, the emotions, and motor, cognitive, and autonomic functions. However, it is not known exactly if serotonin affects these directly, or if it has an overall role in co-ordinating the nervous system.
This document summarizes thrombolytic drugs, which are used to treat life-threatening blood clots. It discusses how thrombolytic drugs work by activating plasminogen to form plasmin, which breaks down fibrin and dissolves blood clots. The main thrombolytic drugs discussed are tissue plasminogen activator (tPA), streptokinase, urokinase, and their uses, mechanisms of action, advantages, and disadvantages in treating conditions like myocardial infarction and pulmonary embolism. The document also mentions antifibrinolytic drugs that inhibit fibrinolysis.
It is a anti- hypertensive drug. It is non-selective beta blocker drug. Hence it is beta blocker drug so it has many side effect.Not only Propranolol but also Timolol,Atenolol are beta blocker drugs.
This document summarizes different types of oral hypoglycemic agents (drugs used to lower blood glucose levels orally). It discusses sulfonylureas, biguanides, meglitinides, thiazolidinediones, and alpha-glucosidase inhibitors. For each class, it describes the mechanism of action, pharmacokinetics, adverse drug reactions, and examples of drugs from each class like glibenclamide, metformin, repaglinide, rosiglitazone, and acarbose. It also briefly mentions newer anti-diabetic drugs like SGLT-2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists that have been approved
This document discusses coagulants and factors involved in the coagulation cascade. It describes 13 clotting factors and how deficiencies can cause bleeding disorders. Vitamin K is important for blood clotting as it allows for the carboxylation of factors II, VII, IX, and X. Other coagulants discussed include fibrinogen, antihemophilic factor, desmopressin, and local hemostatics that can control bleeding from specific sites.
1. Diuretics are drugs that cause increased excretion of water and sodium in urine. They are classified based on their mechanism and efficacy as high ceiling loop diuretics, medium efficacy thiazides, weak carbonic anhydrase inhibitors, and potassium-sparing diuretics.
2. Loop diuretics like furosemide inhibit sodium reabsorption in the ascending loop of Henle. Thiazides like hydrochlorothiazide act in the distal convoluted tubule. Carbonic anhydrase inhibitors inhibit the enzyme carbonic anhydrase.
3. Diuretics are used to treat heart failure, liver cir
Insulin is a hormone that regulates blood glucose levels. There are different types of insulin preparations categorized by their onset and duration of action: rapid-acting insulin has an onset of 15 minutes; short-acting insulin has an onset of 30-60 minutes; intermediate-acting insulin has an onset of 1-2 hours; and long-acting insulin has an onset of 2-8 hours. Insulin can also be administered as a combination of short-acting and intermediate/long-acting insulins to better control blood glucose throughout the day. Insulin is usually administered via subcutaneous injection in the arm, thigh, or abdomen using a syringe or portable pen device.
This document summarizes different types of antianginal drugs. It discusses the pathophysiology of angina pectoris and different causes of chest pain. It then describes various classes of antianginal drugs including nitrates, beta blockers, calcium channel blockers, potassium channel openers, and other drugs. For each class, it discusses mechanisms of action, pharmacokinetics, uses, and adverse effects. The document provides an overview of treatment approaches for angina pectoris and ischemic heart disease.
Hyperlipidemia is a common disorder caused by abnormalities in lipid metabolism or transport. It results in high levels of lipids like cholesterol and triglycerides in the blood. Hyperlipidemia is classified based on the abnormal lipid levels and is primarily treated through lifestyle changes and medications that lower lipid levels. Common drug classes used to treat hyperlipidemia work by inhibiting cholesterol synthesis, breaking down fats, or blocking lipid absorption.
Diuretics act by inhibiting sodium reabsorption in the nephron, increasing sodium and water excretion and reducing extracellular fluid volume. They are classified based on their site of action - carbonic anhydrase inhibitors (site 1), loop diuretics (site 2), thiazides (site 3), and potassium-sparing diuretics (site 4). Loop diuretics like furosemide are sulfonamide derivatives that act distinctly on the loop of Henle. Thiazide diuretics like hydrochlorothiazide are benzothiadiazine derivatives that inhibit sodium reabsorption in the distal convoluted tubule. Potassium-sparing diuretics include sodium channel blockers
The document discusses body fluid compartments and their compositions. It notes that total body water makes up 60% of body weight, with two thirds located intracellularly and one third extracellularly. The extracellular fluid consists of interstitial fluid and blood plasma. Key electrolytes like sodium, potassium, calcium, and chloride are discussed along with their concentrations in plasma, interstitial, and intracellular fluids. Various volume expanders used to increase blood volume are also described, including crystalloids like saline and lactated Ringer's, as well as colloids like albumin, dextrans, gelatin, hydroxyethyl starch, and polyvinylpyrrolidone. Their mechanisms of action, properties, uses,
This document discusses coagulants and anticoagulants. It begins by explaining hemostasis, the process of stopping bleeding, which involves vasoconstriction, platelet plug formation, and blood clotting. It then describes the coagulation cascade and specific coagulation factors. Coagulants promote clotting and are classified as systemic (e.g. vitamin K, fibrinogen) or local styptics (e.g. thrombin, adrenaline). Anticoagulants prevent clotting and include heparin, warfarin, and antiplatelet drugs like aspirin. Both types of drugs are used to treat thromboembolic conditions.
This document summarizes drugs that affect blood and their uses. It discusses haematinics like iron, vitamin B12, and folic acid, which are used to treat anaemias caused by deficiencies in red blood cell production. It also covers coagulants and anticoagulants. Coagulants like vitamin K and fibrinogen promote coagulation, while anticoagulants like heparin, low molecular weight heparins, fondaparinux, and oral anticoagulants reduce coagulability of blood and are used to prevent thrombosis. Local haemostatics are used to stop bleeding from accessible sites. Care must be taken with patients on medications or with conditions that can affect haemostasis
The document is a student submission on the topic of haemostasis and coagulation to their pharmacology department. It provides an overview of haemostasis and the three stages of coagulation, describes various coagulants, anticoagulants, vitamin K, heparin and other agents used to control bleeding and clotting. The submission also reviews the mechanisms, uses and adverse effects of different coagulation and anticoagulation drugs.
Drugs used in Congestive heart failure shoaib241087
This document provides an overview of drugs used to treat congestive heart failure (CHF). It begins with definitions and classifications of CHF, then describes diagnostic methods. The main treatment strategies and drugs are discussed, including inotropic drugs like digoxin, dobutamine, and dopamine. Renin-angiotensin system inhibitors like ACE inhibitors are also covered. The document provides details on mechanisms of action, pharmacokinetics, uses, interactions, and side effects of common CHF drugs.
This document provides information about antianginal drugs used to treat angina pectoris. It discusses the three main types of angina and describes the mechanisms of action and uses of various antianginal drug classes including nitrates, beta-blockers, calcium channel blockers, and potassium channel openers. Specific drugs discussed include nitroglycerin, isosorbide mononitrate, atenolol, metoprolol, nifedipine, and nicorandil. Nursing responsibilities related to administration and patient education for these antianginal medications are also reviewed.
This document discusses antihyperlipidemic agents used to treat hyperlipidemia, a condition of high lipid levels in the blood. It begins by defining hyperlipidemia and describing its causes such as diet, genetics, and medical conditions. It then covers the main classes of antihyperlipidemic drugs like HMG CoA inhibitors, fibrates, bile acid sequesterants, and their mechanisms and examples like lovastatin, atorvastatin, clofibrate, and cholestyramine. The document concludes by explaining how these drugs work to lower lipid levels through inhibiting cholesterol synthesis and absorption or increasing lipid catabolism.
Calcium channel blockers are used to treat angina and hypertension by blocking L-type calcium channels. This prevents calcium entry into cardiac and smooth muscle cells, causing vasodilation, decreased heart rate and blood pressure. Nitrates are commonly used to treat angina via conversion to nitric oxide which causes smooth muscle relaxation and vasodilation, reducing workload on the heart. Verapamil and diltiazem have more prominent cardiac effects while dihydropyridines like nifedipine are potent vasodilators. Calcium channel blockers are effective for various types of angina, hypertension, arrhythmias and other uses.
This document discusses different classes of hypoglycemic agents used to treat type 2 diabetes. It describes 5 classes: sulfonyl ureas, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, and meglitinides/phenylalanine analogues. Sulfonyl ureas work by stimulating insulin secretion from pancreatic beta cells. Biguanides like metformin increase insulin sensitivity. Thiazolidinediones are insulin sensitizers that enhance insulin action in target tissues like liver and muscle. Alpha-glucosidase inhibitors prevent glucose absorption from the gut. Meglitinides stimulate acute insulin release. The document provides examples of drugs in each class and briefly summarizes their mechanisms of action and
Digitalis is obtained from the leaves of Digitalis purpurea. It has positive inotropic effects on the heart by enhancing myocardial activity and contractility. This increases cardiac output and shifts the stroke volume-preload curve towards normal in patients with congestive heart failure (CHF), improving cardiac function and relieving symptoms. Digitalis is used to treat CHF and cardiac arrhythmias, but it has contraindications like tachycardia, hypokalemia, and myocardial infarction.
1. Shock is defined as inadequate tissue perfusion resulting in cellular dysfunction. It can occur with normal or low blood pressure and results from various causes like sepsis, hemorrhage, cardiac failure, etc.
2. Early goal-directed therapy for septic shock involves rapid fluid resuscitation, antibiotics, and vasopressors to maintain adequate perfusion. Dopamine, norepinephrine, and epinephrine are commonly used vasopressors.
3. Cardiogenic shock results from inadequate cardiac output, usually from acute myocardial infarction or myocarditis. It requires fluids, inotropes like dobutamine, and revascularization when possible.
Seretonin (5HT) and Its Antagonists PharmacologyPranatiChavan
Serotonin is a chemical that has a wide variety of functions in the human body. It is sometimes called the happy chemical, because it contributes to wellbeing and happiness.
The scientific name for serotonin is 5-hydroxytryptamine, or 5-HT. It is mainly found in the brain, bowels, and blood platelets.
Serotonin is used to transmit messages between nerve cells, it is thought to be active in constricting smooth muscles, and it contributes to wellbeing and happiness, among other things. As the precursor for melatonin, it helps regulate the body’s sleep-wake cycles and the internal clock.
It is thought to play a role in appetite, the emotions, and motor, cognitive, and autonomic functions. However, it is not known exactly if serotonin affects these directly, or if it has an overall role in co-ordinating the nervous system.
This document summarizes thrombolytic drugs, which are used to treat life-threatening blood clots. It discusses how thrombolytic drugs work by activating plasminogen to form plasmin, which breaks down fibrin and dissolves blood clots. The main thrombolytic drugs discussed are tissue plasminogen activator (tPA), streptokinase, urokinase, and their uses, mechanisms of action, advantages, and disadvantages in treating conditions like myocardial infarction and pulmonary embolism. The document also mentions antifibrinolytic drugs that inhibit fibrinolysis.
It is a anti- hypertensive drug. It is non-selective beta blocker drug. Hence it is beta blocker drug so it has many side effect.Not only Propranolol but also Timolol,Atenolol are beta blocker drugs.
This document summarizes different types of oral hypoglycemic agents (drugs used to lower blood glucose levels orally). It discusses sulfonylureas, biguanides, meglitinides, thiazolidinediones, and alpha-glucosidase inhibitors. For each class, it describes the mechanism of action, pharmacokinetics, adverse drug reactions, and examples of drugs from each class like glibenclamide, metformin, repaglinide, rosiglitazone, and acarbose. It also briefly mentions newer anti-diabetic drugs like SGLT-2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists that have been approved
This document discusses coagulants and factors involved in the coagulation cascade. It describes 13 clotting factors and how deficiencies can cause bleeding disorders. Vitamin K is important for blood clotting as it allows for the carboxylation of factors II, VII, IX, and X. Other coagulants discussed include fibrinogen, antihemophilic factor, desmopressin, and local hemostatics that can control bleeding from specific sites.
1. Diuretics are drugs that cause increased excretion of water and sodium in urine. They are classified based on their mechanism and efficacy as high ceiling loop diuretics, medium efficacy thiazides, weak carbonic anhydrase inhibitors, and potassium-sparing diuretics.
2. Loop diuretics like furosemide inhibit sodium reabsorption in the ascending loop of Henle. Thiazides like hydrochlorothiazide act in the distal convoluted tubule. Carbonic anhydrase inhibitors inhibit the enzyme carbonic anhydrase.
3. Diuretics are used to treat heart failure, liver cir
Insulin is a hormone that regulates blood glucose levels. There are different types of insulin preparations categorized by their onset and duration of action: rapid-acting insulin has an onset of 15 minutes; short-acting insulin has an onset of 30-60 minutes; intermediate-acting insulin has an onset of 1-2 hours; and long-acting insulin has an onset of 2-8 hours. Insulin can also be administered as a combination of short-acting and intermediate/long-acting insulins to better control blood glucose throughout the day. Insulin is usually administered via subcutaneous injection in the arm, thigh, or abdomen using a syringe or portable pen device.
This document summarizes different types of antianginal drugs. It discusses the pathophysiology of angina pectoris and different causes of chest pain. It then describes various classes of antianginal drugs including nitrates, beta blockers, calcium channel blockers, potassium channel openers, and other drugs. For each class, it discusses mechanisms of action, pharmacokinetics, uses, and adverse effects. The document provides an overview of treatment approaches for angina pectoris and ischemic heart disease.
Hyperlipidemia is a common disorder caused by abnormalities in lipid metabolism or transport. It results in high levels of lipids like cholesterol and triglycerides in the blood. Hyperlipidemia is classified based on the abnormal lipid levels and is primarily treated through lifestyle changes and medications that lower lipid levels. Common drug classes used to treat hyperlipidemia work by inhibiting cholesterol synthesis, breaking down fats, or blocking lipid absorption.
Diuretics act by inhibiting sodium reabsorption in the nephron, increasing sodium and water excretion and reducing extracellular fluid volume. They are classified based on their site of action - carbonic anhydrase inhibitors (site 1), loop diuretics (site 2), thiazides (site 3), and potassium-sparing diuretics (site 4). Loop diuretics like furosemide are sulfonamide derivatives that act distinctly on the loop of Henle. Thiazide diuretics like hydrochlorothiazide are benzothiadiazine derivatives that inhibit sodium reabsorption in the distal convoluted tubule. Potassium-sparing diuretics include sodium channel blockers
The document discusses body fluid compartments and their compositions. It notes that total body water makes up 60% of body weight, with two thirds located intracellularly and one third extracellularly. The extracellular fluid consists of interstitial fluid and blood plasma. Key electrolytes like sodium, potassium, calcium, and chloride are discussed along with their concentrations in plasma, interstitial, and intracellular fluids. Various volume expanders used to increase blood volume are also described, including crystalloids like saline and lactated Ringer's, as well as colloids like albumin, dextrans, gelatin, hydroxyethyl starch, and polyvinylpyrrolidone. Their mechanisms of action, properties, uses,
This document discusses coagulants and anticoagulants. It begins by explaining hemostasis, the process of stopping bleeding, which involves vasoconstriction, platelet plug formation, and blood clotting. It then describes the coagulation cascade and specific coagulation factors. Coagulants promote clotting and are classified as systemic (e.g. vitamin K, fibrinogen) or local styptics (e.g. thrombin, adrenaline). Anticoagulants prevent clotting and include heparin, warfarin, and antiplatelet drugs like aspirin. Both types of drugs are used to treat thromboembolic conditions.
This document summarizes drugs that affect blood and their uses. It discusses haematinics like iron, vitamin B12, and folic acid, which are used to treat anaemias caused by deficiencies in red blood cell production. It also covers coagulants and anticoagulants. Coagulants like vitamin K and fibrinogen promote coagulation, while anticoagulants like heparin, low molecular weight heparins, fondaparinux, and oral anticoagulants reduce coagulability of blood and are used to prevent thrombosis. Local haemostatics are used to stop bleeding from accessible sites. Care must be taken with patients on medications or with conditions that can affect haemostasis
This document discusses coagulation, anticoagulants, and fibrinolytics. It begins by describing the coagulation cascade and fibrinolysis system, which work to stop bleeding through platelet plug formation and blood clotting. It then discusses natural anticoagulants like prostacyclin and antithrombin III that prevent inappropriate clotting. Various coagulants and anticoagulants are outlined, including heparin and low molecular weight heparins, vitamin K, and newer oral anticoagulants. Adverse effects and clinical uses of different agents are also summarized.
The hemophilia are disorders of hemostasis resulting from a deficiency of a procoagulant. Hemophilia is an inherited bleeding disorder affecting approximately 1 in 7500 males.
Heamatinics , coagulants & anti coagulants.pptxsowmyad517
Haematinics are agents used to treat anemia by increasing red blood cell production. They work by increasing erythropoietin levels and include iron, vitamin B12, and folic acid. Deficiencies can lead to anemia.
Coagulation is the process where blood forms clots, changing from a fluid to solid mass. Coagulants and anticoagulants are produced in the liver and help turn clotting on and off as needed. Vitamin K is an important coagulant while heparin is a common anticoagulant used to prevent clots.
This document discusses hemorrhage in oral surgery, including:
- Defining hemorrhage as prolonged or uncontrolled bleeding.
- Local causes of hemorrhage from soft tissues or bone during oral surgery procedures.
- Systemic causes like bleeding disorders or anticoagulant use.
- Types of hemorrhage including primary, reactionary, and secondary bleeding.
- Management techniques for primary hemorrhage in normal patients including ligation of vessels, cautery, hemostatic agents, and hypotensive anesthesia.
This seminar includes hemostasis,mechanism of blood clotting and associated blood dyscrasias commonly seen in children and their treatments with a note on antifibrinolytics
This document discusses coagulopathy, which refers to medical disorders involving abnormal blood clotting due to deficiencies or issues with platelets, clotting factors, or the fibrinolytic system. It defines various bleeding disorders and coagulation tests. Specific conditions covered include immune thrombocytopenic purpura (ITP), von Willebrand disease, hemophilia A/B, and disseminated intravascular coagulation (DIC). Treatment involves replacing the deficient clotting factor, managing underlying causes, or administering medications depending on the condition causing the coagulopathy. Complications can include excessive bleeding, joint damage, and transmission of infections.
Haemostasis is the physiologic system of competent blood vessels, endothelial cells, platelets and numerous plasma proteins that act in a finely controlled manner to preserve blood vessel integrity and prevent pathologic hemorrhage or thrombosis.
Haemostasis is achieved by :-
Vascular constriction
Formation of platelet plug
Formation of blood clot
Growth of fibrous tissue into the clot
The document discusses blood clotting and drugs that affect the clotting process. It describes the four phases of clotting - vascular, platelet, coagulation, and fibrinolytic. It then covers classes of drugs that prevent clotting, dissolve clots, prevent bleeding, and treat clotting deficiencies. Specific drugs discussed include heparin, warfarin, aspirin, streptokinase, tissue plasminogen activator, vitamin K, and factors VIII and IX for treating hemophilia. The mechanisms, effects, preparations and administration of these drugs are outlined.
This document discusses coagulants and anticoagulants. It describes how thrombosis occurs via venous and arterial pathways and the process of hemostasis. Coagulation involves a balance between procoagulants and anticoagulants. Common coagulation factors and pathways are outlined. Vitamin K and other coagulants like fibrinogen and antihemophilic factor are discussed. Anticoagulants include heparins, oral anticoagulants like warfarin, and other agents. Mechanisms, uses, and adverse effects of various coagulants and anticoagulants are summarized.
This document discusses perioperative bleeding and homeostasis. It begins with defining bleeding and describing different types. It then covers preoperative bleeding risk assessment, including medication and bleeding history, physical exam, and tools to evaluate risk. Methods of achieving homeostasis during and after surgery are outlined, including mechanical, thermal, pharmacological, and TEG monitoring. Predictors of postoperative bleeding in cardiac surgery and guidelines for assessing bleeding risk from British and European societies are presented.
This document discusses haemorrhage and haemostasis in dentistry. It defines haemorrhage as the escape of blood from blood vessels. The mechanisms of primary and secondary haemostasis that work to stop bleeding are described. Common bleeding disorders like hemophilia A and B, von Willebrand's disease, and those caused by vitamin K deficiency or liver disease are outlined. Methods for managing bleeding during dental procedures and treating bleeding disorders are provided. The roles of public health dentists and dental hygienists in addressing bleeding disorders are also mentioned.
The document summarizes key aspects of haemostasis including the vascular, platelet and clotting phases. It describes tests used to diagnose bleeding disorders affecting primary (platelets) and secondary (clotting factors) hemostasis. Clinical features of platelet and coagulation disorders are compared. The implications of bleeding disorders for periodontal treatment are discussed, highlighting the need to modify procedures and use hemostatic measures depending on the nature and severity of the underlying condition.
This document provides information on platelets, hemostasis, coagulation of blood, and related topics. It describes the components and functions of platelets, including their granules that contain factors involved in coagulation. The stages of hemostasis and coagulation are outlined, including vasoconstriction, formation of the platelet plug, development of a fibrin clot, and clot retraction. Coagulation factors, the enzyme cascade theory of coagulation, and natural anticoagulation mechanisms are also summarized. Bleeding disorders like hemophilia, purpura, and von Willebrand disease are briefly described.
This document provides an overview of haemostasis (hemostasis). It consists of five main sections:
1. Components of haemostasis - the vascular system, platelets, coagulation, fibrinolysis, and coagulation inhibition systems.
2. The haemostatic process - consisting of vasoconstriction, platelet plug formation, coagulation cascade, and fibrin clot formation and dissolution.
3. Haemostatic disorders - bleeding disorders due to problems with vessels, platelets, or coagulation factors, and thrombotic disorders.
4. Specific coagulation factor deficiencies - von Willebrand disease, hemophilia A/B, liver disease, vitamin K deficiency.
5
This document provides an overview of oral anticoagulants. It begins by describing hemostasis and the coagulation cascade. It then discusses different types of anticoagulants, including their mechanisms of action and indications. Specifically, it provides details on warfarin, including its history, mechanism as a vitamin K antagonist, dosing, side effects, drug and food interactions. It also briefly mentions newer oral anticoagulants that were developed due to disadvantages of warfarin, seeking alternatives with fixed dosing and less drug interactions.
This document discusses pharmacokinetics, which is the movement of drugs through the body via absorption, distribution, metabolism, and excretion. It describes the various mechanisms of drug transport across cell membranes, including passive diffusion, ion trapping, filtration, and active or facilitated transport. Factors affecting drug absorption such as solubility, dose, and food are also covered. The document then discusses distribution of drugs to tissues, plasma protein binding, and accumulation of drugs in tissues like fat, bone, and liver.
This document discusses psychotic disorders and their pharmacotherapy. It defines psychotic disorders as illnesses that make it difficult to think clearly and behave appropriately. It describes several types of psychosis including schizophrenia, schizoaffective disorder, delusional disorder, and dissociative disorders. Symptoms are outlined along with possible causes such as genetics and drug abuse. Diagnosis involves medical history, exams, and scans. Treatment involves antipsychotic drugs which work to reduce disturbed behaviors associated with delusions and hallucinations. Atypical antipsychotics are most commonly used now due to their better efficacy and safety profile.
This document discusses macrolide antibiotics, including their mechanism of action, types, and uses. It describes several macrolide antibiotics like erythromycin, clarithromycin, azithromycin, and roxithromycin. It covers their mechanisms of action, spectra of activity, pharmacokinetics, clinical uses, side effects, and interactions. It also briefly discusses newer macrolides like telithromycin and ketolides, as well as the lincosamide antibiotic clindomycin.
Non parametric study; Statistical approach for med student Dr. Rupendra Bharti
Non-parametric statistics are statistical methods that do not rely on assumptions about the probability distributions of the variables being assessed. They make fewer assumptions than parametric tests and can be used with ordinal or nominal data. Some common non-parametric tests include the chi-square test, McNemar's test, sign test, Wilcoxon signed-rank test, Mann-Whitney U test, Kruskal-Wallis test, and Spearman's rank correlation test. Non-parametric tests are useful when the data is ranked or does not meet the assumptions of parametric tests, as they provide a distribution-free way to perform statistical hypothesis testing.
Various dermatological conditions and pharmacological approach for management Dr. Rupendra Bharti
This document discusses dermatological conditions and their management. It covers the structure and function of skin, modes of treatment for skin disorders including topical, systemic, intralesional and UV radiation. It discusses factors affecting drug absorption through the skin and various skin preparations like vehicles, antibacterials, antifungals, antivirals, sunscreens, keratolytic agents and corticosteroids. It provides details on specific drugs, their preparations, doses and indications for treating bacterial, fungal and viral skin infections.
Histaminic Pharmacology; clinical approach toward patients Dr. Rupendra Bharti
Histamine is a substance produced in the body that causes allergic reactions. Scientists discovered histamine in 1910 and developed antihistamines to treat allergic reactions in the 1930s. Antihistamines work by blocking histamine receptors in the body. Histamine causes allergic symptoms by binding to H1 and H2 receptors and triggering immune responses. Allergic reactions can range from mild symptoms to life-threatening anaphylaxis. Diagnosis involves testing for allergen-specific IgE antibodies and avoidance of triggers is key for treatment.
1. The document discusses various treatments for cough, asthma, and status asthmaticus. It outlines medications commonly used for their mucolytic, antitussive, bronchodilating, and anti-inflammatory effects such as bromhexine, carbocisteine, codeine, salbutamol, ipratropium bromide, and corticosteroids.
2. Asthma types and triggers are defined. Diagnosis involves pulmonary function tests and management involves both pharmacological and non-pharmacological approaches. Treatment selection is based on asthma severity and control.
3. Status asthmaticus is described as a life-threatening condition requiring immediate treatment including oxygen, nebulized bronch
This document provides information on therapeutic drug monitoring, including sample information required for accurate interpretation and therapeutic ranges for various drugs. It discusses therapeutic drug monitoring for anti-seizure drugs like carbamazepine and valproic acid, cardiac drugs like digoxin and lidocaine, aminoglycoside antibiotics like amikacin and gentamicin, lithium for bipolar disorder, methotrexate for cancer treatment, theophylline, immunosuppressants for transplant patients like cyclosporine and tacrolimus, and various sample collection and testing methods. The goal of therapeutic drug monitoring is to ensure drug levels are within therapeutic ranges to achieve efficacy while avoiding toxicity.
Chronopharmacology is the science concerned with how the pharmacological effects of drugs vary over biological times and circadian rhythms. It takes into account that many physiological functions and disease states fluctuate over 24-hour cycles. Optimizing drug dosing according to circadian rhythms can increase efficacy and safety. Examples given include dosing asthma medications in the evening to prevent nighttime attacks, dosing blood pressure medications at night to prevent heart issues in the morning, and dosing ulcer medications at bedtime to reduce nighttime acid secretion. Recent advances include developing drug delivery systems to match circadian rhythms.
Protein therapeutics can help treat diseases by replacing missing proteins, augmenting existing pathways, or providing novel functions. Insulin was one of the first successful protein therapeutics, but producing it recombinantly in E. coli addressed issues with sourcing and costs. While proteins are often well-tolerated and specific, challenges include stability, delivery, stimulating immune responses, and post-translational modifications. Advances in recombinant technology and production methods aim to overcome these challenges to develop more effective protein-based therapies.
This document provides an overview of clinical auditing for healthcare staff. It defines clinical auditing as a quality improvement process that systematically reviews care against criteria to improve patient outcomes. The document outlines the five stages of a clinical audit: planning, selecting standards and criteria, measuring performance, making improvements, and sustaining improvements. It describes each stage in detail and provides guidance on topics selection, criteria identification, and involving stakeholders throughout the audit process. The goal is to use clinical auditing to discover opportunities to improve care delivery and uphold professional standards.
Chelating agents are compounds that bind to heavy metals to form stable complexes that can be safely excreted from the body. They work by competing with the body's ligands for heavy metals. Common chelating agents include EDTA, dimercaprol, penicillamine, deferoxamine, and deferiprone. They are used to treat poisoning from metals like lead, arsenic, mercury, and iron. The ideal chelating agent has high affinity for toxic metals over calcium and the body's natural ligands, is water soluble, and forms complexes that match the metal's distribution in the body.
This document discusses various laxatives and purgatives used to treat constipation. It classifies them based on their mechanism of action into bulk forming agents, stool softeners, stimulant purgatives, and osmotic purgatives. It provides examples of commonly used drugs from each class and describes their doses, mechanisms of action, and side effects. The document also discusses antidiarrheal drugs and classifications of diarrhea. It outlines specific antimicrobial treatments for infectious causes of diarrhea and describes non-specific antidiarrheal drugs that decrease intestinal secretion and motility.
This document discusses nausea, vomiting, and antiemetics. It defines nausea, retching, and vomiting and describes the symptoms and causes of nausea and vomiting. It discusses the anatomy of emesis, including the chemoreceptor trigger zone and vomiting center in the brainstem. It outlines the mechanisms of vomiting and describes various types of drug-induced vomiting. It also discusses the therapeutic use of emetic agents and the management of nausea and vomiting, including lifestyle changes, pharmacotherapy using various classes of antiemetics, and prokinetic drugs.
This document discusses peptic ulcer disease and its treatment. It begins by describing the gastric mucus-bicarbonate barrier and gastric secretions. It then outlines the three phases of gastric acid secretion and discusses pathophysiology of peptic ulcer disease. Risk factors for peptic ulcer disease are identified as H. pylori infection, NSAID use, smoking, alcohol, and stress. Diagnostic testing options include serology tests, stool antigen tests, urea breath tests, and endoscopy. Treatment involves acid suppression with proton pump inhibitors or H2 receptor antagonists as well as eradicating H. pylori infections.
This document discusses bioequivalence and summarizes key concepts. It defines bioequivalence as two products having similar rates and extents of absorption such that their effects are essentially the same. Bioequivalence studies compare test and reference products to show they are therapeutically equivalent. Such studies must use appropriate designs, subjects, and measures like pharmacokinetic or pharmacodynamic parameters to demonstrate equivalence. Meeting bioequivalence standards allows generic copies of off-patent drugs to be approved, increasing access to affordable medicines.
This document discusses treatment strategies and management of obesity. It defines obesity as excess adiposity with ectopic fat deposition. Normal mechanisms of adipose tissue and fat storage are described. The epidemiology of obesity globally and in India is examined. Causes and pathophysiology of obesity are explained. Diagnostic criteria including BMI, waist circumference, skin fold thickness and imaging tests are covered. Complications of obesity and prevention strategies focusing on diet and lifestyle are outlined. Pharmacological treatments including phentermine, orlistat, GLP-1 receptor agonists, and their effects and adverse reactions are summarized. Bariatric surgery is also mentioned as a treatment option.
The document discusses osteoporosis and its management. It provides details on:
- The composition and types of bone tissue in the human skeleton.
- Key cells involved in bone remodeling including osteoblasts, osteoclasts, and osteocytes.
- Minerals and vitamins important for bone health such as calcium, vitamin D, and parathyroid hormone.
- Classes of drugs used to treat osteoporosis including bisphosphonates, calcitonin, teriparatide, denosumab, and hormone therapies. Side effects and considerations for each drug class are covered.
Opioids are drugs that bind to opioid receptors in the central nervous system to relieve pain. This document discusses the clinical pharmacology of opioids including their mechanisms of action, types, and effects. It describes natural opioids like morphine and codeine derived from opium, semi-synthetic opioids created from modifications to natural opioids, and fully synthetic opioids like fentanyl. The document outlines how different opioids act on mu, kappa, and delta receptors to produce analgesia and other effects. It also covers the pharmacokinetics, indications, and side effects of various opioids.
Tranexamic acid is an antifibrinolytic drug that inhibits fibrinolysis by reversibly binding to plasminogen. It is effective at reducing surgical bleeding across many procedures like cardiac, orthopedic, and cranial surgery. It also reduces bleeding in gynecological conditions like heavy menstrual bleeding and postpartum hemorrhage. Tranexamic acid is generally well tolerated with side effects including headache, nausea, and diarrhea. It is given orally, intravenously, or topically depending on the condition being treated.
Mercurius is named after the roman god mercurius, the god of trade and science. The planet mercurius is named after the same god. Mercurius is sometimes called hydrargyrum, means ‘watery silver’. Its shine and colour are very similar to silver, but mercury is a fluid at room temperatures. The name quick silver is a translation of hydrargyrum, where the word quick describes its tendency to scatter away in all directions.
The droplets have a tendency to conglomerate to one big mass, but on being shaken they fall apart into countless little droplets again. It is used to ignite explosives, like mercury fulminate, the explosive character is one of its general themes.
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
The skin is the largest organ and its health plays a vital role among the other sense organs. The skin concerns like acne breakout, psoriasis, or anything similar along the lines, finding a qualified and experienced dermatologist becomes paramount.
DECLARATION OF HELSINKI - History and principlesanaghabharat01
This SlideShare presentation provides a comprehensive overview of the Declaration of Helsinki, a foundational document outlining ethical guidelines for conducting medical research involving human subjects.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Kosmoderma Academy, a leading institution in the field of dermatology and aesthetics, offers comprehensive courses in cosmetology and trichology. Our specialized courses on PRP (Hair), DR+Growth Factor, GFC, and Qr678 are designed to equip practitioners with advanced skills and knowledge to excel in hair restoration and growth treatments.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
2. Coagulants
• Coagulation: The process of changing of blood
from a fluid state to a solid state is known as
coagulation. Normally, this is a natural process in
the body to prevent blood loss by plugging the
injured site.
• The vascular system must maintain an intricate
balance between the tendency to clot or form a
solid state, and the need to “unclot,” or reverse
coagulation, to keep the vessels open and the
blood flowing.
3. After an injury to the body tissues, there is a natural
mechanism, which helps to stop the blood loss by
involvement of a complex haemostatic mechanism.
This mechanism is as follows:
4. BLOOD
CLOTTING
FACTORS
Component or
Factor
Common Synonym
I Fibrinogen
II Prothrombin
III Tissue thromboplastin
IV Calcium
V Proaccelerin
VI Accerin, supposed to be active form of
factor V
VII Proconvertin
VIII Antihemophilic factor (AHF)
IX Christmas factor, plasma thromboplastin
component (PTC)
X Stuart-Prower factor
XI Plasma thromboplastin antecedent (PTA)
XII Hageman factor
XIII Fibrin-stabilizing factor
XIV Prekallekrein
XV kallekrein
XVI Platelet factor
5. COAGULANTS
Coagulants are the drugs that promote
coagulation and control bleeding.
• They are also called hemostatic agents.
• These drugs are of two types
– Systemic coagulants.
– Local coagulants (styptics).
7. Systemic coagulants
Vitamin-K
• Vitamin K (Coagulation vitamin) is essential for
the coagulation process.
• It is not directly involved in the clotting
process but required for the synthesis of four
clotting factors in the liver: Factor II,VII,IX and
X.
8. • It occurs naturally in two forms:
– Phylloquinone (K1) from plant source and
– Menaquinone (K2) which is synthesized by colonic
bacteria (E.coli) in the colon.
• K3 is the synthetic form and is available as
– Fat-soluble forms (Menadione,
Acetomenaphthone) and
– water-soluble forms (Menadione sod. Bisulfate
and Menadione sod. Diphosphate).
9. • Dietary sources:
– Green leafy vegetables such as cabbage, spinach
and liver, cheese, cereals, nuts, and egg yolk etc.
– Wheat germ oil is the richest source.
• Physiological functions:
– Vit-K is essential for formation of clotting factor-II,
VII, IX, X, protein-C & S.
10. Deficiency Symptoms
• Vit-K is only temporarily concentrated in liver and
this store can be exhausted within one week.
• The deficiency of vit-K occurs due to liver disease,
obstructive jaundice, malabsorption, long-term
antimicrobial therapy, which alters intestinal
flora.
• The most important manifestation is bleeding
tendency due to lowering of the levels of
prothrombin and other clotting factors in blood.
11. • Haematuria is usually first to occur; other
common sites of bleeding are gastrointestinal
tract, nose and under the skin where it
presents in the form of haemorrhagic spots.
• Recommended dietary allowance (RDA)
– Normal adult requirement is 50–100 μg/day.
– As it can be synthesized in the colon, even 3–10
μg/day may be sufficient.
12. Vit-K use:
• For prevention of haemorrhagic disease of the
newborn: All newborns especially premature
infants have low levels of prothrombin and
other clotting factors.
– Vit- K: 1 mg IM soon after birth has been
recommended routinely.
– Alternatively, 5–10 mg IM to the mother 4–12
hours before delivery can be given.
13. • Patients on prolonged antimicrobial therapy.
• As an antidote in overdose of oral
anticoagulants.
• In patients suffering from liver disease
(cirrhosis, viral hepatitis).
14. • Patients with obstructive jaundice or
malabsorption syndromes (sprue, regional
ileitis, steatorrhoea, etc).
– The therapy given is Vit-K 10 mg IM/day, or
orally along with bile salts for better
absorption.
• Menadione (K3) should not be used in patients
with G-6-PD deficiency.
• In the newborn menadione or its salts can
precipitate kernicterus.
15. Ethamsylate
• It increases capillary wall stability by
antihyaluronidase action.
• It decreases PGI2 synthesis, and corrects
abnormalities of platelet adhesion and
promotes platelet aggregation.
• It is used in the prevention and treatment of
capillary bleeding.
16. • Common indications
– menorrhagia, PPH, after abortion, epistaxis, after
tooth extraction and hematuria.
• Side effects
– nausea, rash, headache, and acute hypotension if
given by fast IV injection.
• It is given in a dose of 250–500 mg TDS orally
or IV.
17. Desmopressin
• It is an analogue to vasopressin & increases
the plasma concentration of factor-VIII, von
Willebrand factor and directly activates
platelets.
• It is a selective V2 agonist, 12 times more
potent than AVP.
• Desmopressin is useful for the treatment of
hemophilia-A and von-willebrand disease.
18. Fibrinogen
• It is obtained from human plasma and is a
promising haemostatic agent.
• It is used to control bleeding in
– Haemophilia
– Hypofibrinogenemia
– Antihaemophilic globulin deficiency.
• It is available as IV infusion 0.5 per bottle.
19. Anti-hemophillic factor
• It contains coagulation factor VIII and is
concentrated human (Antihaemophilic globulin)
AHG obtained from pooled human plasma.
• It is also synthesized by recombinant DNA
technology.
• It is therapeutically used in haemophilia and AHG
deficiency.
• It is given in a dose of 10–20 IU/kg by IV infusion,
repeated 6–12 hourly.
20. Tranexamic acid & Epsilon aminocaproic acid
• They are antifibronolytic agent.
• They inhibit the activation of plasminogen and
dissolution of clot.
• They are available as oral and IV form.
• Tranexamic acid is given in a dose of 500-1000mg
TDS, orally & IV.
• Side effects
– nausea, vomiting, thromboembolic states, allergic
reactions, disturbed colour vision, etc.
21. • They are indicated in:
– To counteract the effect of fibrinolytic drugs.
– For controlling the bleeding in
• tonsillectomy,
• prostatic surgery,
• tooth extraction in haemophiliacs.
– Menorrhagia, menometrorrhagia & DUB.
– Recurrent epistaxis.
22. LOCAL COAGULANTS (STYPTICS)
• Local coagulants are also known as styptics or
haemostatics (haemo-blood and statics- to
stop).
• These substances are used locally to stop the
bleeding from the oozing surfaces such as
abrasions, bleeding tooth socket after tooth
extraction etc.
23. • Normal haemostasis involves three steps:
– Vasoconstriction or contraction of injured vessel wall
for a few minutes.
– Adhesion and aggregation of platelets to form a plug.
– Formation of a blood clot.
24. • This is followed by dissolution of the clot by
the process of fibrinolysis and maintenance of
normal circulation.
• The most preferred and effective method of
stopping the external bleeding is manual
pressure, cotton-gauze pressure pack or by
suturing.
25. Role of adrenaline
• Control of bleeding may be aided by applying
adrenaline locally as it causes local vasoconstriction.
• A cotton pad soaked with 0.1% adrenaline is used to
control capillary bleeding such as epistaxis and after
tooth extraction etc.
• Adrenaline is available in combination with
lignocaine to provide better surgical field, but should
be avoided in patients suffering from hypertension or
cardiovascular disease.
26. Thrombin
• Obtained from bovine plasma is used topically
to control capillary bleeding.
• It may cause hypersensitivity reactions also.
27. Gelatin foam, oxidized cellulose
• Theses are absorbable materials, available as film or
sponge and are used in surgical procedures to
control the bleeding of capillaries or arterioles.
• After applied dry, they swell up and form meshwork,
which helps in the clotting mechanism and stops
bleeding.
• These materials are absorbed within 4 weeks.
• The main adverse effects seen with these are tissue
necrosis, vascular stenosis & nerve damage.
28.
29.
30. Astringents
• Such as tannic acid or
metallic salts (alum)
are occasionally
applied for bleeding
gums, cuts during
shaving, bleeding piles,
etc.
32. Blood Vessel Injury
IX IXa
XI XIa
X Xa
XII XIIa
Tissue Injury
Tissue Factor
Thromboplastin
VIIa VII
X
Prothrombin Thrombin
Fibrinogen Fribrin monomer
Fibrin polymer
XIII
Intrinsic Pathway Extrinsic Pathway
Factors affected
By Heparin
Vit. K dependent Factors
Affected by Oral Anticoagulants
Recall !
33. Why anticoagulants ?
To reduce the coagulability of blood
Blood clots – Thrombus
Arterial Thrombosis:
Adherence of platelets to arterial walls – “White” in color -
Often associated with MI, stroke and ischemia
Venous Thrombosis:
Develops in areas of stagnated blood flow (deep vein
thrombosis), “Red” in color- Associated with Congestive
Heart Failure, Cancer, Surgery
Thrombus dislodge from arteries and veins and become an
embolus
Venous emboli can block arterioles in the lung and pulmonary
circulation
Thromboembolism
34. Figure. Classification of established anticoagulants and new anticoagulants that
were recently licensed for use or are in advanced stages of clinical
development. fIXa indicates factor IXa. *Indirectly inhibit coagulation by
interacting with antithrombin. †AVE5026 is an ultralow-molecular-weight
heparin that primarily inhibits fXa and has minimal activity against thrombin.
35. Anticoagulant drugs to treat
thromboembolism
Drug Class Prototype Action Effect
Anticoagulant
Parenteral
Heparin Inactivation of clotting
Factors
Prevent venous
Thrombosis
Anticoagulant
Oral
Warfarin Decrease synthesis of
Clotting factors
Prevent venous
Thrombosis
Antiplatelet
drugs
Aspirin Decrease platelet
aggregation
Prevent arterial
Thrombosis
Thrombolytic
Drugs
Streptokinase Fibinolysis Breakdown of
thrombi
38. WARFARIN
• 1948: synthesis of warfarin by student Harold
Campbell.
• Most widely used anticoagulant in the world
• Coumarin derivative, water soluble vit K
antagonist.
• Low cost and highly effective, if given in right
way.
The name warfarin is derived from WARF (Wisconsin Alumni
Research Foundation) and –arin from coumarin.
39. Vitamin K-dependent clotting factors
(FII, FVII, FIX, FX, Protein C/S/Z)
Epoxide
Reductase
-Carboxylase
(GGCX)
MECHANISM OF ACTION: Warfarin inhibits the vitamin K cycle
Warfarin
Inactivation
CYP2C9
Pharmacokinetic
Post translational modification
40.
41. PLASMA HALF-LIVES OF VITAMIN K-DEPENDENT
PROTEINS
Peak anticoagulant effect may be delayed by 72 to 96 hours
COAGULATION FACTORS HALF-LIFE (h)
II 60
VII 4-6
IX 24
X 48-72
Protein –C 8
Protein- S 30
42. VKORC1: New Target Protein for Warfarin
Epoxide
Reductase
-Carboxylase
(GGCX)
Clotting Factors
(FII, FVII, FIX, FX, Protein C/S/Z)
Rost et al. & Li, et al., Nature (2004)
(VKORC1)
43. Effect of VKORC1 Genotype on Anticoagulation
• Three polymorphic variants of VKORC1
• Non-A, Non-A : wild type – Requiring more warfarin dose
• Non-A/A : Heterozygous – Requiring 25% dose reduction
• A/A : Homozygous - Requiring 50% dose reduction
• Means wild type having more resistance to warfarin while
homozygous is more sensitive.
• Asians have the highest prevalence of VKORC1 variants,
followed by whites and blacks
• Polymorphisms in VKORC1 likely explain 30% of the variability
in warfarin dose requirements.
• VKORC1 variants are more prevalent than variants of CYP2C9
Genotype Freq in Asians (%) Dose reduction
Non-A,Non-A : wild type 7 --
Non-A/A : Heterozygous 30 26
A/A : Homozygous 63 50
44. DOSING
• Usual dose is 5 mg/day (1-20 mg)
• Lower doses require in
• Elderly
• Pt on increased risk of bleeding eg. Pt on aspirin
• Heart failure
• Liver disease
• Renal impairment
• Malnutrition
• Thyrotoxicosis
• Asian patients: Explained by genetic variation in
hepatic enzymes (CYP3C9 & VKORC1 Polymorphism)
• High intake dietary Vit-K (green vegetables e.g.
broccoli) reduces the efficacy of Warfarin.
• Practically best time to give warfarin is ~ 6 PM.
45. Why to add concomitant parenteral anticoagulation ?
• Because of delayed onset of action, concomitant
parenteral anticoagulant should be given in pts with
established thrombosis or high risk for thrombosis
until INR has been in therapeutic range for at least 2
days.
• Warfarin monotherapy decreases the levels of two
endogenous anticoagulants, proteins C and S, thus
increasing thrombogenic potential. Overlapping
warfarin for at least 5 days with an immediately
effective parenteral anticoagulant counteracts the
procoagulant effect of unopposed warfarin.
• Usually a minimum 5 days of concomitant parenteral
anticoagulation is recommended.
46. Commencement of oral anticoagulant therapy
• If the baseline INR≤1.3 the patient will receive 5mg of
warfarin once daily on days 1 and 2.
• The INR is checked on day 3 and 4 and the warfarin
dose is adjusted according to the schedule.
47. Monitoring
• B/z of narrow therapeutic window of warfarin
• Standard procedure is to check the PT-INR as
follows:
INR daily until it is in therapeutic range
3 times weekly for 2 weeks
Once stable & warfarin dose is known
INR every 3-4 weeks or more frequently if
introduction of any new medications
48. What is PT-INR
• Warfarin therapy is most often monitored using the
prothrombin time, a test sensitive to reductions in
the levels of prothrombin, factor VII, and factor X.
• This test involved addition of thromboplastin (a
reagent containing TF, phospholipid & Ca++) to
citrated plasma and determining the time to clot
formation.
• Thromboplastins vary in their sensitivity to
reductions in the levels of the vitamin K–dependent
clotting factors
• INR represent the PT according to international
reference thromboplastin, as approved by WHO.
49. INTERNATIONAL NORMALISED RATIO (INR)
INR = [PTpt] ISI
[PTRef]
PTpt – prothrombin time of patient
PTRef – prothrombin time of normal pooled sample
ISI – International Sensitivity Index
Highly sensitive thromboplastins have an ISI of 1.0
Most current thromboplastins have ISI values that range from 1.0 to 1.4
52. Indications
• Atrial fibrillation
• Prosthetic heart valve
• Venous thromboembolism
• Primary pulmonary hypertension
• Rarely after Acute MI
(If associated with high risk of thromboembolism e.g. AF, mobile or pedunculated
mural thrombus or prior venous thromboembolism)
53. Side effects of Warfarin
Bleeding
Skin necrosis
Purple toe syndrome
Teratogenicity
Osteoporosis
Others: Agranulocytosis, leukopenia, diarrhoea,
nausea, anorexia.
54. Bleeding
• Most common complication
• In form of
• Mild: epistaxis, hematuria
• Severe: Retroperotoneal or gastrointestinal bleeding
• Life-threatening : Intracranial bleed
• Rate of major bleeding (defined as any visit to hospital for
hemorrhage) is 1- 3% per person-year
• Half of the complications occurs because INR
exceeds therapeutic range
• Can be minimized by keeping INR in therapeutic
range
55. Interventions according to INR/symptoms
Asymptomatic pts with raised INR
INR INTERVENTION
3.5 - 4.5 Withhold warfarin until in therapeutic
range
Decrease the dose of warfarin
> 4.5 Low dose sublingual/oral Vit K (not
routinely)
4.5 – 9.0 Vit k 1 mg
> 9.0 Vit k 2-3 mg
Higher doses of vitamin K (up to 10 mg) can be administered if more rapid reversal of the
INR is required
Although vitamin K administration results in a more rapid reduction in the INR,
there is no evidence that it reduces the risk of hemorrhage
56. Symptomatic pts with raised INR
SYMPTOMS INTERVENTION
Mild bleeding Withhold warfarin
Severe bleeding Vit K 10 mg slow i/v infusion ± FFP (15
ml/kg)
Life threatening bleeding or pt can’t
tolerate volume overload
Prothrombin complex concentrate
(II,IX & X)
Prosthetic valves pts Vit K should be strictly avoided,
unless there is life threatening
intracranial bleed (Valve thrombosis)
Subcutaneous Vit K gives variable results and should be avoided
57. SKIN NECROSIS
• Rare but very serious complication of warfarin
(prevalence of 0.01-0.1 %)
• Occurs 2 to 5 days after initiation of warfarin
• Usually occurs after high dose of warfarin
• Typical presentation is :
– Well-demarcated erythematous lesions form on the thighs,
buttocks, breasts, or toes.
– Typically, the center of the lesion becomes progressively
necrotic.
– Examination of skin biopsies taken from the borders of
these lesions reveals thrombi in the microvasculature
59. • Mechanism : Not well understood but a precipitous fall in
plasma protein C or S levels (natural anticoagulants) before
warfarin exert anticoagulant effect, results in procoagulant
state triggering thrombosis of adipose tissue
microvasculatures.
• Treatment :
– Discontinuation of warfarin and reversal with vitamin K, if needed
– An alternative anticoagulant, such as heparin or LMWH, should be
given to patients with thrombosis
– Protein C concentrates or recombinant activated protein C may
accelerate healing of the skin lesions in protein C deficient patients
– Frozen plasma may be useful for those with protein S deficiency
– Occasionally, skin grafting is necessary when there is extensive skin
loss.
• Prevention :
– Start with low dose warfarin in pts with known Protein C or S
deficiency
– Overlapping with a parenteral anticoagulant when initiating warfarin
therapy
60. Purple toes syndrome
• Extremely uncommon cutaneous
complication
• Characterized by the sudden appearance of
bilateral, painful, purple nonhemorrhagic
lesions on the toes and sides of the feet that
blanch with pressure
• Usually develops 3-8 weeks after the start of
warfarin therapy
• Mechanism: release of atheromatous plaque
emboli
• Discontinue COUMADIN therapy if such
phenomena are observed. Consider
alternative drugs if continued anticoagulation
therapy is necessary.
Pharmacotherapy. 2003 May;23(5):674-7
61. Teratogenicity
• Occurs in 3.5 – 6 %
• Depends on time of gestation and dose of warfarin given
• Usually in first trimester of pregnancy
• It causes characteristic embryopathy consist of :
• Nasal hypoplasia and
• Chondrodysplasia punctata (epiphyseal and vertebral
bone stippling)
• Cleft lip and (or) palate
• Choanal stenosis/atresia
• Central nervous system abnormalities
• Coarctation of aorta (Rare malformations described
following first trimester exposure to warfarin)
• Occurs especially if warfarin dose is > 5 mg/day
62. Lateral view X-ray showing calcifications and irregular
ossification of lumbar and sacral vertebrae, consistent with
warfarin embryopathy
63. OSTEOPOROSIS
• Long- term use of warfarin (> 1 yr)
• More common in males
• 60% increased risk of osteoporosis-related
fracture in men
• Mechanism: combination of reduced intake of
vitamin K, which is necessary for bone health,
and inhibition by warfarin of vitamin K-mediated
carboxylation of certain bone proteins, rendering
them nonfunctional
• Beta-adrenergic antagonists may protect against
osteoporotic fractures
65. Pregnancy
• It causes…
• Fetal abnormalities (Teratogenic)- in first trimister
• Chances of intracranial bleeding in baby while passage
through birth canal – in third trimister
• Because of this, warfarin is contraindicated in
1st (first 12 weeks) & 3rd trimsters (last 2
weeks)
• Warfarin does not passes in breast milk & is
safe for nursing mothers.
66. ACENOCOUMAROL (acitrom)
• Same as warfarin with following differences:
– Shorter half life 10-16 hrs
– More rapid onset of action
– Shorter duration of action (2 days)
– Causes GI disturbances, oral ulcerations and
dermatitis
• 4 mg on day one, 4-8 mg on the day 2nd then
maintenance dose 1-8 mg according to
response by PT test
67. THE OVERALL ANTICOAGULATION QUALITY IS SIGNIFICANTLY BETTER WITH
WARFARIN AS COMPARED TO ACENOCOUMAROL
72%
67%
64%
66%
68%
70%
72%
%Responders
Warfarin Acenocoumarol
Thrombosis And Haemostasis 1994; 71(2): 188-191
69. What’s wrong with warfarin?
1. Narrow therapeutic range
2. Slow onset of action
3. Slow offset of action (long duration of action,
long elimination half life)
4. Multiple drug and dietary interactions
5. Monitoring required to maintain in therapeutic
range
6. Difficult to manage for invasive procedures
7. Under-use of therapy due to fear of adverse
events and complexity of management
73. Dabigatran etexilate (Pradaxa)
• Oral Direct thrombin
(factor IIa) inhibitor
• It is a prodrug & does
not exhibit any
pharmacological
activity
• Initially recommended
by FDA on October 19,
2010 for Non-valvular
AF
74. Mechanism of Action
• Dabigatran and its acyl glucuronides are competitive,
direct thrombin inhibitors.
• Both free and clot-bound thrombin, and thrombin-
induced platelet aggregation are inhibited by the
active moieties.
75. Pharmacokinetics
• Dabigatran etexilate mesylate is absorbed as the
dabigatran etexilate ester.
• The ester is then hydrolyzed, forming dabigatran,
the active moiety.
• The t1/2 is 15 to 17 hrs.
• 90% is excreted unchanged in urine.
• The absolute bioavailability of dabigatran following
oral administration is approximately 3 to 7% .
76. • Dabigatran is also a substrate for P-
glycoprotein ( a trans-membrane pump
expelling drugs out of cell).
• So P- glycoprotein inhibitors (e.g. amiodarone,
verapamil & clarithromycin) can increase
whereas inducers (e.g. rifampicin, st. john’s
wart) may reduce dabigatran level in plasma.
77. INDICATIONS AND USAGE
Reduction of Risk of Stroke and Systemic Embolism
in Non-valvular Atrial Fibrillation
Treatment of Deep Venous Thrombosis and
Pulmonary Embolism
Reduction in the Risk of Recurrence of Deep Venous
Thrombosis and Pulmonary Embolism
80. • If a dose of dabigatran is not taken at the scheduled
time, the dose should be taken as soon as possible on
the same day;
• the missed dose should be skipped if it cannot be taken
at least 6 hours before the next scheduled dose.
• The dose of dabigatran should not be doubled to make
up for a missed dose.
81. Converting pts from or to Warfarin
• From warfarin to dabigatran
– Stop warfarin & start dabigatran once INR fall below 2
• From dabigatran to warfarin
– Adjust the starting time of warfarin based on creatinine clearance
CrCL (ml/min) Days before stopping
dabigatran
> 50 3 days
50 - 30 2 days
30 - 15 1 day
< 15 or dialysis not recommended
82. Converting pts from or to parenteral anticoagulants
From parenteral anticoagulants to dabigatran
– Intermittent parenteral anticoagulant
– Start dabigatran 0-2 hrs before next dose
– Continuous parenteral anticoagulant (e.g. UFH)
– Start dabigatran at the time of stopping parenteral anticoagulant
• From dabigatran to parenteral anticoagulants
• Wait for 12 hrs (CrCl> 30 ml/min) or 24 hrs (CrCl< 30 ml/min)
after last dose of dabigatran before starting parenteral
anticoagulant
83. Dabigatran in pts planned for elective surgery
• If possible, stop dabigatran 1-2 days before
(CrCl> 50 ml/min) or 3-5 days before (CrCl<
50 ml/min) invasive or surgical procedures.
• Longer periods may be considered if pt
undergoing
1. Major surgery
2. Spinal puncture
3. Placement of spinal or epidural catheter or port
85. Monitoring anticoagulant effect of dabigatran
• Need not to assess regularly (ex. In the setting of
emergency surgery)
• In emergency most accessible tests are
1. TCT
2. aPTT
• If the TCT is normal, it is safe to assume that the
level of dabigatran is very low and that the
patient’s risk of bleeding development is similar
to that of other patients undergoing the
procedure
86. Antidote
• Specific agent not available
• Though limited data, following agents may be
used
– Activated prothrombin complex concentrate
– Recombinant factor VIIa
– Concentrate of coagulant factors II, IX and X
– Hemodialysis (because only 35% of dabigatran is bound to
plasma proteins)
Protamine sulfate and Vit-K are not helpful
87. Adverse effects
• Bleeding – increases with age
• GI events
– Dyspepsia (12%)
– Abdominal pain
– Gastritis including GERD, esophagitis, erosive gastritis,
gastric hemorrhage and GI ulcers
• Hypersensitivity reaction (<0.1%)
• An unexplained increase in acute myocardial
infarction in the dabigatran group versus warfarin
(~0.2% increased risk for a AMI re-ly trial)
90. Rivaroxaban (Xarelto)
• Direct factor Xa inhibitor
• Half life: 7 - 9 hours
• Peak plasma concentration 0.5 – 3 hours after
administration
• Have excellent bio-availability of 80-100%
• 2/3rd of rivaroxaban is metabolized by CYP3A4
system in liver
• 1/3rd of rivaroxaban excreted unchanged in urine
while ½ of the metabolized excreted renally while
other half via fecal route.
91. • To reduce the risk of DVTs and PEs in patients
undergoing knee or hip replacement surgery
(Jul 1, 2011)
• For prevention of thromboembolism and
stroke in patients with nonvalvular atrial
fibrillation (Nov 4, 2011 )
• Treatment of deep vein thrombosis (DVT) and
pulmonary embolism (PE), as well as to reduce
the risk of recurrent DVT and PE (Nov 2, 2012)
Rivaroxaban: FDA Approval
(First approved in July 1st, 2011)
92. Doses of rivaroxaban
– Therapeutic dose : 20 mg once daily
– Prophylactic dose : 10 mg once daily
• No specific dose adjustment advised in
moderate renal function impairment but it
should be used with caution
• Contraindicated in severe renal impairment
• No dose adjustment required for body weight
95. Apixaban (Eliquis)
• Direct factor Xa inhibitor
• Half life – 8 to 11 hours
• Peak plasma concentration 1 – 3 hours after
administration
• Have excellent bio-availability of 66%
• Metabolized in liver
• 25 % of apixaban is renally excreted, so no dose
adjustment are required in renal failure pts
• 75% excreted by fecal route
96. • Apixaban only partially metabolized by CYP3A4
system, so strong CYP3A4 inhibitor/ inducer may
affect its plasma level but this appears to be
minimal as per its anticoagulants effect are
concerned
• Apixaban is minimally interact with P glycoprotein
hence its effects are not affected significantly.
Hence no clinically significant drug interactions
97. • To reduce the risk of stroke and dangerous
blood clots (systemic embolism) in patients
with atrial fibrillation that is not caused by a
heart valve problem (Dec 28, 2012 )
FDA recommendation
(FDA first approved on Dec. 28, 2012)
98. Recommended Dose
Reduction of Risk of Stroke and Systemic Embolism in
Patients with Nonvalvular Atrial Fibrillation
– The recommended dose of apixaban for most patients is 5 mg
taken orally twice daily.
– The recommended dose is 2.5 mg twice daily in patients with any
2 of the following characteristics:
• age ≥80 years
• body weight ≤60 kg
• serum creatinine ≥1.5 mg/dL
99. Prophylaxis of Deep Vein Thrombosis Following Hip or
Knee Replacement Surgery
The recommended dose is 2.5 mg taken orally twice
daily. The initial dose should be taken 12 to 24 hours
after surgery.
• In patients undergoing hip replacement surgery, the
recommended duration of treatment is 35 days.
• In patients undergoing knee replacement surgery, the
recommended duration of treatment is 12 days.
100. Treatment of DVT and PE
The recommended dose of apixaban is 10 mg taken
orally twice daily for 7 days, followed by 5 mg taken
orally twice daily.
Reduction in the Risk of Recurrence of DVT and PE
The recommended dose of apixaban is 2.5 mg taken
orally twice daily after at least 6 months of treatment
for DVT or PE.
105. Heparin
• In 1916, McLean discovered an anticoagulant
substance in liver.
• In 1918, Howell and Holt named it heparin (due to its
extraction from liver).
• In 1937, heparin was used in clinical practice after
extracting the purified form.
• It is a strong organic acid having molecular weight of
10,000-30,000 Da.
106. • As it is present in the mast cells, it is normally
present in all body tissues, which contain mast
cells.
• Commercially, it is obtained from pig
intestinal mucosa & ox lung.
• It acts as anticoagulant both in vivo & vitro.
• It is also known as unfractionated heparin
(UFH).
107. Mechanism of action
• Heparin binds to antithrombin III (natural
endogenous anticoagulant) and heparin-antithrombin-
III complex is formed.
• This heparin-antithrombin-III complex inactivates the
clotting factors of both intrinsic & common pathway
(XIIa, XIa, IX, Xa, XIIIa, II) by binding to them.
• Thus, the anticoagulant effect is exerted mainly by
inhibition of factor Xa & thrombin mediated
conversion of fibrinogen to fibrin (refer coagulation
cascade).
109. • Only approximately one third of an administered
dose of heparin binds to AT, and this fraction is
responsible for most of its anticoagulant effect.
• The remaining two thirds has minimal anticoagulant
activity at therapeutic concentrations, but at
concentrations greater than those usually obtained
clinically, both high- and low affinity heparin catalyze
the AT effect of a second plasma protein,
heparin cofactor II
110. • The heparin-AT complex inactivates a number of
coagulation enzymes, including
• thrombin factor (IIa) and
• factors Xa, IXa, XIa, and XIIa.
• Thrombin and factor Xa are the most responsive to
inhibition, and human thrombin is 10-fold more
sensitive to inhibition by the heparin-AT complex
than factor Xa.
• For inhibition of thrombin, heparin must bind to
both the coagulation enzyme and AT, but binding to
the enzyme is less important for inhibition of
activated factor X (factor Xa).
111. • Molecules of heparin with fewer than 18
saccharides do not bind simultaneously to thrombin
and AT and therefore are unable to catalyze
thrombin inhibition.
• In contrast, very small heparin fragments containing
the high-affinity pentasaccharide sequence
catalyze inhibition of factor Xa by AT.
• By inactivating thrombin, heparin not only prevents
fibrin formation but also inhibits thrombin-induced
activation of factor V and factor VIII
112.
113. Pharmacological effects of heparin
• As anticoagulant
• As antiplatelet agent: by inhibiting the platelet
aggregation.
• By activating lipoprotein lipase from the
vessels wall & tissues, it acts as lipaemia
clearing agent.
114. Pharmacokinetics
• It is not absorbed by oral route due to its large size &
highly ionized nature.
• Therefore, it is given by IV route (acts immediately)
and subcutaneous route (acts within an hour).
• It does not cross BBB & placenta. Hence, can be given
safely in pregnancy.
• It is metabolized in liver by heparinase enzyme and
excreted through kidneys.
• The plasma t ½ is 1-2 hours and is dose dependent.
• It is prolonged in kidney & liver diseases and shortened
in pulmonary embolism.
115. Dose
Adult: 5000–10,000 IU, IV bolus dose
followed by 750–1000 IU/hr IV infusion.
Children: 50–100 IU/kg.
116. Indications
• Prophylaxis of postoperative venous
thrombosis.
• Post MI.
• Pulmonary embolism.
• Deep venous thrombosis.
• Heparinization of center line & chemo-pods.
117. Adverse effects
• First clinical sign of adverse effect of heparin
is: hematuria.
• The other side effects are
– bleeding,
– thrombocytopenia,
– reversible alopecia,
– osteoporosis,
– hepatotoxicity, and
– rarely hypersensitivity reaction.
118. • Heparin induced thrombocytopenia is a
common entity and was generally manifested
as decreased platelet count. In this condition,
withdrawal of drug is helpful.
• On intramuscular injection, it may cause
hematomas.
• The monitoring of activated partial
thromboplastin time (aPTT) ratio is
mandatory, if the ratio of aPTT is greater than
three, there is increase risk of bleeding.
119. Protamine sulfate (heparin
antagonist)
• It is a strong base and obtained from fish
sperm.
• Protamine sulfate acts as an antidote for
heparin overdose and is given in a dose of 1
mg IV for every 100 IU of heparin.
• It is used after cardiovascular surgeries when
it has been administered in higher doses and
the action needs to be terminated rapidly.
120. Low-molecular-weight heparin
• UH (mw 3k - 30k) is a heterogeneous
mixture of polysacchride chains
(glycosaminoglycans)
• LMWH (mw 5k) is obtained by alkaline
degradation of heparin benzyl ester
• LMWH molecules are enriched with short
chains with higher anti-Xa:IIa ratio
122. Heparin Sodium Injection, USP (porcine), preserved with
benzyl alcohol, is available as follows:
• Each mL of the 5,000 Units per mL preparation
contains:
• 5,000 USP Heparin Units (porcine);
• 6 mg sodium chloride;
• 15 mg benzyl alcohol (as a preservative);
• Water for Injection q.s. Hydrochloric acid
and/or sodium hydroxide may have been added
for pH adjustment (5.0-7.5).
123. Advantages of LMWH over UH
• Decreased “heparin resistance”
– pharmacokinetics of UH are influenced by its
bindings to plasma protein, endothelial cell
surfaces, macrophages, and other acute phase
reactants
– LMWH has decreased binding to
nonanticoagulant-related plasma proteins
124. Advantages of LMWH over UH
• No need for laboratory monitoring
– when given on a weight-adjusted basis, the
LMWH anticoagulant response is predictable and
reproducible
• Higher bioavailability - 90% vs 30%
• Longer plasma half-life
– 4 to 6 hours vs 0.5 to 1 hour
– renal (slower) vs hepatic clearance
125. Advantages of LMWH over UH
• Less inhibition of platelet function
– potentially less bleeding risk, but not shown in
clinical use
• Lower incidence of thrombocytopenia and
thrombosis (HIT syndrome)
– less interaction with platelet factor 4
– fewer heparin-dependent IgG antibodies
126. Monitoring of LMWH
• Unnecessary in majority of patients
• May be useful in specific instances
– renal insufficiency (creatinine >2.0 mg/dl)
– obese patients with altered drug pK
– major bleeding risk factors
• aPTT not useful - low anti-IIa activity
• anti-factor Xa assay is more appropriate, but
not widely available
127. Various LMWHs with dose
Drug Therapeutic Dose Prophylactic Dose
Enoxaparin 1mg/kg, subcutaneously, twice
daily .
20-40 mg, subcutaneously,
once daily.
Deltaparin 200 IU/kg subcutaneously, once
daily.
2500 IU subcutaneously, once
daily.
Parnaparin 6400 IU subcutaneously, once
daily.
3200 IU subcutaneously, once
daily.
Reviparin 3436 IU subcutaneously, once
daily.
0.25 mL (1432 IU)
subcutaneously, once daily.
Ardeparin 2500-5000 IU subcutaneously,
once daily.
2500 IU subcutaneously, once
daily.
Nadroparin 4000-6000 IU subcutaneously,
once daily/ twice daily.
3000 IU subcutaneously, once
daily/ twice daily.
Tinzaparin 3500 IU subcutaneously, once
daily.
1700 IU subcutaneously, once
daily.
*All are available in prefilled syringes forms.
128. Indications of LMWHs
• Prophylaxis of deep venous thrombosis (DVT)
in immobilized patients such as post-surgical
or coma patients.
• Post MI .
• Prophylaxis of pulmonary embolism.
• Treatment of deep venous thrombosis.
• For the maintenance of patency of cannula in
dialysis patient, centre line & chemo-pods.
129. Fondaparinux
• It is a synthetic derivative of heparin.
• It has pharmacological similarity to LMWHs with
longer plasma half-life (17-21 hours).
• It has 100% bioavailability.
• It is given in a dose of 5-10mg SC, OD.
• The adverse effects like thrombocytopenia &
osteoporosis are even lesser than LMWHs.
• Idraparinux is an ultra long acting derivative of
fondaparinux with t ½ of 5-6 days.
130. Danaparoid
• It is a mixture of heparin like natural
substances (84% heparin sulfate +12%
dermatan salfate + 4% chondroitin sulfate).
• It is obtained from pig intestinal mucosa.
• It has longer plasma t ½ of 24 hours.
• It is used in patient with heparin induced
thrombocytopenia as an alternative therapy.
132. Lepirudin
• It is a recombinant preparation of hirudin.
• It inhibits thrombin directly.
• Indicated in heparin induced
thrombocytopenia.
• It cannot be given repeatedly due to formation
of anti-hirudin antibodies and higher risk of
anaphylaxis.
• There is no antidote available against
lepirudin.
133. Bivalirudin
• Synthetic analogue of hirudin with
pharmacological actions similar to lepirudin.
• It has fast onset & offset of action due to its
reversible binding nature.
• It does not form anti-hirudin antibodies.
134. Argatroban
• It is a reversible direct thrombin inhibitor and
given by IV infusion.
• It is used in-patients with heparin-induced
thrombocytopenia as an alternative therapy.