Botanicals (Herbal Medications) & Nutritional Supplements discusses botanicals and dietary supplements. It provides an overview of their historical use and regulation in the US. Specifically, it discusses Echinacea and Garlic, covering their chemistry, pharmacologic effects, clinical trials, adverse effects, interactions and dosing. For Echinacea, it summarizes that while some trials found it reduced cold symptoms, recent ones using different species found no benefit. For both, it emphasizes the need for more research on safety and efficacy.
This document discusses angiotensin receptor blockers (ARBs) which are used to treat hypertension and other cardiovascular conditions. It notes that ARBs work by competitively blocking the angiotensin receptor type 1, leading to vasodilation and other effects. Some examples of individual ARB drugs are provided like losartan, candesartan, and valsartan. The document compares ARBs to ACE inhibitors, noting that ARBs do not cause cough like ACE inhibitors. It concludes by discussing the theoretical rationale and benefits of combining ARBs with ACE inhibitors to more completely suppress the renin-angiotensin system.
This document discusses drugs that inhibit the renin-angiotensin system for treating hypertension and other conditions. It describes how ACE inhibitors work by inhibiting the angiotensin converting enzyme and decreasing angiotensin II formation, while also increasing bradykinin levels. Angiotensin receptor blockers competitively block the angiotensin II receptor. Both classes lower blood pressure by vasodilation and reduced sodium retention. They are used to treat hypertension, heart failure, diabetic nephropathy, and myocardial infarction. Adverse effects include hypotension, hyperkalemia, and cough with ACE inhibitors.
This document discusses different classes of diuretic drugs, including their mechanisms of action, examples, and side effects. The main classes covered are:
1. Salidiuretics (thiazides) such as hydrochlorothiazide which increase sodium and chloride excretion in the distal renal tubules.
2. Loop diuretics such as furosemide which act on the ascending limb of Henle's loop to increase excretion of sodium, chloride, magnesium and calcium.
3. Carbonic anhydrase inhibitors like acetazolamide which inhibit the enzyme carbonic anhydrase in the kidneys and other tissues.
4. Potassium-sparing diuretics including sp
This document discusses angiotensin converting enzyme (ACE) inhibitors, which are a class of drugs used to treat hypertension and other cardiovascular conditions. It first provides background on hypertension and its classification. It then explains that ACE is responsible for converting angiotensin I to the potent vasoconstrictor angiotensin II, and for breaking down bradykinin. ACE inhibitors work by decreasing angiotensin II production and increasing bradykinin levels, resulting in vasodilation. Common ACE inhibitors listed include captopril, enalapril, and lisinopril. The document notes ACE inhibitors are used to treat hypertension, heart failure, myocardial infarction, and diabetic neuropathy,
Hypertension is a major health problem affecting 25% of adults and 50% of those over 60. It causes dangerous complications like heart attack, heart failure, stroke, and renal failure. The causes are mostly unknown except for 5% of secondary cases. Lifestyle modifications like reduced salt and fat intake, weight loss, exercise, and stopping smoking are beneficial for reducing blood pressure and complications. There are several classes of antihypertensive drugs that work through different mechanisms like reducing blood volume and pressure, blocking nerve signals, dilating blood vessels, and inhibiting hormone systems. The choice of drugs depends on individual patient factors and risks.
1. Angiotensin converting enzyme inhibitors (ACEIs) block the conversion of angiotensin I to angiotensin II, inhibiting the renin-angiotensin system.
2. ACEIs are used to treat hypertension, congestive heart failure, myocardial infarction, diabetic nephropathy, and scleroderma renal crisis.
3. Common adverse effects of ACEIs include hypotension, cough, and hyperkalemia. ACEIs are contraindicated in pregnancy and bilateral renal artery stenosis due to risks of hypotension, renal failure, and fetal complications.
introduction to oral hypoglycemic agents with description about sulphonylurea and glinides along with their MOA, indication, side effects and brand name
This document discusses angiotensin receptor blockers (ARBs) which are used to treat hypertension and other cardiovascular conditions. It notes that ARBs work by competitively blocking the angiotensin receptor type 1, leading to vasodilation and other effects. Some examples of individual ARB drugs are provided like losartan, candesartan, and valsartan. The document compares ARBs to ACE inhibitors, noting that ARBs do not cause cough like ACE inhibitors. It concludes by discussing the theoretical rationale and benefits of combining ARBs with ACE inhibitors to more completely suppress the renin-angiotensin system.
This document discusses drugs that inhibit the renin-angiotensin system for treating hypertension and other conditions. It describes how ACE inhibitors work by inhibiting the angiotensin converting enzyme and decreasing angiotensin II formation, while also increasing bradykinin levels. Angiotensin receptor blockers competitively block the angiotensin II receptor. Both classes lower blood pressure by vasodilation and reduced sodium retention. They are used to treat hypertension, heart failure, diabetic nephropathy, and myocardial infarction. Adverse effects include hypotension, hyperkalemia, and cough with ACE inhibitors.
This document discusses different classes of diuretic drugs, including their mechanisms of action, examples, and side effects. The main classes covered are:
1. Salidiuretics (thiazides) such as hydrochlorothiazide which increase sodium and chloride excretion in the distal renal tubules.
2. Loop diuretics such as furosemide which act on the ascending limb of Henle's loop to increase excretion of sodium, chloride, magnesium and calcium.
3. Carbonic anhydrase inhibitors like acetazolamide which inhibit the enzyme carbonic anhydrase in the kidneys and other tissues.
4. Potassium-sparing diuretics including sp
This document discusses angiotensin converting enzyme (ACE) inhibitors, which are a class of drugs used to treat hypertension and other cardiovascular conditions. It first provides background on hypertension and its classification. It then explains that ACE is responsible for converting angiotensin I to the potent vasoconstrictor angiotensin II, and for breaking down bradykinin. ACE inhibitors work by decreasing angiotensin II production and increasing bradykinin levels, resulting in vasodilation. Common ACE inhibitors listed include captopril, enalapril, and lisinopril. The document notes ACE inhibitors are used to treat hypertension, heart failure, myocardial infarction, and diabetic neuropathy,
Hypertension is a major health problem affecting 25% of adults and 50% of those over 60. It causes dangerous complications like heart attack, heart failure, stroke, and renal failure. The causes are mostly unknown except for 5% of secondary cases. Lifestyle modifications like reduced salt and fat intake, weight loss, exercise, and stopping smoking are beneficial for reducing blood pressure and complications. There are several classes of antihypertensive drugs that work through different mechanisms like reducing blood volume and pressure, blocking nerve signals, dilating blood vessels, and inhibiting hormone systems. The choice of drugs depends on individual patient factors and risks.
1. Angiotensin converting enzyme inhibitors (ACEIs) block the conversion of angiotensin I to angiotensin II, inhibiting the renin-angiotensin system.
2. ACEIs are used to treat hypertension, congestive heart failure, myocardial infarction, diabetic nephropathy, and scleroderma renal crisis.
3. Common adverse effects of ACEIs include hypotension, cough, and hyperkalemia. ACEIs are contraindicated in pregnancy and bilateral renal artery stenosis due to risks of hypotension, renal failure, and fetal complications.
introduction to oral hypoglycemic agents with description about sulphonylurea and glinides along with their MOA, indication, side effects and brand name
CARE OF PAEDIATRIC, GERIATRIC, PREGNANT AND LACTATING Ramesh Ganpisetti
This document discusses care considerations for several patient populations: paediatric/geriatric patients, pregnant/lactating women. It outlines key pharmacokinetic changes for each group like decreased absorption, distribution, metabolism and excretion in paediatric/geriatric patients. In pregnancy, it notes increased volume and altered absorption, distribution, elimination. Risks of drug transfer to fetus/breastmilk are also covered. The document recommends avoiding certain drugs in pregnancy/lactation and tailored dosing for paediatric/geriatric patients due to their physiological differences.
Sulfonylureas for Diabetes: A deep insightRxVichuZ
This powerpoint presentation solely deals with Sulfonylureas, that come under Insulin secretagogues. Their complete pharmacological profile, with pharmacovigilance parameters, important catchpoints and mnemonics have been explained.
This document discusses cardiac glycosides, a class of organic compounds that increase the force of heart contractions and decrease the heart rate. It notes that digoxin, digitoxin, bufotoxin, and ouabain are examples obtained from plants like Digitalis lanata and toad skin. The document explains that cardiac glycosides act on the sodium-potassium ATPase pump, directly affecting myocardial contractility and mildly constricting blood vessels. While having little effect on the central nervous system, they can cause diuresis in congestive heart failure patients. The document outlines mechanisms of action and lists arrhythmias and other adverse effects, then discusses uses and interactions with other drugs.
The osmolarity limit for peripheral parenteral nutrition (PPN) formulas is between 600 and 900 mOsm. Higher osmolarity solutions above 1100 mOsm can be used if lipid emulsion is added, but this is not recommended for patients with high triglycerides. Alternatively, hydrocortisone and heparin can be added to solutions up to 1200 mOsm to prevent phlebitis. The typical PPN composition provides amino acids between 2.5-5% and dextrose concentrations around 25 g/L due to limitations in osmolarity.
This document discusses hematinics, which are nutrients that help form blood cells. It defines hematinics as iron, vitamin B12, and folate, and notes deficiencies can cause anemia. Various oral and parenteral hematinic preparations are listed, along with side effects like constipation. Interactions between hematinics and other drugs are described, such as penicillamine decreasing iron absorption. Hematopoietic growth factors that stimulate red blood cell production, like erythropoietin, are also mentioned.
Hypertension is defined as a systolic blood pressure over 140 mmHg or a diastolic blood pressure over 90 mmHg. It can be caused by environmental factors like stress, high sodium intake, smoking, and obesity. Antihypertensive drugs work through various mechanisms like diuretics which increase sodium excretion, ACE inhibitors which inhibit angiotensin II synthesis, and calcium channel blockers which relax smooth muscles. Lifestyle modifications and medication are important to control blood pressure and prevent complications of hypertension like heart disease and stroke.
- Oral contraceptives were first approved in the 1960s and became the most popular form of birth control by 1965. They contain hormones that prevent pregnancy by blocking ovulation and thickening cervical mucus.
- There are two main types - combined pills containing estrogen and progestin, and progestin-only pills. Combined pills are available in monophasic or multiphasic formulations, while progestin-only pills are taken continuously.
- Oral contraceptives work by preventing ovulation, thickening cervical mucus, and thinning the uterine lining. Potential side effects include weight gain, nausea and mood changes, while benefits include reduced menstrual cramps and prevention of certain cancers. Interactions with some antibiotics
Furosemide is a loop diuretic that works by inhibiting sodium and chloride reabsorption in the ascending limb of the loop of Henle, leading to increased excretion of sodium, chloride, calcium, and water from the body. It is commonly used to treat fluid retention, edema, and hypertension. Some key points are that it acts more rapidly than thiazide diuretics, can be used in patients with renal impairment, and causes diuretic effects within 0.5-1 hour when taken orally. Common side effects include hypokalemia, hypomagnesaemia, and ototoxicity when combined with other drugs.
Autacoids are endogenous compounds that act as local hormones near their site of synthesis. They have short half-lives and include substances like histamine, serotonin, prostaglandins, and kinins. Autacoids are involved in processes like inflammation, allergic reactions, neurotransmission, and gastric acid secretion. Histamine promotes smooth muscle contraction and gastric acid secretion by interacting with H1 and H2 receptors. Serotonin is derived from tryptophan and is found in the GI tract, blood platelets, and CNS, where it contributes to feelings of well-being. H1 receptor antagonists are used to treat allergic reactions while H2 receptor antagonists reduce gastric acid secretion and treat ulcers.
This document discusses diabetes mellitus and insulin. It defines diabetes as a metabolic disorder characterized by chronic hyperglycemia resulting from defects in insulin secretion or action. It notes diabetes is associated with risks of late complications affecting the eyes, kidneys, nerves, and cardiovascular system. The document outlines diagnostic criteria for diabetes and classifications including type 1, type 2, gestational, and secondary forms. It describes complications of diabetes such as retinopathy, kidney failure, heart disease, and neuropathy. The document discusses insulin, its structure, biosynthesis, and mechanisms of action. It provides details on six classes of oral medications used to treat diabetes, including how sulfonylureas, biguanides, thiazolidinediones, alpha-
Atarax (hydroxyzine hydrochloride) is an antihistamine used to treat itching from conditions like hives and eczema. It is also used to treat anxiety and as premedication for dental procedures. It works by blocking histamine receptors. Atarax tablets come in 10mg or 25mg doses and should be stored at room temperature between 15-30 degrees Celsius. Common side effects include dry mouth and drowsiness. Atarax can interact with other CNS depressants and its use requires caution in certain conditions.
This document discusses antibiotic dosing during renal failure. It explains the importance of dose adjustments with renal impairment due to decreased drug elimination. It compares methods to calculate glomerular filtration rate (GFR) and creatinine clearance, such as the Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault equations. It also describes different types of dialysis and considerations for dosing antibiotics in patients receiving dialysis or continuous renal replacement therapy.
Pharmacology is the study of drugs and their interactions with living systems. It includes how drugs act at molecular and whole body levels, their therapeutic effects as well as side effects. Key aspects of pharmacology include pharmacodynamics, which examines how drugs act on the body, and pharmacokinetics, which examines what the body does to drugs. Drugs primarily act by interacting with receptors or through nonspecific chemical interactions, altering enzyme activity or having antimetabolite effects. Understanding how drugs are absorbed, distributed, metabolized and excreted is crucial to predicting their effects.
Diabetes Mellitus and Oral antidiabetic agents - quick review228amna
This document provides information about sulfonylurea oral antidiabetic drugs. It begins with an introduction to diabetes mellitus and oral antidiabetic agents. It then discusses sulfonylureas in detail, including their classification, mechanisms of action, pharmacokinetics, drug interactions, contraindications, and adverse effects. Sulfonylureas are insulin secretagogues that stimulate insulin release from the pancreas and decrease blood glucose levels. They include first-generation drugs like tolbutamide and second-generation drugs like glyburide and glipizide.
The document discusses various factors used to determine drug dosages for pediatric and geriatric patients, including age, weight, body surface area, and medical condition. It provides examples of calculating dosages based on these factors and describes special considerations for cancer chemotherapy dosing, such as using standard regimens, abbreviations for drugs, and dosing based on body weight or surface area.
This presentation discusses the calcium and vitamin D supplement Caldolin. It contains calcium carbonate which maintains calcium homeostasis and helps form bone mass. It also contains vitamin D3 which ensures calcium absorption, decreases bone resorption, and promotes bone mineralization. Caldolin is recommended as a dietary supplement for those with inadequate calcium intake, including during pregnancy, lactation, menopause, and for the aged. It can also treat calcium deficiency states like osteoporosis, osteomalacia, and rickets. The presentation provides dosage instructions and notes possible side effects like constipation or diarrhea. It concludes with market information on leading calcium supplements in Bangladesh.
Diuretics
Pharmacology
Katzung
Abnormalities in fluid volume and electrolyte composition are common and important clinical disorders. Drugs that block specific transport functions of the renal tubules are valuable clinical tools in the treatment of these disorders. Although various agents that increase urine volume (diuretics) have been described since antiquity, it was not until 1937 that carbonic anhydrase inhibitors were first described and not until 1957 that a much more useful and powerful diuretic agent (chlorothiazide) became available. Technically, a “diuretic” is an agent that increases urine volume, whereas a “natriuretic” causes an increase in renal sodium excretion and an “aquaretic” increases excretion of solute-free water. Because natriuretics almost always also increase water excretion, they are usually called diuretics. Osmotic diuretics and antidiuretic hormone antagonists (see Agents That Alter Water Excretion) are aquaretics that are not directly natriuretic.
Renin Angiotensin Aldosterone System and its applicationsDrSahilKumar
This document provides an overview of the renin angiotensin system (RAS) and its applications. It discusses the history and components of the RAS, including renin, angiotensinogen, angiotensin peptides, and angiotensin receptors. It also summarizes the effects of the RAS and drugs that act on it, such as ACE inhibitors, ARBs, direct renin inhibitors, and aldosterone antagonists. The document provides details on the mechanisms, pharmacokinetics, uses, and side effects of these drug classes for conditions like hypertension, heart failure, and diabetic nephropathy.
This document summarizes different types of drugs used to treat diabetes mellitus. It discusses insulin, the main types of which include rapid-acting, short-acting, intermediate-acting, and long-acting insulins. It also discusses oral hypoglycemic drugs that help control blood sugar levels, including sulfonylureas that stimulate insulin secretion, biguanides that overcome insulin resistance, and others such as alpha-glucosidase inhibitors. New drug classes are also mentioned, like GLP-1 receptor agonists and DPP-4 inhibitors that enhance the body's own insulin response after meals. The document provides details on the mechanisms and examples of specific drugs within each class.
This document discusses phytochemicals, herbal supplements, and dietary supplements. It notes that while some herbal supplements have promising effects in preclinical studies, clinical evidence is often limited due to flaws in study design and placebo effects. It also describes regulations around supplements in the US that classify them as dietary rather than medicinal products, limiting required evidence of efficacy and safety. Key herbal supplements like echinacea, garlic, and ginkgo are then discussed in more detail.
Herbal Medicine : Effect of clinical laboratory test Sarvan Mani
This document summarizes how herbal medicines can interfere with clinical laboratory tests in three main ways: direct assay interference, physiological effects of toxicity/enzyme induction, and contamination with undisclosed drugs. It provides the specific example of how the Chinese herbal medicine Chan Su can cause falsely elevated digoxin levels due to cross-reactivity in immunoassays that use polyclonal antibodies against digoxin. The document also notes that herbal medicines are widely used but loosely regulated in the United States and discusses the importance of communication between clinicians and laboratories when interpreting abnormal laboratory results in patients using herbal medicines.
CARE OF PAEDIATRIC, GERIATRIC, PREGNANT AND LACTATING Ramesh Ganpisetti
This document discusses care considerations for several patient populations: paediatric/geriatric patients, pregnant/lactating women. It outlines key pharmacokinetic changes for each group like decreased absorption, distribution, metabolism and excretion in paediatric/geriatric patients. In pregnancy, it notes increased volume and altered absorption, distribution, elimination. Risks of drug transfer to fetus/breastmilk are also covered. The document recommends avoiding certain drugs in pregnancy/lactation and tailored dosing for paediatric/geriatric patients due to their physiological differences.
Sulfonylureas for Diabetes: A deep insightRxVichuZ
This powerpoint presentation solely deals with Sulfonylureas, that come under Insulin secretagogues. Their complete pharmacological profile, with pharmacovigilance parameters, important catchpoints and mnemonics have been explained.
This document discusses cardiac glycosides, a class of organic compounds that increase the force of heart contractions and decrease the heart rate. It notes that digoxin, digitoxin, bufotoxin, and ouabain are examples obtained from plants like Digitalis lanata and toad skin. The document explains that cardiac glycosides act on the sodium-potassium ATPase pump, directly affecting myocardial contractility and mildly constricting blood vessels. While having little effect on the central nervous system, they can cause diuresis in congestive heart failure patients. The document outlines mechanisms of action and lists arrhythmias and other adverse effects, then discusses uses and interactions with other drugs.
The osmolarity limit for peripheral parenteral nutrition (PPN) formulas is between 600 and 900 mOsm. Higher osmolarity solutions above 1100 mOsm can be used if lipid emulsion is added, but this is not recommended for patients with high triglycerides. Alternatively, hydrocortisone and heparin can be added to solutions up to 1200 mOsm to prevent phlebitis. The typical PPN composition provides amino acids between 2.5-5% and dextrose concentrations around 25 g/L due to limitations in osmolarity.
This document discusses hematinics, which are nutrients that help form blood cells. It defines hematinics as iron, vitamin B12, and folate, and notes deficiencies can cause anemia. Various oral and parenteral hematinic preparations are listed, along with side effects like constipation. Interactions between hematinics and other drugs are described, such as penicillamine decreasing iron absorption. Hematopoietic growth factors that stimulate red blood cell production, like erythropoietin, are also mentioned.
Hypertension is defined as a systolic blood pressure over 140 mmHg or a diastolic blood pressure over 90 mmHg. It can be caused by environmental factors like stress, high sodium intake, smoking, and obesity. Antihypertensive drugs work through various mechanisms like diuretics which increase sodium excretion, ACE inhibitors which inhibit angiotensin II synthesis, and calcium channel blockers which relax smooth muscles. Lifestyle modifications and medication are important to control blood pressure and prevent complications of hypertension like heart disease and stroke.
- Oral contraceptives were first approved in the 1960s and became the most popular form of birth control by 1965. They contain hormones that prevent pregnancy by blocking ovulation and thickening cervical mucus.
- There are two main types - combined pills containing estrogen and progestin, and progestin-only pills. Combined pills are available in monophasic or multiphasic formulations, while progestin-only pills are taken continuously.
- Oral contraceptives work by preventing ovulation, thickening cervical mucus, and thinning the uterine lining. Potential side effects include weight gain, nausea and mood changes, while benefits include reduced menstrual cramps and prevention of certain cancers. Interactions with some antibiotics
Furosemide is a loop diuretic that works by inhibiting sodium and chloride reabsorption in the ascending limb of the loop of Henle, leading to increased excretion of sodium, chloride, calcium, and water from the body. It is commonly used to treat fluid retention, edema, and hypertension. Some key points are that it acts more rapidly than thiazide diuretics, can be used in patients with renal impairment, and causes diuretic effects within 0.5-1 hour when taken orally. Common side effects include hypokalemia, hypomagnesaemia, and ototoxicity when combined with other drugs.
Autacoids are endogenous compounds that act as local hormones near their site of synthesis. They have short half-lives and include substances like histamine, serotonin, prostaglandins, and kinins. Autacoids are involved in processes like inflammation, allergic reactions, neurotransmission, and gastric acid secretion. Histamine promotes smooth muscle contraction and gastric acid secretion by interacting with H1 and H2 receptors. Serotonin is derived from tryptophan and is found in the GI tract, blood platelets, and CNS, where it contributes to feelings of well-being. H1 receptor antagonists are used to treat allergic reactions while H2 receptor antagonists reduce gastric acid secretion and treat ulcers.
This document discusses diabetes mellitus and insulin. It defines diabetes as a metabolic disorder characterized by chronic hyperglycemia resulting from defects in insulin secretion or action. It notes diabetes is associated with risks of late complications affecting the eyes, kidneys, nerves, and cardiovascular system. The document outlines diagnostic criteria for diabetes and classifications including type 1, type 2, gestational, and secondary forms. It describes complications of diabetes such as retinopathy, kidney failure, heart disease, and neuropathy. The document discusses insulin, its structure, biosynthesis, and mechanisms of action. It provides details on six classes of oral medications used to treat diabetes, including how sulfonylureas, biguanides, thiazolidinediones, alpha-
Atarax (hydroxyzine hydrochloride) is an antihistamine used to treat itching from conditions like hives and eczema. It is also used to treat anxiety and as premedication for dental procedures. It works by blocking histamine receptors. Atarax tablets come in 10mg or 25mg doses and should be stored at room temperature between 15-30 degrees Celsius. Common side effects include dry mouth and drowsiness. Atarax can interact with other CNS depressants and its use requires caution in certain conditions.
This document discusses antibiotic dosing during renal failure. It explains the importance of dose adjustments with renal impairment due to decreased drug elimination. It compares methods to calculate glomerular filtration rate (GFR) and creatinine clearance, such as the Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault equations. It also describes different types of dialysis and considerations for dosing antibiotics in patients receiving dialysis or continuous renal replacement therapy.
Pharmacology is the study of drugs and their interactions with living systems. It includes how drugs act at molecular and whole body levels, their therapeutic effects as well as side effects. Key aspects of pharmacology include pharmacodynamics, which examines how drugs act on the body, and pharmacokinetics, which examines what the body does to drugs. Drugs primarily act by interacting with receptors or through nonspecific chemical interactions, altering enzyme activity or having antimetabolite effects. Understanding how drugs are absorbed, distributed, metabolized and excreted is crucial to predicting their effects.
Diabetes Mellitus and Oral antidiabetic agents - quick review228amna
This document provides information about sulfonylurea oral antidiabetic drugs. It begins with an introduction to diabetes mellitus and oral antidiabetic agents. It then discusses sulfonylureas in detail, including their classification, mechanisms of action, pharmacokinetics, drug interactions, contraindications, and adverse effects. Sulfonylureas are insulin secretagogues that stimulate insulin release from the pancreas and decrease blood glucose levels. They include first-generation drugs like tolbutamide and second-generation drugs like glyburide and glipizide.
The document discusses various factors used to determine drug dosages for pediatric and geriatric patients, including age, weight, body surface area, and medical condition. It provides examples of calculating dosages based on these factors and describes special considerations for cancer chemotherapy dosing, such as using standard regimens, abbreviations for drugs, and dosing based on body weight or surface area.
This presentation discusses the calcium and vitamin D supplement Caldolin. It contains calcium carbonate which maintains calcium homeostasis and helps form bone mass. It also contains vitamin D3 which ensures calcium absorption, decreases bone resorption, and promotes bone mineralization. Caldolin is recommended as a dietary supplement for those with inadequate calcium intake, including during pregnancy, lactation, menopause, and for the aged. It can also treat calcium deficiency states like osteoporosis, osteomalacia, and rickets. The presentation provides dosage instructions and notes possible side effects like constipation or diarrhea. It concludes with market information on leading calcium supplements in Bangladesh.
Diuretics
Pharmacology
Katzung
Abnormalities in fluid volume and electrolyte composition are common and important clinical disorders. Drugs that block specific transport functions of the renal tubules are valuable clinical tools in the treatment of these disorders. Although various agents that increase urine volume (diuretics) have been described since antiquity, it was not until 1937 that carbonic anhydrase inhibitors were first described and not until 1957 that a much more useful and powerful diuretic agent (chlorothiazide) became available. Technically, a “diuretic” is an agent that increases urine volume, whereas a “natriuretic” causes an increase in renal sodium excretion and an “aquaretic” increases excretion of solute-free water. Because natriuretics almost always also increase water excretion, they are usually called diuretics. Osmotic diuretics and antidiuretic hormone antagonists (see Agents That Alter Water Excretion) are aquaretics that are not directly natriuretic.
Renin Angiotensin Aldosterone System and its applicationsDrSahilKumar
This document provides an overview of the renin angiotensin system (RAS) and its applications. It discusses the history and components of the RAS, including renin, angiotensinogen, angiotensin peptides, and angiotensin receptors. It also summarizes the effects of the RAS and drugs that act on it, such as ACE inhibitors, ARBs, direct renin inhibitors, and aldosterone antagonists. The document provides details on the mechanisms, pharmacokinetics, uses, and side effects of these drug classes for conditions like hypertension, heart failure, and diabetic nephropathy.
This document summarizes different types of drugs used to treat diabetes mellitus. It discusses insulin, the main types of which include rapid-acting, short-acting, intermediate-acting, and long-acting insulins. It also discusses oral hypoglycemic drugs that help control blood sugar levels, including sulfonylureas that stimulate insulin secretion, biguanides that overcome insulin resistance, and others such as alpha-glucosidase inhibitors. New drug classes are also mentioned, like GLP-1 receptor agonists and DPP-4 inhibitors that enhance the body's own insulin response after meals. The document provides details on the mechanisms and examples of specific drugs within each class.
This document discusses phytochemicals, herbal supplements, and dietary supplements. It notes that while some herbal supplements have promising effects in preclinical studies, clinical evidence is often limited due to flaws in study design and placebo effects. It also describes regulations around supplements in the US that classify them as dietary rather than medicinal products, limiting required evidence of efficacy and safety. Key herbal supplements like echinacea, garlic, and ginkgo are then discussed in more detail.
Herbal Medicine : Effect of clinical laboratory test Sarvan Mani
This document summarizes how herbal medicines can interfere with clinical laboratory tests in three main ways: direct assay interference, physiological effects of toxicity/enzyme induction, and contamination with undisclosed drugs. It provides the specific example of how the Chinese herbal medicine Chan Su can cause falsely elevated digoxin levels due to cross-reactivity in immunoassays that use polyclonal antibodies against digoxin. The document also notes that herbal medicines are widely used but loosely regulated in the United States and discusses the importance of communication between clinicians and laboratories when interpreting abnormal laboratory results in patients using herbal medicines.
Clinical trials and drug discovery & development 01-03-2011nadirqureshi996
The document discusses the multi-step process of new drug development from pre-clinical testing through clinical trials. It describes how drugs are initially tested in vitro and in animals to assess safety and efficacy before beginning human trials. The process involves early discussions with regulatory agencies, animal and short/long-term toxicity testing, and takes an average of 8.5 years before a drug can be approved.
The document discusses drug discovery and the new drug development process. It describes how drugs are developed to treat diseases, which can be infections, genetic disorders, or results of environmental conditions. The development process is long and complex, involving many scientific and technical experts. The document also provides numerous examples of plant-based drugs and the plants and chemicals they are derived from to treat various medical conditions.
This document discusses herbal cough remedies and regulation of herbal medicines. It provides epidemiological data showing widespread use of herbal medicines globally, with up to 80% of the population in Africa using traditional herbal medicine. Herbal medicines account for a significant portion of the pharmaceutical market. The document then reviews WHO guidelines for quality, safety and efficacy assessment of herbal medicines and compares regulation standards between countries like Germany, Egypt, and the United States. It also lists some common herbal cough remedies available in Egypt.
This document discusses pharmacovigilance as it relates to herbal medications. It defines pharmacovigilance and outlines its goals of improving patient safety, public health, and risk assessment of medicines. It then discusses specific challenges in monitoring the safety of herbal medicines, including quality control issues due to their complex chemical profiles. Several methods for herbal pharmacovigilance are described, including spontaneous adverse event reporting, prescription event monitoring, and reporting by herbal practitioners. Some herbs with known safety risks are highlighted as examples.
Following file comprises of information about interactions taking place between herbs-drug, herbs-herbs, it also highlights some of the cases of clinical laboratory test interactions taking place due to use of herbal medicines.
Phytochemical, Antioxidant and Antibacterial Studies on Bambusa arundinacea a...SUS GROUP OF INSTITUTIONS
This study was formulated to check the phytochemical, antioxidant, antibacterial potential of
Bambusa arundinacea (Bamboo) and Mangifera indica (Mango) trees. Aqueous, ethanolic and
methanolic extracts were prepared from leaves of former and stem bark of later. The phytochemical
screening of the extracts showed the presence of various bioactive compounds such as
carbohydrates, flavonoids, saponins and proteins in B. arundinacea, alkaloids, flavonoids, tannins,
saponins, steroids and cardiac glycosides in M. indica. Total phenolic concentration and
percentage of free radical scavenging activity was more in ethanolic extracts of B. arundinacea and
M. indica followed by methanolic extracts and aqueous extracts. Highest percentage of ferric
reducing antioxidant power was found in ethanolic extracts and lowest in aqueous extracts indicates
that ethanolic extracts has more antioxidant potential than the other two extracts. Ethanolic extracts
of both plants had higher inhibition on the tested Gram positive (B. subtilis & S. aureus) as well as
Gram negative (E.coli & P. aeruginosa) bacteria evidenced from the zones of inhibition. M. indica
showed more therapeutic potential as compared to B. arundinacea and ethanolic as well as
methanolic extracts of both the tested plants were more effective than aqueous extracts due to better
extraction power of organic solvents. Overall study indicates that B. arundinacea and M. indica are
potential source of natural antioxidants, phytochemicals and antibacterials that can be used for the
development of novel drugs and may represent new source of antimicrobials with stable, biologically
active components that can establish a scientific base for further use in modern medicines.
This document discusses nutraceuticals and their potential uses. It begins by classifying nutraceuticals into nutrients, herbals/phytochemicals, and dietary supplements. It then discusses some specific nutraceuticals like artichoke extract, green tea catechins, and apple extracts, outlining their bioactive components and potential health benefits such as cholesterol lowering, antioxidant effects, and neuroprotective properties. The document also discusses using nutraceuticals like apple varieties to help treat metabolic syndrome and compares this approach to using atorvastatin.
Turmeric is a plant that has been used for thousands of years for its potential anti-inflammatory properties. The active compound in turmeric is curcumin, which some studies have shown can inhibit inflammation through various pathways in the body. However, curcumin has poor absorption into the bloodstream when taken orally, and more research is still needed to determine if turmeric provides clear anti-inflammatory benefits to humans without risks like increased cancer risk. The document analyzes the pharmacology, uses, risks and limitations of using turmeric as an anti-inflammatory therapy.
HydroCurcTM is a product containing curcuminoids, which are chemical compounds derived from turmeric. Curcuminoids such as curcumin are known to have various biological activities including antioxidant and anti-inflammatory properties. Research has shown curcuminoids may help reduce the risk of diseases like cancer and cardiovascular disease. However, curcumin itself has poor bioavailability and stability, limiting its potential medical uses. New formulations are being developed to improve the bioavailability of curcuminoids.
This presentation was made in Sept 2010 at Manila during the Poultry show. Target audience were nutritionists , poultry consultants and feed manufacturers
1) Phytotherapy can pose safety risks due to intrinsically toxic phytoconstituents, excessive ingestion, or interactions with other medicines.
2) Toxic phytoconstituents include aristolochic acids, β-asarone, estragole, pyrrolizidine alkaloids, and lectins. Excessive ingestion of ginseng, liquorice, or parsley can also cause adverse effects.
3) Interactions between herbal medicines like St. John's Wort and conventional drugs like oral contraceptives or HIV protease inhibitors can reduce the therapeutic effects of those drugs. Proper regulation and safety studies of herbal medicines are needed.
Pharmacological and Biochemical Action of Angelica Sinensis (Dong Quai): Natu...paperpublications3
This document summarizes the history, traditional uses, major constituents, and pharmacological actions of Angelica sinensis (Dong Quai). It has been used in traditional Chinese medicine for thousands of years to treat various women's health issues. The main active compounds include phthalides (like ligustilide), ferulic acid, polysaccharides, and coumarins. Preclinical studies have shown Dong Quai extracts have anti-inflammatory, estrogenic, anticancer and neuroprotective effects. However, clinical evidence is limited and it can interact with drugs or cause side effects like headaches. More research is still needed to validate its therapeutic potential and safety.
Pharmacovigilance of drugs of natural origin.pdfKipaPape
PHARMACOVIGILANCE OF DRUGS OF NATURAL ORIGIN.
WHO AND AYUSH GUIDELINES FOR SAFETY MONITORING OF NATURAL MEDICINE.
SPONTANEOUS REPORTING SCHEMES FOR BIODRUG ADVERSE REACTIONS
BIO DRUG-DRUG AND BIO DRUG-FOOD INTERACTIONS WITH SUITABLE EXAMPLES
Herbal medicine safety studies at the NTPAbraham Nyska
The document discusses several 2-year cancer studies conducted by the National Toxicology Program (NTP) on common herbal supplements. The studies found:
1) Goldenseal caused liver cancer in rats and mice. Its active component berberine tested positive for genetic toxicity.
2) Ginkgo biloba extract caused liver and thyroid cancer in mice and thyroid tumors in rats. It contains compounds that tested positive for mutagenicity.
3) Kava kava extract study results are not discussed but the study was conducted similarly to the others.
The document provides details on the study designs and tumor findings for each supplement. It emphasizes that herbal medicines contain complex mixtures that can have carcin
Regulatory requirements on herbal drugs understading the global perspectivessuserd3ff07
This document discusses regulatory requirements for herbal drugs from a global perspective. It outlines challenges countries face in regulating herbal medicines, including assessing safety and efficacy, quality control, and monitoring adverse effects. Regulations vary significantly between countries and regions. Europe implemented strict regulations after an herbal supplement mix-up caused kidney failure in thousands of women. The US regulates herbal supplements as dietary supplements rather than drugs. Other countries discussed include India, Malaysia, Singapore, China, the Philippines, Nigeria, Saudi Arabia, Australia, Canada, and Japan. The conclusion emphasizes the need for standardized, strengthened global regulation of herbal medicines given increased use and reports of adverse effects.
This document provides an introduction to botanical medicines, covering their history, science, uses, and dangers. It discusses how botanicals are extracted and prepared as medicines, as well as how their effectiveness is studied through in vitro, in vivo, and clinical trials. While botanicals have been used for thousands of years, the book notes that research on their effects is still developing and opinions vary on their role in medicine. It emphasizes the need for more rigorous clinical research and cooperation between conventional and complementary practitioners to establish the safety and efficacy of herbal medicines.
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The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive functioning. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
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The document provides information about the Post Graduate Common Entrance Test to be held on July 1st, 2017 from 2:30 pm to 4:30 pm for various Masters programs. It lists instructions for candidates regarding filling the answer sheet correctly and details about the structure of the test, which will consist of 75 multiple choice questions worth 100 marks to be completed within 120 minutes. Candidates are advised to carefully read and follow the guidelines for appearing in the exam.
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
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2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
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1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
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7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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1. 65. Botanicals (Herbal Medications)
& Nutritional Supplements
Cathi E. Dennehy, PharmD, & Candy Tsourounis, PharmD.
Basic & Clinical Pharmacology – 10th
Ed. (2007)
INTRODUCTION
The medical use of botanicals in their natural and unprocessed form undoubtedly began
when the first intelligent animals noticed that certain food plants altered particular body
functions. Much information exists about the historical use and effectiveness of botanical
products. Unfortunately, the quality of this information is extremely variable and much is
useless or false. An unbiased and regularly updated compendium of basic and clinical
reports regarding botanicals is Pharmacists Letter/Prescribers Letter Natural Medicines
Comprehensive Database (see references). A useful evidence-based website,
www.naturalstandard.com, is available to institutions. Another compendium is the
Report of the German Commission E (a committee that sets standards for herbal
medications in that country). Interest in the endocrine effects and possible nutritional
benefits of certain purified chemicals such as glucosamine, melatonin, high-dose
vitamins, and minerals has led to a parallel development of consumer demand for such
substances.
The alternative medicinal substances are distinguished from similar botanical substances
used in traditional medicine (morphine, digitalis, atropine, etc) by virtue of being
available without a prescription and, unlike over-the-counter medications, being legally
considered dietary supplements rather than drugs (thus avoiding conventional Food and
Drug Administration oversight). Among the purified chemicals, glucosamine and
melatonin are of significant pharmacologic interest.
This chapter provides an evidence-based approach to the pharmacology and clinical
efficacy of several of the commonly used and commercially available botanicals and
dietary supplements. Ephedrine, the active principle in Ma-huang, is discussed in Chapter
9.
REGULATORY FACTORS
Dietary supplements (which include vitamins, minerals, cofactors, herbal medications,
and amino acids) are not considered over-the-counter drugs in the USA but rather food
supplements. In 1994, the United States Congress, influenced by growing "consumerism"
2. as well as strong manufacturer lobbying efforts, passed the Dietary Supplement and
Health Education Act (DSHEA). This misguided act prevented adequate FDA oversight
of these substances. Thus, DSHEA has allowed a variety of substances with
pharmacologic activityif classified as dietary supplementsto be sold without a
prescription or any FDA review of efficacy or safety prior to product marketing. Dietary
supplements are governed under Current Good Manufacturing Practice in Manufacturing,
Packaging or Holding Human Food (CGMP) regulations. Although administered by the
FDA, CGMP regulations are often inadequate to ensure product purity, potency, and
other variables such as accurate product identification and appropriate botanical
harvesting. Therefore, much of the criticism regarding the dietary supplement industry
involves a lack of product purity and variations in potency.
CLINICAL ASPECTS OF THE USE OF BOTANICALS
Many United States consumers have embraced the use of botanicals and other
supplements as a "natural" approach to their health care. Unfortunately, misconceptions
regarding safety and efficacy of the agents are common, and the fact that a substance can
be called "natural" of course does not guarantee its safety. In fact, these products can be
adulterated, misbranded, or contaminated either intentionally or unintentionally in a
variety of ways. Furthermore, the doses recommended for active botanical substances
may be much higher than those considered clinically safe. For example, the doses
recommended for several Ma-huang preparations contain three to five times the
medically recommended daily dose of the active ingredient, ephedrinedoses that
impose significant risks for patients with cardiovascular disease.
Adverse effects have been documented for a variety of botanical medications.
Unfortunately, chemical analysis is rarely performed on the products involved. This leads
to uncertainty about whether the primary herb or an adulterant caused the adverse effect.
In some cases, the chemical constituents of the herb can clearly lead to toxicity. Some of
the herbs that should be used cautiously or not at all are listed in Table 65-1.
BOTANICAL SUBSTANCES
ECHINACEA (ECHINACEA PURPUREA)
Chemistry
The three most widely used species of Echinacea are Echinacea purpurea, E pallida, and
E angustifolia. The chemical constituents include flavonoids, lipophilic constituents (eg,
alkamides, polyacetylenes), water-soluble polysaccharides, and water-soluble caffeoyl
conjugates (eg, echinacoside, chicoric acid, caffeic acid). Within any marketed echinacea
formulation, the relative amounts of these components are dependent upon the species
used, the method of manufacture, and the plant parts used. The German Commission E
has approved two formulations for clinical use: the fresh pressed juice of aerial parts of E
purpurea and the alcoholic root extract of E pallida. E purpurea has been the most
widely studied in clinical trials. Although the active constituents of echinacea are not
2
3. completely known, chicoric acid from E purpurea and echinacoside from E pallida and E
angustifolia, as well as alkamides and polysaccharides, are most often noted as having
immune-modulating properties. Most commercial formulations, however, are not
standardized for any particular constituent.
Pharmacologic Effects
A. IMMUNE MODULATION
The effect of echinacea on the immune system is controversial. Human studies using
commercially marketed formulations of echinacea have shown increased phagocytosis
but not immunostimulation. In vitro, however, E purpurea juice increased production of
interleukin-1, -6, -10, and tumor necrosis factor-α by human macrophages. Enhanced
natural killer cell activity and antibody-dependent cellular toxicity was also observed
with E purpurea extract in cell lines from both healthy and immunocompromised
patients. Studies using the isolated purified polysaccharides from E purpurea have also
shown cytokine activation. Polysaccharides by themselves, however, are unlikely to
accurately reproduce the activity of the entire extract.
B. ANTI-INFLAMMATORY EFFECTS
Certain echinacea constituents have demonstrated anti-inflammatory properties in vitro.
Inhibition of cyclooxygenase, 5-lipoxygenase, and hyaluronidase may be involved. In
animals, application of E purpurea prior to application of a topical irritant reduced both
paw and ear edema. There are too few clinical trials in humans to warrant the use of
echinacea in wound healing.
C. ANTIBACTERIAL, ANTIFUNGAL, ANTIVIRAL, AND ANTIOXIDANT
EFFECTS
Some in vitro studies have reported weak antibacterial, antifungal, antiviral, and
antioxidant activity with echinacea constituents. The applicability of these findings to
clinical trials is discussed below.
Clinical Trials
Echinacea is most often used to enhance immune function in individuals who have colds
and other respiratory tract infections. Older reviews and cold treatment trials reported
favorable results for the aerial parts of E purpurea in reducing symptoms or time to
recovery if the agent was administered within the first 24 hours of a cold. To date,
however, most of these trials have contained multiple variables (eg, formulation, dose,
duration) that make it difficult to make a clear therapeutic recommendation or ensure
reproducible outcomes. At best, symptoms and duration may be reduced by about 25-
30%. Recent trials investigating preparations of E angustifolia and combinations of
echinacea containing E angustifolia for cold treatment, however, have failed to find a
benefit. Echinacea has also been evaluated as a prophylactic agent in the prevention of
upper respiratory tract infection in adults and as a treatment and prophylactic agent for
colds in children. These trials have generally reported no effect.
3
4. Echinacea has been used investigationally to enhance hematologic recovery following
chemotherapy. It has also been used as an adjunct in the treatment of urinary tract and
vaginal fungal infections. These indications require further research before they can be
accepted in clinical practice. E purpurea is ineffective in treating recurrent genital herpes.
Adverse Effects
Flu-like symptoms (eg, fever, shivering, headache, vomiting) have been reported
following the intravenous use of echinacea extracts. Adverse effects with oral
commercial formulations are minimal and most often include unpleasant taste,
gastrointestinal upset, or central nervous system effects (eg, headache, dizziness).
Allergic reactions such as rash, acute asthma, and anaphylaxis have been infrequently
reported.
Drug Interactions & Precautions
Until the role of echinacea in immune modulation is better defined, this agent should be
avoided in patients with immune deficiency disorders (eg, AIDS, cancer), autoimmune
disorders (eg, multiple sclerosis, rheumatoid arthritis), and patients with tuberculosis. The
German Commission E recommends limiting the chronic use of echinacea to no more
than 8 weeks. While there are no reported drug interactions for echinacea, some
preparations have a high alcohol content and should not be used with medications known
to cause a disulfiram-like reaction. Theoretically echinacea should also be avoided in
persons taking immunosuppressant medications (eg, organ transplant recipients).
Dosage
Because of recent negative trials using E angustifolia for colds and a lack of clinical trials
examining E pallida, only the dosing for E purpurea is provided here. E purpurea freshly
pressed juice is given at a dosage of 6-9 mL/d in divided doses two to five times daily.
Echinacea is generally taken at the first sign of a cold.
GARLIC (ALLIUM SATIVUM)
Chemistry
The pharmacologic activity of garlic involves a variety of organosulfur compounds. The
most notable of these is allicin, which is responsible for the characteristic garlic odor.
Pharmacologic Effects
A. CARDIOVASCULAR EFFECTS
In vitro, allicin and related compounds inhibit HMG-CoA reductase, which is involved in
cholesterol biosynthesis (see Chapter 35). Several clinical trials have investigated the
lipid-lowering potential of garlic. Some have shown significant reductions in cholesterol
and others no effect. The most recent meta-analysis suggested a minor (5%) reduction of
4
5. total cholesterol that was insignificant when dietary controls were in place. Results of a
study by the National Center of Complementary and Alternative Medicine (NCCAM)
evaluating three different sources of garlic (fresh, powdered, and aged garlic extract) in
adults with moderately elevated cholesterol are likely to be published in 2006 and may
provide further insight into the efficacy of this botanical for this indication.
Clinical trials report antiplatelet effects (possibly through inhibition of thromboxane
synthesis) following garlic ingestion and mixed effects on fibrinolytic activity. These
effects in combination with antioxidant effects (eg, increased resistance to low-density
lipoprotein oxidation) and reductions in total cholesterol may be beneficial in patients
with atherosclerosis. In preliminary trials involving atherosclerotic patients, significant
reductions in plaque volume were observed for patients taking garlic versus placebo.
Garlic constituents may affect blood vessel elasticity and blood pressure. Proposed
mechanisms include opening of potassium channels in vascular smooth muscle,
stimulation of nitric oxide synthesis, and inhibition of angiotensin-converting enzyme.
Epidemiologic studies suggest that individuals chronically consuming low doses of garlic
(averaging 460 mg/d) may have reductions in aortic stiffness. A meta-analysis of garlic's
antihypertensive properties revealed a mild effect with a 7.7 mm Hg decrease in systolic
pressure and a 5 mm Hg decrease in diastolic pressure.
B. ENDOCRINE EFFECTS
The effect of garlic on glucose homeostasis does not appear to be significant in persons
with diabetes. Certain organosulfur constituents in garlic, however, have demonstrated
hypoglycemic effects in nondiabetic animal models.
C. ANTIMICROBIAL EFFECTS
In vitro, allicin has demonstrated activity against some gram-positive and gram-negative
bacteria as well as fungi (Candida albicans), protozoa (Entamoeba histolytica), and
certain viruses. The primary mechanism involves the inhibition of thiol-containing
enzymes needed by these microbes. The antimicrobial effect of garlic has not been
extensively studied in clinical trials. Given the availability of effective prescription
antimicrobials, the usefulness of garlic in this area appears limited.
D. ANTINEOPLASTIC EFFECTS
In rodent studies, garlic inhibits procarcinogens for colon, esophageal, lung, breast, and
stomach cancer, probably by detoxification of carcinogens and reduced carcinogen
activation. The evidence for anticarcinogenic properties in vivo is largely epidemiologic.
For example, certain populations with high dietary garlic consumption appear to have a
reduced incidence of stomach cancer.
Adverse Effects
Following oral ingestion, adverse effects may include nausea (6%), hypotension (1.3%),
allergy (1.1%), and bleeding (rare). Breath odor has been reported with an incidence of
20-40% at recommended doses using enteric-coated formulations. Contact dermatitis
5
6. may occur with the handling of raw garlic.
Drug Interactions & Precautions
Because of reported antiplatelet effects, patients using anticlotting medications (eg,
warfarin, aspirin, ibuprofen) should use garlic cautiously. Additional monitoring of blood
pressure and signs and symptoms of bleeding is warranted. Garlic may reduce the
bioavailability of saquinavir, an antiviral protease inhibitor, but it does not appear to
affect the bioavailability of ritonavir.
Dosage
Products should be standardized to contain 1.3% alliin (the allicin precursor) or have an
allicin-generating potential of 0.6%. Enteric-coated formulations are recommended to
minimize degradation of the active substances. A daily dose of 600-900 mg/d of
powdered garlic is most common. This is equivalent to one clove of raw garlic (2-4 g) per
day.
GINKGO (GINKGO BILOBA)
Chemistry
Ginkgo biloba extract is prepared from the leaves of the ginkgo tree. The most common
formulation is prepared by concentrating 50 parts of the crude leaf to prepare one part of
extract. The active constituents in ginkgo are flavone glycosides and terpenoids (ie,
ginkgolides A, B, C, J, and bilobalide).
Pharmacologic Effects
A. CARDIOVASCULAR EFFECTS
In animal models and some human studies, ginkgo has been shown to increase blood
flow and reduce blood viscosity, thus enhancing tissue perfusion. Enhancement of
endogenous nitric oxide (see Chapter 19) and antagonism of platelet-activating factor
may be involved.
Ginkgo biloba has been studied for its effects on mild to moderate occlusive peripheral
arterial disease. Randomized studies involving 120-160 mg of standardized ginkgo leaf
extract (EGb761) for up to 6 months have generally reported significant improvements in
pain-free walking distance as compared with placebo. Efficacy may be comparable to
pentoxyfylline (see Chapter 20) for this indication. (It should be noted that physical
conditioning is as effective as pentoxyfylline in improving walking distance.)
B. METABOLIC EFFECTS
Antioxidant and radical-scavenging properties have been observed for the flavonoid
fraction of ginkgo as well as some of the terpene constituents. In vitro, ginkgo has
demonstrated superoxide dismutase-like activity and superoxide anion- and hydroxyl
6
7. radical-scavenging properties. It has also demonstrated a protective effect in limiting free
radical formation in animal models of ischemic injury and in reducing markers of
oxidative stress in patients undergoing coronary artery bypass surgery.
C. CENTRAL NERVOUS SYSTEM EFFECTS
In aged animal models, chronic administration of ginkgo for 3-4 weeks led to
modifications in central nervous system receptors and neurotransmitters. Receptor
densities increased for muscarinic, α2, and 5-HT1a receptors and decreased for β
adrenoceptors. Increased serum levels of acetylcholine and norepinephrine and enhanced
synaptosomal reuptake of serotonin have also been reported. Additional mechanisms that
may be involved include reversible inhibition of monoamine (MAO) A and B, reduced
corticosterone synthesis, inhibition of amyloid-beta fibril formation, and enhanced
GABA levels.
Ginkgo is frequently used to treat cerebral insufficiency and dementia of the Alzheimer
type. The term cerebral insufficiency, however, includes a variety of manifestations
ranging from poor concentration and confusion to anxiety and depression as well as
physical complaints such as hearing loss and headache. For this reason, studies evaluating
cerebral insufficiency tend to be more inclusive and difficult to assess than trials
evaluating dementia. A meta-analysis by the Cochrane Collaboration found that ginkgo
showed promising evidence for improvement of cognitive function in patients with
cognitive impairment and dementia. The duration of the largest of these studies was 1
year. Recent studies on the effects of ginkgo for memory enhancement in healthy
nondemented elderly adults did not show a benefit with 6 weeks of use. Ginkgo is
currently under investigation as a prophylactic agent for dementia of the Alzheimer type.
D. MISCELLANEOUS EFFECTS
Ginkgo has been studied for its effects in allergic and asthmatic bronchoconstriction,
erectile dysfunction, tinnitus and hearing loss, short-term memory loss in healthy
nonelderly adults, and macular degeneration. In all of these conditions, the evidence is
insufficient to warrant clinical use at this time.
Adverse Effects
Adverse effects have been reported with a frequency comparable to that of placebo.
These include nausea, headache, stomach upset, diarrhea, allergy, anxiety, and insomnia.
A few case reports noted bleeding complications in patients using ginkgo. In a few of
these cases, the patients were also using either aspirin or warfarin.
Drug Interactions & Precautions
Ginkgo may have antiplatelet properties and should not be used in combination with
antiplatelet or anticoagulant medications. A case of an enhanced sedative effect was
reported when ginkgo was combined with trazodone. Seizures have been reported as a
toxic effect of ginkgo, most likely related to seed contamination in the leaf formulations.
Ginkgo seeds are epileptogenic. Ginkgo formulations should be avoided in individuals
7
8. with preexisting seizure disorders.
Dosage
Ginkgo biloba dried leaf extract should be standardized to contain 24% flavone
glycosides and 6% terpene lactones. Products should be concentrated to a 50:1 ratio. The
daily dose ranges from 120-240 mg of the dried extract in two or three divided doses.
Onset of effect may require 2-4 weeks.
GINSENG
Chemistry
Ginseng botanical preparations may be derived from any of several species of the genus
Panax. Of these, crude preparations or extracts of Panax ginseng, the Chinese or Korean
variety, and P quinquefolium, the American variety, are most often available to
consumers in the United States. The active principles appear to be a dozen or more
triterpenoid saponin glycosides called ginsenosides or panaxosides. It is recommended
that commercial P ginseng formulations be standardized to contain 4-7% ginsenosides.
Other plant materials are commonly sold under the name ginseng but are not from Panax
species. These include Siberian ginseng (Eleutherococcus senticosus) and Brazilian
ginseng (Pfaffia paniculata). Of these, Siberian ginseng is more widely available in the
USA. Siberian ginseng contains eleutherosides but no ginsenosides. Currently, there is no
recommended standardization for eleutheroside content in Siberian ginseng products.
Pharmacology
An extensive literature exists on the potential pharmacologic effects of ginsenosides.
Unfortunately, the studies differ widely in the species of Panax used, the ginsenosides
studied, the degree of purification applied to the extracts, the animal species studied, and
the measurements used to evaluate the responses. Some of the more commonly reported
beneficial pharmacologic effects include modulation of immune function, ergogenic
("energizing") activity, nootropic ("mind-enhancing") activity, antioxidant activity, anti-
inflammatory effects, antistress activity (ie, stimulation of pituitary-adrenocortical
system), analgesia, vasoregulatory effects, antiplatelet activity, improved glucose
homeostasis, and anticancer properties.
Clinical Trials
Ginseng is most often used to help improve physical and mental performance.
Unfortunately, the clinical trials are of small sample size and report either an
improvement in mental function and physical performance or no effect. Some
randomized controlled trials evaluating "quality of life" have claimed significant benefits
in some subscale measures of quality of life but rarely in overall composite scores using
P ginseng. Better results have been observed with P quinquefolium in lowering
8
9. postprandial glucose indices in subjects with and without diabetes. Newer trials have
shown some immunomodulating benefits of P quinquefolium and P ginseng in preventing
upper respiratory tract infections. Epidemiologic studies have suggested a reduction in
several types of cancer with P ginseng. Systematic reviews, however, have generally
failed to find conclusive evidence for the use of P ginseng for any particular condition.
Until better clinical studies are published, no recommendation can be made regarding the
use of P ginseng or P quinquefolium for any specific indication.
Adverse Effects
A variety of adverse effects have been reported. Weak estrogenic properties may cause
the vaginal bleeding and mastalgia reported by some patients. Central nervous system
stimulation (eg, insomnia, nervousness) and hypertension have been reported in patients
using high doses (more than 3 g/d) of P ginseng. Methylxanthines found in the ginseng
plant may contribute to this effect. The German Commission E lists high blood pressure
as a contraindication to the use of Siberian ginseng but not P ginseng.
Drug Interactions & Precautions
Irritability, sleeplessness, and manic behavior have been reported in psychiatric patients
using ginseng in combination with other medications (phenelzine, lithium, neuroleptics).
Ginseng should be used cautiously in patients taking any psychiatric, estrogenic, or
hypoglycemic medications. Ginseng has antiplatelet properties and should not be used in
combination with warfarin. Similar to echinacea, cytokine stimulation has been observed
for both P ginseng and P quinquefolium, necessitating cautious use in individuals who are
immunocompromised, are taking immune stimulants or suppressants, or have
autoimmune disorders.
Dosing
The German Commission E recommends 1-2 g/d of crude P ginseng root or its
equivalent. Two hundred milligrams of ginseng extract is equivalent to 1 g of the crude
root. Ginsana has been used as a standardized extract in some clinical trials and is
available in the USA. Dosing for Siberian ginseng is 2-3 g/d of the crude root.
MILK THISTLE (SILYBUM MARIANUM)
Chemistry
The fruit and seeds of the milk thistle plant contain a lipophilic mixture of flavonolignans
known as silymarin. Silymarin comprises 2-3% of the dried herb and is composed of
three primary isomers, silybin (also known as silybinin or silibinin), silychristin
(silichristin), and silydianin (silidianin). Silybin is the most prevalent and potent of the
three isomers and accounts for about 50% of the silymarin complex. Products should be
standardized to contain 70-80% silymarin.
9
10. Pharmacologic Effects
A. LIVER DISEASE
In animal models, milk thistle limits hepatic injury associated with a variety of toxins,
including Amanita mushrooms, galactosamine, carbon tetrachloride, acetaminophen,
radiation, cold ischemia, and ethanol. In vitro studies and some in vivo studies
demonstrate that silymarin reduces lipid peroxidation, scavenges free radicals, and
enhances glutathione and superoxide dismutase levels. This may contribute to membrane
stabilization and reduce toxin entry.
Milk thistle appears to have anti-inflammatory properties. In vitro, silybin strongly and
noncompetitively inhibits lipoxygenase and leukotriene formation. Inhibition of
leukocyte migration has been observed in vivo and may be a factor when acute
inflammation is present. Silymarin also inhibits tumor necrosis factor-α-mediated
activation of nuclear factor kappa B (NF-κB), which promotes inflammatory responses.
One of the most unusual mechanisms claimed for milk thistle involves an increase in
RNA polymerase I activity in nonmalignant hepatocytes but not in hepatoma or other
malignant cell lines. By increasing this enzyme's activity, enhanced protein synthesis and
cellular regeneration may occur in diseased but not malignant cells. Milk thistle may have
a role in hepatic fibrosis. In an animal model of cirrhosis, it reduced collagen
accumulation, and in an in vitro model it reduced expression of the profibrogenic
cytokine transforming growth factor-β.
It has been suggested that milk thistle may be beneficial in the management of
hypercholesterolemia and gallstones. A small trial in humans showed a reduction in bile
saturation index and biliary cholesterol concentration. The latter may reflect a reduction
in liver cholesterol synthesis. To date, however, there is insufficient evidence to warrant
the use of milk thistle for these indications.
B. CHEMOTHERAPEUTIC EFFECTS
Preliminary in vitro and animal studies have been carried out with skin, lung, bladder,
colon, tongue, breast, and prostate cancer cell lines. In murine models of skin cancer,
silybinin and milk thistle reduced tumor initiation and promotion. It also inhibited cell
growth and proliferation by inducing a G1 cell cycle arrest in cultured human breast and
prostate cancer cell lines. However, the use of milk thistle in the treatment of cancer has
not yet been adequately studied and should not be recommended to patients.
Clinical Trials
Milk thistle has been used to treat acute and chronic viral hepatitis, alcoholic liver
disease, and toxin-induced liver injury in human patients. A recent systematic review of
13 randomized trials involving 915 patients with alcoholic liver disease or hepatitis B or
C found no significant reductions in all-cause mortality, liver histology, or complications
of liver disease. A significant reduction in liver-related mortality among all trials was
documented, but not among trials of better design and controls. It was concluded that the
effects of milk thistle in improving liver function or mortality from liver disease are
10
11. currently poorly substantiated. Until additional well-designed clinical trials (possibly
exploring higher doses) can be performed, a clinical effect can be neither supported nor
ruled out.
Milk thistle has not been well studied in humans as an antidote following acute exposure
to liver toxins. Parenteral silybin, however, is marketed and used in Europe as an antidote
in Amanita phalloides mushroom poisoning, based on favorable outcomes reported in
case-control studies.
Adverse Effects
Milk thistle has rarely been reported to cause adverse effects when used at recommended
dosage. In clinical trials, the incidence of adverse effects (eg, gastrointestinal upset,
dermatologic, headaches) was comparable to that of placebo.
Drug Interactions, Precautions, & Dosing
There are no reported drug-drug interactions or precautions for milk thistle.
Recommended dosage is 280-420 mg/d, calculated as silybin, in three divided doses.
ST. JOHN'S WORT (HYPERICUM PERFORATUM)
Chemistry
St. John's wort, also known as hypericum, contains a variety of constituents that may
contribute to its pharmacologic activity. Hypericin, a marker of standardization for
currently marketed products, was thought to be the primary antidepressant constituent.
Recent attention has focused on hyperforin, but a combination of several compounds is
probably involved. Commercial formulations are usually prepared by soaking the dried
chopped flowers in methanol to create a hydroalcoholic extract that is then dried.
Pharmacologic Effects
A. ANTI-DEPRESSANT ACTION
The hypericin fraction was initially reported to have MAO-A and -B inhibitor properties.
Later studies found that the concentration required for this inhibition was higher than that
which could be achieved with recommended dosages. In vitro studies using the
commercially formulated hydroalcoholic extract have shown inhibition of nerve terminal
reuptake of serotonin, norepinephrine, and dopamine. While the hypericin constituent did
not show reuptake inhibition for any of these systems, a concentrated hyperforin extract
did. Chronic administration of the commercial extract has also been shown to
significantly down-regulate the expression of cortical β adrenoceptors and up-regulate the
expression of serotonin receptors (5-HT2) in a rodent model.
Other effects observed in vitro include opioid sigma receptor binding using the hypericin
fraction and GABA receptor binding using the commercial extract. Interleukin-6
11
12. production is also reduced in the presence of the extract.
The most systematic review and meta-analysis, which involved 37 randomized controlled
trials, demonstrated that St. John's wort is more efficacious than placebo and as
efficacious as some prescription antidepressants for mild to moderate depression.
Efficacy for more severe depression, however, is still in question. Most trials used doses
of St. John's wort ranging from 900 mg/d (for mild to moderate depression) to 1800 mg/d
(for severe depression) and lasted 4-8 weeks.
B. ANTIVIRAL AND ANTICARCINOGENIC EFFECTS
The hypericin constituent of St. John's wort is photolabile and can be activated by
exposure to certain wavelengths of visible or ultraviolet A light. Parenteral formulations
of hypericin (photoactivated just before administration) have been used investigationally
to treat HIV infection (given intravenously) and basal and squamous cell carcinoma
(given by intralesional injection). In vitro, photoactivated hypericin inhibits a variety of
enveloped and nonenveloped viruses as well as the growth of cells in some neoplastic
tissues. Inhibition of protein kinase C and of singlet oxygen radical generation have been
proposed as possible mechanisms. The latter could inhibit cell growth or cause cell
apoptosis. These studies were carried out using the isolated hypericin constituent of St.
John's wort; the usual hydroalcoholic extract of St. John's wort has not been studied for
these indications and should not be recommended for patients with viral illness or cancer.
Adverse Effects
Photosensitization has been reported, and patients should be instructed to wear sunscreen
while using this product. Hypomania, mania, and autonomic arousal have also been
reported in patients using St. John's wort.
Drug Interactions & Precautions
Inhibition of reuptake of various amine transmitters has been highlighted as a potential
mechanism of action for St. John's wort. Drugs with similar mechanisms (ie,
antidepressants, stimulants) should be used cautiously or avoided in patients using St.
John's wort due to the risk of serotonin syndrome or MAO crisis (see Chapters 16 and
30). This herb may induce hepatic CYP enzymes (3A4, 2C9, 1A2) and the P-glycoprotein
drug transporter. This has led to case reports of subtherapeutic levels of numerous drugs,
including digoxin, birth control drugs (and subsequent pregnancy), cyclosporine, HIV
protease and nonnucleoside reverse transcriptase inhibitors, warfarin, irinotecan,
theophylline, and anticonvulsants.
Dosage
The most common commercial formulation of St. John's wort is the dried hydroalcoholic
extract. Products should be standardized to 2-5% hyperforin, although most still bear the
older standardized marker of 0.3% hypericin. The recommended dosing for mild to
moderate depression is 900 mg of the dried extract per day in three divided doses. Onset
12
13. of effect may take 2-4 weeks. Long-term benefits beyond 12 weeks have not been
sufficiently studied.
SAW PALMETTO (SERENOA REPENS OR SABAL SERRULATA)
Chemistry
The active constituents in saw palmetto berries are not well defined. Phytosterols (eg, β-
sitosterol), aliphatic alcohols, polyprenic compounds, and flavonoids are all present.
Marketed preparations are lipophilic extracts that contain 85-95% fatty acids and sterols.
Pharmacologic Effects
Saw palmetto is most often used in the treatment of benign prostatic hyperplasia (BPH).
Enzymatic conversion of testosterone to dihydrotestosterone (DHT) by 5α-reductase is
inhibited by saw palmetto in vitro. Specifically, saw palmetto shows a noncompetitive
inhibition of both isotypes (I and II) of this enzyme, thereby reducing DHT production. In
vitro, saw palmetto also inhibits the binding of DHT to androgen receptors. Additional
effects that have been observed in vitro include inhibition of prostatic growth factors,
blockade of α1 adrenoceptors, and inhibition of inflammatory mediators produced by the
5-lipoxygenase pathway.
The clinical pharmacology of saw palmetto in humans is not well defined. One week of
treatment in healthy volunteers failed to influence 5α-reductase activity, DHT
concentration, or testosterone concentration. Six months of treatment in patients with
benign prostatic hyperplasia also failed to affect prostate-specific antigen (PSA) levels, a
marker that is typically reduced by enzymatic inhibition of 5α-reductase. In contrast,
other researchers have reported a reduction in epidermal growth factor, DHT levels, and
estrogen expression after 3 months of treatment in patients with benign prostatic
hyperplasia. Results of recent meta-analyses and reviews suggested that saw palmetto is
significantly more effective than placebo in alleviating urologic symptoms (eg, peak
flow, nocturia, international prostate symptom scores) associated with mild to moderate
BPH. Saw palmetto, 320 mg/d, was also shown to have comparable efficacy to 5 mg/d of
finasteride (a prescription 5α-reductase inhibitor) and 0.4 mg/d of tamsulosin (a
prescription α-blocker) in clinical trials lasting 6 months and 1 year, respectively. In
marked contrast, a recent well-controlled, double-blind 1-year study showed no
significant effect of saw palmetto on symptoms or objective measures in moderate to
severe BPH. The efficacy of saw palmetto in BPH beyond 5 years has not been studied.
Adverse Effects
Adverse effects are rare and reported with an incidence of 1-3%. The most common
include gastrointestinal upset, hypertension, decreased libido, abdominal pain, impotence,
back pain, urinary retention, and headache. In comparison to tamsulosin and finasteride,
saw palmetto is less likely to affect sexual function (eg, ejaculation) in men.
13
14. Drug Interactions, Precautions, & Dosing
No drug-drug interactions have been reported for saw palmetto. Because saw palmetto
has no effect on the PSA marker, it will not interfere with prostate cancer screening using
this test. Recommended dosing of a standardized dried extract (containing 85-95% fatty
acids and sterols) is 160 mg orally twice daily. Patients should be instructed that it may
take 4-6 weeks for onset of clinical effects.
PURIFIED NUTRITIONAL SUPPLEMENTS
COENZYME Q10
Introduction
Coenzyme Q10, also known as CoQ, CoQ10, and ubiquinone, is found in the
mitochondria of many organs, including the heart, kidney, and liver, and in skeletal
muscle. After ingestion, the reduced form of coenzyme Q10, ubiquinol, predominates in
the systemic circulation. Coenzyme Q10 is a potent antioxidant and may have a role in
maintaining healthy muscle function, although the clinical significance of this effect is
unknown. Reduced serum levels have been reported in Parkinson's disease.
Clinical Uses
A. HYPERTENSION
Various open label and controlled studies have identified small reductions in systolic and
diastolic blood pressure of approximately 10 mm Hg following 10 weeks of therapy.
Although this observation appears to be consistent, better designed studies are required.
B. HEART FAILURE
Older studies suggested that coenzyme Q10 was effective as adjunctive therapy in the
treatment of heart failure. Current research suggests that the supplement does not alter
cardiac function (as determined with Swan-Ganz catheter measurements and
echocardiography) in cardiomyopathy patients with class I, II, or III NY Heart
Association status. Furthermore, patients with lower than normal endogenous coenzyme
Q10 levels do not display subjective or objective improvements in heart failure
assessments when given coenzyme Q10 supplements.
C. ISCHEMIC HEART DISEASE
The effects of coenzyme Q10 on coronary artery disease and chronic stable angina are
modest but appear promising. Double-blind, placebo-controlled trials have demonstrated
that coenzyme Q10 supplementation improved a number of clinical measures in patients
with a history of acute myocardial infarction (AMI). Improvements have been observed
in lipoprotein a, high-density lipoprotein cholesterol, exercise tolerance, and time to
development of ischemic changes on the electrocardiogram during stress tests. In
addition, very small reductions in cardiac deaths and rate of reinfarction in patients with
previous AMI were reported (absolute risk reduction 1.5%).
14
15. D. NEUROLOGIC DISEASES
Coenzyme Q has been reported to slow the progression of early Parkinson's disease when
given at high dosage (300-1200 mg/d), although the time to requirement for levodopa
treatment was not shortened. Another study indicated that migraine attacks were reduced
in frequency at a dosage of 300 mg/d. No benefit was found in the treatment of
amyotrophic lateral sclerosis or Huntington's disease.
Adverse Effects
Coenzyme Q10 is well tolerated, rarely leading to any adverse effects at doses as high as
3000 mg/d. In clinical trials gastrointestinal upset, anorexia, and nausea have been
reported. Cases of maculopapular rash and thrombocytopenia have very rarely been
observed. Other rare adverse effects include irritability, dizziness, and headache.
Drug Interactions
Coenzyme Q10 shares a structural similarity with vitamin K, and an interaction has been
observed between coenzyme Q10 and warfarin. Coenzyme Q10 supplements may
decrease the effects of warfarin therapy. This combination should be avoided or very
carefully monitored.
A reduction in endogenous coenzyme Q10 levels has been observed in patients beginning
HMG-CoA reductase inhibitors. The clinical significance of this reduction is currently
unknown, and the long-term effects of coenzyme Q10 supplementation in patients taking
HMG-CoA reductase inhibitors has not been studied clinically. Anecdotal evidence has
suggested that adding coenzyme Q10 to HMG-CoA reductase inhibitor therapy may help
to prevent the rare adverse effect of myopathy, which can ultimately progress to
rhabdomyolysis. Clinical trials are needed to confirm this effect.
Dosage
As a dietary supplement, 30 mg of coenzyme Q10 is adequate to replace low endogenous
levels. For neural or cardiac effects, typical doses are 100-600 mg/d given in two or three
divided doses. These therapeutic doses increase endogenous levels to 2-3 mcg/mL
(normal for healthy adults, 0.7-1 mcg/mL).
GLUCOSAMINE
Introduction
Glucosamine is found in human tissue, is a substrate for the production of articular
cartilage, and also serves as a cartilage nutrient. Glucosamine is commercially derived
from crabs and other crustaceans. As a dietary supplement, glucosamine is primarily used
for pain associated with knee osteoarthritis.
15
16. Pharmacologic Effects & Clinical Uses
Endogenous glucosamine is used for the production of glycosaminoglycans and other
proteoglycans in articular cartilage. In osteoarthritis, the rate of production of new
cartilage is exceeded by the rate of degradation of existing cartilage. Supplementation
with glucosamine is thought to increase the supply of the necessary glycosaminoglycan
building blocks, leading to better maintenance and strengthening of existing cartilage.
Many clinical trials have been conducted on the effects of both oral and intra-articular
administration of glucosamine. Early studies demonstrated significant improvements in
overall mobility, range of motion, and strength in patients with osteoarthritis. Some
recent evidence has shown mixed results, with both positive and negative trials. One
meta-analysis found an overall moderate effect in knee osteoarthritis improvement,
although study limitations may have overestimated treatment benefits. However, the most
recent large double-blind trial, which compared glucosamine, chondroitin sulfate, the
combination, and placebo, found no benefit for this therapy. It is possible that specific
subgroups may benefit from glucosamine. More research is needed to better define the
specific patient populations that stand to benefit from glucosamine.
Adverse Effects
Glucosamine is very well tolerated. In clinical trials, mild diarrhea and nausea were
occasionally reported. Cross allergenicity in people with shellfish allergies is a potential
concern; however, this is unlikely if the formulation has been adequately manufactured
and purified.
Drug Interactions & Precautions
There are no known drug interactions with glucosamine.
Dosage
The dosage used most often in clinical trials is 500 mg three times daily or 1500 mg once
daily. Glucosamine does not have direct analgesic effects, and improvements, if any, may
not be observed for 1-2 months. Although all salt forms of glucosamine (sulfate and
hydrochloride) should dissolve and be available for absorption, there is some evidence
that the sulfate formulation may be superior clinically.
MELATONIN
Introduction
Melatonin, a serotonin derivative produced by the pineal gland and some other tissues
(see also Chapter 16), is believed to be responsible for regulating sleep-wake cycles.
Release coincides with darkness; it typically begins around 9 PM and lasts until about 4
AM. Melatonin release is suppressed by daylight. Melatonin has also been studied for a
16
17. number of other functions, including contraception, protection against endogenous
oxidants, prevention of aging, and treatment of depression, HIV infection, and a variety
of cancers. Currently, melatonin is most often administered to prevent jet lag and to
induce sleep.
Pharmacologic Effects & Clinical Uses
A. JET LAG
Jet lag, a disturbance of the sleep-wake cycle, occurs when there is a disparity between
the external time and the traveler's endogenous circadian clock (internal time). The
internal time regulates not only daily sleep rhythms but also body temperature and many
metabolic systems. The synchronization of the circadian clock relies on light as the most
potent "zeitgeber" (time giver).
Jet lag is especially common among frequent travelers and airplane cabin crews. Typical
symptoms of jet lag may include daytime drowsiness, insomnia, frequent awakenings,
and gastrointestinal upset. Clinical studies with administration of melatonin have reported
subjective reduction in daytime fatigue, improved mood, and a quicker recovery time
(return to normal sleep patterns, energy, and alertness). Unfortunately, many of these
studies were characterized by inconsistencies in dosing, duration of therapy, and time of
drug administration. In addition to melatonin, maximizing exposure to daylight on arrival
at the new destination can aid in resetting the internal clock.
B. INSOMNIA
Melatonin has been studied in the treatment of various sleep disorders, including
insomnia and delayed sleep-phase syndrome. It has been shown to improve sleep onset,
duration, and quality when administered to healthy volunteers, suggesting a
pharmacologic hypnotic effect. Melatonin has also been shown to increase rapid-eye-
movement (REM) sleep.
Clinical studies in patients with sleep disorders have shown that oral melatonin
supplementation may alter sleep architecture. Subjective improvements in sleep quality
and improvements in sleep onset and sleep duration have been reported. However, the
significance of these findings is impaired by many study limitations.
Patients older than 65 years of age tend to suffer from sleep maintenance insomnia;
melatonin serum levels have been reported to be low in these patients. Elderly patients
with sleep maintenance insomnia who received immediate-release and sustained-release
melatonin had improved sleep onset time. They did not, however, experience an
improvement in sleep maintenance or total sleep time.
C. FEMALE REPRODUCTIVE FUNCTION
Melatonin receptors have been identified in granulosa cell membranes, and significant
amounts of melatonin have been detected in ovarian follicular fluid. Melatonin has been
associated with midcycle suppression of luteinizing hormone surge and secretion. This
may result in partial inhibition of ovulation. Nightly doses of melatonin (75-300 mg)
17
18. given with a progestin through days 1-21 of the menstrual cycle resulted in lower mean
luteinizing hormone levels. Therefore, melatonin should not be used by women who are
pregnant or attempting to conceive. Furthermore, melatonin supplementation may
decrease prolactin release in women and therefore should be used cautiously or not at all
while nursing.
D. MALE REPRODUCTIVE FUNCTION
In healthy men, chronic melatonin administration (≥ 6 months) decreased sperm quality,
possibly by aromatase inhibition in the testes. Until more is known, melatonin should not
be used by couples who are actively trying to conceive.
Adverse Effects
Melatonin appears to be well tolerated and is often used in preference to over-the-counter
"sleep-aid" drugs. Although melatonin is associated with few adverse effects, some next-
day drowsiness has been reported as well as tachycardia, depression, vivid dreams, and
headache. Sporadic case reports of movement disorders and psychoses have also
appeared.
Drug Interactions
Melatonin drug interactions have not been formally studied. Various studies, however,
suggest that melatonin concentrations are altered by a variety of drugs, including
nonsteroidal anti-inflammatory drugs, antidepressants, β-adrenoceptor agonists and
antagonists, scopolamine, and sodium valproate. The relevance of these effects is
unknown. Melatonin is metabolized by CYP450 1A2 and may interact with other drugs
that either inhibit or induce the 1A2 isoenzyme.
Dosage
A. JET LAG
The optimal timing and dose of melatonin have not been established. Current information
suggests 5-8 mg of the immediate-release formulation given on the evening of departure
and for 1-3 nights after arrival at the new destination. Exposure to daylight at the new
time zone is also important to regulate the sleep-wake cycle.
B. INSOMNIA
Doses of 0.3-10 mg of the immediate-release formulation orally given once nightly have
been tried. The lowest effective dose should be used first and may be repeated in 30
minutes up to a maximum of 10-20 mg. Sustained-release formulations may be used but
currently do not appear to offer any advantages over the immediate-release formulations.
Sustained-release formulations are also more costly.
REFERENCES
18
19. General
Blumenthal M et al: Herbal Medicine: Expanded Commission E Monograph. American
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Jellin JM et al: Pharmacist's Letter/Prescriber's Letter Natural Medicines
Comprehensive Database, 4th ed. Therapeutic Research Faculty, 2006.
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Coenzyme Q10
Berman M et al: Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac
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Hodgson JM et al: Coenzyme Q10 improves blood pressure and glycaemic control: A
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Khatta M et al: The effect of coenzyme Q10 in patients with congestive heart failure. Ann
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Schults CW et al: Effects of coenzyme Q10 in early Parkinson's disease: Evidence of
slowing of the functional decline. Arch Neurol 2002;59:1541.
Singh RB et al: Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent
myocardial infarction. Mol Cell Biochem 2003;246:75.
Echinacea
Goel V et al: Efficacy of a standardized echinacea preparation (EchinalinTM
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treatment of the common cold: A randomized double-blind, placebo-controlled trial. J
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Melchart D et al: Echinacea for preventing and treating the common cold. Cochrane
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Turner RB et al: An evaluation of Echinacea angustifolia in experimental rhinovirus
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Garlic
19
20. Ackermann RT et al: Garlic shows promise for improving some cardiovascular risk
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Khanum F et al: Anticarcinogenic properties of garlic: A review. Crit Rev Food Sci Nutr
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Stevinson C, Pittler MH, Ernst E: Garlic for treating hypercholesterolemia. A meta-
analysis of randomized clinical trials. Ann Intern Med 2000;133:420.
Ginkgo
Ahlemeyer B et al: Neuroprotective effects of Ginkgo biloba extract. Cell Mol Life Sci
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Horsch S et al: Gingko biloba special extract EGb761 in the treatment of peripheral
arterial occlusive disease (PAOD)--a review based on randomized controlled studies. Int
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Ginseng
Coleman CI et al: The effects of Panax ginseng on quality of life. J Clin Pharm Therapeut
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Predy GN et al: Efficacy of an extract of North American ginseng containing poly-
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randomized controlled trial. Can Med Assoc J 2005;173:1043.
Yun TK: Experimental and epidemiological evidence on non-organ specific cancer
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2003;523-524:63.
Glucosamine
Clegg D et al: Glucosamine, chondroitin sulfate, and the two in combination for painful
knee osteoarthritis. N Engl J Med 2006;354:795.
McAlindon T et al: Effectiveness of glucosamine for symptoms of knee osteoarthritis:
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Milk Thistle
Jacobs BP et al: Milk thistle for the treatment of liver disease: A systematic review and
meta-analysis. Am J Med 2002;113:506.
20
21. Rambaldi A et al: Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases.
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Singh RP et al: Mechanisms and preclinical efficacy of silibinin in preventing skin
cancer. Eur J Cancer 2005;41:1969.
St. John's Wort
Butterweck V: Mechanism of action of St. John's wort in depression: What is known?
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Hypericum Depression Trial Study Group: Effect of Hypericum perforatum (St John's
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Linde K et al: St. John's wort for depression--meta-analysis of randomised controlled
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Szegedi A et al: Acute treatment of moderate to severe depression with hypericum extract
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Saw Palmetto
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Boyle P et al: Updated meta-analysis of clinical trials of Serenoa repens extract in the
treatment of symptomatic benign prostatic hypertrophy. BJU International 2004;93:751.
Raynaud JP et al: Inhibition of type 1 and type 2 5α-reductase activity by free fatty acids,
active ingredients in Permixon®. J Steroid Biochem Molec Biol 2002;82:233.
Melatonin
Baskett JJ et al: Does melatonin improve sleep in older people? A randomised crossover
trial. Age Ageing 2003;32:164.
Petrie K et al: A double-blind trial of melatonin as a treatment for jet lag in international
cabin crew. Biol Psychiatry 1993;33:526.
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