Lecture 5 - Endocrine Disorders PDF

Phytotherapy (PG-906 clinical, PG-907 General) Herbal therapy for Endocrine and Metabolic Disorders. root Pharm D ninth semester students By: Dr/Shimaa Abdelgawad Lecturer of Pharmacog...

Phytotherapy (PG-906 clinical, PG-907 General) Herbal therapy for Endocrine and Metabolic Disorders. root Pharm D ninth semester students By: Dr/Shimaa Abdelgawad Lecturer of Pharmacognosy, Faculty of Pharmacy, Fayoum University THE ENDOCRINE SYSTEM: Works via chemical messengers (hormones) that are secreted by glands directly into the circulatory system to regulate target organ function. The feedback loop works to control the release of these hormones and maintain homeostasis i.e the state of steady conditions vital for life. THE ENDOCRINE SYSTEM: Each gland of the endocrine system releases specific hormones into the bloodstream. These hormones travel through circulatory system to other cells and help to coordinate body processes.  GLANDS OF THE ENDOCRINE SYSTEM They include: Adrenal glands: Two glands that sit on top of the kidneys that release the hormone cortisol. Pineal gland: A gland found near the center of the brain that may be linked to sleep patterns, release melatonin.  GLANDS OF THE ENDOCRINE SYSTEM Hypothalamus: A part of the lower middle brain that tells the pituitary gland when to release hormones. Release dopamine, GHRH. GnRH, TRH. Pituitary gland: A gland found at the base of brain behind the sinuses. It is often called the "master gland" because it influences many other glands. Release Growth hormone, FSH, LH, TSH, Prolactin, Oxytocin, and Vasopressin. GLANDS OF THE ENDOCRINE SYSTEM Ovaries: The female reproductive organs that release eggs and produce sex hormones (estrogen & progesterone). Testes: The male reproductive glands that produce sperm and sex hormones (testosterone). Islet cells in the pancreas: Cells in the pancreas control the release of the hormones: insulin and glucagon.  GLANDS OF THE ENDOCRINE SYSTEM Thymus: A gland in the upper chest that helps develop the body's immune system early in life. Release Thymosin hormone. Thyroid: A butterfly-shaped gland in the front of the neck that controls metabolism. Release Thyroid hormones (T3 & T4). Parathyroid: Four tiny glands in the neck that play a role in bone development. Release Parathyroid hormone (PTH) and Calcitonin.  ENDOCRINE DISORDERS ❑ A malfunction in the endocrine systems (either the glands, hormones, receptors or organs impacted by hormones) can cause an endocrine disorder. ❑ The various dysfunctions can cause wide- ranging effects on the body. ❑ The disorders arise from the effects caused by too little or too much secretion of a hormone or problems with receiving the hormone. ❑ A metabolic disorder occurs when an improper level of a hormone alters the body’s metabolism and impacts its function (for example, diabetes). ENDOCRINE DISORDERS Examples of endocrine disorders: Cushing's Syndrome Diabetes Gout Hyperthyroidism Hypothyroidism Obesity Osteoporosis Paget's Disease Estrogen dominance. Polycystic Ovarian Syndrome (PCOS). Metabolic syndrome DEFINITION: Metabolic syndrome is a cluster of conditions including central obesity + hyperglycemia + hyperlipidemia + hypertension that occur together, increasing your risk of heart disease, stroke and type 2 diabetes.  SYMPTOMS: Some symptoms can be seen, while others are not as obvious. ❑ Large waistline is a primary symptom (apple or pear-shaped trunk). ❑ High blood pressure → headache, chest pain, dizziness, nausea. ❑ High blood triglycerides, and low HDL cholesterol, or “good” cholesterol, usually do not cause any symptoms. ❑ High blood sugar may cause the following symptoms: ▪ Blurred vision. ▪ Increased thirst. ▪ Increased urination, especially at night. ▪ Tiredness and weakness. RISK FACTORS OR CAUSES: 1- Unhealthy lifestyle: eating unhealthy diet, smoking and lack of enough sleeping time. 2- Age: Your risk of metabolic syndrome increases as you get older. 3- Family history and genetic 4- Other medical conditions: such as CVD, insulin resistance, Polycystic ovary syndrome, psoriasis, sleep apnea. 5- Sex: In older adults, women have a higher risk of metabolic syndrome than men.  TREATMENT: 1-Healthy lifestyle changes: eating healthy, exercise, stop smoking, sleep well and relaxation. 2-Medicines: Medicines to lower your blood pressure: These include ACE inhibitors, angiotensin receptor blockers, diuretics, and beta blockers. Some diuretics and beta blockers can raise the risk of type 2 diabetes in people who have metabolic syndrome. Medicines to control blood triglyceride and “good” HDL cholesterol levels: such as statins and niacin These medicines can cause digestive problems. Some statins can raise the risk of type 2 diabetes in people who have metabolic syndrome. Omega fatty acids, which are commonly found in fish oils, also can help lower blood triglycerides.  TREATMENT:. 2-Medicines: Medicines to lower blood sugar levels: Insulin sensitizers such as thiazolidinediones can help treat high blood sugar levels. These medicines can cause liver damage, anemia, heart failure, and blood sugar levels that are too low or too high. Weight-loss medicines: can help you lose weight by making you feel less hungry. They can also reduce how much fat your body absorbs from your food. 3- Herbal medicine Natural herbal remedies for : 1. Garlic 2. Bitter melon 3. Fenugreek ❑ Botanical origin ❑ Active constituent 4. Gymnema ❑ Mechanism of action 5. Artichoke ❑ Dosage 6. Red Yeast ❑ Side effects 7. Moringa ❑ Contraindications ❑ Drug interactions 8. Garcinia 9. Green tea 10. Psyllium husk 1- Garlic ‫الثوم‬ Bulb  1- Garlic Botanical origin Bulb of Allium sativum , family: Liliaceae. Active constituents Volatile oil contains Sulphur compounds like alliin, allicin, ajoene, diallyl disulphide, diallyl trisulphide, methyl allyl trisulphide, allyl propyl disulphide.  1- Garlic Mechanism of action: 1- Anti Hypercholesterolemia: due to diallyl disulphides and diallyl trisulphides. Garlic can reduce the activity of the thiol enzymes (HMG-CoA reductase and coenzyme A) which are essential enzymes for cholesterol biosynthesis. 2- Anti-hypertensive: due to allicin allicin effect on the elastic properties of the blood vessels (vasodilation) through the nitric oxide system. 3- Hypoglycemic effect: due to alliin It Increases serum insulin levels by increase in insulin secretion from beta cells in pancreas.  1- Garlic Dosage: Garlic extracts: up to 2400 mg daily. Indications: in treatment of metabolic disorders: anti hypercholesterolemia, anti-hypertensive and hypoglycemic Adverse effect reaction: Garlic extracts are usually standardized by the Bad breath. amount of allicin (1.1% to 1.3%). It's a good Heartburn. idea to look for supplements that are coated Gas. (enteric coating) so they will dissolve in the Diarrhea. intestine and not in the stomach.  1- Garlic Contraindications: Bleeding disorder Drug interactions: Saquinavir (Invirase): medication taken for HIV. Garlic decrease its absorption and effect. Anticoagulants alongside with garlic cause bruising and bleeding.  2-Bitter melon or karela ‫الخيار المر أو القرع المر‬ Leaves & fruits  2-Bitter melon Botanical origin Leaves and fruits of Momordica charantia. Family: Cucurbitaceae. Active constituents 1- Polysaccharides. 2- Proteins and peptides such as polypeptide-p. 3- Saponins and terpenoids such as charantin. Charantin 4-Flavonoids such as quercetin, rutin, kaempferol, and isorhamnetin  2-Bitter melon Mechanism of action Hypoglycemic effects (equal to metformin with far fewer side effects). ❑ It promotes insulin secretion. ❑ Improving glucose uptake by adipose or muscle tissues. ❑ Inhibiting glucose absorption from the intestines and glucose production from the liver.  2-Bitter melon Dosage: Dried fruit: 0.5-12 g 3 times daily for up to 16 weeks. Adverse reaction: Extract: 100 to 200 mg 3 GI effects (eg, times daily abdominal pain, diarrhea). Indications: Headache. Hypoglycemic For treatment of type 2 coma and atrial diabetes. fibrillation.  2-Bitter melon Contraindications: Drug interactions: Pregnancy/Lactation→ Antidiabetic drugs. emmenagogue and abortifacient Medications moved by Patients deficient in glucose-6- pumps in cells (P- phosphate dehydrogenase should Glycoprotein Substrates). avoid consumption of bitter melon Pazopanib (used in renal preparations → due to the presence cancer) → bitter melon of vicine in the seeds. decreases its metabolism & Patients with impaired hepatic increase the effects and side function. effects of pazopanib. Surgery. 3-Fenugreek ‫الحلبة‬ Seed  3-Fenugreek Botanical origin Seeds of Trigonella foenum-graecum Family: Leguminosae. Active constituents Trigonelline Steroidal sapogenins: Diosgenin. Proteins: rich in lysine and tryptophan. Flavonoids: Quercetin, Rutin, vitexin, Isovitexin Alkaloids: Trigonelline & Choline. Diosgenin  3-Fenugreek Mechanism of action 1- Antidiabetic: ↑↑ Peripheral glucose uptake and antioxidant effect. - Increase in the liver glycogen content after fenugreek galactomannan treatment can be brought about by an increase in glycogenesis and/or a decrease in glycogenolysis. - Slow down nicotinic acid metabolism which increase glucose uptake from blood and its subsequent oxidation. - prevents destruction of β-cells due to its free radical scavenger activity (due to trigonelline).  3-Fenugreek Mechanism of action 2- Anti hyperlipidemic: - Fenugreek increases the excretion of bile acids with depletion of cholesterol stores in the liver. - Moreover, saponins may form complexes with cholesterol in the intestine, reducing its absorption; also, the fiber content may reduce the rate of diffusion towards the mucosal surface and thus reduce cholesterol absorption → improving lipid metabolism in type II diabetic patients (↑ HDL, ↓ LDL & ↓ TG).  3-Fenugreek Dosage: Dried seed: 5-10 g/day. Extract: 0.6-1.2 g/day. Adverse reaction: Indications: Diarrhea 1- For diabetes mellitus. 2-For hypercholesterolemia. Stomach upset 3- For metabolic syndrome. Bloating, and gas Allergic reactions in some people.  3-Fenugreek Contraindications: Pregnancy: malformations in the baby, as well as early contractions. Drug interactions: Allergies: People who are allergic to Antidiabetics. other plants in the Fabaceae family, Anticoagulants. including soybeans, peanuts, green Theophylline: Using peas, and other. fenugreek while taking Surgery: Fenugreek might slow blood theophylline might reduce the clotting. effects of theophylline. Diabetics: Fenugreek can affect blood sugar levels in people with diabetes.  ‫‪4-Gymnema‬‬ ‫عشبة الجيمنيما أو‬ ‫جورمار‬ ‫‪Leaves‬‬  4-Gymnema Botanical origin Leaves of Gymnema sylvestre Family: Asclepiadaceae. Active constituents 1- Oleanane saponins: gymnemic acids. 2-Polypeptide: gurmarin. Gymnemic acid  4-Gymnema Mechanism of action 1- Hypoglycemic: 1) Increases secretion of insulin. 2) Promotes regeneration of β-cells. 3) Increases utilization of glucose: it is shown to increase the activities of enzymes responsible for utilization of glucose (phosphorylase), decrease in gluconeogenic enzymes and sorbitol dehydrogenase. 4) Inhibit glucose absorption from intestine.  4-Gymnema Mechanism of action 2-Hypolipidemic: Increase fecal excretion of cholesterol (↓ LDL & ↓ TG). 3- Anti-obesity: Gymnemic acid blocks the sugar receptors on your taste buds → Reduces sugar cravings by making sweet foods taste less appealing.  4-Gymnema Dosage: Powder: 2-4g/day Extract: 100 mg 3–4 times daily. Indications: Adverse reaction: For treatment of: Headache Metabolic disorders Nausea Hypercholesterolemia Diabetes Dizziness. Obesity Hypoglycemia.  4-Gymnema Drug interactions: Antidiabetic drugs. Medications changed by the liver Contraindications: (Cytochrome P450) enzymes. Phenacetin: (analgesic and Pregnancy and breast- antipyretic drug), decrees its feeding. metabolism and increase the effects Surgery. and side effects of phenacetin. Tolbutamide: increases its metabolism and decrease the effects of tolbutamide. 5- Artichoke ‫الخرشوف‬ The aerial part (globe)  5- Artichoke Botanical origin The aerial parts (globe) of Cynara scolymus. Family: Asteraceae. Active constituents Cynaropicrin 1- Volatile oils: sesquiterpene lactones (Cynaropicrin) 2- Caffeic acid derivatives: [e.g. dicaffeoyl- quinic acid (Cynarin), caffeoylquinic acid (chlorogenic acid)]. 3- Flavonoids: (luteolin, apigenin). Cynarin  5- Artichoke Mechanism of action 1- Hypolipidemic: (i) inhibits the oxidation of LDL. (ii) inhibits the incorporation of acetate, thus reducing cholesterol biosynthesis. (iii) inhibits the enzyme hydroxy-methyl- glutaryl CoA (HMGCoA) reductase, a key enzyme in the cholesterol biosynthesis. 2- Hypotensive: promotes the enzyme eNOS → vasodilator → reduce systolic and diastolic blood pressure.  5- Artichoke Adverse reaction: Dosage: Allergic contact dermatitis (the Dried plant: 4-9 g/ day sesquiterpene lactone Extract: 320-640 mg 3 Cynaropicrin is a times daily. potentially allergenic Indications: molecule), with cross- For treatment of: sensitivity to other Hypercholesterolemia. Compositae /Asteraceae Metabolic syndrome. plants (e.g. feverfew, Liver dysfunction. chamomile, calendula). Gas, upset stomach, and diarrhea  5- Artichoke Contraindications: Drug interactions: Pregnancy and breast-feeding. Antidiabetic drugs. Gallstones. Antihypertensives. Bile duct obstruction. Medications changed by Allergy to ragweed and related the liver (Cytochrome plants. P450) enzymes. 6- Moringa ‫مورينجا‬ Leaves  6- Moringa Botanical origin Leaves of Moringa oleifera Family: Moringaceae Moringin Active constituents 1- Glucosinolates: glucomoringin & moringin. 2- Phenolic acids: caffeic acid, chlorogenic acid, o-coumaric acid, ellagic acid, ferulic acid and gallic acid. 3- Flavonoids: kaempferol, myricetin, quercetin, vitexin and epicatechin. Glucomoringin  6- Moringa Mechanism of action 1-Antihyperlipidemic: reduce LDL, triglycerides. 2-Antihypertensive: due to positive inotropic effect on heart as well as its ability as anti-hypercholesterolemia. 3-Anti-diabetic: aid insulin secretion and control blood sugar levels by inhibiting alpha-glucosidase. 5-Anti-obesity: Moringa help to control body weight due to its as anti-hypercholesterolemia, antidiabetic and anti- inflammatory effects.  6- Moringa Dosage: Moringa dried powder: 6-10 grams by mouth Adverse reaction: daily. When consumed Indications: in large quantities, 1-Antihyperlipidemic some people may 2-Antihypertensive experience 3-Anti-diabetic stomach upset. 4-Anti-obesity  6- Moringa Drug interactions: Medications changed by the liver Contraindications: (Cytochrome P450): Levothyroxine (Synthroid) Pregnancy (hormonal replacement in treatment Hypothyroidism of hypothyroidism). Medications moved by pumps in cells (P-glycoprotein substrates). ‫‪7- Red Yeast Rice‬‬ ‫خميرة األرز الحمراء‬  7- Red Yeast Rice Botanical origin Red yeast rice is produced by solid state fermentation of washed and cooked rice (Oryza sativa L., Fam. Poaceae) using the fungus Monascus purpureus. Active constituents Monacolin K Red yeast rice is standardized to contain 0.4% monacolin K.  7- Red Yeast Rice Mechanism of action Monacolin K inhibits HMG CoA reductase and thus cholesterol synthesis. (↑ HDL, ↓ LDL & ↓ TG).  7- Red Yeast Rice Dosage: Extract: 1.2-2.4 g/daily Adverse reaction: Indications: Stomach upset, heartburn, dizziness For hypercholesterolemia and flatulence. and hypertriglyceridemia. Muscle pain, tenderness, and weakness. Liver toxicity.  7- Red Yeast Rice Drug interactions: Cyclosporine → muscle problems. Contraindications: Gemfibrozil Pregnancy and breast-feeding. → muscle problems. Liver problems. Niacin → muscle problems. Hypolipidemic (statins) → ↑ side effects of it. ‫‪8- Garcinia or Gambooge‬‬ ‫‪or Malabar Tamarind‬‬ ‫الغرسنية الصمغية أو الغرسنية‬ ‫الكمبودية أو التمرهندي المليباري‬ ‫‪Fruit rind‬‬  8- Garcinia Botanical origin Fruit rind of Garcinia cambogia Family: Clusiaceae Active constituents Hydroxy-citric acid (HCA)  8- Garcinia Mechanism of action - Suppresses appetite. - Inhibits lipogenesis. - Lowers the production of cholesterol and fatty acids. - Increases the production of glycogen in the liver. - Increases the body’s production of heat by activating the process of thermogenesis. - Inhibited the actions of a specific enzyme in the liver called ATP Cytrate Lyase. This enzyme is specifically responsible for the conversion of carbohydrates to fat. - HCA competitively inhibits adenosine triphosphate-citrate (pro-3S)-lyase, an extra-mitochondrial enzyme that plays a role in fatty acid biosynthesis.  8- Garcinia Dosage: Adverse reaction: Standardized extract Nausea containing 50% HCA: 500- Upset stomach 1000 mg 3 times daily, ½ hr. Diarrhea before meals. Headache Indications: Dizziness For treatment of metabolic syndrome & obesity Dry mouth. Low clinical evidence when Mania (euphoria, used alone but clinically delusions, effective when used in overexcitement, very fast combination with niacin- speech, decreased need bound chromium. for sleep, and irritability).  8- Garcinia Contraindications: Drug interactions: ❑ Hypersensitivity Green tea. ❑ Pregnancy and lactation Montelukast ❑ Diabetics Selective serotonin ❑ People suffering any dementia reuptake inhibitors. syndrome. 9-Green tea ‫الشاي األخضر‬ Leaves  9-Green tea Botanical origin The prepared leaves and leaf buds of Caffeine. Thea sinensis Linn. (Camellia Thea) Family: Theaceae. Active constituents 1- Alkaloids: Caffeine. 2-Poly phenols (catechins): epigallocatechin gallate (EGCG). EGCG  9-Green tea Mechanism of action Green tea has important roles in fat metabolism by: Reducing food intake. Interrupting lipid emulsification and absorption. Suppressing adipogenesis and lipid synthesis. Increasing energy expenditure via thermogenesis, fat oxidation and fecal lipid excretion.  9-Green tea Dosage: Adverse reaction: Dried leaves: Daily intake of 3 to 5 Dry mouth, dizziness, cups/day (720 to 1,200 mL) of green nausea, vomiting, tea provides at least 180 mg of heartburn, catechins constipation, diarrhea, Green tea catechins or extract: 160 fatigue, palpitation, to 2,488 mg/day, often in divided light-headedness, dosages (treatment duration, 2 weeks nocturia, sore throat, to 3 months). insomnia, and ECGC: 400 mg twice daily for 8 increased appetite; weeks. abdominal discomfort. Indications: Hepatotoxicity has For treatment of obesity, metabolic been reported (due to syndrome. EGCG).  9-Green tea Drug interactions: Atorvastatin: GT decrease its serum concentration Contraindications: Bortezomib: GT decrease its antineoplastic effect Hepatic failure. Folic acid: GT decrease its serum concentration. Garcinia: Garcinia may enhance the effect of green tea. Lisinopril: GT decrease its serum concentration. Warfarin: GT enhance the adverse effect of warfarin. risk of bleeding due to antiplatelet effects of green tea. 10-Psyllium husk ‫قشور السيليوم‬  10-Psyllium husk Botanical origin Seed husks of Plantago ovata. Family: Plantaginaceae Active constituents Water soluble fiber  10-Psyllium husk Mechanism of action - Significantly reduce postprandial serum glucose and insulin concentrations in non-diabetic individuals. - Improves glucose homeostasis by delaying gastric emptying, slowing the rate of intestinal absorption of glucose, or altering hormone secretion and/or sensitivity to a carbohydrate load. - Reducing serum and liver cholesterol and triglyceride levels. - Reduce blood pressure.  10-Psyllium husk Dosage: Adverse reaction: 5–10 g, with meals Bloating. and plenty of water. Allergy. Indications:  10-Psyllium husk Drug interactions: Contraindications: Psyllium can interact with several Children medications and affect their absorption. The drugs of greatest Bowel spasms or bowel concern include: obstruction Tegretol Colon or rectal cancer Lanoxin Allergy to psyllium Iron supplements Phenylketonuria (PKU), an Lithium inherited metabolic disorder Glucophage Zyprexa Thank you