Gary W. Chune, MD

• Assistant Professor of Internal Medicine
• Division of Endocrinology, Scott & White Hospitals,
• Texas A&M Health Sciences Center
• Temple, Texas

In addition thyroid gland ultrasound report levothroid 100 mcg low price, aprotinin should not be administered to patients who have already been exposed to the drug within the previous 12 months due to the possibility of anaphylactic reactions thyroid nodules blog cheap levothroid 200mcg on-line. Agents Used to Treat Anemia Anemia is defined as a below-normal plasma hemoglobin concentration resulting from a decreased number of circulating red blood cells or an abnormally low total hemoglobin content per unit of blood volume thyroid yawning levothroid 100mcg sale. Anemia can be caused by chronic blood loss thyroid symptoms vitamin d deficiency purchase levothroid 100 mcg on line, bone marrow abnormalities thyroid issues buy discount levothroid 100 mcg, increased hemolysis thyroid nodules found during pregnancy discount levothroid 200mcg with amex, infections, malignancy, endocrine deficiencies, renal failure, and P. A large number of drugs cause toxic effects on blood cells, hemoglobin production, or erythropoietic organs, which in turn may cause anemia. In addition, nutritional anemias are caused by dietary deficiencies of substances such as iron, folic acid, or vitamin B12 (cyanocobalamin) that are necessary for normal erythropoiesis. Iron Iron is stored in intestinal mucosal cells as ferritin (an iron-protein complex) until needed by the body. Iron deficiency results from acute or chronic blood loss, from insufficient intake during periods of accelerated growth in children, or in heavily menstruating or pregnant women. Thus, iron deficiency results from a negative iron balance due to depletion of iron stores and/or inadequate intake, culminating in hypochromic microcytic anemia (due to low iron and small-sized red blood cells). Gastrointestinal disturbances caused by local irritation are the most common adverse effects of iron supplements. Folic acid the primary use of folic acid is in treating deficiency states that arise from inadequate levels of the vitamin. Folate deficiency may be caused by 1) increased demand (for example, pregnancy and lactation), 2) poor absorption caused by pathology of the small intestine, 3) alcoholism, or 4) treatment with drugs that are dihydrofolate reductase inhibitors (for example, methotrexate or trimethoprim). A primary result of folic acid deficiency is megaloblastic anemia (large-sized red blood cells), which is caused by diminished synthesis of purines and pyrimidines. If excessive amounts of the vitamin are ingested, they are excreted in the urine and feces. Cyanocobalamin (vitamin B12) Deficiencies of vitamin B12 can result from either low dietary levels or, more commonly, poor absorption of the vitamin due to the failure of gastric parietal cells to produce intrinsic factor (as in pernicious anemia) or a loss of activity of the receptor needed for intestinal uptake of the vitamin. In patients with bariatric surgery (surgical gastrointestinal treatment for obesity), vitamin B12 supplementation is required in large oral doses, sublingually or once a month by the parenteral route. Nonspecific malabsorption syndromes or gastric resection can also cause vitamin B12 deficiency. The vitamin may be administered orally (for dietary deficiencies), intramuscularly, P. Therefore, megaloblastic anemia should not be treated with folic acid alone but, rather, with a combination of folate and vitamin B12. Therefore, darbepoetin has decreased clearance and has a half life about three times that of erythropoietin. Due to its delayed onset of action, darbepoetin has no value in acute treatment of anemia. The protein is usually administered intravenously in renal dialysis patients, but the subcutaneous route is preferred. Side effects are generally well tolerated but may include elevation in blood pressure and arthralgia in some cases. The recommendations for all patients receiving erythropoietin include a minimum effective dose that does not exceed a hemoglobin level of 12 g/dL, and this should not rise more than 1 g/dL over a 2-week period. Agents Used to Treat Sickle-Cell Disease Clinical trials have shown that hydroxyurea can relieve the painful clinical course of sickle-cell disease (Figure 20. Hydroxyurea is currently also being used to treat chronic myelogenous leukemia and polycythemia vera. In sickle-cell disease, the drug apparently increases fetal hemoglobin levels, thus diluting the abnormal hemoglobin S (HbS). Polymerization of HbS is delayed in the treated patients so that painful crises are not caused by sickled cells blocking capillaries and causing tissue anoxia. Important side effects of hydroxyurea include bone marrow suppression and cutaneous vasculitis. It is important that hydroxyurea is administered under the supervision of a physician experienced in the treatment of sickle-cell disease. The patient, who was in her second trimester of pregnancy, was treated for 7 days with intravenous unfractionated heparin. The pain resolved during the course of therapy, and the patient was discharged on Day 8. Which one of the following drugs would be most appropriate out-patient follow-up therapy for this patient, who lives 100 miles from the nearest hospital? Physical examination and vital signs were unremarkable except for subconjunctival hemorrhages and bleeding gums. The patient has been receiving oral warfarin since his valve replacement 1 year earlier. Which one of the following therapies would provide the most rapid recovery from the observed bleeding secondary to warfarin treatment? Hyperlipidemias can also result from a single inherited gene defect in lipoprotein metabolism or, more commonly, from a combination of genetic and lifestyle factors. Antihyperlipidemic drugs must be taken indefinitely; when therapy is terminated, plasma lipid levels return to pretreatment levels. Treatment Goals Plasma lipids consist mostly of lipoproteinsв"spherical macromolecular complexes of lipids and specific proteins (apolipoproteins). Roman numerals in the white circles refer to specific genetic types of hyperlipidemias summarized on the facing page. If indicated, niacin and fibric acid derivatives are the most efficacious in lowering triacylglycerol levels. Drugs that Lower the Serum Lipoprotein Concentration Antihyperlipidemic drugs target the problem of elevated serum lipids with complementary strategies. Some of these agents decrease production of the lipoprotein carriers of cholesterol and triglyceride, whereas others increase the degradation of lipoprotein. Still others decrease cholesterol absorption or directly increase cholesterol removal from the body. However, they are always accompanied by the requirement that dietary saturated and transfats1 be low, and the caloric content of the diet must be closely monitored. Therapeutic benefits include plaque stabilization, improvement of coronary endothelial function, inhibition of platelet thrombus formation, and anti-inflammatory activity. By inhibiting de novo cholesterol synthesis, they deplete the intracellular supply of cholesterol (Figure 21. Therapeutic uses: these drugs are effective in lowering plasma cholesterol levels in all types of hyperlipidemias (Figure 21. Thus, additional strategies, such as diet, exercise, or additional agents, may be warranted. Pharmacokinetics: Pravastatin and fluvastatin are almost completely absorbed after oral administration; oral doses of lovastatin and simvastatin are from 30 to 50 percent absorbed. Excretion takes place principally through the bile and feces, but some urinary elimination also occurs. Adverse effects: It is noteworthy that during the 5-year trials of simvastatin and lovastatin, only a few adverse effects, related to liver and muscle function, were reported (Figure 21. Therefore, it is prudent to evaluate liver function and measure serum transaminase levels periodically. Muscle: Myopathy and rhabdomyolysis (disintegration or dissolution of muscle) have been reported only rarely. In most of these cases, patients usually suffered from renal insufficiency or were taking drugs such as cyclosporine, itraconazole, erythromycin, gemfibrozil, or niacin. Contraindications: these drugs are contraindicated during pregnancy and in nursing mothers. Niacin can be used in combination with statins, and a fixed-dose combination of lovastatin and long-acting niacin is available. Mechanism of action: At gram doses, niacin strongly inhibits lipolysis in adipose tissueв"the primary producer of circulating free fatty acids. The liver normally utilizes these circulating fatty acids as a major precursor for triacylglycerol synthesis. Moreover, by boosting secretion of tissue plasminogen activator and lowering the level of plasma fibrinogen, niacin can reverse some of the endothelial cell dysfunction contributing to thrombosis associated with hypercholesterolemia and atherosclerosis. Therapeutic uses: Niacin lowers plasma levels of both cholesterol and triacylglycerol. Therefore, it is particularly useful in the treatment of familial hyperlipidemias. Niacin is also used to treat other severe hypercholesterolemias, often in combination with other antihyperlipidemic agents. Niacin, its nicotinamide derivative, and other metabolites are excreted in the urine. Adverse effects: the most common side effects of niacin therapy are an intense cutaneous flush (accompanied by an uncomfortable feeling of warmth) and pruritus. Administration of aspirin prior to taking niacin decreases the flush, which is prostaglandin mediated. The sustained-release formulation of niacin, which is taken once daily at bedtime, reduces bothersome initial adverse effects. Niacin inhibits tubular secretion of uric acid and, thus, predisposes to hyperuricemia and gout. They then bind to peroxisome proliferator response elements, which are localized in numerous gene promoters. Fibrate-mediated gene expression ultimately leads to decreased triacylglycerol concentrations by increasing the expression of lipoprotein lipase (Figure 22. Fenofibrate is a prodrug, producing an active metabolite, fenofibric acid, which is responsible for the primary effects of the drug. Therapeutic uses: the fibrates are used in the treatment of hypertriacylglycerolemias, causing a significant decrease in plasma triacylglycerol levels. Both drugs undergo extensive biotransformation and are excreted in the urine as their glucuronide conjugates. Gastrointestinal effects: the most common adverse effects are mild gastrointestinal disturbances. Lithiasis: Because these drugs increase biliary cholesterol excretion, there is a predisposition to the formation of gallstones. Muscle: Myositis (inflammation of a voluntary muscle) can occur with both drugs; thus, muscle weakness or tenderness should be evaluated. Myopathy and rhabdomyolysis have been reported in a few patients taking gemfibrozil and lovastatin together. Drug interactions: Both fibrates compete with the coumarin anticoagulants for binding sites on plasma proteins, thus transiently potentiating anticoagulant activity. Contraindications: the safety of these agents in pregnant or lactating women has not been established. They should not be used in patients with severe hepatic and renal dysfunction or in patients with preexisting gallbladder disease. The resin/bile acid complex is excreted in the feces, thus preventing the bile acids from returning to the liver by the enterohepatic circulation. Lowering the bile acid concentration causes hepatocytes to increase conversion of cholesterol to bile acids, resulting in a replenished supply of these compounds, which are essential components of the bile. The final outcome of this sequence of events is a decreased total plasma cholesterol concentration. Because they are insoluble in water and are very large (molecular weights are greater than 106), they are neither absorbed nor metabolically altered by the intestine. Gastrointestinal effects: the most common side effects are gastrointestinal disturbances, such as constipation, nausea, and flatulence. Colesevelam has fewer gastrointestinal side effects than other bile acid sequestrants. Impaired absorptions: At high doses, cholestyramine and colestipol (but not colesevelam) impair the absorption of the fat-soluble vitamins (A, D, E, and K). Drug interactions: Cholestyramine and colestipol interfere with the intestinal absorption of many drugsв"for example, tetracycline, phenobarbital, digoxin, warfarin, pravastatin, fluvastatin, aspirin, and thiazide diuretics. Therefore, drugs should be taken at least 1 to 2 hours before, or 4 to 6 hours after, the bile acidв"binding resins. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood. Both ezetimibe and ezetimibe-glucuronide are slowly eliminated from plasma, with a half-life of approximately 22 hours. Ezetimibe has no clinically meaningful effect on the plasma concentrations of the fat-soluble vitamins A, D, and E. Patients with moderate to severe hepatic insufficiency should not be treated with ezetimibe. Combination drug therapy It is often necessary to employ two antihyperlipidemic drugs to achieve treatment goals in plasma lipid levels. However, the clinical value of ezetimibe either alone or in combination with statins is uncertain. Until this discrepancy is resolved, many experts recommend clinicians maximize statin dosages and use niacin, fibrates, and resins before considering ezetimibe, Figure 21. These agents are inhibitors of renal ion transporters that decrease the reabsorption of Na+ at different sites in the nephron. As a result, Na+ and other ions, such as Cl-, enter the urine in greater than normal amounts along with water, which is carried passively to maintain osmotic equilibrium. Diuretics thus increase the volume of urine and often change its pH as well as the ionic composition of the urine and blood. The efficacy of the different classes of diuretics varies considerably, with the increase in Na+ secretion varying from less than two percent for the weak, potassium-sparing diuretics to over 20 percent for the potent loop diuretics.

Digoxin should be prescribed concurrently as it is the most effective drug for restoring compensation by increasing cardiac contractility thyroid gland not producing enough hormones buy levothroid 100mcg amex. Enalapril dose of 5 mg twice a day should be increased by 5 mg/day at 1­2 week intervals till hypotension or other side effects appear or 40 mg/day dose is reached thyroid websites purchase levothroid 100 mcg line. Since the patient is in a decompensated state thyroid cancer items generic levothroid 50mcg mastercard, a blocker cannot be added at this stage thyroid nodules and smoking levothroid 200mcg mastercard, because chances of deterioration of cardiac status are high thyroid gland vascularity generic 200mcg levothroid. However thyroid symptoms mental health order 200mcg levothroid fast delivery, after compensation has been restored by digoxin, diuretic and enalapril and the patient is in a stable condition, a suitable blocker may be started at a very low dose, to be upward titrated later, because blockers afford further morbidity and mortality benefits. Therefore, he has been put on anticoagulant medication with warfarin to prevent thromboembolism. His heart (ventricular) rate can be controlled by a drug which depresses A-V conduction. For this purpose verapamil or diltiazem or propranolol should be given orally and dose adjusted to maintain a heart rate between 60­70/min. This patient is having one or more episodes of angina practically every day; therefore, he should be prescribed regular medication to prevent the episodes. Considering the age of the patient (>55 years), diagnosis of isolated systolic hypertension, history of stroke in the past, absence of diabetes/heart failure/ischaemic heart disease/chronic kidney disease, the most suitable antihypertensive drug for this patient is a thiazide diuretic (hydrochlorothiazide/chlorthalidone) or a long-acting dihydropyridine calcium channel blocker (like amlodipine). Therapy may be initiated with either of these classes of drugs and later modified depending on the response and tolerability. Induction of brisk diuresis with furosemide alone is not the appropriate treatment of cirrhotic edema and ascites. It can be supplemented by furosemide, because spironolactone alone is a weak diuretic. In this patient, use of furosemide alone resulted in further hypokalaemia and alkalosis. Because of secondary hyperaldosteronism, the response to furosemide decreased within few days. At this stage, the patient should be managed by temporarily stopping furosemide and instituting spironolactone (50 mg 6 hourly) therapy along with appropriate i. After restoration of the fluid/electrolyte balance and his mental status, the patient should be put on maintenance therapy with spironolactone (100­400 mg/day) and furosemide (40­160 mg/day) with dose adjustment according to response. If hormonal side effects of spironolactone occur, it may be substituted by the other aldosterone antagonist eplerenone. The potassium sparing nonaldosterone antagonist diuretic amiloride is an alternative. There are several reasons which could account for failure of this patient of iron deficiency anaemia to respond to the oral iron medication she has been taking: · Taking 160 mg of ferric ammonium citrate (iron content 20%) would provide just 32 mg of elemental iron/day. This is grossly inadequate to treat iron deficiency, for which 200 mg of elemental iron/day is required to yield optimum response. This patient is taking acid suppressant medication (rabeprazole, a proton pump inhibitor). Since there are obvious factors in this case which can be tackled, it would be inappropriate to abandon oral iron therapy at this stage and jump on to injectable iron. Proper selection of oral iron preparation and its dose, and careful management of therapy may yield a response in this patient. A ferrous salt with high iron content like ferrous sulphate or ferrous fumarate (both having ~33% iron) should be prescribed in a dose of 200 mg 3 times a day (total 600 mg or 200 mg elemental iron/day). However, therapy should be initiated with a low dose to be gradually increased as the gastrointestinal tract adjusts to the medication and tolerance to side effects develops. The doses should preferably be taken in empty stomach, but if gastric discomfort occurs, it may be given with food. Selection of ferrous salt would reduce dependence on gastric acid for absorption of iron. The obvious cause in this patient is the additive hypoprothrombinaemic action of inj ceftriaxone given for treatment of pelvic infection. This complication could have been prevented either by selecting an antibiotic that does not cause hypoprothrombinaemia/interact with warfarin or by reducing the dose of warfarin when ceftriaxone was started. Because Hb level is 9 g/dl, blood transfusion is not required at this stage, but must be kept handy in case she bleeds further. Changing the antibiotic to one which does not cause hypoprothrombinaemia or bleeding may be considered on the basis of bacteriological sensitivity of the organism causing pelvic infection. Thus, apart from lifestyle changes to regulate diet, reduce body weight and increase physical exercise, he requires lipid lowering medication. However, it alone cannot prevent recurrences, which most commonly are caused by persistent Contd. Since the same cannot be confirmed in the absence of testing facility, he should be given the benefit of H. This child has developed acute muscular dystonia, an extrapyramidal motor reaction that can be caused by drugs with dopaminergic D2 receptor blocking action. Antiemetics with D2 blocking action are chlorpromazine and related neuroleptics like triflupromazine, prochlorperazine, etc. It is likely that the girl was given injection of one of these drugs by the local doctor, following which the vomiting had subsided and the dystonia had developed within 2­3 hours. Though the dystonic reaction usually passes off within a few hours, it can be rapidly reversed by a parenterally administered centrally acting anticholinergic drug. Since the parents are alarmed and to afford quick relief, she may be given a deep intramuscular injection of 10­15 mg of promethazine or hydroxyzine, which have anticholinergic, antihistaminergic, sedative and antiemetic properties. This patient of diarrhoea seems to have lost only small amount of fluid and there are no signs of dehydration. Thus, there is no need of rehydration therapy, but normal fluid intake and nutrition should be continued. The features of this patient including fever are indicative of moderately severe enteroinvasive infection. A well absorbed fluoroquinolone like ciprofloxacin or ofloxacin would be suitable first line antibiotic for empiric therapy. Antimotility-antidiarrhoeal drug is contraindicated in this patient, because in all likelyhood there is enteroinvasive infection, so that restriction of bowel clearance can favour further bowel wall invasion and systemic spread of the pathogen. Abdominal pain can be dampened by an antispasmodic drug like dicyclomine 20 mg 6­8 hourly. Therefore, prophylaxis covering aerobic as well as anaerobic organisms and both gram-negative as well as gram-positive bacteria would be appropriate. Normally, there is no need to repeat the injection, but if the surgery lasts more than 2 hours, a repeat injection after surgery may be given. Moreover, it has a convenient once a day oral dosing schedule and is generally well tolerated. These could be the considerations on the basis of which the doctor has decided to use moxifloxacin. However, moxifloxacin is not appropirate for this patient because she is receiving amitryptyline, a tricyclic antidepressant which has proarrhythmic potential. Moxifloxacin can prolong Q-T interval and increase the risk of serious cardiac arrhythmias such as Torsades de pointes when given along with amitryptyline. Other antibiotics which are active against gram-positive cocci and suitable for treating sinusitis are amoxicillin alone or with clavulanic acid, a first generation cephalosporin or azithromycin. In this patient antibiotic therapy should be started on the basis of clinical diagnosis, because the patient is quite sick. Moreover, blood culture is not necessarily positive in all cases of typhoid fever. The most appropriate antibiotic is ceftriaxone (or a similar 3rd generation cephalosporin like cefoperazone, cefotaxime), becuase it produces the fastest and surest response. The daily dose for this boy would be (75 mg/kg x 25 kg) = 1875 mg or rounded off to 2. In case of typhoid fever, a single antibiotic is sufficient, since addition of another antibiotic has not been found to hasten or improve the response. The most appropriate drugs and regimens for treating chlamydial endocervicitis are: Azithromycin 1. Both these regimens are adequate to treat uncomplicated gonococcal infection as well as concurrent chlamydial and gonococcal infection. While azithromycin has the advantage of single dose treatment, doxycycline needs twice daily dosing for one week, but is cheaper. Other first choice antibiotics like amoxicillin and ceftriaxone for gonorrhoea are not effective against chlamydia. The recommended dose range of gentamicin for a person with normal renal function is 3­5 mg/kg/day (or 4 mg/kg/day on average). For a patient with creatinine clearance value of 50 ml/min, the dose has to be reduced to 50%, or 2 mg/kg/day. With renal impairment, this patient is not suitable for once daily dosing regimen, and he should be treated with the conventional 8 hourly regimen. As such, he may be injected with gentamicin 40 mg every 8 hours making it 120 mg/24 hours. The usual dose-range of cefotaxime for an adult is 1­2 g every 6­12 hours (2­8 g/day). This patient has renal impairment, half life of cefotaxime is likely to be prolonged. Since the patient has distressing urinary symptoms and is febrile, empirical antimicrobial treatment should be started after urine has been collected for bacteriological testing. The first line antimicrobials for this purpose are fluoroquinolones, cotrimoxazole, amoxicillinclavulanate, an oral 1st or 2nd generation cephalosporin, or nitrofurantoin. Any of these may be selected and prescribed for 3­5 days depending on symptom resolution. Nitrofurantoin is usually not preferred because it needs at least 7 days treatment, and often causes nausea and gastric pain. It relieves symptoms of bladder and uretheral irritation and can be given with the selected antimicrobial drug. Because this patient has suffered >3 episodes of cystitis within one year, she should be advised long term prophylactic therapy. The suitable prophylactic drug for her is cephalexin 250 mg once daily at bed time, because it is not contraindicated in pregnant women. Though this patient is not presently pregnant, she may conceive during use of the prophylactic drug. The other recommended prophylactic drugs, viz cotrimoxazole, nitrofurantoin and norfloxacin are all contraindicated during pregnancy. However, chemotherapy should be started immediately, because the culture and sensitivity tests take 6 weeks or more and defering treatment for such a long time may jeopardise outcome. This is a defaulted patient who has taken isoniazid and rifampin only for 3 months. For the initial 2 months, he should be given all 5 first line drugs, viz isoniazid 300 mg + rifampin 600 mg + pyrazinamide 1. Streptomycin should be stopped after that and the 4 oral drugs given for another 1 month. Pyrazinamide should be discontinued and 3 drugs rifampin, isoniazid and ethambutol should be continued for 5 more months. The regimen may be modified when the culture and sensitivity report becomes available. Since the patient had taken the standard multidrug therapy for the prescribed one year, and had responded clinically, the most likely cause of relapse is reactivation of dormant (persister) bacilli. As such, he should be treated with the same drugs, viz rifampin 600 mg + clofazimine 300 mg once a month alongwith dapsone 100 mg + clofazimine 50 mg daily for one year. The treatment of choice for Candida esophagitis is oral fluconazole 100 mg/day for 3 weeks, because it is highly effective and well tolerated. These may be treated with itraconazole 200/day or voriconazole 200 mg twice daily. Uncontrolled diabetes is an important predisposing factor in the causation of esophageal candidiasis, and appears to have played a role in this patient. Since the patient already had a complication of diabetes (Candida infection) it is desirable to shift her to insulin therapy (at least till the esophagitis is fully cured). The dose and frequency of insulin injections should be guided by repeated blood glucose monitoring. The intensity of action of glibenclamide (if continued in this case) is likely to be affected unpredictably. Thus, even if this drug is continued, close monitoring of blood glucose level and dose adjustment of the sulfonylurea is required. Therefore, it would be prudent to give prophylactic medication to further cut down chances of acquiring the infection. The dental surgeon should be advised to immediately start taking- Zidovudine 300 mg + Lamivudine 150 mg twice daily for 4 weeks. While majority of asexual schizonts are killed by chloroquine and the fever subsides, some survive and multiply to cause fever again. As broughtout above, recrudescence indicates chloroquine-resistance, which is particularly likely in this case, because the infection appears to be contacted from an area where chloroquineresistance among P. As such, she should be treated with an alternative drug effective against chloroquine-resistant P. Quinine 600 mg three times a day for 7 days along with doxycycline 100 mg once daily for 7 days. Artesunate 100 mg twice daily for 3 days, along with a single dose of sulfadoxine 1500 mg + pyrimethamine 75 mg. The primaquine therapy should be continued to complete the 14-day course, so as to totally eradicate the P.

Order levothroid 200mcg overnight delivery. महिलाओं को क्यों होता है थायराइड का खतरा 4 घरेलू नुस्खे रखेंगे बचाव // Thyroid In Women.

Fennel Flower (Black Seed). Levothroid.

• Are there safety concerns?
• How does Black Seed work?
• What is Black Seed?
• Dosing considerations for Black Seed.
• Digestive problems including intestinal gas and diarrhea, asthma, allergies, cough, bronchitis, flu, congestion, high blood pressure, boosting the immune system, cancer prevention, birth control, menstrual disorders, increasing breast-milk flow, achy joints (rheumatism), headache, skin conditions, and many other uses.

Source: http://www.rxlist.com/script/main/art.asp?articlekey=96867

Secondary hyperaldosteronism: Spironolactone is the only potassium-sparing diuretic that is routinely used alone to induce a net negative salt balance thyroid gland cortisol buy 200 mcg levothroid otc. It is particularly effective in clinical situations associated with secondary hyperaldosteronism thyroid cancer day order levothroid 50 mcg with visa. Heart failure: Spironolactone prevents the remodeling that occurs as compensation for the progressive failure of the heart thyroid cancer in lungs 100 mcg levothroid mastercard. Pharmacokinetics: Spironolactone is completely absorbed orally and is strongly bound to proteins thyroid nodules in spanish generic 200 mcg levothroid with amex. Adverse effects: Spironolactone frequently causes gastric upsets and can cause peptic ulcers thyroid gland operation video dailymotion purchase 200mcg levothroid mastercard. Because it chemically resembles some of the sex steroids thyroid symptoms anger cheap levothroid 100 mcg line, spironolactone may act at receptors in other organs to induce gynecomastia in males and menstrual irregularities in females; therefore, the drug should not be given at high doses on a chronic basis. It is most effectively employed in mild edematous states, for which it is given for a few days at a time. Although they have a K+-sparing diuretic action similar to that of spironolactone, their ability to block the Na+/K+-exchange site in the collecting tubule does not depend on the presence of aldosterone. Both triamterene and amiloride are frequently used in combination with other diuretics, usually for their potassium-sparing properties. For example, much like spironolactone, they prevent the loss of K+ that occurs with thiazides and furosemide. The side effects of triamterene are leg cramps and the possibility of increased blood urea nitrogen as well as uric acid and K+ retention. Carbonic anhydrase inhibitors are more often used for their other pharmacologic actions rather than for their diuretic effect, because they are much less efficacious than the thiazides or loop diuretics. Mechanism of action: Acetazolamide inhibits carbonic anhydrase located intracellularly (cytoplasm) and on the apical membrane of the proximal tubular epithelium (Figure 22. The decreased ability to exchange Na+ for H+ in the presence of acetazolamide results in a mild diuresis. Changes in the composition of urinary electrolytes induced by acetazolamide are summarized in Figure 22. Treatment of glaucoma: the most common use of acetazolamide is to reduce the elevated intraocular pressure of open-angle glaucoma. Acetazolamide decreases the production of aqueous humor, probably by blocking carbonic anhydrase in the ciliary P. It is useful in the chronic treatment of glaucoma but should not be used for an acute attack; pilocarpine is preferred for an acute attack because of its immediate action. Topical carbonic anhydrase inhibitors, such as dorzolamide and brinzolamide, have the advantage of not causing any systemic effects. Mountain sickness: Less commonly, acetazolamide can be used in the prophylaxis of acute mountain sickness among healthy, physically active individuals who rapidly ascend above 10,000 feet. Acetazolamide given nightly for 5 days before the ascent prevents the weakness, breathlessness, dizziness, nausea, and cerebral as well as pulmonary edema characteristic of the syndrome. Adverse effects: Metabolic acidosis (mild), potassium depletion, renal stone formation, drowsiness, and paresthesia may occur. If the substance that is filtered subsequently undergoes little or no reabsorption, then the filtered substance will cause an increase in urinary output. Because osmotic diuretics are used to effect increased water excretion rather than Na+ excretion, they are not useful for treating conditions in which Na+ retention occurs. They are used to maintain urine flow following acute toxic ingestion of substances capable of producing acute renal failure. Osmotic diuretics are a mainstay of treatment for patients with increased intracranial pressure or acute renal failure due to shock, drug toxicities, and trauma. Maintaining urine flow preserves long-term kidney function and may save the patient from dialysis. The expansion of extracellular water results because the presence of mannitol in the extracellular fluid extracts water from the cells and causes hyponatremia until diuresis occurs. Which of the following drugs would be appropriate for them to take to prevent mountain sickness? Overview the neuroendocrine system, which is controlled by the pituitary and hypothalamus, coordinates body functions by transmitting messages between individual cells and tissues. This contrasts with the nervous system which communicates locally by electrical impulses and neurotransmitters directed through neurons to other neurons or to specific target organs, such as muscle or glands. The endocrine system releases hormones into the bloodstream, which carries these chemical messengers to target cells throughout the body. Hormones have a much broader range of response time than do nerve impulses, requiring from seconds to days, or longer, to cause a response that may last for weeks or months. For example, in several instances, the release of hormones is stimulated or inhibited by the nervous system, and some hormones can stimulate or inhibit nerve impulses. Chapters 24 to 26 focus on drugs that affect the synthesis and/or secretion of specific hormones and their actions. In this chapter, the central role of the hypothalamic and pituitary hormones in regulating body functions is briefly presented (Figure 23. In addition, drugs affecting thyroid hormone synthesis and/or secretion are discussed. Hypothalamic and Anterior Pituitary Hormones the hormones secreted by the hypothalamus and the pituitary are all peptides or low-molecular-weight proteins that act by binding to specific receptor sites on their target tissues. The hormones of the anterior pituitary are regulated by neuropeptides that are called either вoereleasingв or вoeinhibitingв factors or hormones. These are produced in cell bodies in the hypothalamus, and they reach the cells of the pituitary by the hypophysial portal system (Figure 23. The interaction of the releasing hormones with their receptors results in the activation of genes that promote the synthesis of protein precursors. These are then processed posttranslationally to the hormones and are released into the circulation. The hypothalamic-releasing hormones are primarily used for diagnostic purposes (that is, to determine pituitary insufficiency). Stress stimulates its secretion, whereas cortisol acting via negative feedback suppresses its release. This pathway ends with the synthesis and release of the adrenocorticosteroids and the adrenal androgens (see Figure 23. Somatotropin influences a wide variety of biochemical processes; for example, through stimulation of protein synthetic processes, cell proliferation and bone growth are promoted. Somatotropin and somatrem should not be used in individuals with closed epiphyses or an enlarging intracranial mass. Originally isolated from the hypothalamus, somatostatin is a small polypeptide that is also found in neurons throughout the body as well as in the intestine and pancreas. Its half-life is longer than that of the natural compound, and a depot form is also available. Gallbladder emptying is delayed, and asymptomatic cholesterol gallstones can occur with long-term treatment. These are effective in suppressing production of the gonadal hormones and, thus, are effective in the treatment of prostatic cancer, P. Adverse effects of gonadorelin include hypersensitivity, dermatitis, and headache. In women, the analogs may cause hot flushes and sweating as well as diminished libido, depression, and ovarian cysts. In men, they initially cause a rise in testosterone that can result in bone pain; hot flushes, edema, gynecomastia, and diminished libido also occur. Gonadotropins: Human menopausal gonadotropin, follicle-stimulating hormone, and human chorionic gonadotropin the gonadotropins are glycoproteins that are produced in the anterior pituitary. The hormone enters a cell, where it activates a tyrosine kinase to promote tyrosine phosphorylation and gene activation. On the other hand, hyperprolactinemia, which is associated with galactorrhea and hypogonadism, is usually treated with D2-receptor agonists, such as bromocriptine and cabergoline. Both of these agents also find use in the treatment of microadenomas and macroprolactinomas. They not only act at the D2 receptor to inhibit prolactin secretion but also cause increased hypothalamic dopamine by decreasing its turnover. Among their adverse effects are nausea, headache, and sometimes, psychiatric problems. Hormones of the Posterior Pituitary In contrast to the hormones of the anterior lobe of the pituitary, those of the posterior lobe, vasopressin and oxytocin, are not regulated by releasing hormones. Instead, they are synthesized in the hypothalamus, transported to the posterior pituitary, and released in response to specific physiologic signals, such as high plasma osmolarity or parturition. Its only use is in obstetrics, where it is employed to stimulate uterine contraction to induce or reinforce labor or to promote ejection of breast milk. Oxytocin causes milk ejection by contracting the myoepithelial cells around the mammary alveoli. Although toxicities are uncommon when the drug is used properly, hypertensive crises, uterine rupture, water retention, and fetal death have been reported. Its antidiuretic and pressor activities are very much lower than those of vasopressin. The chemically synthesized nonapeptide has replaced that extracted from animal posterior pituitaries. In the kidney, it binds to the V 2 receptor to increase water permeability and resorption in the collecting tubules. It also finds use in controlling bleeding due to esophageal varices or colonic diverticula. Other effects of vasopressin are mediated by the V1 receptor, which is found in liver, vascular smooth muscle (where it causes constriction), and other tissues. As might be expected, the major toxicities are water intoxication and hyponatremia. Caution must be used when treating patients with coronary artery disease, epilepsy, and asthma. This analog is now preferred for diabetes insipidus and nocturnal enuresis and is longer-acting than vasopressin. Thyroid Hormones the thyroid gland facilitates normal growth and maturation by maintaining a level of metabolism in the tissues that is optimal for their normal function. The two major thyroid hormones are triiodothyronine (T3; the most active form) and thyroxine (T4). Although the thyroid gland is not essential for life, inadequate secretion of thyroid hormone (hypothyroidism) results in bradycardia, poor resistance to cold, and mental and physical slowing (in children, this can cause mental retardation and dwarfism). If, however, an excess of thyroid hormones is secreted (hyperthyroidism), then tachycardia and cardiac arrhythmias, body wasting, nervousness, tremor, and excess P. Thyroid hormone synthesis and secretion the thyroid gland is made up of multiple follicles that consist of a single layer of epithelial cells surrounding a lumen filled with colloid (thyroglobulin), which is the storage form of thyroid hormone. A summary of the steps in thyroid hormone synthesis and secretion is shown in Figure 23. Oxidation to iodine (I2) by a peroxidase is followed by iodination of tyrosines on thyroglobulin. Mechanism of action Both T4 and T3 must dissociate from thyroxine-binding plasma proteins prior to entry into cells, either by diffusion or by active transport. In the cell, T4 is enzymatically deiodinated to T3, which enters the nucleus and attaches to specific receptors. Food, calcium preparations, and aluminum-containing antacids can decrease the absorption of T4 but not of T3. T4 is converted to T3 by one of two distinct deiodinases, depending on the tissue. Drugs that induce the P450 enzymes, such as phenytoin, rifampin, and phenobarbital, accelerate metabolism of the thyroid hormones (Figure 23. Toxicity is directly related to T4 levels and manifests itself as nervousness, heart palpitations and tachycardia, intolerance to heat, and unexplained weight loss. The goal of therapy is to decrease synthesis and/or release of additional hormone. This can be accomplished by removing part or all of the thyroid gland, by inhibiting synthesis of the hormones, or by blocking release of the hormones from the follicle. Removal of part or all of the thyroid: this can be accomplished either surgically or by destruction of the gland by beta particles emitted by radioactive iodine (131I), which is selectively taken up by the thyroid follicular cells. Younger patients are treated with the isotope without prior pretreatment with methimazole (see below), whereas the opposite is the case in elderly patients. Most patients become hypothyroid as a result of this drug and require treatment with levothyroxine. The effects of these drugs are slow in onset; thus, they are not effective in the treatment of thyroid storm (see below). Thyroid storm: ОІ-Blockers that lack sympathomimetic activity, such as propranolol, are effective in blunting the widespread sympathetic stimulation that occurs in hyperthyroidism. An alternative in patients suffering from severe heart failure or asthma is the calciumchannel blocker, diltiazem. Blockade of hormone release: A pharmacologic dose of iodide inhibits the iodination of tyrosines (the so-called вoeacute Wolff-Chaikoff effectв), but this effect lasts only a few days. What is more important, iodide inhibits the release of thyroid hormones from thyroglobulin by mechanisms not yet understood. However, it is employed to treat potentially fatal thyrotoxic crisis (thyroid storm) or prior to surgery, because it decreases the vascularity of the thyroid gland. Iodide is not useful for long-term therapy, because the thyroid ceases to respond to the drug after a few weeks. Adverse effects are relatively minor and include sore mouth and throat, swelling of the tongue or larynx, rashes, ulcerations of mucous membranes, and a metallic taste in the mouth. It blocks iodination and coupling of tyrosines in thyroglobulin to form thyroid hormones. Octreotide: treatment of diarrhea associated with vasoactive intestinal peptide tumors C. Overview the pancreas is both an endocrine gland that produces the peptide hormones insulin, glucagon, and somatostatin and an exocrine gland that produces digestive enzymes.

The risk of retrolental fibroplasia in premature infants exposed to high oxygen concentrations can be reduced by 100 mg/kg/day oral vitamin E thyroid nodules removal order 50mcg levothroid amex. Alongwith vit A to enhance its absorption and storage thyroid symptoms youtube purchase 100mcg levothroid free shipping, and in hypervitaminosis A to reduce its toxicity thyroid nodules found on ultrasound levothroid 200mcg with amex. Large doses (400­600 mg/day) have been reported to afford symptomatic improvement in intermittent claudication thyroid cancer information generic levothroid 100mcg mastercard, fibrocystic breast disease and nocturnal muscle cramps thyroid gland assessment order levothroid 50 mcg mastercard. For its antioxidant property thyroid blood supply discount levothroid 50mcg amex, vit E has been promoted for recurrent abortion, sterility, menopausal syndrome, toxaemia of pregnancy, atherosclerosis, ischaemic heart disease, cancer prevention, several skin diseases, prevention of neurodegenerative disorders, postherpetic neuralgia, scleroderma and many other conditions, but without convincing evidence of benefit. Toxicity Even large doses of vit E for long periods have not produced any significant toxicity, but creatinuria and impaired wound healing have been reported; abdominal cramps, loose motions and lethargy have been described as side effects of vit. Antioxidant vitamins (vit E, carotene, vit C) in prevention of cardiovascular disease and cancer Antioxidants are believed to quench free radicals. Many endogenous and dietary compounds like superoxide dismutase, ferritin, transferrin, ceruloplasmin, tocopherol, carotene and ascorbic acid have antioxidant and free radical scavenging properties. On this theoretical basis supported by some epidemiological observations, cohort studies and prospective trials carotene, vit C and especially vit E have been claimed to protect against atherosclerosis leading to coronary artery disease as well as many types of cancers (lung, breast, mouth, skin, esophagus, stomach, etc. As a result, vit E and others are being aggressively promoted and many physicians are prescribing them for prophylaxis of these conditions. Learning from mass media, people on their own also are consuming them on a large scale. Several large observational studies (involving tens of thousands of subjects) and their metaanalysis have failed to demonstrate any benefit of antioxidant vitamins in terms of cardiovascular event/cancer prevention in well nourished population. It is present in the outer layers of cereals (rice polishing), pulses, nuts, green vegetables, yeasts, egg and meat. B12 Cyanocobalamin Hydroxocobalamin Methylcobalamin C Ascorbic acid Labile in solution 60 mg Absorption and fate Physiological amounts are absorbed by active transport. Prophylactically (2­10 mg daily) in infants, pregnant women, chronic diarrhoeas, patients on parenteral alimentation. Acute alcoholic intoxication: thiamine 100 mg is added to each vac of glucose solution infused. In neurological and cardiovascular disorders, hyperemesis gravidarum, chronic anorexia and obstinate constipation-thiamine has been used even without definite proof of its deficiency- symptoms improve dramatically if thiamine deficiency has been causative. Riboflavin (vit B2) Chemistry and source A yellow flavone compound found in milk, egg, liver, green leafy vegetables, grains. Absorption and fate Well absorbed by active transport and phosphorylated in the intestine. Body does not significantly store riboflavin; larger doses are excreted unchanged in urine. Thiamine and riboflavin are both synthesized by colonic bacteria but this does not become available to the host. Deficiency symptoms Riboflavin deficiency generally occurs in association with other deficiencies. Characteristic lesions are angular stomatitis; sore and raw tongue, lips, throat, ulcers in mouth; vascularization of cornea. Therapeutic uses to prevent and treat ariboflavinosis (2­20 mg/day oral or parenteral), generally along with other B complex members. Niacin (vit B3) Chemistry and source Niacin refers to Nicotinic acid as well as Nicotinamide-pyridine compounds, initially termed pellagra preventing factor. The amino acid tryptophan (mainly from animal protein) can be regarded as a provitamin, as it is partially converted in the body to nicotinic acid (60 mg tryptophan = 1 mg nicotinic acid). Maize eaters have suffered from pellagra because corn flour is poor in tryptophan and it is believed to contain a niacin antagonist. Thus, daily requirement of niacin is affected by the amount of tryptophan in diet. Physiological amounts are metabolized in the body, while large doses are excreted unchanged in urine. These pyridine nucleotides act as hydrogen acceptors in the electron transport chain in tissue respiration, glycolysis and fat synthesis. Nicotinic acid (but not nicotinamide) in large doses is a vasodilator, particularly of cutaneous vessels. Diarrhoea-with enteritis, stomatitis, glossitis, salivation, nausea and vomiting. Dementia-with hallucinations preceded by headache, insomnia, poor memory, motor and sensory disturbances. Chronic alcoholics are particularly at risk of developing pellagra, because in addition to dietary deficiency, niacin absorption is impaired in them. Nicotinamide is preferred, especially for injection, because it does not cause flushing and other side effects seen with nicotinic acid. Nicotinic acid (not nicotinamide) has been used in peripheral vascular disease and as hypolipidaemic (Ch. Adverse effects Nicotinic acid, in pharmacological doses, has many side effects and toxicities (p. Pyridoxine (vit B6) Chemistry and source Pyridoxine, Pyriodoxal and Pyridoxamine are related naturally occurring pyridine compounds that have vit B6 activity. Absorption and fate All three forms of the vitamin are well absorbed from the intestine. Pyridoxine has been shown to interact with steroid hormone receptors, but its clinical implication is not clear. Prolonged intake of large doses of pyridoxine can give rise to dependence, and mega doses (0. However, suppression of lactation has been noted in nonsuckling postpartal women given high doses of pyridoxine: may be due to increased dopamine action on pituitary lactotropes. Isoniazid reacts with pyridoxal to form a hydrazone, and thus inhibits generation of pyridoxal phosphate. Due to formation of hydrazones, the renal excretion of pyridoxine compounds is increased. Hydralazine, cycloserine and penicillamine also interfere with pyridoxine utilization and action. Pyridoxine, by promoting formation of dopamine from levodopa in peripheral tissues, reduces its availability in the brain, abolishing the therapeutic effect in parkinsonism, but not when a peripheral decarboxylase inhibitor is combined with it. Deficiency symptoms Deficiency of vit B6 usually occurs in association with that of other B vitamins. Prophylactically (2­5 mg daily) in alcoholics, infants and patients with deficiency of other B vitamins. To prevent and treat (10­50 mg/day) isoniazid, hydralazine and cycloserine induced neurological disturbances. Acute isoniazid poisoning has been successfully treated with massive doses (in grams) of pyridoxine. Pyridoxine responsive anaemia (due to defective haeme synthesis) and homocystinuria are rare genetic disorders that are benefited by large doses of pyridoxine (50­200 mg/day). Pantothenic acid Pantothenic acid is an organic acid, widely distributed in food sources, especially liver, mutton, egg yolk and vegetables. It is a component of coenzyme-A which functions in carbohydrate, fat, steroid and porphyrin metabolism by catalysing acetate transfer reactions. Experimental deficiency in man causes insomnia, intermittent diarrhoea, flatulence, vomiting, leg cramps and paresthesias. Calcium/sodium pantothenate is included in B complex and multivitamin preparations. Biotin Biotin is a sulfur containing organic acid found in egg yolk, liver, nuts and many other articles of food. Avidin, a heat labile protein in egg white, binds and prevents the absorption of biotin. Biotin is a coenzyme for several carboxylases involved in carbohydrate and fat metabolism. Deficiency symptoms include seborrheic dermatitis, alopecia, anorexia, glossitis and muscular pain. Spontaneous deficiency of biotin has been noted only in subjects consuming only raw egg white and in patients on total parenteral nutrition. Except for these unusual instances and rare genetic abnormalities of biotin dependent enzymes, there are no clearly defined therapeutic uses of biotin. Citrus fruits (lemons, oranges) and black currants are the richest sources; others are tomato, potato, green chillies, cabbage and other vegetables. It is partly oxidized to active (dehydroascorbic acid) and inactive (oxalic acid) metabolites. E (mg) Thiamine Riboflavin (mg) (mg) Niacin (mg) Pyridoxine (mg) Pantothenic (mg) Biotin (mg) Folic acid (mg) B12 (µg) Vit. It directly stimulates collagen synthesis and is very important for maintenance of intercellular connective tissue. A number of illdefined actions have been ascribed to ascorbic acid in mega doses, but none is proven. Deficiency symptoms Severe vit C deficiency Scurvy, once prevalent among sailors is now seen only in malnourished infants, children, elderly, alcoholics and drug addicts. Symptoms stem primarily from connective tissue defect: increased capillary fragility-swollen and bleeding gums, petechial and subperiosteal haemorrhages, deformed teeth, brittle bones, impaired wound healing, anaemia and growth retardation. Anaemia: Ascorbic acid enhances iron absorption and is frequently combined with ferrous salts (maintains them in reduced state). Anaemia of scurvy is corrected by ascorbic acid, but it has no adjuvant value in other anaemias. Large doses (2­6 g/day) of ascorbic acid have been tried for a variety of purposes (common cold to cancer) with inconsistent results. No definite beneficial effect has been noted in asthma, cataract, cancer, atherosclerosis, psychological symptoms, infertility, etc. However, severity of common cold symptoms may be somewhat reduced, but not the duration of illness or its incidence. Improved working capacity at submaximal workloads has been found in athletes but endurance is not increased. Prevention of ascorbic acid deficiency in individuals at risk (see above) and in infants: 50­100 mg/ day. Postoperatively (500 mg daily): though vit C does not enhance normal healing, suboptimal healing can be guarded against. It has also been found to accelerate healing of bedsores Chapter 68 Vaccines and Sera Vaccines and sera are biological products which act by reinforcing the immunological defence of the body against foreign agencies (mostly infecting organisms or their toxins). Vaccines impart active immunity-act as antigens which induce production of specific antibodies by the recipient himself. Antisera and Immune globulins impart passive immunity-readymade antibodies (produced by another person or animal who has been actively immunized) are transferred. Active immunization is more efficacious and longer lasting than passive immunization, but the former needs a latent period of one to many weeks, whereas the latter affords immediate protection. Acutely ill, debilitated or immunocompromised individuals may not be able to generate an adequate antibody response and require passive protection. Vaccines and sera are potentially dangerous products and mostly used in public health programmes-their manufacture, quality control, distribution and sale is strictly supervised by State health authorities. These biologicals are standardized by bioassay and need storage in cold to maintain potency. Vaccines are of 3 types: (i) Killed (Inactivated) vaccines: consist of microorganisms killed by heat or chemicals. They generally require to be given by a series of injections for primary immunization. The immunity is relatively shorter-lasting; booster doses are mostly needed at intervals of months or years. The limited virulence of organisms in the live vaccine may be sufficient to cause a disease; live vaccines are contraindicated in them. Two live vaccines, if not given together, should preferably be administered with a gap of 1 month. Vaccination should be deferred in the presence of any acute (especially respiratory) infection and during pregnancy. Antibiotics added during production of vaccines and present in trace amounts in viral vaccines may cause reaction in individuals sensitive to these. Egg proteins (in vaccines prepared on chick embryo) and other materials used for vaccine culture may be responsible for allergic reactions. Adrenaline injection (1 in 1000) should be available to control allergic reaction to the vaccine, if it occurs. The latent period between vaccination and development of immunity and the period for which it lasts depends primarily on the organism, but varies somewhat in different individuals. Viral vaccines and toxoids generally afford more prolonged protection than bacterial vaccines. Local tenderness, fever and malaise lasting 1­2 days are common after the first dose. However, it is not approved for use in children below 2 years and in pregnant women. Administered as 3 doses on alternate days in the form of enteric coated capsules it affords protection for 3 years. Side effects are negligible: only 2% cases have reported diarrhoea, abdominal pain or rashes. It also induces a state of diminished adrenergic reactivity and aids sensitization to other antigens. In addition to local pain and induration, severe systemic (even fatal) reactions have been reported, but extremely rarely-high fever with hypotonic hyporesponsive child, convulsions, alterations of consciousness and focal neurological signs. It is also contraindicated in children with history of convulsions or other neurological disease. Cholera vaccine It is a suspension of phenol/formalin killed Inaba and Ogawa strains of V.