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The classic effects of deficiency are rickets (in children) and osteomalacia (in adults) cheap 500 mg zithromax overnight delivery bacteria large intestine. Studies suggest that vitamin D may protect against arthritis discount zithromax 100mg fast delivery antibiotic natural alternatives, diabetes, heart disease, autoimmune disorders, and cancers of the colon, breast, and prostate. However, in a 2011 report—Dietary Reference Intakes for Calcium and Vitamin D—an expert panel concluded that, although such claims might eventually prove true, the current evidence does not prove any benefits beyond bone health. Vitamin E (Alpha-Tocopherol) Vitamin E (alpha-tocopherol) is essential to the health of many animal species but has no clearly established role in human nutrition. Observational studies of the past suggested that vitamin E protected against cardiovascular disease, Alzheimer disease, and cancer. Moreover, there is evidence that high-dose vitamin E may actually increase the risk for heart failure, cancer progression, and all-cause mortality. However, only four stereoisomers are found in our blood, all of them variants of alpha-tocopherol. The vitamin is also found in nuts, wheat germ, whole-grain products, and mustard greens. Accordingly, this limit should be exceeded only when there is a need to manage a specific disorder (e. Symptoms of deficiency include ataxia, sensory neuropathy, areflexia, and muscle hypertrophy. Potential Benefits Vitamin E has a role in protecting red blood cells from hemolysis. The higher dose associated with halting macular degeneration carries substantial risk, as detailed in the discussion that follows. Potential Risks High-dose vitamin E appears to increase the risk for hemorrhagic stroke by inhibiting platelet aggregation. These results are consistent with the theory that high doses of antioxidants may cause cancer or accelerate cancer progression. Studies have also linked high-dose vitamin E therapy with an increased risk for death, especially in older people. Finally, high-dose vitamin E (in combination with vitamin C) can blunt the beneficial effects of exercise on insulin sensitivity. Forms and Sources of Vitamin K Vitamin K occurs in nature in two forms: (1) vitamin K, or phytonadione1 (phylloquinone), and (2) vitamin K. Two other forms2 —vitamin K 4 (menadiol) and vitamin K 3 (menadione)—are produced synthetically. At this time, phytonadione is the only form of vitamin K available for therapeutic use. For most individuals, vitamin K requirements are readily met through dietary sources and through vitamin K synthesized by intestinal bacteria. Because bacterial colonization of the gut is not complete until several days after birth, levels of vitamin K may be low in newborns. Pharmacokinetics Intestinal absorption of the natural forms of vitamin K (phytonadione and vitamin K ) is adequate only in the presence of bile salts. Because the natural forms of vitamin K require bile salts for their uptake, any condition that decreases availability of these salts (e. Malabsorption syndromes (sprue, celiac disease, cystic fibrosis of the pancreas) can also decrease vitamin K uptake. Other potential causes of impaired absorption are ulcerative colitis, regional enteritis, and surgical resection of the intestine. Disruption of intestinal flora may result in deficiency by eliminating vitamin K–synthesizing bacteria. In infants, diarrhea may cause bacterial losses sufficient to result in deficiency. Consequently, to rapidly elevate prothrombin levels and reduce the risk for neonatal hemorrhage, the American Academy of Pediatrics and the Centers for Disease Control and Prevention recommend that all infants receive a single injection of phytonadione (vitamin K ) immediately after delivery. This previously routine prophylactic1 intervention has recently been challenged by parents who believe that the risks outweigh benefits. Subsequent to increases in parents declining prophylaxis, there has been an increase in life-threatening vitamin K deficiency bleeding in recent years. As discussed in Chapter 44, the anticoagulant warfarin acts as an antagonist of vitamin K and thereby decreases synthesis of vitamin K–dependent clotting factors. As a result, warfarin produces a state that is functionally equivalent to vitamin K deficiency. If the dosage of warfarin is excessive, hemorrhage can occur secondary to lack of prothrombin. Hyperbilirubinemia When administered parenterally to newborns, vitamin K derivatives can elevate plasma levels of bilirubin, thereby posing a risk for kernicterus. The incidence of hyperbilirubinemia is greater in premature infants than in full-term infants. Although all forms of vitamin K can raise bilirubin levels, the risk is higher with menadione and menadiol than with phytonadione. Therapeutic Uses and Dosage Vitamin K has two major applications: (1) correction or prevention of hypoprothrombinemia and bleeding caused by vitamin K deficiency and (2) control of hemorrhage caused by warfarin. Vitamin K Replacement As discussed, vitamin K deficiency can result from impaired absorption and from insufficient synthesis of vitamin K by intestinal flora. For children and adults, the usual dosage for correction of vitamin K deficiency ranges between 5 and 15 mg/day. To prevent hemorrhagic disease in neonates, it is recommended that all newborns be given an injection of phytonadione (0. Warfarin Antidote Vitamin K reverses hypoprothrombinemia and bleeding caused by excessive dosing with warfarin, an oral anticoagulant. Preparations and Routes of Administration Phytonadione (vitamin K ) is available in 5-mg tablets, marketed as Mephyton,1 and in parenteral formulations (2 and 10 mg/mL) sold generically. For example, this might be indicated in management of life- threatening bleeding due to vitamin K antagonists (e. Water-Soluble Vitamins The group of water-soluble vitamins consists of vitamin C and members of the vitamin B complex: thiamine, riboflavin, niacin, pyridoxine, pantothenic acid, biotin, folic acid, and cyanocobalamin. They are grouped together because they were first isolated from the same sources (yeast and liver). Vitamin C is not found in the same foods as the B vitamins and hence is classified by itself. Two compounds—pangamic acid and laetrile—have been falsely promoted as B vitamins. Vitamin C (Ascorbic Acid) Actions Vitamin C participates in multiple biochemical reactions. Among these are synthesis of adrenal steroids, conversion of folic acid to folinic acid, and regulation of the respiratory cycle in mitochondria. At the tissue level, vitamin C is required for production of collagen and other compounds that comprise the intercellular matrix that binds cells together.

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Rubella 75 Question 4 Which one of the following factors does not infuence the transmission of herpes to the fetus? Woman’s partner with herpes virus infection Question 5 A 28-year old woman had recurrent genital herpes at 28 and 33 weeks’ gestation and was started on suppressive antiviral therapy buy 100mg zithromax visa antibiotics oral contraceptives. She is currently 39 weeks’ gestation and presents in spontaneous labour with no active lesions order zithromax 100 mg fast delivery antibiotics for uti cats. Both forceps and ventouse delivery Question 6 A 32-year-old para 2 woman presented at 28 weeks’ gestation with abdominal pain and uterine tightenings. Abdominal examination revealed no obvious uterine activity and on speculum examination the cervix was closed and long. She was given antibiotics for a suspected urinary tract infection and was discharged home. Her past history revealed history of premature labour at 32 and 34 weeks’ gestation. She subsequently presents with abdominal pain and urinary retention at 32 weeks’ gestation. Abdominal examination reveals uterine contractions of 3 in 10 minutes and speculum examination revealed 6 cm dilated cervical os. Her vulva also reveals multiple painful vesicles suggestive of primary herpes infection. Both forceps and ventouse delivery 76 Question 7 A 32-year-old woman presented with painful vulva at 36 weeks’ gestation. Clinical examination revealed multiple painful vesicles suggestive of genital herpes infection. However, she presents at 38 weeks’ in second stage and delivered vaginally within half an hour of admission to labour ward. Examination reveals that she has vesicular lesions on the abdomen and her arms and legs suspicious of chickenpox. A blood test for IgG antibody and IgM antibody for varicella infection is requested and a swab is taken from vesicular fuid for virology. The results come back 24 hours later and reveal positive for varicella IgG antibody but negative for IgM antibodies. She had developed this rash 10 hours previously and thought that she had developed a food allergy. On questioning she gives a history of coming in close contact, 3 days earlier, with her niece, who had developed chickenpox rash. She was prescribed oral acyclovir for 7 days but was warned to report back if unwell. Tree days later she presents to the emergency department with severe shortness of breath. She is planning to conceive in the next couple of months and would like to know the risks to her and the fetus if she gets pregnant. Cordocentesis Instructions For each clinical scenario below, choose the single most appropriate screening test from the above list of options. A 28-year-old south Asian woman with a history of irregular menstrual cycles attends for her dating scan at 12 weeks’ gestation and wishes to have the Down syndrome screening test. A 40-year-old woman, who teaches children with special needs, is 12 weeks into her frst pregnancy and is very anxious about the risk of Down syndrome. She wishes to have a diagnostic test, but is not ready to take the risk of miscarriage associated with invasive testing. A 38-year-old G2 para 1 at 13 weeks’ gestation attends fetal medicine unit for counselling afer the screen-positive combined screening results with a risk of 1:50 Down syndrome. No intervention needed Instructions For each clinical scenario below, choose the single most appropriate immediate plan of action from the above list of options. A 30-year-old para 1 woman at 32 weeks’ gestation seeks advice when her child is diagnosed with chickenpox and she is not sure whether she had chickenpox or not. A 23-year-old nulliparous woman at 36 weeks’ gestation attends the antenatal clinic afer a recent diagnosis of genital herpes in the department of sexual health. She is on oral acyclovir and is anxious about the fetal efects and the mode of delivery. She was recently treated for sepsis secondary to urinary tract infection as an inpatient and was discharged on oral antibiotics. Aspirin 75 mg + folic acid 5 mg Instructions For each clinical scenario below, choose the single most appropriate intervention from the above list of options. A 42-year-old G2 para 1 woman attends the antenatal clinic afer her dating scan at 12 weeks’ gestation. She had early onset pre-eclampsia and fetal growth restriction requiring preterm delivery at 32 weeks’ in her frst pregnancy. A 30-year-old nulliparous woman at 10 weeks’ gestation attends the antenatal clinic. She is taking multivitamins and concerned about the risks of diabetes in pregnancy. A 32-year-old nulliparous woman attends her booking antenatal visit at 10 weeks’ gestation. You have been asked to see this woman as she had a pulmonary embolism 2 years ago, while taking combined oral contraceptive pills. Serial growth scans Instructions For each clinical scenario below, choose the single most appropriate advice from the above list of options. A 30-year-old para 4 woman with four normal vaginal deliveries was referred for small for gestational age at 28 weeks. A 20-year-old para 1 woman with a previous normal vaginal delivery has anomaly scan at 20 weeks’ gestation which states that the placenta is posterior low. A 41-year-old para 2 woman with history of severe pre-eclampsia and fetal growth restriction in her frst pregnancy attends the antenatal clinic at 22 weeks’ gestation. Her anomaly scan is normal and she has been taking aspirin 75 mg from 12 weeks onwards. Grade 1: the placenta is implanted into the lower segment but encroaches on the cervical os B. Grade 2: the placenta is implanted into the lower segment but does not reach the margin of the cervical os C. Paediatricians need to be alerted about the symptoms of maternal herpes in labour. Primary genital herpes acquired within 6 weeks of delivery is associated with a signifcant risk of transmission to the fetus. Caesarean section is indicated in all women who give history of herpes simplex virus infection during pregnancy.

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Streptomycin is also indicated for several uncommon infections (plague cheap zithromax 500mg fast delivery bacteria killing light, tularemia zithromax 500 mg for sale antibiotics human bite, brucellosis). When combined with ampicillin or penicillin G, streptomycin may be used for enterococcal endocarditis. Paromomycin Paromomycin is an aminoglycoside employed only for local effects within the intestine. The drug is approved for oral therapy of intestinal amebiasis and has been used investigationally against other intestinal parasites. The dosage for amebiasis in adults and children is 8 to 12 mg/kg 3 times daily for 7 days. In approaching these drugs, we begin with the sulfonamides, followed by trimethoprim, and then conclude with trimethoprim/sulfamethoxazole, an important fixed-dose combination. Sulfonamides Sulfonamides were the first drugs available for systemic treatment of bacterial infections. After their introduction in the 1930s, their use produced a sharp decline in morbidity and mortality from susceptible infections. With the advent of penicillin and newer antimicrobial drugs, use of sulfonamides has greatly declined. With the introduction of trimethoprim/sulfamethoxazole in the 1970s, indications for the sulfonamides expanded. Basic Pharmacology Similarities among the sulfonamides are more striking than the differences. Accordingly, rather than focusing on a representative prototype, we will discuss the sulfonamides as a group. Older sulfonamides had low solubility; therefore they often crystallized out in the urine, causing injury to the kidneys. The sulfonamides in current use are much more water soluble, and hence the risk for renal damage is low. Sulfonamides suppress bacterial growth by inhibiting synthesis of tetrahydrofolate, a derivative of folic acid (folate). Bacteria are unable to take up folate from their environment, so they must synthesize folic acid from precursors. Rather, they simply take up folic acid obtained from the diet, using a specialized transport system for uptake. Because mammalian cells use preformed folic acid rather than synthesizing it, sulfonamides are harmless to us. Microbial Resistance Many bacterial species have developed resistance to sulfonamides. Resistance is especially high among gonococci, meningococci, streptococci, and shigellae. Resistance may be acquired by spontaneous mutation or by transfer of plasmids that code for antibiotic resistance (R factors). Antimicrobial Spectrum The sulfonamides are active against a broad spectrum of microbes. Susceptible organisms include gram-positive cocci (including methicillin-resistant Staphylococcus aureus), gram-negative bacilli, Listeria monocytogenes, actinomycetes (e. Therapeutic Uses Although the sulfonamides were once employed widely, their applications are now limited. Two factors explain why: (1) introduction of bactericidal antibiotics that are less toxic than the sulfonamides and (2) development of sulfonamide resistance. About 90% of these infections are due to Escherichia coli, a bacterium that is usually sulfonamide sensitive. Of the sulfonamides available, sulfamethoxazole (in combination with trimethoprim) is generally favored. Sulfamethoxazole has good solubility in urine and achieves effective concentrations within the urinary tract. Other Uses Sulfonamides are useful drugs for nocardiosis (infection with Nocardia asteroides), Listeria species infection, and infection with P. In addition, sulfonamides are alternatives to doxycycline and erythromycin for infections caused by C. Sulfonamides are used in conjunction with pyrimethamine to treat two protozoal infections: toxoplasmosis and malaria caused by chloroquine-resistant Plasmodium falciparum. Topical sulfonamides are used to treat superficial infections of the eyes and to suppress bacterial colonization in burn patients. However, benefits in this disorder do not result from inhibiting microbial growth. Pharmacokinetics Absorption Sulfonamides are well absorbed after oral administration. When applied topically to the skin or mucous membranes, these drugs may be absorbed in amounts sufficient to cause systemic effects. Concentrations in pleural, peritoneal, ocular, and similar body fluids may be as much as 80% of the concentration in blood. Sulfonamides readily cross the placenta, and levels achieved in the fetus are sufficient to produce antimicrobial effects and toxicity. Acetylated derivatives lack antimicrobial activity but are just as toxic as the parent compounds. Acetylation may decrease sulfonamide solubility, thereby increasing the risk for renal damage from crystal formation. Thus the rate of renal excretion is the principal determinant of their half-lives. Prominent among these are hypersensitivity reactions, blood dyscrasias, and kernicterus, which occurs in newborns. Renal damage from crystalluria was a problem with older sulfonamides but is less common with the sulfonamides used today. Hypersensitivity Reactions Sulfonamides can induce a variety of hypersensitivity reactions, which are seen in about 3% of patients. To minimize photosensitivity reactions, patients should avoid prolonged exposure to sunlight, wear protective clothing, and apply a sunscreen to exposed skin. P a t i e n t E d u c a t i o n Sulfonamides • Instruct patients to complete the prescribed course of treatment, even though symptoms may abate before the full course is over. Rather, they are usually reserved for ophthalmic infections, burns, and bacterial vaginosis caused by Gardnerella vaginalis and a mixed population of anaerobic bacteria. The most severe hypersensitivity response to sulfonamides is Stevens-Johnson syndrome, a rare reaction with a mortality rate of about 25%. Symptoms include widespread lesions of the skin and mucous membranes, combined with fever, malaise, and toxemia. The reaction is most likely to occur with long-acting sulfonamides, which are now banned in the United States. To minimize the risk for severe reactions, sulfonamides should be discontinued immediately if skin rash of any sort is observed. In addition, sulfonamides should not be given to patients with a history of hypersensitivity to chemically related drugs, including thiazide diuretics, loop diuretics, and sulfonylurea-type oral hypoglycemics—although the risk for cross-reactivity with these agents is probably low (see later section “Drug Interactions”).

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