By Y. Porgan. Missouri State University.

To a certain extent generic 100 mcg levothroid with amex, vomiting is a protective mechanism which can result from various noxious stimuli quality 200 mcg levothroid. Drugs used in nausea and vomiting belong to several different therapeutic classifications generic 200 mcg levothroid mastercard. Peripherally metoclopoamide stimulates the release of acetylcholine, which in turn, increases the rate of gastric emptying (used in esophapeal reflux) Indication as chlorpromazine • Scopolamine, an anticholinergic drug is very effective in reliving nausea & vomiting associated with motion sickness. Drugs used to induce vomiting In case of poisoning with noncorrosive agents, and assuming incomplete absorption of the poison has taken place, induction of vomiting can be carried out The drug used for this purpose is emetine, the active ingredient of ipecacuanha (syrup of ipecac). Drugs used in the treatment of haemorrhoids Haemorrhoids are varicose veins of the anal canal which can be very distressing for the sufferer. There is no pharmacological cure for this disorder, which is often self-limiting, if not, may require surgical intervention. The use of drugs may however, linder the sufferings: • Stool softeners may alleviate constipation; lessen straining which can worsen the condition. Drugs used in inflammatory bowel disease (ulcerative colitis and crohn’s disease) • Ulcerative colitis is an inflammatory condition of the rectum and colon; crohni’s disease can involve the whole intestine. In the absence of adequate iron, small erythrocytes with insufficient hemoglobin are formed resulting in microcytic hypochromic anemia. Nutritional deficiency Low intake of iron containing foods, reduced absorption as a result of mucosal damage, co- administration of drugs that chelate iron e. Pharmacokinetics of Iron Daily requirement of Iron - Male 10mg - Female 15 mg Increases in growing children, pregnant and lactating women Sources - Dietary - mostly in the organic form from meat, cereals, etc. Body composition of Iron Total content of Iron in the body is about 4000mg in an adult male, of which about 2/3 – 2500 mg is present in circulating red blood cells see table. Table: Iron distribution in normal adults Iron content (mg) Men Women Hemoglobin 3050 1700 Myoglobin 430 30 Enzymes 10 8 Transport (transferin 8 6 Storage ( ferritin and 750 300 other form) Total 4246 2314 N. The above estimations are based on the assumptions that: 96 The average male adult weighs 80 kg and has a mean Hb level of 16 g/dL and the female adult weighs 55 kg and has a mean Hb level of 14 g/dL. Iron crosses the stinal mucosal cell by active transport; then according to mucosal iron store, it can either be available to transferrin to be transported to plasma or be stored in the mucosal cell as ferritin. Storage: Iron is stored primarily as ferritin in intestinal mucosal cells and in macrophages in the liver, spleen and bone. Elimination: Very small amount are execrated in stool by exfoliation of intestinal mucosal cells and trace amounts are execrated in bile, urine and sweat with total daily excretion not more than 1mg/day. Treatment of iron deficiency anemia consists of administration of oral or parenteral iron preparation. Oral Iron Therapy: Only ferrous salts should be used because of most efficient absorption. Ferrous sulfate, ferrous gluconate, ferrous fumarate are the most commonly used oral iron preparations. About 25% of oral iron given as ferrous salt can be absorbed; therefore 200-400mg elemental irons should be given daily to correct iron deficiency most rapidly. Side effects: Oral iron therapy can cause nausea, vomiting, epigastric discomfort, abdominal cramps, constipation and diarrhea. Parenteral iron therapy: Should be reserved for patient unable to tolerate or absorb oral iron. Patients with extensive chronic blood loss who can not be maintained with oral iron alone including patients with various post gastrectomy conditions, previous small bowel resection, inflammatory bowel disease involving proximal small bowel and malabsorption syndromes need parenteral iron therapy. Intravenous administration may result in very severe allergic reactions and thus should be avoided if possible. Side effect: include local pain, tissue staining, headache, light headedness, fever, arthralgia, nausea, vomiting, urticaria, back pain, bronchospasm, and rarely anaphylaxis and death. Acute iron Toxicity Is exclusively seen in young children who ingest a number of iron tablets and rarely seen in adults as a result of suicide or repeated blood transfusions. Signs and symptoms Necrotizing gastroenteritis with vomiting, abdominal pain and bloody diarrhea, shock, metabolic acidosis, coma Treatment Whole bowel irrigation. It is mainly obtained from animal products and serves as a co factor for essential biochemical reaction in humans. Excess vitamin B12 is transported to the liver for storage and excreted in the urine. Clinical uses - Vit B12 is used to treat or prevent deficiency of vit B 12 Deficiency of Vit B 12 results in: - Megaloblastic anemia - Neurological syndrome involving spinal cord and peripheral nerves Causes: The causes for Pernicious anemia are defective secretion of intrinsic factor necessary for absorption of vitB 12, partial or total gastrectomy, diseases that affect distal ileum, malabsoption syndrome e. Almost all cases of vit B12 deficiencies are caused by malabsorption Treatment Vit B12 therapeutic preparations are cyanocoblamin and hydroxycobalamin and For intrinsic factor deficiency the vitamin should be given parenterally and patients with pernicious anemia will need life-long therapy. Body stores of folates are relatively low and daily requirement is high and hence folic acid deficiency and magaloblasitc anemia can develop within 1 -6 months after the in take of folic acid stops. Congenital malformation in newborn like spina bifida are also consequences of folate deficiency during pregnancy. Causes Dietary deficiency, alcoholics with liver disease, hemolytic anemia, malabsorption syndrome, patients with cancer, leukemia, myeloprolferative disorders, chronic skin diseases, patients on renal dialysis and patients on drugs that impair absorption or metabolism e.

Usually cheap 200 mcg levothroid otc, normal vision is recovered a few weeks after the end of the treatment levothroid 50mcg without a prescription, although in some cases generic 50mcg levothroid free shipping, this recovery may not occur until some months after the completion of treatment. Other adverse effects include a reduction of urate excretion (hence producing gout), gastrointestinal disorders and hypersensitivity skin reactions. It is a white-whitish crystalline powder, highly hygroscopic and soluble in water that must be stored in airtight containers. It can also be used in the treatment of other bacterial infections such as those produced by Yersinia pestis, Francisella tularensis, and Brucella spp. It is less nephrotoxic than other aminoglycosides, although it may produce renal failure when administered with other nephrotoxic agents. Drugs: structure, pharmacokinetics and toxicity 609 Para-aminosalicylic acid This compound and its salts are active only against M. It is well absorbed in the gastrointestinal tract and distributes well throughout the body, although it is poorly distributed in the cerebrospinal fluid. Commonly, capreomycin affects the fre- quency of urination or the amount of urine, increases thirst and may produce loss of appetite, nausea and vomiting. Due to its toxic effects, it must not be given in com- bination with aminoglycosides such as kanamycin or streptomycin. Cycloserine This is a broad-spectrum antibiotic that inhibits many microorganisms such as Escherichia coli, Staphylococcus aureus, Nocardia spp. Due to its high toxicity, it is only used against bacilli resistant to the main antituberculosis drugs. It is fairly well absorbed in the gastrointestinal tract, being distributed to most tissues and fluids, including cerebrospinal fluid. It may pro- duce diverse adverse reactions involving the central nervous system, from mild headache or restlessness to severe psychosis and seizures, and is therefore contra- indicated in patients with epilepsy, depression or anxiety. Amikacin is also active against atypical mycobacteria that cause opportun- istic infections, such as those of the Mycobacterium avium complex. They are distributed in body tissues and fluids, and cross the placenta but do not reach the cerebrospinal fluid. Like most aminoglycosides, amikacin and kanamycin affect auditory function and must be given with care to patients with auditory dysfunctions. Kanamycin may also produce some gastrointestinal effects, such as nausea, vomiting, and sto- matitis, especially when taken by mouth. It is well absorbed from the gastrointestinal tract, and diffuses into all body tissues and flu- ids, including cerebrospinal fluid. It is well absorbed from the gastrointestinal tract, and distributes to all body tissues and fluids, including cerebrospinal fluid. Drugs: structure, pharmacokinetics and toxicity 611 Fluoroquinolones Among the fluoroquinolones, there are drugs with several degrees of activity against M. Fluoroquinolones are well absorbed from the gastrointestinal tract (presence of food reduces absorption), and peak plasma concentrations are obtained rapidly, usually after 1-2 hours, where they are partially bound to plasma proteins. Half-life is variable, ranging from 4 hours in the case of ciprofloxacin to 10-13 hours in the case of moxifloxacin. This drug has not been approved for use in children, since the safety and efficacy of this drug has not yet been established for this age group. It may be used in anti-tuberculosis regimens, al- though these may not be as effective as the standard short-course therapy. It is well absorbed in the gastrointestinal tract and peak concentrations of 1-2 mg/L are ob- tained four hours after administration of a 150 mg dose. Other frequent adverse effects include conjunctivitis, vertigo, toxic epidermal necrolysis, exfoliative dermatitis, hemolytic anemia, and hepato- toxicity with jaundice. This resistance has traditionally been attributed to the unusual multi-layer cell envelope and active multidrug efflux pumps (De Rossi 2006, Jarlier 1994). Drug resistance mechanisms 613 antibiotics in the cytoplasm have revealed other systems that function in synergy with the permeability barrier and efflux systems to provide natural resistance. In other bacterial species, acquired drug resistance is mediated by plasmids or transposons, but in contrast, M. However, it is important to observe that some resistant strains do not present these classic mutations, suggesting the possibility of the existence of other mechanisms such as efflux pumps and altera- tions in the permeability of the cell wall. This property has been attributed to its ability to inhibit semi-dormant bacilli residing in acidic environments (Mitchison 1985). Often these mutations affect a putative regulatory sequence in the embC–embA intergenic region (Ramaswamy 2000). Drug interactions 617 Fitness and Drug Resistance The relation between drug resistance and fitness cost has led to the assumption that removal of antibiotic selective pressure would favor the elimination of resistant bacteria, because mutations conferring drug resistance usually affect replication and this is a disadvantage when resistant bacteria have to compete with sensitive bacteria in the absence of antibiotic (Andersson 1999). In fact, antibiotic resistance, caused by target alteration or by other mechanisms, can confer a reduction in fit- ness expressed as reduced growth, virulence or transmission (Andersson 2006). However, this cost can be compensated, usually without loss of resistance, by sec- ond-site mutations during the evolution of the resistant bacteria (Bjorkman 2000). There are only limited data available on the effect of different drug resistance con- ferring mutations on the relative fitness of M.

It is well absorbed from the gastrointestinal tract discount levothroid 50mcg line, and diffuses into all body tissues and flu- ids buy cheap levothroid 50 mcg on-line, including cerebrospinal fluid buy levothroid 100mcg overnight delivery. It is well absorbed from the gastrointestinal tract, and distributes to all body tissues and fluids, including cerebrospinal fluid. Drugs: structure, pharmacokinetics and toxicity 611 Fluoroquinolones Among the fluoroquinolones, there are drugs with several degrees of activity against M. Fluoroquinolones are well absorbed from the gastrointestinal tract (presence of food reduces absorption), and peak plasma concentrations are obtained rapidly, usually after 1-2 hours, where they are partially bound to plasma proteins. Half-life is variable, ranging from 4 hours in the case of ciprofloxacin to 10-13 hours in the case of moxifloxacin. This drug has not been approved for use in children, since the safety and efficacy of this drug has not yet been established for this age group. It may be used in anti-tuberculosis regimens, al- though these may not be as effective as the standard short-course therapy. It is well absorbed in the gastrointestinal tract and peak concentrations of 1-2 mg/L are ob- tained four hours after administration of a 150 mg dose. Other frequent adverse effects include conjunctivitis, vertigo, toxic epidermal necrolysis, exfoliative dermatitis, hemolytic anemia, and hepato- toxicity with jaundice. This resistance has traditionally been attributed to the unusual multi-layer cell envelope and active multidrug efflux pumps (De Rossi 2006, Jarlier 1994). Drug resistance mechanisms 613 antibiotics in the cytoplasm have revealed other systems that function in synergy with the permeability barrier and efflux systems to provide natural resistance. In other bacterial species, acquired drug resistance is mediated by plasmids or transposons, but in contrast, M. However, it is important to observe that some resistant strains do not present these classic mutations, suggesting the possibility of the existence of other mechanisms such as efflux pumps and altera- tions in the permeability of the cell wall. This property has been attributed to its ability to inhibit semi-dormant bacilli residing in acidic environments (Mitchison 1985). Often these mutations affect a putative regulatory sequence in the embC–embA intergenic region (Ramaswamy 2000). Drug interactions 617 Fitness and Drug Resistance The relation between drug resistance and fitness cost has led to the assumption that removal of antibiotic selective pressure would favor the elimination of resistant bacteria, because mutations conferring drug resistance usually affect replication and this is a disadvantage when resistant bacteria have to compete with sensitive bacteria in the absence of antibiotic (Andersson 1999). In fact, antibiotic resistance, caused by target alteration or by other mechanisms, can confer a reduction in fit- ness expressed as reduced growth, virulence or transmission (Andersson 2006). However, this cost can be compensated, usually without loss of resistance, by sec- ond-site mutations during the evolution of the resistant bacteria (Bjorkman 2000). There are only limited data available on the effect of different drug resistance con- ferring mutations on the relative fitness of M. Host and environmental factors, as well as strain genetic diversity can also influence the transmission dynamics of drug-resistant bacteria, while virulence of strains may reflect other genomic differences uncoupled from drug resistance. Drug interactions In general, when two or more drugs are administered simultaneously to a patient, there is a possibility that the drugs involved may interact between them. This inter- action may result in changes (increase or decrease) of the effective concentration of one or more of the drugs involved, which most can usually be solved by adjusting the doses of the affected drug. The interaction may also produce an enhancement in adverse effects produced by any of the drugs, which is frequently solved by using alternative drugs that are not affected by the interaction. Since the antituberculosis treatment itself consists of the administration of two or more drugs, and in some occasions it is given simultaneously with other drug regimes (i. Few drugs interact to alter the concentration of the antituberculosis drugs (Centers for Disease Control and Prevention 2003a, Martindale 2004, Yew 2002). Then, other drugs that share or interact with the cytochrome P450 system may have significant levels of interaction with the rifamycins. As a consequence, rifabutin levels may increase up to four-fold, and other rifabutin-derived metabolites may also reach higher levels. Its administra- tion may result in a decrease in the concentration of rifabutin to one third of its normal serum concentrations. Drugs affected by the rifamycins Since rifamycins induce microsomal liver enzymes, they accelerate the metabolism of some other drugs reducing their half-lives and their concentrations, sometimes to sub-therapeutic levels. This problem can be solved easily by increasing the dosage of the drugs affected, which have to return to normal doses two weeks after com- pletion of the rifamycin treatment. One exception to this general rule can be the case of oral contraceptives in women, and other contraceptive methods should be recommended. Drug interactions 619 Maybe, the most important family of drugs affected by the rifamycins is the antiret- roviral agents, both the protease inhibitors and the non-nucleoside reverse tran- scriptase inhibitors. Other drugs, whose concentrations can be decreased by the use of rifamycins in- clude atovaquone, azathioprine, chloramphenicol, cyclosporine, cimetidine, clofi- brate, corticosteroids, coumarin anticoagulants, dapsone, diazepam and other ben- zodiazepines, doxycycline, fluconazole, haloperidol, hexobarbital, itraconazole, ketoconazole, lamotrigine, methadone, ondansetron, oral hypoglycemics, pheny- toin, quinine, rofecoxib, statins, sulphasalazine, tacrolimus, the bronchodilator theophylline, thyroid hormones, and several cardiovascular drugs including beta blockers, digitalis alkaloids and antiarrhythmics such as disopyramide, lorcainide, mexiletine, propafenone, quinidine, tocainide, and verapamil and other calcium- channel blockers. Since both drugs are metabolized in the liver, the incidence of hepatotoxicity can be increased 620 Drugs and Drug Interactions and liver function should be monitored regularly. Fluoroquinolones Several drugs (such as those containing divalent cations, including antacids or vitamin supplements) decrease the absorption of fluoroquinolones (Ginsburg 2003).

The distribution of the prevalence of resistance to each individual drug is illustrated in figure 11 generic 200mcg levothroid with amex. Exceptionally high prevalences and outliers were found in many countries/ settings levothroid 50mcg mastercard. However the range of resistance prevalence varied considerably within regions (Figure 12) discount levothroid 50 mcg mastercard. The ranges in the Western Pacific Region and especially in the European region were much wider than for the other regions. The range of any resistance to each of the four drugs was by far the widest in the European region. The ranges of values for the African Region and the Americas were quite narrow, those of the Western Pacific Region wider, while the widest are observed in the European Region, reflecting the diversity of the resistance prevalence. The median prevalences of any resistance in the Regions of Africa, the Americas and Europe were around 20%, while the median prevalence in the Western Pacific Region reached 32. This was also true for the prevalence of resistance to 3 or 4 drugs, where Kazakhstan was an outlier (62. The Puerto Rico outlier (25%) is an artefact caused by the small sample size (n = 4). For most of the parameters the African Region had the lowest medians as well as the smallest ranges. We therefore explored stratification in three geographical subregions – Western, Central and Eastern Europe (Table 3). This was also true for the ranges of the parameters – narrow for Central Europe, somewhat wider for Western Europe, and widest for the Eastern European subregion. A high rate of immigration from areas with a higher prevalence of resistance, such as countries of the former Soviet Union, is one possible reason. The following analysis includes data from the three global reports, as well as data provided between the publication of reports. The present report examines time trends for resistance in new cases in 46 settings: 20 settings provided two data points and 26 three or more data points (Table 4). Twelve showed only slight variations in prevalence, while significant changes were observed in five settings: Poland, Peru, Argentina,b Henan Province (China),c and Thailand. In three of these settings (Argentina, Henan (China), and Thailand) the decrease was significant. Seven settings showed an increase over time, of which only Poland and Ivanovo Oblast were significant. New Zealand and Norway reported a doubling and Botswana a tripling of the prevalence. Figure 17 depicts the trend of prevalence of any resistance among new cases in Botswana. Tomsk Oblast (Russian Federation) showed a steady and significant increase, reaching a level of resistance 1. Tomsk Oblast, Russian Federation, and Slovakia both reported significant increases. Regarding any resistance among previously treated cases (Figure 20), a significant decrease was observed in Argentina, Ivanovo Oblast, Russian Federation, Peru and the Republic of Korea. There are only two significant decreases (Argentina and the Republic of Korea) and one significant increase (Nepal). All other settings showed variations with large confidence intervals; the upper limit for Belgrade, Serbia and Montenegro, reached 27. Three settings showed a significant increase; Estonia, Lithuania, and Tomsk Oblast (Russian Federation). Surveillance data from nine settings are displayed in Figure 23 and Figure 24, which show the prevalence ratios and 95% confidence intervals. As these data had to be adjusted, no confidence intervals could be calculated and, consequently, the level of significance of any increase or decrease could not be determined. Dynamics in settings reporting two data points Figure 23: Prevalence ratios of any resistance among combined cases, 1994–2002 With regard to prevalence of any resistance (Figure 23) only one setting, Belgium, showed a significant decrease over time. No other survey settings reported statistically significant changes over two data points. A borderline significant increase was observed in Ivanovo Oblast (Russian Federation). An initial decrease followed by a stabilization of prevalence was seen in Latvia (Figure 26). The following patient-related factors were retained: level of education67 and purchasing power. Preferences for the private sector could not be included as a factor, as no aggregate data were available. The human poverty index67 and the out-of-pocket expenditure,68 as a percentage of total health expenditure, measure the purchasing power. Although the model included the fairness indexa,72 (the responsiveness of the health system relative to people’s expectationsb) as a measurement of functionality, it could not be included in the final analysis.