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By: Paul Reynolds, PharmD, BCPS
- Critical Care Pharmacy Specialist, University of Colorado Hospital
- Clinical Assistant Professor, Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado
http://www.ucdenver.edu/academics/colleges/pharmacy/Departments/ClinicalPharmacy/DOCPFaculty/Q-Z/Pages/Paul-Reynolds,-PharmD.aspx
Unlike natural phosphorus bacteria encyclopedia generic 125 mg keftab otc, phosphorus in the form of additives is not bound to antibiotic resistance case study buy keftab 750mg low cost protein antibiotic resistance jobs buy discount keftab 125 mg line. Rather antibiotic vs virus buy keftab 125mg on-line, it’s found in the form of salt and highly absorbable by the intestinal tract (6). However, food manufacturers are not required to list the exact amount of additive phosphorus on the food label. While additive phosphorus content varies depending on the type of soda, most dark-colored sodas are believed to contain 50–100 mg in a 200-mL serving (7). As a result, sodas, especially those that are dark, should be avoided on a renal diet. Avocados are often touted for their many nutritious qualities, including their heart-healthy fats, fiber, and antioxidants. While avocados are usually a healthy addition to the diet, individuals with kidney disease may need to avoid them. Therefore, avocados, including guacamole, should be avoided on a renal diet, especially if you have been told to watch your potassium intake. Canned foods, such as soups, vegetables, and beans, are often purchased because of their low cost and convenience. However, most canned foods contain high amounts of sodium, as salt is added as a preservative to increase its shelf life (9). Due to the amount of sodium found in canned goods, it’s often recommended that people with kidney disease avoid or limit their consumption. Choosing lower sodium varieties or those labeled “no salt added” is typically best. Additionally, draining and rinsing canned foods, such as canned beans and tuna, can decrease the sodium content by 33–80%, depending on the product (10). Avoiding, limiting, or buying low sodium varieties is likely best to reduce your overall sodium consumption. Often for healthy individuals, whole wheat bread is usually recommended over refined, white flour bread. Whole wheat bread may be a more nutritious choice, mostly due to its higher fiber content. However, white bread is usually recommended over whole wheat varieties for individuals with kidney disease. The more bran and whole grains in the bread, the higher the phosphorus and potassium contents. For example, a 1-ounce (30-gram) serving of whole wheat bread contains about 57 mg of phosphorus and 69 mg of potassium. In comparison, white bread contains only 28 mg of both phosphorus and potassium (11, 12). Note that most bread and bread products, regardless of whether they’re white or whole wheat, also contain relatively high amounts of sodium (13). It’s best to compare the nutrition labels of various types of bread, choose a lower sodium option, if possible, and monitor your portion sizes. All bread contains sodium, so it’s best to compare food labels and choose a lower sodium variety. Like whole wheat bread, brown rice is a whole grain that has a higher potassium and phosphorus content than its white rice counterpart. One cup of cooked brown rice contains 150 mg of phosphorus and 154 mg of potassium, while 1 cup of cooked white rice contains only 69 mg of phosphorus and 54 mg of potassium (14, 15). You may be able to fit brown rice into a renal diet, but only if the portion is controlled and balanced with other foods to avoid an excessive daily intake of potassium and phosphorus. Bulgur, buckwheat, pearled barley, and couscous are nutritious, lower phosphorus grains that can make a good substitute for brown rice. While they’re naturally low in sodium, 1 medium banana provides 422 mg of potassium (16). It may be difficult to keep your daily potassium intake to 2,000 mg if a banana is a daily staple. However, pineapples contain substantially less potassium than other tropical fruits and can be a more suitable, yet tasty, alternative (17). Pineapple is a kidney-friendly fruit, as it contains much less potassium than certain other tropical fruits. They’re also a natural source of phosphorus and potassium and a good source of protein. For example, 1 cup (240 mL) of whole milk provides 222 mg of phosphorus and 349 mg of potassium (18). Yet, consuming too much dairy, in conjunction with other phosphorus-rich foods, can be detrimental to bone health in those with kidney disease. This may sound surprising, as milk and dairy are often recommended for strong bones and muscle health. However, when the kidneys are damaged, too much phosphorus consumption can cause a buildup of phosphorus in the blood, which can pull calcium from your bones. This can make bones thin and weak over time and increase the risk of bone breakage or fracture (19). It may be important to limit dairy intake to avoid the buildup of protein waste in the blood. Dairy alternatives like unenriched rice milk and almond milk are much lower in potassium, phosphorus, and protein than cow’s milk, making them a good substitute for milk while on a renal diet. Despite milk’s high calcium content, its phosphorus content may weaken bones in those with kidney disease. While oranges and orange juice are arguably most well known for their vitamin C contents, they’re also rich sources of potassium. Moreover, there are 473 mg of potassium in 1 cup (240 mL) of orange juice (20, 21). Given their potassium content, oranges and orange juice likely need to be avoided or limited on a renal diet. Grapes, apples, and cranberries, as well as their respective juices, are all good substitutes for oranges and orange juice, as they have lower potassium contents. Processed meats have long been associated with chronic diseases and are generally considered unhealthy due to their preservative contents (22, 23, 24, 25). Processed meats typically contain large amounts of salt, mostly to improve taste and preserve flavor. Therefore, it may be difficult to keep your daily sodium intake to less than 2,000 mg if processed meats are abundant in your diet. If you have been told to monitor your protein intake, it’s important to limit processed meats for this reason as well. Likewise, there are 244 mg of sodium in 2 tablespoons of sweet pickle relish (26, 27). Processed olives also tend to be salty, as they’re cured and fermented to taste less bitter. Five green pickled olives provide about 195 mg of sodium, which is a significant portion of the daily amount in only a small serving (28). Many grocery stores stock reduced sodium varieties of pickles, olives, and relish, which contain less sodium than the traditional varieties. However, even reduced sodium options can still be high in sodium, so you will still want to watch your portions. This means that just 1 cup of dried apricots provides 75% of the 2,000-mg low potassium restriction. It’s best to avoid apricots, and most importantly dried apricots, on a renal diet. Just one medium-sized baked potato (156 g) contains 610 mg of potassium, whereas one average-sized baked sweet potato (114 g) contains 541 mg of potassium (31, 32). Fortunately, some high potassium foods, including potatoes and sweet potatoes, can be soaked or leached to reduce their potassium contents. Cutting potatoes into small, thin pieces and boiling them for at least 10 minutes can reduce the potassium content by about 50% (33). Potatoes that are soaked in water for at least 4 hours before cooking are proven to have an even lower potassium content than those not soaked before cooking (34). Considerable amounts of potassium can still be present in double-cooked potatoes, so it’s best to practice portion control to keep potassium levels in check. Tomatoes are another high potassium fruit that may not fit the guidelines of a renal diet. Unfortunately, for those on a renal diet, tomatoes are commonly used in many dishes.
Sealed containers from drug companies all have expiratory dates printed or stamped antibiotic drugs list buy keftab line. For the past 3 or 4 days antibiotics for sinus and throat infection purchase generic keftab online, I have been feeling a burning sensation in my eyes for seeming no reason virus utah safe 375mg keftab. It is also used to infection types discount keftab 375 mg on line treat a certain type of pneumonia (pneumocystis pneumonia) in patients with a weakened immune system. Bactrim tablets are white and round and contain 80 milligrams (mg) of trimethoprim and 400 mg of sulfamethoxazole. Bactrim Ds 800 Mg/160 Mg Tablet is used to treat chronic respiratory problems such as chronic Energizer Lithium Batteries Sale bronchitis. Bactrim is a combination of two synthetic (man-made) antibiotics, sulfamethoxazole and trimethoprim. If your medicine is available in double your normal dose, and you can safely split the pills, you may be able to get a. F: 68 1 days: 800/160 1/14/2020: 1: Infected finger: Took one pill started having headaches. Applesauce is certainly a good choice or a viscous liquid such as a syrup works as well. Bactrim is a medication used mainly for the treatment of bacterial infections that can affect your urine system, middle ear infections, intestines and respiratory system. It may also be administered for the use of urinary tract infection, malaria and a few other diseases as per your doctor’s discretion. Learn about the reported side effects, related class drugs, and Jovens Podem Tomar Cialis how these medications will affect your daily lifestyle. Com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. Swollen brain Doctors give trusted answers on uses, effects, side-effects, and cautions: Dr. Sulfamethoxazole is a sulfa drug, which can interrupt dihydrofolic acid production Combination product of trimethoprim and sulfamethoxazole in a fixed 1:5 ratio; both are synthetic folate antagonists. This medication should not be used to treat viral infections such as the cold or flu. Get the facts Your options Take antibiotics for a sore throat caused by a bacterial infection. Over time, these bacteria get tougher and can cause longer and more serious infections. If you have a sudden, severe sore throat without coughing, sneezing, or other cold symptoms, you could have strep throat. They can also prevent serious but rare problems such as rheumatic fever in children. It can make breathing easier and relieve a runny nose and, which can make your throat hurt. If your sore throat is caused by a virus, it will likely go away on its own in 4 to 5 days. If your sore throat is caused by a virus, there are no risks or side effects of not taking antibiotics. Personal stories Personal stories about taking antibiotics for sore throat These stories are based on information gathered from health professionals and consumers. And I wanted to get over it as soon as possible so I could go back to my volunteer job at the local hospital. Tetracycline molecules comprise a group of broad-spectrum antibiotics whose primary mechanism of action is the inhibition of protein synthesis through the binding of the bacterial ribosome. This trigger is absent in a patient with diabetic neuropathy, hence why they will likely maintain pressure on the ulcered foot and hinder wound healing. It has been hypothesized that persistently high concentrations of cytokines within the wound maintain the inflammatory response and induce high concentrations of proteases, which degrade growth factors, receptors, and matrix proteins that are essential for proper wound healing. Three formulations were stored in airtight, light-protected containers at -20°C, 4°C, and 25°C, respectively, for 70 days until analysis. Three formulations were stored in airtight, light-protected containers at -20°C, 4°C, and 25°C, respectively, for 70 days. The samples then were sonicated for 30 minutes at room temperature and centrifuged at 11 000 rpm for 10 minutes. After, 10 µL of the supernatant was added to 990 µL of a 126-ng/mL solution of doxycycline-d₃ hyclate in methanol/water (50:50). The resulting solution was mixed thoroughly and submitted for analysis within the authors’ laboratory. Ratio of peak area of doxycycline to peak area of d₃-doxycyline was plotted against doxycycline concentrations and used to produce a standard curve in the form of Y = a + bX using weighted least squares linear regression. Each batch of unknown samples was accompanied by a standard series and a set of quality control samples. A spectrometer system equipped with an electrospray ionization probe was used in the positive ion mode with multiple reaction monitoring for the quantitative analysis. The microplate reactions were mixed and prewarmed to 37°C, 10 µL of substrate (40 µM, final concentration 4 µM) was added, and real-time kinetics were collected over 10 minutes at 1-minute intervals using excitation and emission wavelengths of 328 nm and 420 nm, respectively. Using this stock, a 1:1 serial dilution was constructed with a range of 1000 µM to 15. The solution was centrifuged at 11 000 rpm for 1 minute, and the supernatant underwent a 1:1 serial dilution with a range of 1000 µM to 15. For each serial dilution concentration, 20 µL was added in duplicate to enzyme reaction wells (previously described) for a final drug range of 200 µM to 3. Clinical chart review The study was conducted in accordance with Good Clinical Practice guidelines and reviewed and approved by Institutional Review Board services (protocol number: Pro00022337) prior to study commencement. General patient information, wound size, wound classification, ulcer location, and photography were deidentified and provided to the Research and Development department of Delivra Corp (Charlottetown, Prince Edward Island, Canada) to maintain patient confidentiality. Storage temperature was the most important factor in terms of stability of the formulations when light was controlled. The 62-year-old woman with type 2 diabetes had a medical history of hypertension, hyperlipidemia, and obesity. The second digit of her right foot had been amputated 2 years prior to presentation. The ulcer in this case study, a pressure-induced diabetic ulcer, was not present at initial presentation to the Mayer Institute. At 1-week follow-up, the ulcer in question was characterized with a surface area of 0. This case study corroborates healing outcomes previously observed by Chin et al,24 justifying the further investigation of a topical wound treatment containing doxycycline. Limitations A number of variables that may have an impact on wound healing were not reviewed, such as oral medication use (consistent or otherwise). Moreover, these limited observational data are not indicative of outright efficacy, but rather supportive of further investigations within a randomized placebo-controlled clinical setting. The authors disclose no financial or other conflicts of interest beyond this pending patent and employee status. Gram coloration, catalase test, colony-mallow growing on chromogenic medium, and coagulase test confirmed the identity of 44 (0. These results point out to the need of a larger knowledge on the contamination means and propagation of this microorganism into the odontological clinic. Keywords: Staphylococcus aureus; Ampicillin-resistant; Odontological clinic environment. Coloração de Gram, teste de catalase, crescimento de colônias-malva sobre meio cromogênico e teste de coagulase confirmaram a identidade de 44 (0,45%) isolados de S. Estes resultados apontam para a necessidade de um maior conhecimento sobre os meios de contaminação e propagação deste microrganismo dentro da clínica odontológica. Among the infectious diseases caused by those bacteria are the septicaemia, pneumonia, endocarditis, osteomyelitis, gastroenteritis and abscess4. In addition, the isolation and the prevalence of multi-resistant strains to antibiotics have been demonstrated in several nosocomial and clinical environments4,12,29. The odontological clinic was also considered an environment of infectious agent cross-transmission.
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Eosinophilia antibiotic resistance new drugs keftab 250mg without prescription, transient lymphocytosis leucopoenia and antibiotics for recurrent urinary tract infections purchase 750 mg keftab free shipping, rarely virus doctor sa600cb buy keftab 375 mg lowest price, thrombocytopenia infection you get from hospital purchase generic keftab pills, thrombocytosis, haemolytic anaemia, aplastic anaemia, agranulocytosis and reversible neutropenia of possible clinical significance. There have been rare reports of increased prothrombin time with or without clinical bleeding in patients receiving cefaclor and warfarin concomitantly. There have also been reports of transient fluctuations in leucocyte count, predominantly lymphocytosis in infants and young children. Slight elevation in serum urea or serum creatinine or abnormalities of urinalysis (haematuria; pyuria), reversible interstitial nephritis. Rarely, reversible hyperactivity, nervousness, insomnia, confusion, hypertonia, dizziness, hallucinations, headache or somnolence have been reported. Transitory abnormalities in clinical laboratory test results have been reported, but their clinical significance is uncertain. The following adverse reactions have been reported in patients treated with other beta-lactam antibiotics. For more severe infections or those caused by less susceptible organisms, doses may be doubled (500 mg every eight hours). For skin and skin structure infections, the dosage is 250 mg two to three times daily. The usual recommended daily dosage for children with mild to moderate infections is 20 mg/kg/day in divided doses every 8 hours. For streptococcal pharyngitis or tonsillitis and impetigo, administration every twelve hours appears equally effective. In more serious infections, otitis media and infections caused by less susceptible organisms, the recommended dosage is 40 mg/kg/day in divided doses every eight to twelve hours (maximum 2 g/day). In the treatment of β-haemolytic streptococcal infections, a therapeutic dosage of cefaclor should be administered for at least ten days. The toxic symptoms following an overdose of cefaclor may include nausea, vomiting, epigastric distress and diarrhoea. In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in the patient. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which in many cases is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Forced diuresis, peritoneal dialysis, haemodialysis or charcoal haemoperfusion have not been established as beneficial for an overdose of cefaclor. Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide. A new era of antiviral drug development has begun since the first antiviral drug, idoxuridine, was approved in June 1963 (3) (Fig. Since then, many antiviral drugs have been developed for clinical use to treat millions of human beings worldwide. Between June 1963 and April 2016, 90 drugs were formally approved to treat 9 human infectious diseases (Table 1) despite the fact that thousands of antiviral inhibitors have been proposed in the literature. Previously, we reviewed the history of 25 approved antiretroviral drugs over 25 years (1984 to 2009) (4, 5). The present study commemorates 90 antiviral drugs approved for the treatment of 9 human infectious diseases over the past 5 decades. The gray arrow shows the dates of approval of antiviral drugs from January 1959 to April 2016. In the drug group, each red star within a sign represents an approved drug, placed according to the year of approval. Yellow stars indicate approved drugs that have been discontinued or abandoned for clinical use. A total of 90 stars thus represent all approved antiviral drugs, and each drug star is positioned according to its approval date (Table 2). In this picture, every approved drug could be conceived as a “superstar,” and its contribution to human health is worthy of being remembered and respected. Therefore, this zodiac-based figure metaphorically recognizes each antiviral drug as a star in the universe, commemorating the significant contributions of antiviral drug discovery and development over the past 50 years. Movies and label information for approved drugs are accessible online (see http://www. The x axis indicates the period from January 1959 to April 2016, and the y axis shows the total number of approved drugs. Table 2 summarizes the information on antiviral drugs regarding their approval dates and mechanisms of drug action. Table S1 in the supplemental material provides details on drug databases and chemical formulas. Interestingly, 11 of 90 antiviral drugs have been approved for the treatment of more than one infectious disease (Table 2), suggesting that antiviral drugs may potentially treat multiple viral infections. More importantly, antiviral drugs from the same drug group share similar mechanisms of drug action to inhibit viral replication during the viral life cycle (Fig. In some cases, approved antiviral drugs could be used as off-label treatments for emerging infectious diseases. Therefore, a comprehensive review that summarizes all approved antiviral drugs will shed light on the development of novel inhibitors against current and emerging viral infections. Influenza viruses that infect humans originate mostly from birds, pigs, or seals (36, 401). Names of antiviral drugs that are currently in use are enclosed in orange oblongs. Those drugs that inhibit more than one virus are shown in the overlapping regions between virus groups. Twelve drug groups ordered by roman numerals are shown at the bottom, and their drug actions that interfere with major stages of the viral life cycle are highlighted by red arrows. Solid black arrows indicate direct biological pathways involving viral replication, and dotted black arrows indicate biological pathways with intermediate pathways inside host cells. Subsequently, the following three perspectives of 90 approved drugs are discussed. In addition, we make a summary of promising antiviral compounds in phase 3 clinical trials (Table 3). To give a comprehensive overview, we highlight the latest progress on antiviral drugs and vaccines against emerging infectious diseases. Below, we give an overview of the origins, pathogenicities, epidemiologies, and clinical complications of these 9 human viruses. Many clinical complications have been reported: lymphoma, psychiatric disorders, gingivitis, cardiovascular disease, lung cancer, kidney disease, osteoporosis, papulosquamous disorders, and dental or salivary gland diseases (for a review, see reference 18). Many clinical complications have been observed, including liver cirrhosis, liver failure, portal hypertension, or hepatocellular carcinoma (26, 27). Influenza B viruses that cause human epidemics are divided into strains but not subtypes. Influenza C viruses cause neither epidemics nor pandemics, because they usually infect humans with mild illnesses. On the other hand, influenza viruses have been discovered in a broad spectrum of animal reservoirs (36). Using respiratory routes, influenza viruses spread mostly through direct contact with contaminated aerosols or droplets. During influenza infection, the typical incubation period is ∼1 to 4 days (average, 2 days), and many clinical complications (e. Papillomaviruses have been widely found in birds, reptiles, marsupials, and mammals, but cross-transfer between species is rare (54). The former leads to the majority of cases of oral herpes infections that cause skin lesions and cold sores. The latter is mainly responsible for genital herpes infections that cause pain during urination and blistering sores. Many clinical complications of herpes zoster in immunocompetent humans have been reported, including pneumonia, cellulitis, neuralgia, encephalitis, myelitis, cranial nerve palsies, or peripheral nerve palsies (83). It has been estimated that 30% of humans have been infected with herpes zoster over their lifetime (83), and the seroprevalence of immunoglobulin G (IgG) antibody to varicella-zoster virus is >86% in children and adults (84).
Your healthcare provider will determine the best antibiotic to antibiotics and breastfeeding order keftab 125 mg overnight delivery use if you are pregnant and need an antibiotic treatment for uti toddlers quality keftab 750 mg. Amoxicillin is also a pregnancy category B infection preventionist job description purchase cheapest keftab and keftab, and like azithromycin antibiotic lecture order keftab 125mg on line, there have not been adequate studies with pregnant women. While the manufacturer’s information does not list alcohol as a contraindication to either antibiotic, it’s important to take note that alcohol can prevent your body from fighting an infection. They have some similarities and some differences, but we can’t really say which is stronger. Instead, it is important to look at what infection is being treated, what bacteria is causing the infection, and any other medical conditions you have and any drugs you take that can interact with azithromycin or amoxicillin. A sinus infection may be caused by a virus or by bacteria (or even a fungus, in rare cases). If your prescriber diagnoses you with a bacterial sinus infection, azithromycin or amoxicillin (or Augmentin) are appropriate, and very common, treatments. Your prescriber will also take into account allergies and other drugs you take that may interact with azithromycin or amoxicillin. If you have a viral infection like the common cold, an antibiotic will not help at all. Each year, 30 million pregnancies are at risk of malaria infection in sub-Saharan Africa, representing a major public health problem. This review summarizes in vitro and in vivo evidence for the therapeutic efficacy of azithromycin and chloroquine when used alone or together and discusses the additional benefits that the combination could have on many sexually transmitted diseases and, possibly, pneumococcal infection during pregnancy. Drug costs are presented along with issues related to drug resistance and surveillance. Azithromycin monotherapy for treatment and prevention of malariaPharmacokineticsAzithromycin is a slow-acting anti-malarial macrolide [19], an analogue of erythromycin with a nitrogen atom inserted into the macrolide nucleus. As a result, there is enhanced penetration of drug into macrophages, fibroblasts and polymorphonuclear neutrophils, permitting greater accumulation within acidified vacuoles and extending the 1. Stable at gastric pH, azithromycin has an absolute bioavailability of 37% following oral administration [21]. It accumulates in hepatic, renal, pulmonary and splenic tissue [22], and gradually leaches into the bloodstream over a period of one week [23]. Mild renal dysfunction and mild-to-moderate hepatic dysfunction do not affect excretion significantly. Among pregnant women, serum concentrations peak within six hours of oral administration and are sustained for 24 hours. As the drug disperses, peak concentrations are maintained three-times longer in the placenta, myometrial and adipose tissues [24]; only 2. Azithromycin is excreted in human milk with no adverse events observed as a consequence [26]. Azithromycin targets the 70 S ribosomal subunit of the apical complex of susceptible micro-organisms including P. Once attached to the apicoplasts of the parasite, azithromycin hinders polypeptide development, triggering premature detachment and movement down the peptide exit tunnel. The potency of azithromycin, as a translation inhibitor, is greatest against the progeny of parasites that inherit a non-functioning apicoplast following drug exposure, thus creating a delayed-death effect [27–29]. It is unknown whether mutations induced by azithromycin are capable of undermining the inhibitory action of other drugs that also target the apicoplast. Safety and tolerabilityDoses of azithromycin between 500 mg and 2,000 mg have been used in all trimesters of human pregnancy for the treatment of upper and lower respiratory tract infections, skin diseases, Chlamydia trachomatis, mycoplasma and group B streptococci infections among women allergic to other antibiotics. Adults treated with a 1,000 mg oral dose of azithromycin report moderate side-effects including diarrhoea or loose stools (7%), nausea (5%), vomiting (2%), and vaginitis (2%); up to 1% of adults experience dizziness, headache, vertigo, and somnolence [33]. There is no evidence of teratogenicity in animal models, even at four-times the human treatment dose [34–36]. EfficacyThe in vitro anti-malarial activity of azithromycin increases 200-fold against P. At 48-hours, azithromycin is 10-fold more active than erythromycin against chloroquine-resistant P. Daily regimens of 250 mg with a loading dose of 500 or 750 mg have shown an impressive chemoprophylactic effect against P. Table 1 Chemoprophylactic effect of azithromycin monotherapy against Plasmodium falciparum in semi-immune non-pregnant adults. Subjects were then inoculated with five Anopheles stephensi mosquitoes that had an average of 3. With unquantifiable plasma concentrations of azithromycin, presumably due to poor absorption, one of four subjects developed parasitaemia in the 14-day post-challenge period [42]. A subsequent trial suggested that a regimen of longer duration might be required against P. Ten non-immune subjects were given a loading dose of 500 mg followed by 250 mg daily for 2 weeks prior to parasite exposure. A concurrent human challenge study with 10 non-immune subjects was conducted using the same regimen, except that 250 mg was given daily for two weeks post-exposure, rather than for just one, producing a 100% protective effect [43]. This high level of protection has not been replicated in the field, however, where multiple infections may be expected. There were two sub-populations in the Indonesian study which may have had slightly different degrees of acquired immunity: the chemoprophylactic effect among soldiers living for six months in the study area was 62. Chloroquine as monotherapy for the treatment and prevention of malariaPharmacokineticsChloroquine has been the first-line treatment of malaria in much of the world for most of the past 60 years. Absolute bioavailability is 70 to 75% while peak plasma concentrations are reached within two hours of oral administration. A single therapeutic dose against a chloroquine-resistant strain will persist six to 10 days in the blood, while its overall half-life is between one and two months [45, 46]. Chloroquine accumulates extensively in the liver, connective tissue and pigmented tissue such as skin and retina, enabling enormous total volume distribution. Greatest concentrations are found in erythrocytes, granulocytes and platelets, and 55% is protein-bound in plasma. Chloroquine is active against erythrocytic life stages of Plasmodium species when haemoglobin is being actively digested. Haem is a toxic bi-product of haemoglobin ingestion and must be eliminated through dimerization. Under normal circumstances, parasites bio-crystallize haem to form haemozoin, the iron-containing pigment that accumulates as non-toxic cytoplasmic granules. Chloroquine prevents this process by concentrating at nanomolar levels outside parasites (10-9) and one million times higher (10-3) in parasite food vacuoles of infected erythrocytes [47]. Thus, the more haemoglobin ingested by parasites, the more toxic their food vacuoles become, rapidly causing cell death. All pfcrt alleles from chloroquine-resistant strains, regardless of geographic origin, encode a conserved K76T amino acid substitution. Some researchers have theorized that pfcrt enables protonated chloroquine to escape the food vacuole while others argue pfcrt binds directly to chloroquine, thereby inhibiting its ability to alter food vacuole pH [49]. Safety and tolerabilityChloroquine is safe and generally well tolerated in treatment doses. Due to its rapid absorption, chloroquine has a narrow therapeutic index, increasing the potential for toxic overdose. Hypotension and cardiac failure can be prompted by a single oral dose of 3500 mg [50]. Despite toxicity at high doses, the most commonly reported side-effect in African populations is pruritus which peaks 24 hours after intake [51]. Chloroquine has been used safely in all trimesters of human pregnancy for decades as both a treatment and chemoprophylactic drug, crossing the placenta without teratogenic effect [52]. Compliance with chloroquine remained low for many reasons including pruritus and its bitter taste which some women associate with medications that induce abortion [53, 54]. In combination with another anti-malarial drug, however, chloroquine might, once again, have a role in malaria control. Five years later, chloroquine inhibited in vitro blood schizont development in 96. In 2001, field sampling failed to find parasites carrying the pfcrt mutation associated with resistance [57] and a clinical trial using chloroquine monotherapy was 100% efficacious (63 of 63) among asymptomatic semi-immune adults who received 600 mg on day 0 and day 1, and 300 mg on day 2 [58]. Most recently, a study in 2005 showed chloroquine to clear parasite infection in 98.