Model: RikoteMaster/embedder-granite
Author: RikoteMaster
Pipeline: sentence-similarity
Library: sentence-transformers
Tags: sentence-transformers, safetensors, xlm-roberta, sentence-similarity, feature-extraction, generated_from_trainer, dataset_size:34441, loss:MultipleNegativesRankingLoss, arxiv:1908.10084, arxiv:1705.00652, base_model:ibm-granite/granite-embedding-107m-multilingual, base_model:finetune:ibm-granite/granite-embedding-107m-multilingual, text-embeddings-inference, endpoints_compatible, region:us
Base models (finetune): id: ibm-granite/granite-embedding-107m-multilingual
Card metadata: tags: sentence-transformers, sentence-similarity, feature-extraction, generated_from_trainer, dataset_size:34441, loss:MultipleNegativesRankingLoss
base_model: ibm-granite/granite-embedding-107m-multilingual
widget: source_sentence: inhibitors as antifungal, and antibacterial agents. and in with sulfonylureas, not combination insulin. During clinical tion in 0.4–0.9%. Adverse an increased rate of infections (upper respiratory and tract), (when Tzd), hypoglycemia (when a dose of insulin agogue lowered hypoglycemia. Linagliptin is the class and appears have properties similar to and tin. It approved for and combination with metformin, pioglitazone. COMBINATION THERAPY—ORAL ANTIDIABETIC & in 2 Diabetes Mellitus Failure to maintain response over the owing a in mass, reduction physical activity, mass, in remains disconcerting problem ment of type Multiple medications may glycemic there a should initiated with biguanide. clinical failure monotherapy, a agent or is be insulin dase inhibitor; sulfonylureas insulin because of adverse safety concerns. Third-line multiple medications, or a injectable intensified insulin
sentences: inhibitors such as antiviral, antifungal, and certain antibacterial agents. Saxagliptin is approved as monotherapy and in combination with biguanides, sulfonylureas, and Tzds. It has not been studied in combination with insulin. During clinical trials, mono- and combination therapy with sitagliptin resulted in an HbA 1c reduc- tion in the range of 0.4–0.9%. Adverse effects include an increased rate of infections (upper respiratory tract and urinary tract), headaches, peripheral edema (when combined with a Tzd), hypoglycemia (when combined with a sulfonylurea), and hypersensitivity reactions (urticaria, facial edema). The dose of a concurrently administered insulin secret- agogue or insulin may need to be lowered to prevent hypoglycemia. Linagliptin is the most recently introduced drug in this class and appears to have properties similar to sitagliptin and saxaglip- tin. It is approved for use as monotherapy and in combination with metformin, glimepiride, and pioglitazone. COMBINATION THERAPY—ORAL ANTIDIABETIC AGENTS & INJECTABLE MEDICATION Combination Therapy in Type 2 Diabetes Mellitus Failure to maintain a good response to therapy over the long term owing to a progressive decrease in beta-cell mass, reduction in physical activity, decline in lean body mass, or increase in ectopic fat deposition remains a disconcerting problem in the manage- ment of type 2 diabetes. Multiple medications may be required to achieve glycemic control. Unless there is a contraindication, medical therapy should be initiated with a biguanide. If clinical failure occurs with metformin monotherapy, a second agent or insulin is added. The second-line drug can be an insulin secret- agogue, Tzd, incretin-based therapy, amylin analog, or a glucosi- dase inhibitor; preference is given to sulfonylureas or insulin because of cost, adverse effects, and safety concerns. Third-line therapy can include metformin, multiple other oral medications, or a noninsulin injectable and metformin and intensified insulin, 61. Glucocorticoids for gastrointestinal use: See Chapter 62. REFERENCES Alesci S et al: Glucocorticoid-induced osteoporosis: From basic mechanisms to clinical aspects. Neuroimmunomodulation 2005;12:1. Bamberger CM, Schulte HM, Chrousos GP: Molecular determinants of gluco- corticoid receptor function and tissue sensitivity to glucocorticoids. Endocr Rev 1996;17:245. Charmandari E, Kino T: Chrousos syndrome: A seminal report, a phylogenetic enigma and the clinical implications of glucocorticoid signaling changes. Eur J Clin Invest 2010;40:932. Charmandari E, Tsigos C, Chrousos GP: Neuroendocrinology of stress. Ann Rev Physiol 2005;67:259. Chrousos GP: Stress and disorders of the stress system. Nat Endocrinol Rev 2009;5:374. Chrousos GP, Kino T: Glucocorticoid signaling in the cell: Expanding clinical implications to complex human behavioral and somatic disorders. In: Glucocorticoids and mood: Clinical manifestations, risk factors, and molecular mechanisms. Proc NY Acad Sci 2009;1179:153. Elenkov IJ, Chrousos GP: Stress hormones, TH1/TH2 patterns, pro/anti-in- flammatory cytokines and susceptibility to disease. Trends Endocrinol Metab 1999;10:359. Elenkov IJ et al: Cytokine dysregulation, inflammation, and wellbeing. Neuroimmunomodulation 2005;12:255. Franchimont D et al: Glucocorticoids and inflammation revisited: The state of the art. Neuroimmunomodulation 2002–03;10:247. Graber AL et al: Natural history of pituitary-adrenal recovery following long-term suppression with corticosteroids. J Clin Endocrinol Metab 1965;25:11. Hochberg Z, Pacak K, Chrousos GP: Endocrine withdrawal syndromes. Endocrine Rev 2003;24:523. Kalantaridou S, Chrousos GP: Clinical review 148:, safely and effectively combined with 5-FU-, irinotecan-, and oxaliplatin-based chemotherapy in the treatment of metastatic colorectal cancer. Bevacizumab is FDA approved as a first-line treatment for metastatic colorectal cancer in combination with any intravenous fluoropyrimidine-contain- ing regimen and is now also approved in combination with che- motherapy for metastatic non-small lung cancer and breast cancer. One potential advantage of this antibody is that it does not appear to exacerbate the toxicities typically observed with cytotoxic che- motherapy. The main safety concerns associated with bevacizumab include hypertension, an increased incidence of arterial throm- boembolic events (transient ischemic attack, stroke, angina, and myocardial infarction), wound healing complications, gastrointes- tinal perforations, and proteinuria. Sorafenib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs), especially VEGF-R2 and VEGF-R3, platelet-derived growth factor-β (PDGFR-β), and raf kinase. It was initially approved for advanced renal cell cancer and is also approved for advanced hepatocellular cancer. Sunitinib is similar to sorafenib in that it inhibits multiple RTKs, although the specific types are somewhat different. They include PDGFR-α and PDGFR-β, VEGF-R1, VEGF-R2, VEGF-R3, and c-kit. It is approved for the treatment of advanced renal cell cancer and for the treatment of gastrointestinal stromal tumors (GIST) after disease progression on or with intolerance to imatinib. Pazopanib is a small molecule that inhibits multiple RTKs, espe- cially VEGF-R2 and VEGF-R3, PDGFR-β, and raf kinase. This oral agent is approved for the treatment of advanced renal cell cancer. Sorafenib, sunitinib, and pazopanib are metabolized in the liver by the CYP3A4 system, and elimination is primarily hepatic with excretion in feces. Each of these agents has potential interac-, source_sentence: 774 VII that detected by parathyroid gland, increases in serum phos- levels reduce the secretion. regulation is the net PTH serum calcium and reduce serum at the amount increase the amount 24,25(OH) D produced. serum calcium by reducing secretion. High phosphate by D calcium phosphate, has less effect, such feedback is again appropriate. 1,25(OH) effect PTH patients chronic are loss this 2 D-mediated loop intestinal absorption often leads secondary The D to PTH being exploited with of absorption. Such useful the management of hyperparathy- roidism chronic kidney be of 1,25(OH) also production This the loop in that FGF23 2 D promoting hypophosphatemia, turn inhibits and 2 production. HORMONAL OF
sentences: rier only when the meninges are inflamed. Concentrations in cerebrospinal fluid are highly variable, ranging from 4% to 64% of serum levels in the setting of meningeal inflammation. As with all antituberculous drugs, resistance to ethambutol emerges rapidly when the drug is used alone. Therefore, ethambutol is always given in combination with other antituberculous drugs. Ethambutol hydrochloride, 15–25 mg/kg, is usually given as a single daily dose in combination with isoniazid or rifampin. The higher dose is recommended for treatment of tuberculous menin- gitis. The dose of ethambutol is 50 mg/kg when a twice-weekly dosing schedule is used. Adverse Reactions Hypersensitivity to ethambutol is rare. The most common serious adverse event is retrobulbar neuritis, resulting in loss of visual acuity and red-green color blindness. This dose-related adverse effect is more likely to occur at dosages of 25 mg/kg/d continued for several months. At 15 mg/kg/d or less, visual disturbances are very rare. Periodic visual acuity testing is desirable if the 25 mg/kg/d dosage is used. Ethambutol is relatively contraindicated in chil- dren too young to permit assessment of visual acuity and red- green color discrimination. PYRAZINAMIDE Pyrazinamide (PZA) is a relative of nicotinamide. It is stable and slightly soluble in water. It is inactive at neutral pH, but at pH 5.5 it inhibits tubercle bacilli at concentrations of approximately 20 mcg/mL. The drug is taken up by macrophages and exerts its activity against mycobacteria residing within the acidic environ- ment of lysosomes. Pyrazinamide (PZA) N C O NH2 N Mechanism of Action & Clinical Uses Pyrazinamide is converted to pyrazinoic acid—the active form of the drug—by mycobacterial pyrazinamidase, which is encoded by, 774 SECTION VII Endocrine Drugs that is detected by the parathyroid gland, increases in serum phos- phate levels reduce the ionized calcium, leading to enhanced PTH secretion. Such feedback regulation is appropriate to the net effect of PTH to raise serum calcium and reduce serum phosphate levels. Likewise, both calcium and phosphate at high levels reduce the amount of 1,25(OH) 2 D produced by the kidney and increase the amount of 24,25(OH) 2 D produced. High serum calcium works directly and indirectly by reducing PTH secretion. High serum phosphate works directly and indirectly by increasing FGF23 levels. Since 1,25(OH) 2 D raises serum calcium and phosphate, whereas 24,25(OH) 2 D has less effect, such feedback regulation is again appropriate. 1,25(OH) 2 D directly inhibits PTH secretion (independent of its effect on serum calcium) by a direct inhibitory effect on PTH gene transcription. This pro- vides yet another negative feedback loop. In patients with chronic renal failure who frequently are deficient in producing 1,25(OH) 2 D, loss of this 1,25(OH) 2 D-mediated feedback loop coupled with impaired phosphate excretion and intestinal calcium absorption often leads to secondary hyperparathyroidism. The ability of 1,25(OH) 2 D to inhibit PTH secretion directly is being exploited with calcitriol analogs that have less effect on serum calcium because of their lesser effect on intestinal calcium absorption. Such drugs are proving useful in the management of secondary hyperparathy- roidism accompanying chronic kidney disease and may be useful in selected cases of primary hyperparathyroidism. 1,25(OH) 2 D also stimulates the production of FGF23. This completes the negative feedback loop in that FGF23 inhibits 1,25(OH) 2 D production while promoting hypophosphatemia, which in turn inhibits FGF23 production and stimulates 1,25(OH) 2 D production. SECONDARY HORMONAL REGULATORS OF BONE MINERAL HOMEOST, host disease after allogeneic stem cell trans- plantation. Cyclosporine has also proved useful in a variety of autoimmune disorders, including uveitis, rheumatoid arthritis, psoriasis, and asthma. Its combination with newer agents is show- ing considerable efficacy in clinical and experimental settings where effective and less toxic immunosuppression is needed. Newer for- mulations of cyclosporine have been developed that are improving patient compliance (smaller, better tasting pills) and increasing bioavailability. Tacrolimus Tacrolimus (FK 506) is an immunosuppressant macrolide antibi- otic produced by Streptomyces tsukubaensis. It is not chemically related to cyclosporine, but their mechanisms of action are similar. Both drugs bind to cytoplasmic peptidylprolyl isomerases that are abundant in all tissues. While cyclosporine binds to cyclophilin, tacrolimus binds to the immunophilin FK-binding protein (FKBP). Both complexes inhibit calcineurin, which is necessary for the activation of the T-cell-specific transcription factor NF-AT. On a weight basis, tacrolimus is 10–100 times more potent than cyclosporine in inhibiting immune responses. Tacrolimus is utilized for the same indications as cyclosporine, particularly in organ and stem cell transplantation. Multicenter studies in the USA and in Europe indicate that both graft and patient survival are similar for the two drugs. Tacrolimus has proved to be effective therapy for preventing rejection in solid-organ transplant patients even after failure of standard rejection therapy, including anti-T- cell antibodies. It is now considered a standard prophylactic agent (usually in combination with methotrexate or mycophenolate mofetil) for graft-versus-host disease. Tacrolimus can be administered orally or intravenously. The half-life of the intravenous form is approximately 9–12 hours. Like cyclosporine, tacrolimus is metabolized primarily by P450 enzymes in the liver, and there is potential for drug interactions. The dosage is determined by trough blood level at, source_sentence: Antiviral 865 TABLE Agents or (HSV) varicella-zoster virus (VZV) Administration Recommended Dosage and Regimen Acyclovir1 Oral First treatment mg tid mg 5 daily × Recurrent genital herpes mg 200 times daily 800 bid 3–5 tid 2 days Genital the host treatment Genital in host treatment 5 until healed Orolabial treatment × days Varicella years) 800 mg qid days Zoster daily Intravenous HSV 5 in host mg/kg treatment 10–15 days Neonatal HSV infection 10–20 mg/kg × Varicella the host treatment mg/kg q8h days (5% treatment lesion 4 Famciclovir1 episode treatment mg × days genital 1000 day Genital in HIV-infected 500 5–10 days herpes 250 Genital in the HIV-infected 500 bid Orolabial or suppression 250-500 mg mg days Oral herpes 1000 mg bid × 10 Recurrent mg Genital herpes HIV-infected 5–10 days herpes once suppression the
sentences: CHAPTER 49 Antiviral Agents 865 TABLE 49–1 Agents to treat or prevent herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Route of Administration Use Recommended Adult Dosage and Regimen Acyclovir1 Oral First episode genital herpes treatment 400 mg tid or 200 mg 5 times daily × 7–10 days Recurrent genital herpes treatment 400 mg tid or 200 mg 5 times daily or 800 mg bid × 3–5 days or 800 mg tid × 2 days Genital herpes in the HIV-infected host treatment 400 mg 3–5 times daily × 5–10 days Genital herpes suppression in the HIV-infected host 400–800 mg bid–tid Herpes proctitis treatment 400 mg 5 times daily until healed Orolabial herpes treatment 400 mg 5 times daily × 5 days Varicella treatment (age ≥ 2 years) 800 mg qid × 5 days Zoster treatment 800 mg 5 times daily × 7–10 days Intravenous Severe HSV treatment 5 mg/kg q8h × 7–10 days Mucocutaneous herpes in the immunocompromised host treatment 10 mg/kg q8h × 7–14 days Herpes encephalitis treatment 10–15 mg/kg q8h × 14–21 days Neonatal HSV infection treatment 10–20 mg/kg q8h × 14–21 days Varicella or zoster in the immunosuppressed host treatment 10 mg/kg q8h × 7 days Topical (5% cream) Herpes labialis treatment Thin film covering lesion 5 times daily × 4 days Famciclovir1 Oral First episode genital herpes treatment 500 mg tid × 5–10 days Recurrent genital herpes treatment 1000 mg bid × 1 day Genital herpes in the HIV-infected host treatment 500 mg bid × 5–10 days Genital herpes suppression 250 mg bid Genital herpes suppression in the HIV-infected host 500 mg bid Orolabial herpes treatment 1500 mg once Orolabial or genital herpes suppression 250-500 mg bid Zoster 500 mg tid × 7 days Valacyclovir1 Oral First episode genital herpes treatment 1000 mg bid × 10 days Recurrent genital herpes treatment 500 mg bid × 3 days Genital herpes in the HIV-infected host treatment 500–1000 mg bid × 5–10 days Genital herpes suppression 500–1000 mg once daily Genital herpes suppression in the HIV, LA Human leukocyte antigen IFN Interferon IGIV Immune globulin intravenous IL Interleukin LFA Leukocyte function-associated antigen MAB Monoclonal antibody MHC Major histocompatibility complex NK cell Natural killer cell SCID Severe combined immunodeficiency disease TCR T-cell receptor TGF-a Transforming growth factor-β TH1, TH2 T helper cell types 1 and 2 TNF Tumor necrosis factor, , especially in adults with impaired renal function and prolonged elevation of drug levels. The sudden absorption of postoperatively instilled kanamycin from the peritoneal cavity (3–5 g) has resulted in curare-like neu- romuscular blockade and respiratory arrest. Calcium gluconate and neostigmine can act as antidotes. Although hypersensitivity is not common, prolonged applica- tion of neomycin-containing ointments to skin and eyes has resulted in severe allergic reactions. ■ SPECTINOMYCIN Spectinomycin is an aminocyclitol antibiotic that is structurally related to aminoglycosides. It lacks amino sugars and glycosidic bonds. NH HN CH3 O O CH3 Spectinomycin O CH3 HO O OH OH Spectinomycin is active in vitro against many gram-positive and gram-negative organisms, but it is used almost solely as an alternative treatment for drug-resistant gonorrhea or gonorrhea in penicillin-allergic patients. The majority of gonococcal isolates are inhibited by 6 mcg/mL of spectinomycin. Strains of gonococci may be resistant to spectinomycin, but there is no cross-resistance with other drugs used in gonorrhea. Spectinomycin is rapidly absorbed after intramuscular injection. A single dose of 40 mg/kg up to a maximum of 2 g is given. There is pain at the injection site and, occasionally, fever and nausea. Nephrotoxicity and anemia have been observed rarely. Spectinomycin is no longer available for use in the United States but may be available elsewhere., source_sentence: Against Gram-Positive Bacilli Aminoglycosides Carbapenems Carbapenems Cephalosporins Chloramphenicol Tetracyclines Macrolides Penicillins Sulfonamides Tetracyclines Tigecycline Trimethoprim TABLE Antimicrobial that require are in with hepatic impairment. Dosage Needed in Contraindicated in Dosage Adjustment Impairment amantadine, aminoglycosides, carbapenems, cycloserine, didanosine, ethionamide, penicillins,3 pyrazinamide, stavudine, telavancin, telbivudine, telithromycin, tenofovir, terbinafine, valacyclovir, zidovudine acid, (long-acting), tetracyclines2 Amprenavir, phenicol, indinavir, metronida- 2Except doxycycline and minocycline. nafcillin and 4Except Alter Antimicrobi
sentences: Against Gram-Positive Cocci Against Gram-Negative Bacilli Aminoglycosides Aminoglycosides Carbapenems Carbapenems Cephalosporins Chloramphenicol Chloramphenicol Quinolones Clindamycin Rifampin Daptomycin Tetracyclines Glycopeptide antibiotics Tigecycline Ketolides Macrolides Oxazolidinones Penicillins Quinolones Rifampin Streptogramins Sulfonamides Tetracyclines Tigecycline Trimethoprim TABLE 51–5 Antimicrobial agents that require dosage adjustment or are contraindicated in patients with renal or hepatic impairment. Dosage Adjustment Needed in Renal Impairment Contraindicated in Renal Impairment Dosage Adjustment Needed in Hepatic Impairment Acyclovir, amantadine, aminoglycosides, aztreonam, carbapenems, cephalosporins,1 clarithromycin, colistin, cycloserine, daptomycin, didanosine, emtricitabine, ethambutol, ethionamide, famciclovir, fluconazole, flucytosine, foscarnet, ganciclovir, lamivudine, penicillins,3 pyrazinamide, quinolones, 4 rimantadine, stavudine, telavancin, telbivudine, telithromycin, tenofovir, terbinafine, trimethoprim- sulfamethoxazole, valacyclovir, vancomycin, zidovudine Cidofovir, methenamine, nalidixic acid, nitrofurantoin, sulfonamides (long-acting), tetracyclines2 Amprenavir, atazanavir, chloram- phenicol, clindamycin, erythromycin, fosamprenavir, indinavir, metronida- zole, rimantadine, tigecycline 1Except ceftriaxone. 2Except doxycycline and possibly minocycline. 3Except antistaphylococcal penicillins (eg, nafcillin and dicloxacillin). 4Except moxifloxacin. Conditions That Alter Antimicrobi, of the integrity of membranes in cells and organelles. A. Nervous System The developing central nervous system of the fetus and young child is the most sensitive target organ for lead’s toxic effect. Epidemiologic studies suggest that blood lead concentrations even less than 5 mcg/dL may result in subclinical deficits in neurocog- nitive function in lead-exposed young children, with no demon- strable threshold for a “no effect” level. The dose response between TABLE 57–1 Toxicology of selected arsenic, lead, and mercury compounds. Form Entering Body Major Route of Absorption Distribution Major Clinical Effects Key Aspects of Mechanism Metabolism and Elimination Arsenic Inorganic arsenic salts Gastrointestinal, respiratory (all mucosal surfaces) Predominantly soft tissues (highest in liver, kidney). Avidly bound in skin, hair, nails Cardiovascular: shock, arrhythmias. CNS: encephalopathy, peripheral neuropathy. Gastroenteritis; pan- cytopenia; cancer (many sites) Inhibits enzymes; interferes with oxidative phosphorylation; alters cell signaling, gene expression Methylation. Renal (major); sweat and feces (minor) Lead Inorganic lead oxides and salts Gastrointestinal, respiratory Soft tissues; redistributed to skeleton (> 90% of adult body burden) CNS deficits; peripheral neuropathy; ane- mia; nephropathy; hypertension; reproductive toxicity Inhibits enzymes; interferes with essential cations; alters membrane structure Renal (major); feces and breast milk (minor) Organic (tetraethyl lead) Skin, gastrointesti- nal, respiratory Soft tissues, especially liver, CNS Encephalopathy Hepatic dealkylation (fast) → trialkyme- tabolites (slow) → dissociation to lead Urine and feces (major); sweat (minor) Mercury Elemental mercury Respiratory tract Soft tissues, especially kidney, CNS CNS: tremor, behavioral (erethism); gingivo, 708 SECTION VII Endocrine Drugs marked adverse effects because there is a recovery period between each dose. The transition to an alternate-day schedule can be made after the disease process is under control. It should be done gradu- ally and with additional supportive measures between doses. When selecting a drug for use in large doses, a medium- or intermediate-acting synthetic steroid with little mineralocorticoid effect is advisable. If possible, it should be given as a single morning dose. C. Special Dosage Forms Local therapy, such as topical preparations for skin disease, oph- thalmic forms for eye disease, intra-articular injections for joint disease, inhaled steroids for asthma, and hydrocortisone enemas for ulcerative colitis, provides a means of delivering large amounts of steroid to the diseased tissue with reduced systemic effects. Beclomethasone dipropionate, and several other glucocorti- coids—primarily budesonide, flunisolide, and mometasone furoate, administered as aerosols—have been found to be extremely useful in the treatment of asthma (see Chapter 20 ). Beclomethasone dipropionate, triamcinolone acetonide, budes- onide, flunisolide, and mometasone furoate are available as nasal sprays for the topical treatment of allergic rhinitis. They are effec- tive at doses (one or two sprays one, two, or three times daily) that in most patients result in plasma levels that are too low to influ- ence adrenal function or have any other systemic effects. Corticosteroids incorporated in ointments, creams, lotions, and sprays are used extensively in dermatology. These preparations are discussed in more detail in Chapter 61 . MINERALOCORTICOIDS (ALDOSTERONE, DEOXYCORTICOSTERONE, FLUDROCORTISONE) The most important mineralocorticoid in humans is aldosterone. However, small amounts of deoxycorticosterone (DOC) are also formed and released. Although the amount is normally insignifi- cant, DOC was of some importance therapeut, source_sentence: Antiprotozoal 923 MEFLOQUINE Mefloquine is effective therapy of other Although toxicity is mefloquine one recommended for most regions with Chemistry Mefloquine is 4-quinoline methanol is chemically quinine. can given because local irritation with parenteral and hours. Mefloquine highly uted and treat- regimen. elimination half-life about 20 allowing dosing chemoprophylaxis. With dos- drug reached over number of interval can be shortened to 4 with daily doses 250 mg, this is not and metabolites of in can be in the months completion therapy. Antimalarial Action & strong P falciparum P is hepatic stages or gametocytes. The of unknown. Sporadic mefloquine been from areas. At resistance appears to uncommon regions Asia high rates border areas resis- tance quinine resistance to Clinical in
sentences: 938 SECTION VIII Chemotherapeutic Drugs Clinical Uses Albendazole is administered on an empty stomach when used against intraluminal parasites but with a fatty meal when used against tissue parasites. A. Ascariasis, Trichuriasis, and Hookworm and Pinworm Infections For adults and children older than 2 years of age with ascariasis and hookworm infections, the treatment is a single dose of 400 mg TABLE 53–1 Drugs for the treatment of helminthic infections. 1 Infecting Organism Drug of Choice Alternative Drugs Roundworms (nematodes) Ascaris lumbricoides (roundworm) Albendazole or pyrantel pamoate or mebendazole Ivermectin, piperazine Trichuris trichiura (whipworm) Mebendazole or albendazole Ivermectin Necator americanus (hookworm); Ancylostoma duodenale (hookworm) Albendazole or mebendazole or pyrantel pamoate Strongyloides stercoralis (threadworm) Ivermectin Albendazole or thiabendazole Enterobius vermicularis (pinworm) Mebendazole or pyrantel pamoate Albendazole Trichinella spiralis (trichinosis) Mebendazole or albendazole; add corticosteroids for severe infection Trichostrongylus species Pyrantel pamoate or mebendazole Albendazole Cutaneous larva migrans (creeping eruption) Albendazole or ivermectin Thiabendazole (topical) Visceral larva migrans Albendazole Mebendazole Angiostrongylus cantonensis Albendazole or mebendazole Wuchereria bancrofti (filariasis); Brugia malayi (filariasis); tropical eosinophilia; Loa loa (loiasis) Diethylcarbamazine Ivermectin Onchocerca volvulus (onchocerciasis) Ivermectin Dracunculus medinensis (guinea worm) Metronidazole Thiabendazole or mebendazole Capillaria philippinensis (intestinal capillariasis) Albendazole Mebendazole Flukes (trematodes) Schistosoma haematobium (bilharziasis), CHAPTER 52 Antiprotozoal Drugs 923 MEFLOQUINE Mefloquine is effective therapy for many chloroquine-resistant strains of P falciparum and against other species. Although toxicity is a concern, mefloquine is one of the recommended chemopro- phylactic drugs for use in most malaria-endemic regions with chloroquine-resistant strains. Chemistry & Pharmacokinetics Mefloquine hydrochloride is a synthetic 4-quinoline methanol that is chemically related to quinine. It can only be given orally because severe local irritation occurs with parenteral use. It is well absorbed, and peak plasma concentrations are reached in about 18 hours. Mefloquine is highly protein-bound, extensively distrib- uted in tissues, and eliminated slowly, allowing a single-dose treat- ment regimen. The terminal elimination half-life is about 20 days, allowing weekly dosing for chemoprophylaxis. With weekly dos- ing, steady-state drug levels are reached over a number of weeks; this interval can be shortened to 4 days by beginning a course with three consecutive daily doses of 250 mg, although this is not stan- dard practice. Mefloquine and acid metabolites of the drug are slowly excreted, mainly in the feces. The drug can be detected in the blood for months after the completion of therapy. Antimalarial Action & Resistance Mefloquine has strong blood schizonticidal activity against P falciparum and P vivax, but it is not active against hepatic stages or gametocytes. The mechanism of action of mefloquine is unknown. Sporadic resistance to mefloquine has been reported from many areas. At present, resistance appears to be uncommon except in regions of Southeast Asia with high rates of multidrug resistance (especially border areas of Thailand). Mefloquine resis- tance appears to be associated with resistance to quinine and halofantrine but not with resistance to chloroquine. Clinical Uses A. Chemoprophylaxis Mefloquine is effective in prophylaxis against most strain, the body to colonize various organs in the process called metastasis. Such tumor stem cells thus can express clonogenic (colony-forming) capability, and they are characterized by chromosome abnormalities reflecting their genetic instability, which leads to progressive selection of subclones that can survive more readily in the multicellular environment of the host. This genetic instability also allows them to become resistant to chemotherapy and radiotherapy. The invasive and metastatic processes as well as a series of metabolic abnormalities associated with the cancer result in tumor-related symptoms and eventual death of the patient unless the neoplasm can be eradicated with treatment. 54 CAUSES OF CANCER The incidence, geographic distribution, and behavior of specific types of cancer are related to multiple factors, including sex, age, race, genetic predisposition, and exposure to environmental car- cinogens. Of these factors, environmental exposure is probably most important. Exposure to ionizing radiation has been well documented as a significant risk factor for a number of cancers, including acute leukemias, thyroid cancer, breast cancer, lung cancer, soft tissue sarcoma, and basal cell and squamous cell skin cancers. Chemical carcinogens (particularly those in tobacco smoke) as well as azo dyes, aflatoxins, asbestos, benzene, and radon have all been well documented as leading to a wide range of human cancers. Several viruses have been implicated in the etiology of various human cancers. For example, hepatitis B and hepatitis C are asso- ciated with the development of hepatocellular cancer; HIV is associated with Hodgkin’s and non-Hodgkin’s lymphomas; human papillomavirus is associated with cervical cancer and head and neck cancer; and Ebstein-Barr virus is associated with nasopharyn- geal cancer. Expression of virus-induced neoplasia may also depend on additional host and environmental factors that modu- late the transformation process. Cellular genes are known that are homologous to the transforming genes of the retroviruses, a family
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