By G. Jose. Life University. 2019.
Chronic treatment of rats with primidone causes depletion of pteroylpenta- glutamates in liver 20 mg female cialis. Efect of chronic primidone treatment on folate-dependent one-carbon Tere is inadequate evidence in humans for metabolism in the rat female cialis 10mg. Physiologically based pharmacokinetics model of primidone and its metab- olites phenobarbital and phenylethylmalonamide in humans female cialis 20 mg, rats female cialis 10 mg, and mice female cialis 20mg. Single-dose pharmacokinetics and anticonvulsant J Chromatogr B Biomed Sci Appl 10mg female cialis, 718(1):199–204 20mg female cialis. Pharmacokinetics of anti-ep- Linnebank M 10 mg female cialis, Moskau S , Semmler A , Widman G, Stofel- ileptic drugs in the dog: a review. Environ Sci Pollut level studies of primidone and its metabolites in the Res Int, 19(6):2096–106. Blood and cere- drugs in serum and plasma using ultra-performance brospinal fuid pharmacokinetics of primidone and its liquid chromatography-electrospray ionization tandem primary pharmacologically active metabolites, pheno- mass spectrometry. Sensitive analytical method for serum children of epileptic mothers and the possible rela- primidone and its active metabolites for single-dose tion to maternal anticonvulsant therapy. Antiepileptic treatment and primidone, phenobarbital and phenylethylmalona- risk for hepatobiliary cancer and malignant lymphoma. Results of a nationwide Veterans interactions in epilepsy: general features and inter- Administration Cooperative Study comparing the actions between antiepileptic drugs. Te efect of selected phenobarbital-induced expression changes of genes antiepileptic drugs on the chromosomes of human involved in key pathways in precancerous liver and lymphocytes in vitro. Evidence-based guide- line update: treatment of essential tremor: report of the Quality Standards subcommittee of the American Academy of Neurology. Efect of hexamidine on level of spon- taneous mutation in a number of subjects Dokl. Salivon; Salopyr; Salopyrine; Saridine-E; In urban water, sulfasalazine can be quanti- Sulcolon; Sulfasalazin; Sulftis; Ulcol; Zopyrin fed by liquid chromatography-mass spectrom- (Porter & Kaplan, 2013). Sulfasalazine is available as an oral dose at 250 or 500 mg, and as an oral suspension of 5 mL. Environmental Health Hazard Assessment, requiring public notice of potential environ- 2. Te crude proportion of sclerosing cholangitis, and a family history of cases of cancer of the colorectum in the sulfasala- cancer of the colorectum (Dyson & Rutter, 2012). Data were extracted from or more treatment course of sulfasalazine (at least medical records. Both cohorts information, limited documentation of covari- included patients with ulcerative colitis or Crohn ates controlled in the analyses. Te studies identifed patients from the same data- adjusted relative risk for colorectal neoplasia was base of patients, but the years of study recruit- close to unity for regular use (> 2 g/day) or cumu- ment were not reported in the study by Eaden lative dose of sulfasalazine. Sixty-eight cases with colorectum alone; of the 43 cases of colorectal neoplasia were identifed and 136 controls from neoplasia, 23 were cancer. Other concerns included the Group could not interpret this study due to the small numbers of exposed cancer cases, lack of lack of information on analytical methods and adjustment for risk factors, and limitations in the the inclusion of studies that were not specifc generalizability of the fndings due to the selec- for treatment with sulfasalazine. An additional group of group would attain body weights of approxi- male rats (stop-exposure group) was treated mately 80% those of the control group fed ad with sulfasalazine in corn oil at 337. Sixty mice from each group were eval- for 26 weeks, and then with corn oil only for the uated at 103 weeks and the remaining 50 mice remainder of the study (79 weeks). Survival of from each group were evaluated at 156 weeks male rats at the highest dose in the core study was (3 years), or at the time when survival reached signifcantly lower than that of controls, with 20%. Survival of all other treated groups was at 103 weeks (~2 years) for the mice treated with similar to that of controls. Te body weight of the urinary bladder in the core study was and survival of the weight-matched vehicle-con- increased with a positive trend in the groups of trol group were similar to those of the treated treated male rats; the incidence in the group at group fed ad libitum. Te tion protocol, the control and treated groups transitional cell neoplasms of the urinary tract weighed 42 g and 34 g at 1 year and had respective observed in the core study were not observed in survival rates of 84% and 88% afer 103 weeks. In exposed females, Exposure to sulfasalazine under ad-libitum there were also low incidences of [rare] transi- feeding conditions for 103 weeks (~2 years) tional cell papilloma of the kidney and of the caused signifcantly increased incidences of urinary bladder. All rats with transitional cell hepatocellular adenoma, and hepatocellular papillomas of the urinary tract also had grossly adenoma or carcinoma (combined) in exposed visible concretions (calculi) in the kidney and/or mice compared with the controls fed ad libitum urinary bladder (Iatropoulos et al. Mechanistic and Other Afer 1 year, mean body weights for the Relevant Data control and treated rats in the frst experiment were similar. Te metabolic scheme for sulfasalazine in Te incidence of transitional cell papilloma of humans is shown in Fig. Slow absorption of small amounts (~10– transitional cell papilloma of the urinary bladder 30%) via the small intestine has been reported also had grossly visible concretions in the kidney before enterohepatic recycling, and with the and/or urinary bladder. In the third experiment, majority of unchanged drug reaching the colon no signifcant increase in the incidence of transi- (Das & Dubin, 1976; Azad Khan et al. Tis cleavage is the A group of 12 male Wistar rats was given rate-limiting step for clearance of sulfasala- 1,2-dimethylhydrazine at a dose of 40 mg/kg bw zine (Das & Dubin, 1976). In of “colon tumours” (mainly adenocarcinomas) the liver, sulfapyridine undergoes hydroxylation was assessed histologically at week 21. All rats and/or N-acetylation to 5′-hydroxysulfapyri- developed tumours of the intestine. In the dine, N4-acetylsulfapyridine, and N4-acetyl-5′- control group receiving 1,2-dimethylhydrazine hydroxysulfapyridine subsequently forming only, there were 70 tumours of the intestine glucuronic acid conjugates, before excretion with a tumour multiplicity of 6. Metabolites (sulfapyridine, and acetylated disease) were similar to those in four healthy and glucuronidated derivatives) were detected in subjects, each given a single oral dose of sulfasala- the serum at 3–5 hours afer dosing (Schröder zine (3 or 4 g). Te metabolism been studied in three healthy male Japanese of sulfasalazine was markedly reduced in patients volunteers (Tokui et al. Maximum plasma concentration (Cmax) of rheumatoid arthritis had a signifcantly higher the metabolite N-acetyl-5-aminosalicylic acid (and more sustained) plasma concentration was 0. It was estimated that an infant would able to cross the placenta (Azad Khan & Truelove, receive sulfapyridine at dose of 3–4 mg/kg bw, 1979; Järnerot et al. In fve patients with afer a maternal dose of 2 g of sulfasalazine per day ulcerative colitis treated with sulfasalazine (0. Sulfapyridine four times per day) throughout and afer preg- and its acetylated and glucuronidated metabo- nancy, sulfasalazine was detected in the umbilical lites have been shown to be excreted by babies, cord blood (mean concentration, 50% of that in 1–2. Analyses of metabolites showed that total concentrations of sulfapyridine were equal in (i) N-Acetyltransferases maternal and cord sera, but concentrations Te sulfasalazine molecule may be consid- of free sulfapyridine were signifcantly lower ered as a slow-release carrier for sulfapyridine, (P < 0. Total concentrations of but there is large inter-individual variation in the acetylated sulfapyridine were signifcantly higher rate of metabolism of sulfapyridine, which can (P < 0. Patients with a “slow” acetylator Small quantities of sulfasalazine and phenotype generally show signifcantly higher, sulfapyridine have also been detected in breast and more sustained plasma concentrations of milk (Azad Khan & Truelove, 1979; Järnerot & sulfapyridine and its non-acetylated metabo- Into-Malmberg, 1979). Te elimination half-life of sulfasalazine in sulfasalazine and total sulfapyridine in milk, patients with a slow-acetylator phenotype may compared with concentrations in maternal be approximately 50–100% longer than in those serum, were approximately 30% and 50%, respec- with a fast-acetylator phenotype (Taggart et al. Studies in 21 Japanese pharmacokinetics of various drugs, including subjects (8 healthy subjects and 13 patients with sulfasalazine. Te rate of elimination of that is 19 times higher than apical-to-basolateral sulfasalazine was similar in rats and mice; plasma permeability, indicative of net mucosal secre- elimination rate constants were 1. In Caco-2 cells and rat jejunum), specifc inhibitors F344/N rats given a low oral dose of 67. Inhibitors of P-glycoprotein had no efect on the movement (b) Role of transporter proteins of sulfasalazine. Te reported, but confounding factors were apparent results indicated that sulfasalazine is a substrate in the study (Erskine et al. Additionally, an indomethacin-in- in mutations conferring 6-thioguanine resist- duced increase in sulfasalazine permeability ance in mouse lymphoma L5178Y cells, with or through the gut wall was also shown in the rat without metabolic activation (Iatropoulos et al. Tus the results of tests greater systemic exposure than rats to sulfapyri- for chromosomal damage in vitro afer treat- dine, the active moiety, afer administration of ment with sulfasalazine were generally negative, similar doses (Zheng et al. In one study, no evidence for genotoxicity In vivo, consistent with results reported in was obtained for sulfasalazine when tested for assays in vitro, no increases in the frequency the induction of micronuclei in mouse bone of chromosomal aberration were observed marrow, with or without pretreatment with folate. N4-acetylsulfapyridine was capable Chinese hamster ovary cells in vitro (Mackay of inducing both sister chromatid exchange and et al. In vivo, no increase micronucleus formation, while N4-acetyl-5′- in the frequency of micronucleated polychro- hydroxysulfapyridine only induced sister chro- matic erythrocytes was observed in the bone matid exchange. Reactions to sulfasalazine may result of metabolic activation, at concentrations that from an idiosyncratic delayed-type hypersensi- reached 400 µg/mL. Sulfapyridine induced a tivity reaction that may afect internal organs in strong, dose-related increase in the frequency variable ways (Jobanputra et al. As with sulfasalazine, the therapy; the pattern of liver injury can be hepa- majority of micronucleated erythrocytes induced tocellular or cholestatic, and may lead to liver by sulfapyridine in mice were shown to contain failure. Te incidence of Te role of metabolites in sulfasalazine-me- clinically restrictive renal impairment has been diated toxicity was investigated in vitro, using estimated at < 1 per 500 patients (World et al. Te mechanism is unclear, although both cytes as target cells in the presence of human liver a delayed cell-mediated response, and a dose-de- microsomes; methaemoglobin formation and pendent efect have been considered (Corrigan cytotoxicity were selected as toxicity end-points. Chromatographic analysis demonstrated documented nephrotoxic potential (Corrigan & that sulfapyridine was converted to a short- Stevens, 2000). Treatment-related alterations hydroxylamine (10–500 µM) caused a concen- in the levels of biomarkers of oxidative stress tration-dependent increase in both methae- were detected in kidney and liver tissues of male moglobinaemia (2. At sulfasalazine nor any of the other test metabolites the highest dose, there were signifcant decreases had such efects. When the microsomal incuba- in the activities of renal and hepatic superoxide tions were conducted in the presence of micro- dismutase, and signifcant increases in catalase molar concentrations of reducing agents (e. In a group of 50 patients where it may undergo redox cycling to nitroso- receiving sulfasalazine at 2. Reduced levels of in sulfasalazine-induced carcinogenesis of the S-adenosylmethionine or 5,10-methylenetet- bladder in male rats. In the rat, Te adverse efects of sulfasalazine have been colonic bacterial folate is incorporated in the linked to sulfapyridine (Das et al. Environmental increased incidences of transitional cell papil- contamination with sulfasalazine in ground- loma of the urinary bladder, and clear evidence water has been noted, but exposure is likely to for carcinogenic activity in male and female be predominantly through use as a medication. B6C3F1 mice on the basis of increased incidences of hepatocellular adenoma and hepatocellular 5. Te data on mutagenicity of sulfasalazine and Te available studies of exposure to sulfasala- its metabolite, sulfapyridine, suggested that the zine included a surveillance study, two cohort parent drug and the metabolite are predomi- studies, three nested case–control studies, and nantly aneugens (Bishop et al. Increased frequencies of micronucleus colorectum among patients with infammatory bowel disease or ulcerative colitis. However, were also concerns about selection bias in some patients reported to have an elevated frequency studies based on clinical populations. Most of these relative risks infammation associated with urolithiasis may were not statistically signifcant. In the studies be a factor in sulfasalazine-induced carcinogen- that evaluated dose–response relationships, no esis of the bladder in male rats. Cleavage of carcinoma (combined) in both sexes; there was the azo bond by bacterial azoreductases in the also an increase in the incidence of hepatocellular colon releases two pharmacologically active carcinoma in females. In contrast, the bacterial assays for gene mutation, with or without incidence of hepatocellular tumours in dietary-re- exogenous metabolic activation. Tests for chro- stricted mice was signifcantly decreased afer mosomal damage in vitro afer treatment with 2 years in the group exposed to sulfasalazine, sulfasalazine were generally negative, although and was similar to that in non-treated mice afer sporadic positive results have been reported. Likewise, no increases in the frequency of chro- In one study in male and female rats given mosomal aberration were observed in male mice sulfasalazine by gavage, there was a signifcant or rats treated with sulfasalazine. Positive results increase in the incidence of transitional cell were consistently obtained in assays for micro- papilloma of the urinary bladder in males; there nucleus formation in male and female mice in was also a non-signifcant increase in the inci- vivo when multiple treatments with sulfasala- dences of rare transitional cell papilloma of the zine were given; the results suggested that these kidney and of rare transitional cell papilloma of results were primarily due to aneuploidy events the urinary bladder in female rats. In a study of dietary restriction in male rats, Sulfasalazine inhibits the activity of dihy- the incidence of transitional cell papilloma of the drofolate reductase, methylenetetrahydrofolate urinary bladder was signifcantly greater in rats reductase, and serine transhydroxymethylase, receiving sulfasalazine than in controls fed ad and also the cellular uptake of folate. No signifcant increase in the incidence folate defciency does not appear to account for of transitional cell papilloma of the urinary the efects of sulfasalazine in humans and mice. N-Hydroxylation multiplicity of 1,2-dimethylhydrazine-induced is known to account for the bioactivation of intestinal tumours. Te Male rats treated orally with sulfasalazine efect of the acetylator phenotype on the metabolism had an increased incidence of transitional cell of sulphasalazine in man. Placental and correlated with increased incidences of calculi mammary transfer of sulfasalazine. Te sulfasalazine-induced carcinogenesis of the disposition and metabolism of sulphasalazine (salic- ylazosulphapyridine) in man. Glomerular and tubular renal functions afer long- term medication of sulphasalazine, olsalazine, and 6. Aliment Pharmacol bioassay for carcinogen hazard evaluation can be Ter, 14(1):1–6. Am J Physiol Gastrointest Liver sulphasalazine in rheumatoid arthritis and infam- Physiol, 297(2):G371–7. Pressurized liquid therapeutic drugs used in infammatory bowel disease extraction combined with capillary electrophore- on the incidence and growth of colonic cancer in the sis-mass spectrometry as an improved methodology dimethylhydrazine rat model. Folic acid and 5-Aminosalicylates and renal function in infammatory sulfasalazine for colorectal carcinoma chemopre- bowel disease: a systematic review. Infamm Bowel Dis, vention in patients with ulcerative colitis: the old 13(5):629–38. Colorectal cancer in infam- metabolite sulphapyridine and 5-aminosalicylic acid in matory bowel disease: what is the real magnitude of human plasma by liquid chromatography/tandem mass the risk? J Chromatogr B Analyt Technol Biomed Life Sci, Eaden J, Abrams K, Ekbom A, Jackson E, Mayberry J 879(5–6):449–56. A review of mebeverine, mesalazine, sulphasalazine and dispers- human carcinogens. Risk for colorectal cancer tions for combination therapies with methotrexate in in ulcerative colitis: changes, causes and management rheumatoid arthritis. Scand J Gastroenterol, infuence of probiotic treatment on sulfasalazine 16(5):693–7. Axonal case-control study from Copenhagen county, Denmark neuropathy with prolonged sulphasalazine use. Lipid peroxidation and anti- Jobanputra P, Amarasena R, Maggs F, Homer D, Bowman oxidant status in kidney and liver of rats treated with S, Rankin E et al.
Contraindicatons Depositon of tetracyclines in growing bone and teeth (by binding to calcium) causes staining and occasionally dental hypoplasia and they should not be given to children under 12 years 10mg female cialis, or to pregnant (Appendix 7c) or lactatng women (Appendix 7b) female cialis 20 mg. However female cialis 20mg, doxycycline may be used in children for treatment and post-exposure prophylaxis of anthrax when an alternatve antbacterial cannot be given (unlicensed indicaton) female cialis 10mg. With the excepton of doxycycline and minocycline 10 mg female cialis, the tetracyclines may exacerbate renal failure and should not be given to patents with kidney disease; hypersensitvity; interactons (Appendix 6c 20 mg female cialis, 6d) Precautons Used with cauton in patents with hepatc impairment or those receiving potentally hepatotoxic drugs female cialis 10 mg. Tetracyclines may increase muscle weakness in patents with myasthenia gravis and exacerbate systemic lupus erythematosus; antacids and aluminium 20mg female cialis, calcium , iron , magnesium and zinc salts decrease the absorpton of tetracyclines; milk also reduces the absorpton of tetracyclines, demeclocyclines and oxytetracycline; cerebrovascular sensitsaton, maculopapular rashes, increased blood urea nitrogen, anaemia. Other rare side-efects include hepatotoxicity, pancreatts, blood disorders, photosensitv- ity (partcularly with demeclocycline) and hypersensitvity reactons (including rash, exfoliatve dermatts, Stevens-Johnson syn- drome, urtcaria, angioedema, anaphylaxis, pericardits). Headache and visual distur- bances may indicate benign intracranial hypertension (discontnue treatment); bulg- ing fontanelles have been reported in in- fants; anaemia. Trimethoprim Pregnancy Category-C Schedule H Indicatons Urinary-tract infectons; bronchits. Precautons Renal impairment; lactaton (Appendix 7b); predispositon to folate defciency; elderly; blood counts on long-term therapy (but practcal value not proven); neonates (specialist supervision required); pregnancy (Appendix 7c). Adverse Efects Rashes, pruritus; depression of haematopoiesis; gastrointestnal disturbances including nausea and vomitng; rarely, exfoliatve dermatts and toxic epidermal necrolysis, photosensitvity and other allergic reactons including angioedema and anaphylaxis; aseptc meningits; erythema, multforme, elevaton of transaminase and bilirubin. Precautons Avoid rapid infusion (risk of anaphylactoid reactons, see Adverse efects); rotate infusion sites; renal impairment (Appendix 7d); elderly; history of deafness-avoid; plasma-vancomycin concentraton measured afer 3 or 4 doses (earlier if renal impairment), blood counts, urinalysis and renal functon tests-use only in hospital setng; monitor auditory functon and plasma-vancomycin concentratons in elderly or in renal impairment; lactaton (Appendix 7b); pregnancy (Appendix 7c); interactons (Appendix 6c); Pseudomembranous colits. Adverse Efects Nephrotoxicity including renal failure and intersttal nephrits; ototoxicity (discontnue if tnnitus occurs); blood disorders; nausea, chills, fever, eosinophilia, anaphylaxis, rashes, including exfoliatve dermatts, erythema multforme (Stevens-Johnson syndrome), toxic epidermal necrolysis and vasculits; phlebits; on rapid infusion, severe hypotension (with shock, cardiac arrest), wheezing, dyspnoea, urtcaria, pruritus, fushing of the upper body (‘red man’ syndrome), pain and muscle spasm of back and chest; hypotension, pruritus, haematopoitc febits. Diethylcar- bamazine is efectve against both adult worms and larvae; a single weekly dose is normally efectve as prophylaxis. During individual treatment, partcularly of persons with heavy micro- flaraemia (>50 000 microflariae/ml blood), a conditon simu- latng meningoencephalits occasionally occurs. This probably results from sludging of moribund microflariae within cere- bral capillaries. The frequency of meningoencephalits associ- ated with diethylcarbamazine therapy of loiasis is reported as 1. Permanent cerebral damage is common among patents who survive and this possibility should be considered when deciding on treatment. Treatment of heavily infected patents should thus begin at low dosage and cortcosteroid and anthistamine cover should be provided for the frst 2 to 3 days. Lymphatc Filariasis: Lymphatc flariasis is caused by infecton with Wuchereria bancrofi (bancrofian flariasis), Brugia malayi or B. Indi- vidual treatment with diethylcarbamazine which has both microflaricidal and macroflaricidal actvity is efectve. Total cumulatve dosages of 72 mg/kg are generally recommended for Wuchereria bancrofi infectons with half this dose used for Brugia malayi and B. In all cases treat- ment is best initated with smaller doses for 2-3 days to avoid the danger of immunological reactons. Rigorous hygiene to the afected limbs with adjunctve measures to minimize infecton and promote lymph fow is important for reducing acute episodes of infammaton. In communites where flariasis is endemic, annual administra- ton of single doses of albendazole 400 mg with either diethyl- carbamazine (6 mg/kg) or ivermectn (200 µg/kg) is efectve for interruptng transmission; this treatment is contnued for at least 5 years. Trials in India and China have shown that the consistent use for 6-12 months of table salt containing diethyl- carbamazine 0. Dose Oral Adult and child- 11 mg/kg body weight daily in three divided doses on the frst day. Thereafer increase gradually to 6 mg/kg body weight given afer food daily for two to three days. Contraindicatons Pregnancy (delay treatment untl afer delivery); infants, elderly, debilitated (usually excluded from mass treatment programmes; see also Precautons); cardiac disease, hypersensitvity, impaired renal functon. Precautons Renal impairment; cardiac disorders; other severe acute diseases-delay diethylcarbamazine treatment untl afer recovery; risk of meningoencephalits in severe infecton (see notes above). Adverse Efects Headache, dizziness, drowsiness, nausea and vomitng; immunological reactons, within a few hour of the frst dose, subsiding by ffh day of treatment and including fever, headache, joint pain, dizziness, anorexia, malaise, nausea and vomitng, urtcaria and asthma in asthmatcs (similar to Mazzot reacton), induced by disintegratng microflariae; microencephalits (with heavy microflaraemia, see notes above); reversible proteinuria; enlargement of lymph nodes. Ivermectn Pregnancy Category-C Indicatons Nematodal infectons such as ascariasis, trichuriasis, strongyloidiasis, enterbiasis, lymphatc flariasis, scabies and pediculosis. Scabies and pediculosis: 150-200 µg/kg of body weight single oral dose highly efectve. Precautons Concurrent Loa Loa infecton, impaired blood-brain barrier functon, pregnancy (Appendix 7c), lactaton, hepatc, cardiovascular, renal or pulmonary disease, anaemia, coagulaton disorder, severe asthma, interactons (Appendix 6c). Adverse Efects Nausea, vomitng, constpaton, abdominal pain and fatgue, rash, arthralgia, fever, myalgia, asthenia, hypotension, tachycardia, edema, lymphadenopathy, sore throat, cough, headache, somnolence, transient eosinophilia, dizziness, diarrhoea, pruritus, orthostatc hypotension, lymph-node tenderness, rare but serious adverse efects such as marked disability and encephalopathies in patents coinfected with heavy burdens of Loa microflaria. Superf- cial infectons afect only the skin, hair, nails or mucous membranes whereas systemic fungal infectons afect the body as a whole. Systemic fungal infectons are sometmes caused by inhala- ton, ingeston or inoculaton of primary pathogens and some- tmes by opportunistc invasion of commensals in patents with lowered host resistance. Amphotericin B is a lipophilic polyene antbiotc; it is fungi- statc against a broad spectrum of pathogenic fungi, including Candida spp. It is used for the empirical treatment of serious fungal infectons and is used in conjunc- ton with fucytosine to treat cryptococcal meningits and systemic candidosis. Amphotericin B has to be administered parenterally as there is litle or no absorpton from the gastrointestnal tract; ampho- tericin B is liable to cause nephrotoxicity. Duraton of therapy varies with the inital severity of the infecton and the clinical response of the patent. In some infectons a satsfactory response is only obtained afer several months of contnuous treatment. Intrathecal infusion has been used successfully in patents with meningeal coccidioidomycosis. Fluconazole an orally actve synthetc imidazole derivatve, possesses fungistatc actvity against dermatophytes, yeasts and other pathogenic fungi. It is widely used in the treatment of serious gastrointestnal and systemic mycoses as well as in the management of superfcial infectons. Fluconazole is also used to prevent fungal infectons in immunocompromised patents. Flucytosine, is a synthetc fuorinated pyrimidine with a narrow spectrum of antfungal actvity, partcularly against Cryptococcus and Candida spp. Flucyto- sine is myelosuppressive and plasma concentratons above 75 µg/ml are associated with myelotoxicity. Griseofulvin is deposited selectvely in keratn precursor cells of skin, hair and nails where it disrupts the mitotc apparatus of fungal cells thus preventng fungal invasion of newly-formed cells. Close atenton should be given to hygiene and to possible reservoirs of reinfecton in clothing, footware and bedding. Nystatn, a polyene antfungal antbiotc derived from Strepto- myces noursei, is efectve against infectons caused by a wide range of yeasts and yeast-like fungi. It is poorly absorbed from the gastrointestnal tract and it is not absorbed from the skin or mucous membranes when applied topically. Potassium iodide aqueous oral soluton is a clear liquid with a characteristc, strong salty taste. It is efectve against sporotrichosis and subcutaneous phycomycosis, which are fungal infectons caused by Sporothrix schenckii and Basidi- obolus haptosporus respectvely. In subcutaneous sporotri- chosis, amphotericin B is ofen efectve in patents unable to tolerate iodides. Itraconazole, by mouth has been tried as an alternatve to potassium iodide in both cutaneous and extracutaneous sporotrichosis. Amphotericin B* Pregnancy Category-B Schedule H Indicatons Life-threatening fungal infectons includ- ing histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, blastomycosis, aspergillosis, cryptaococcosis, mucormycosis, sporotrichosis and candidiasis; visceral and mucocutaneous leishmaniasis unresponsive to pentavalent antmony compounds; severe meningits, perioral candidiasis. Regular kidney, liver functon tests and blood counts must be conducted; lactaton; antneoplastc therapy. Precautons Close medical supervision throughout treatment and inital test dose required (see note, below); renal impairment (Appendix 7d); pregnancy (Appendix 7c); hepatc and renal functon tests; blood counts and plasma electrolyte monitoring; cortcosteroids (avoid, except to control reactons); lactaton; avoid rapid infusion (risk of arrhythmias); interactons (Appendix 6c); geriatric use. Anaphylaxis occurs rarely, with intravenous amphotericin B and a test dose is advisable before the frst infusion. Adverse Efects Fever, headache, anorexia, weight loss, nausea and vomitng, malaise, diarrhoea, muscle and joint pain, dyspepsia and epigastric pain; renal functon disturbances including hypokalaemia, hypomagnesaemia and renal toxicity; blood disorders; cardiovascular toxicity (including arrhythmias); neurological disorders (including peripheral neuropathy); abnormal liver functon (discontnue treatment); rash; anaphylactoid reactons (see above); pain and thrombophlebits at injecton site; respiratory failure. Storage Store in a tghtly closed container between 2 to 8⁰C, protected from light. Dose Adult- Pessaries/vaginal tablets: 100 mg pessary/vaginal tablet to be inserted into vagina at night before going to bed as deep as possible for consecutve 6 to 7 days or 200 mg for 3 consecutve night before going to bed or 500 mg single dose. Cream: Rub on afected area 2 to 3 tmes by applying in thin layer and rubbing, contnue for 14 days afer healing. Adverse Efects Local irritaton, burning sensaton and itching, abnormal liver functon, unpleasant mouth sensaton. Oral: systemic loading dose of 400 mg on frst day and thereafer 200 to 400 mg once daily for at least 28 days. Contraindicatons Sensitvity to primaquine; infants below 1 year of age; alcohol; coadministraton of cisapride, terfenadine. Precautons Renal impairment (Appendix 7d); lactaton (Appendix 7b); monitor liver functon- discontnue if signs or symptoms of hepatc disease (risk of hepatc necrosis; Appendix 7a); interactons: (Appendix 6b, 6c); pregnancy (Appendix 7c); immunocompromised patents. Flucytosine Pregnancy Category-C Schedule H Indicatons Adjunct to amphotericin B (or fuconazole) in cryptococcal meningits; adjunct to amphotericin B in systemic candidiasis; septcemia, pulmonary infecton. Contraindicatons Renal impairment; elderly; blood disorders, pregnancy (Appendix 7c); hypersensitvity. Precautons Elderly; renal impairment; also the use with amphotericin B (both nephrotoxic); liver- and kidney functon tests and blood counts required (weekly in renal impairment or in blood disorders); lactaton (Appendix 7b); interactons (Appendix 6c); pregnancy (Appendix 7c). Adverse Efects Rash, nausea, vomitng and diarrhoea; alter- atons in liver functon tests; less frequently, confusion, hallucinatons, convulsions, head- ache, sedaton, vertgo; blood disorders in- cluding leukopenia, potentally fatal throm- bocytopenia and aplastc anaemia; cardiac arrest, myocardial toxicity, dyspnoea, azo- temia, ataxia, hypoglycemia. Griseofulvin* Pregnancy Category-C Indicatons Fungal infectons of the skin, scalp, hair and nails where topical treatment has failed or is inappropriate; athlete’s foot. Dose Oral Adult- 500 mg once a day or in divided doses, in severe infectons dose may be doubled. Contraindicatons Severe liver disease (Appendix 7a); pregnancy (Appendix 7c) (avoid pregnancy during and for 1 month afer treatment; men should not father children within 6 months of treatment; porphyria; systemic lupus erythematosus and related disorders. May impair ability to perform skilled tasks, for example operatng machinery, driving. Adverse Efects Headache, nausea, vomitng, diarrhoea, rashes, dizziness, fatgue reported; dry mouth and angular stomatts; leukopenia, agranulocytosis; proteinuria reported; photosensitvity; lupus erythematosus, toxic epidermal necrolysis, erythema multforme; serum sickness, angioedema; peripheral neuropathy; confusion and impaired coordinaton. Ketoconazole Pregnancy Category-C Schedule H Indicatons Malassezia fulliculits dermatophytosis and chronic conditons which cannot be treated topically; infectons resistant to fuconazole; blastomycosis, candidiasis, chromomycosis. Monitor liver functon before treatment, then on weeks 2 and 4 of treatment, then every month. Avoid or use with cauton if abnormal liver functon tests (avoid in actve liver disease) or if history of hepatotoxicity with other drugs. Adverse Efects Nausea, vomitng, abdominal pain; pruritus; less commonly diarrhoea, headache, dizzi- ness, drowsiness and rash; very rarely, fatal liver damage (see Hepatotoxicity above), dys- pepsia, raised intracranial pressure, adreno- cortcal insufciency, erectle dysfuncton, menstrual disorders, azoospermia (with high doses), gynaecomasta, thrombocytopenia, photophobia and alopecia. Nystatn* Pregnancy Category-C Schedule H Indicatons Oral, oesophageal, intestnal, vaginal and cutaneous candidiasis. Dose Oral Adult- Intestnal candidiasis: 5,00,000 units every six h, doubled in severe infectons. Child- 1 month to 12 years: 1,00,000 units 4 tmes daily, immunocompromised children may require higher doses up to 5,00,000 units. Topical applicaton Dissolve one tablet in glycerine and apply locally 3 to 4 tmes. Adverse Efects Nausea, vomitng, diarrhoea at high doses; oral irritaton and sensitzaton; rash and rarely, erythema multforme (Steven’s- Johnson syndrome); eczema, burning. Cystcercosis is a systemic infecton caused by the larval form (cystcercus) of Taenia solium. In man, echinococcosis is due to the larval stage of Echi- nococcus granulosus or E. The larvae (onco- spheres) develop by expansion (cystc echinococcosis) or tumour-like infltraton (alveolar echinococcosis), respectvely, in the liver, lungs, or other organs. Diphyllobothriasis: In diphyllobothriasis, niclosamide or praziquantel in a single dose is highly efectve. Echinococcosis: In echinococcosis, surgery (or, if this is not possible, a tech- nique such as ‘puncture-aspiraton-injecton-reaspiraton’) is the treatment of choice for operable cystc disease due to Echinococcus granulosus but chemotherapy with benzimida- zoles, such as mebendazole and albendazole, may be of value as adjunctve therapy. They are contraindicated for the treat- ment of cestode infectons in pregnancy; pregnancy should be excluded before treatment with albendazole (non-hormonal contracepton during and for 1 month afer treatment). Hymenolepiasis: In hymenolepiasis, praziquantel is more efectve than niclosa- mide, although resistance to praziquantel has been reported. Repeated treatment may be necessary to cure intense infec- tons or to eliminate the parasite within a family group or insttuton. It thus ofers the prospect of a cure for neurocystcercosis, which has been treatable only by surgery, ant-infammatory cortcosteroids and antconvulsants. However, because dying and disintegratng cysts may induce localized cerebral oedema, treatment with praziquantel must always be undertaken in a hospital setng. Albendazole also kills neurocystcerci when given daily for one month; a cortcosteroid or an anthistamine is also given to reduce any infammatory reacton. Intestnal Nematode Infectons: Intestnal nematode infectons include ascariasis, capillariasis, enterobiasis, hookworm infecton, strongyloidiasis, trichos- trongyliasis and trichuriasis. Ascariasis: Ascariasis is an infecton, usually of the small intestne, caused by Ascaris lumbricoides (roundworm). Single doses of levami- sole or pyrantel are efectve; the broad-spectrum anthelmin- thics, albendazole or mebendazole are also efectve.
Contraindications: Hypersensitivity to narcotics of the same chem- ical class female cialis 20 mg, management of acute or postoperative pain 10mg female cialis, use in outpatient surgeries 20mg female cialis. Warnings/precautions • Use with caution in patients with the following conditions: head injury with increased intracranial pressure female cialis 10mg, serious alco- holism female cialis 10 mg, prostatic hypertrophy 10 mg female cialis, chronic pulmonary disease female cialis 20mg, severe liver or kidney disease 20 mg female cialis, postoperative patients with pul- monary disease , disorders of biliary tract . If nausea and vomiting per- sist, it may be necessary to administer an antiemetic, eg, droperidol or prochlorperazine. This drug can cause severe hypotension in a patient who is volume depleted or if given along with a phe- nothiazine or general anesthetic. Editorial comments • Transdermal fentanyl has become an important therapy for severe chronic pain. When such combination therapy is contem- plated, the dose of one or the other drugs should be reduced by 50% or more. Mechanism of action: Iron in ferrous sulfate replaces ferrous iron in formation of hemoglobin which is reduced in anemia. Eggs, coffee, tea, milk inhibit iron absorption and should be avoided when taking ferrous sulfate. Adverse reactions • Common: constipation, black stools, epigastric pain (15%), heartburn. Clinically important drug interactions • Drugs that increase effects/toxicity of ferrous sulfate: ascorbic acid (vitamin C). Advice to patient • Avoid driving and other activities requiring mental alertness or that are potentially dangerous until response to drug is known. Parameters to monitor: Efficacy of treatment: improvement of symptoms of rhinitis including sneezing, rhinorrhea, itchy/ watery eyes. Interactions with erythromicin, cimetidine, and ketoconazole do not appear to be clinically sig- nificant. Mechanism of action: Inhibits steroid 5α-reductase, thereby blocking the conversion of testosterone to 5α-hydroxytestos- terone. Contraindications: Hypersensitivity to finasteride, women of childbearing age, children. Warnings/precautions: Women who may become pregnant should not come in contact with crushed tablet. Advice to patient: Use two forms of birth control including hor- monal and barrier methods. Parameters to monitor • Efficacy of action: decreased size of enlarged prostate, decreased hesitancy, improvement in size and force of urinary stream, decreased dribbling. Among these are prostate cancer, infection, hypotonic bladder, stricture, various neurologic conditions. Improvement in sexual dys- function is seen in the majority of patients with long-term use. Adjustment of dosage • Kidney disease: Creatinine clearance <10 mL/min: decrease dose by 25–50%. Adjustment of dosage in hepatic disease has not been fully evaluated; it is recommended to monitor flecainide plasma levels because of significantly increased half-life. Onset of Action Duration 1–6 h 12–30 h Food: Foods that increase urinary pH may cause increased levels of flecainide in patients on a strict vegetarian diet. Foods or bev- erages such as acidic juices that lower urinary pH may decrease effectiveness of flecainide. Advice to patient • Notify dentist or treating physician prior to surgery if taking this medication. Clinically important drug interactions • Drugs that increase effects/toxicity of flecainide: β blockers, amiodarone, disopyramide, verapamil, cimetidine, high-dose antacids, carbonic anhydrase inhibitors. Parameters to monitor • Determine serum levels of flecainide, particularly in patients with kidney or liver impairment. Trough levels are particularly important; the probability of adverse reactions increases greatly if this level is >1 µg/mL. Editorial comments • Flecainide is suited for patients with symptomatic and persist- ent atrial fibrillation and atrial tachycardias that are refractory to radiofrequency ablation. Patients must have a structually normal heart and be monitored closely for side effects and effi- cacy. Warnings/precautions • Use with caution in patients with the following conditions: kidney, liver disease, high dose pelvic radiation, akylating anti- neoplastic drugs. Advice to patients • Use good mouth care to avoid adverse reactions in the oral cavity. Editorial comments • Use latex gloves and safety glasses when handling cytotoxic drugs. Mechanism of action: Inhibits fungal cytochrome P450 synthe- sis of ergosterol, resulting in decreased cell wall integrity and leakage of essential cellular components. Start fluconazole several days before the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises about 1000 cells/ mm3. Adjustment of dosage • Kidney disease: Creatinine clearance 10–50 mL/min: admin- ister 50% of usual dose. Warnings/precautions • Use with caution in patients with hypersensitivity to other azoles, kidney disease. Advice to patient • Report symptoms of possible liver dysfunction: jaundice, anorexia, dark urine, pale stools, nausea, vomiting. Clinically important drug interactions • Fluconazole increases effects/toxicity of following drugs: cyclosporine, glipizide, glyburide, phenytoin, theophylline, tolbutamide, warfarin, zidovudine, cisapride. Adjustment of dosage • Kidney disease: Creatinine clearance 20–40 mL/min: adminis- ter q12h; creatinine clearance 10–20 mL/min: increase dosage interval to q24h; creatinine clearance <10 mL/min: increase dosage interval to q24–48h. Warnings/precautions: Use with caution in patients with kidney disease, bone marrow depression (extreme caution). Clinically important drug interactions: Flucytosine increases effects/toxicity of amphotericin B. Therapeutic concentrations are 25–100 µg/mL with peak plasma concentrations between 40 and 60 µg/mL. Editorial comments • Flucytosine is generally administered with amphotericin B to improve its efficacy. Adjustment of dosage • Kidney disease: Guidelines are not available for adjustment of dosage in patients with kidney disease; monitor closely for pos- sible increased toxicity. Warnings/precautions: Use with caution in patients with the fol- lowing conditions: renal insufficiency, fever, infection, bone marrow depression, epilepsy, spasicity, peripheral neuropathy. Advice to patient • Use two forms of birth control including hormonal and barrier methods. Adverse reactions • Common: fatigue, weakness, paresthesia, muscle pain, edema (19%), visual disturbances, nausea and vomiting (36%), cough (44%), rash, fever (69%), chills, infection (44%), stomatitis. Treat with peroxide, tea, topical anesthetics such as benzocaine, lido- caine or antifungal drug. Editorial comments • Use latex gloves and safety glasses when handling cytotoxic drugs. Mechanism of action: Inhibits migration of polymorphonuclear leukocytes; stabilizes lysosomal membranes; inhibits produc- tion of products of arachidonic acid cascade. Contraindications: Systemic fungal, viral, or bacterial infections, myasthenia gravis, severe cardiovascular disease. Increased potassium excretion and retention of sodium and water occur with therapy. Monitoring of serum electrolytes, especially potassium, is required for patients on this medication. Repeat after 45 seconds and thereafter at 60-second intervals if necessary for a maximum of 4 additional times after initial dosing. If no response 5 minutes after 5 mg total drug is administered, it is unlikely that a benzodiazepine is the cause of toxicity and additional drug should not be adminis- tered. Repeat after 45 seconds and at 60-second intervals if necessary to a maxi- mum of 4 additional times. Contraindications: Hypersensitivity to flumazenil or benzodi- azepines, patients receiving a benzodiazepine for life-threatening indications (status epilepticus, controlling intracranial pressure), patient exhibiting severe overdose from tricyclic antidepressant, treatment of benzodiazepine dependence, management of with- drawal syndrome from benzodiazepines. Warnings/precautions • Use with caution in patients with the following conditions: seizure disorder or myoclonic jerking, concurrent sedative–hypnotic withdrawal, recent administration of repeated benzodiazepine, concurrent tricyclic antidepressant overdose, alcohol-dependent patient, head injuries, psychiatric patient, severe liver disease. Flumazenil is only considered as an adjunct to reversing the effects of benzodiazepine overdose. Take steps to enable patient to emerge slowly from benzodi- azepine overdose to avoid withdrawal reaction. Clinically important drug interactions: Drugs that increase toxic- ity of flumazenil: mixed drug overdoses, tricyclic antidepressant overdose. Editorial comments • Flumazenil does not reverse the amnesic effect of benzodi- azepine overdose. Accordingly, the physician should advise patient’s family or caregiver of the need to follow the patient carefully following recovery. Flumazenil should be used cautiously in outpatients and hospitalized patients because of the possibility that patients may have frequent benzodiazepines use or dependence. Mechanism of action: Inhibits elaboration of many of the media- tors of allergic inflammation, eg, leukotrienes and other products of the arachidonic acid cascade. Contraindications: Untreated fungal, bacterial, or viral infec- tions, ocular herpes simplex, septic ulcers, nasal surgery or trauma, untreated infections of nasal mucosa, hypersensitivity to corticosteroids. Warnings/precautions: Use with caution in patients with tuber- culosis of the respiratory tract (active or quiescent), exposure to measles or chicken pox. These should be individualized according to the dis- ease being treated and the response of the patient. This drug should not be used in large amounts or for prolonged periods during pregnancy. Contraindications: Hypersensitivity to corticosteroids, marked impaired circulation, occlusive dressing if primary skin infec- tion; monotherapy in primary bacterial infections (eg, impetigo, cellulitis, rosacea), ophthalmic use, plaque psoriasis (wide- spread). Warnings/precautions • Use with caution in patients with primary skin infection and in those receiving other immunosuppressant drugs. Advice to patient • Avoid long-term application to the following areas of the body: eyes, face, rectum, genitals, skinfolds. These are areas most susceptible to development of skin atrophy and decol- oration. Adverse reactions • Common: itching, burning, skin dryness, erythema, folliculi- tis, hypertrichosis, allergic contact dermatitis, skin maceration, secondary infection, striae, millaria, skin atrophy. Parameters to monitor • Signs of infection: increased pain, purulent exudate, erythema. Organisms most likely to pro- duce intercurrent infection include Candida, Mycobacterium, Toxoplasma, pneumocystis, Nocardi, Ameba. This condition may become clinically significant after 3–4 weeks of drug application. Patients using topical steroids over large areas of the body for prolonged periods are also at risk. Editorial comments: Only 5% strength is suggested for topical treatment of superficial basal cell carcinoma. Mechanism of action: Blocks methylation of deoxyuridylic acid by inhibiting thymidylate synthetase. Warnings/precautions • Use with caution in patients with kidney or liver disease, high- dose pelvic radiation or who are concomitantly using other neoplastic drugs, in particular alkylating agents. Advice to patient • Use two forms of birth control including hormonal and barrier methods. Adverse reactions • Common: dermatitis, alopecia (reversible), stomatitis, nausea, vomiting, diarrhea, anorexia, mucositis. Clinically important drug interactions: Allopurinol, cimetidine increase effects/toxicity of fluorouracil. Treat with peroxide, tea, top- ical anesthetics such as benzocaine, lidocaine or antifungal drug. Editorial comments • Fluorouracil is used alone or in combination with other modalities of treatment, eg, radiation therapy, surgery, other chemotherapeu- tic agents. Warnings/precautions • Use with caution in patients with the following conditions: diabetes mellitus, seizures, liver or kidney disease. Patients should wear a bracelet identifying the condition and possibility of developing hypoglycemia. Adverse reactions • Common: anorexia, body pain, nausea, insomnia, anxiety, tremor, dry mouth. Mechanism of action: Stimulates receptors in androgen-responsive organs, thereby promoting growth and development of male sex organs. Drug should be administered only by physician who is aware of possible adverse effects of drug on bone maturation. Contraindications: Hypersensitivity, males with carcinoma of the breast, known or suspected carcinoma of the prostate, seri- ous cardiac, renal, or hepatic decompensation. Editorial comments • This drug is listed without details in the Physician’s Desk Reference, 54th edition, 2000. Mechanism of action: Inhibits cyclooxygenase, resulting in inhi- bition of synthesis of prostaglandins and other inflammatory mediators. Mechanism of action: Prevents uptake of androgens and blocks nuclear binding of androgens in prostatic tissue. Warnings/precautions • Warn patient not to discontinue therapy without consulting with physician. Advice to patient • To cut down on diarrhea, reduce intake of dairy products, use antidiarrheal agents, and eat foods high in fiber. Adverse reactions • Common (seen with combination therapy): diarrhea, skin rash, hot flashes, loss of libido, impotence, nausea, vomiting, gyneco- mastia. Clinically important drug interactions: Flutamide may increase effects/toxicity of warfarin. Editorial comments • Use of flutamide at doses higher than those recommended has resulted in production of testicular interstitial cell adenoma.
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