Fluocinonide Cream advair diskus 500 mcg generic asthmatic bronchitis 7 month, Ointment discount advair diskus 250 mcg without a prescription asthma symptoms in 12 month old, and Gel The active component is the corticosteroid ﬂuocinonide generic advair diskus 500mcg line asthma definition yolo, (preservatives), mineral oil, polyoxyl 20 cetostearyl ether, which is the 21-acetate ester of ﬂuocinolone acetonide. This white cream vehicle is disodium, propyl gallate, propylene glycol, sodium hydrox- greaseless, nonstaining, anhydrous, and completely water ide or hydrochloric acid (to adjust the pH), and water (puri- miscible. In this formulation, the active ingredient is totally nonstaining, and completely water miscible. It provides the occlusive Another strength of cream contains ﬂuocinolone and emollient effects desirable in an ointment. In of butylated hydroxytoluene, cetyl alcohol, citric acid, another formulation, the ointment contains ﬂuocinolone edetate disodium, methylparaben and propylparaben acetonide 0. The mixture is heated until about 70°–80°C, and then a 2% aqueous solution of triethanola- 1. The mixture is stirred well and then cooled to solution of carboxyvinyl polymer (20 g), puriﬁed give a creamy preparation having a viscosity of water (47 g), and a 1% aqueous solution of 65,000 centipoises and a pH of 4. Inactives ical name is ﬂuorometholone [9-Fluoro-11(beta),17-dihy- are white petrolatum, mineral oil, and petrolatum and droxy-6(alpha)-methylpregna-1,4-diene-3,20-dione]. Formulations of Semisolid Drugs 159 Flurandrenolide Topical Film Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 0. Add and dissolve ﬂurandrenolide in propylene including water over a period of 20–30 minutes, glycol, glycerine, and ethyl alcohol. Fluticasone Propionate Ointment Bill of Materials Scale (mg/g) Item Material Name Quantity/kg (g) 0. Transfer the drug mixture from step 3 into the manufacturing vessel from step 2 while mixing. Melt microcrystalline wax, hard parafﬁn, and Mix and homogenize for 10 minutes under vac- sorbitan sesquioleate in a fat-melting vessel at uum at 0. Cool to a temperature of 25°–30°C with con- turing vessel through stainless steel ﬁlter. Disperse ﬂuticasone propionate in propylene glycol, mix, and homogenize at a temperature of 40°–45°C. Each gram of ointment contains ﬂuti- 11-hydroxy-16-methyl-3-oxo-17-(1-oxopropoxy)androsta-1, casone propionate 0. The topical corticosteroids constitute a class of pri- Fluticasone Propionate Cream Fluticasone propionate cream 0. Each gram of cream con- diﬂuoro-11-hydroxy-16-methyl-3-oxo-17-(1-oxopro- tains ﬂuticasone propionate 0. Fluticasone Propionate Cream Bill of Materials Scale (mg/g) Item Material Name Quantity/kg (g) 0. Transfer the drug mixture of step 5 into step 4 1000 in a fat-melting vessel at 70°C. Add puriﬁed water to the manufacturing vessel cream to contain labeled amount of drug per and heat to 70°–80°C. Transfer the fat phase of step 1 through a stain- with product identiﬁcation label. Formulations of Semisolid Drugs 161 Foscarnet Cream Bill of Materials Scale (mg/100 g) Item Material Name Quantity/kg (mg) 3. Melt items 2, 3, and 5 at 70°C in a small con- step 2 to the step 3 while stirring. Transfer the ointment to stainless steel drum ﬁlter to mixer and cool it down to 50°C. Formulations of Semisolid Drugs 163 Gentamicin Sulfate Cream Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 0. Quantity of gentamicin sulfate per batch will vary according to the actual potency. While homogenization is in progress, set the steel ﬁlter while mixing at speed 10 rpm, vac- temperature at 25°C so that the cream temper- uum 0. Stop the homogenizer, set the mixer at temper- cream in stainless steel container and ﬁll. Gentamicin Sulfate Ointment Gentamicin sulfate ointment is a sterile, topical anti-infective (equivalent to 3. Gentamicin sulfate is the sulfate salt of gentamicin tamicin sulfate equivalent to 0. Immediately The suppository mass is manufactured at a temperature of transfer the hot mass to the heated storage ves- 120°C. Care must be taken to see that molten suppository sel or heated vessel of suppository ﬁlling mass does not accidentally spill on the person. Glycerin Suppositories Bill of Materials Scale (mg/suppository) Item Material Name Quantity/1000 Suppositories (g) 900. Formulations of Semisolid Drugs 165 Glycolic Acid Cream Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 3. Gramicidin, Neomycin, Nystatin, and Triamcinolone Ointment Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 0. Rinse homogenizer with liquid parafﬁn and add heat to 70°C to melt; transfer to Becomix rinsings. Mix till ointment is smooth, transfer to a stain- twice with ﬁne-gap setting to make smooth dis- less steel vessel, and ﬁll. Charge items 1, 2 (balance quantity), 3, and 6 in a separate stainless steel vessel and homogenize 166 Handbook of Pharmaceutical Manufacturing Formulations: Semisolid Products Halobetasol Propionate Cream and Ointment The cream contains halobetasol propionate, a synthetic halobetasol propionate in a cream base of cetyl alcohol, corticosteroid for topical dermatological use. The corti- glycerin, isopropyl isostearate, isopropyl palmitate, ste- costeroids constitute a class of primarily synthetic steroids areth-21, diazolidinyl urea, methylchloroisothiazolinone, used topically as an anti-inﬂammatory and antipruritic methylisothiazolinone, and water. Heparin Gel-Cream Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 0. Formulations of Semisolid Drugs 167 Hexachlorophen Cream Bill of Materials Scale (mg/g) Item Material Name Quantity/kg (g) 45. While both solutions are at 65°–70°C, form the primary emulsion by pumping the aqueous solu- 1. Strain olive oil through voile cloth or equivalent tion from step 5 into the oil mixture from step 3 into a suitable stainless steel-jacketed tank. Homogenize primary emulsion through a Troy ate mix, add cetyl alcohol, lanolin, petrolatum, Mill, or similar device, into the balance of aque- and polysorbate 40 with mixing. Add and dissolve hexachlorophene in the oil emulsion should strained through voile cloth or mix, then add and disperse the simethicone. Cool emulsion to 40°–50°C with agitation glycerin, methylparaben, and borax as puriﬁed under vacuum. Reserve 4 mL of solution from step 5 in a separate container to rinse equipment in step 2. Other formulations include base containing sorbitan sesquioleate, water, aquaphor, cream, which contains hydrocortisone acetate 1% or 2.
Triiodothyronine repletion in infants during cardiopulmonary bypass for congenital heart disease purchase advair diskus 500 mcg with amex asthma symptoms middle age. Comparison between dobutamine and levosi- mendan for management of postresuscitation myocardial dysfunction quality advair diskus 250 mcg asthma x-ray in children. Effects of levosimendan on right ventricular afterload in patients with acute respiratory distress cheap advair diskus 250mcg mastercard asthmatic bronchitis x-ray. Duration of haemodynamic action of a 24-h infusion in patients with congestive heart failure. Effects of serial levosimendan infusions on left ventricular performance and plasma biomarkers of myocardial injury and neuro- hormonal and immune activation in patients with advanced heart failure. Levosimendan improves right ventriculovascular coupling in a porcine model of right ventricular dysfunction. Levosimendan for the treatment of acute heart failure syndromes: time to identify subpopulations of responding patients. Preconditioning effects of levosimendan in coronary artery bypass-grafting—a pilot study. Use of levosimendan, a new inodilator, for postoperative myocardial stunning in a premature neonate. Pharmacokinetics of levosimendan in pediatric patients evaluated for cardiac surgery. Specifically, the principal groups of pediatric patients with cardiovascular disease who may benefit from afterload reduction therapies include the following: 1. Patients with normal cardiac anatomy and myocardial function who have sys- temic hypertension. Patients with normal cardiac anatomy but impaired myocardial function, either caused by primary myocardial disease (e. The vasodilators are pharmacological agents that produce relaxation of smooth muscle in the wall of blood vessels, leading to reduced vascular resistance and the potential for increased blood flow. Some vasodilators act on arterial vessels, others on venous vessels, and a third group on both arteries and veins. The vasodilators can be classified according to their predominant site of action or by their mechanism of action. In this chapter, these agents are classified by their mechanism of action (see Table 4-1). Vasodilators 79 therefore, reducing its blood level leads to less vasoconstriction. Dose every 8 to 12 hours and titrate dose for response Neonates: Oral: initial or “test” dose 0. Titrate dose to maximum of 6 mg/kg/day in two to four divided doses Adults: Oral: initial dose 12. Titrate dose upward by 25 mg/dose at 1- to 2-week intervals to a maxi- mum dose of 450 mg/day. Usual dose range is 25 to 100 mg/day in two divided doses Note: Dosing for all age groups should be titrated to an individual patient’s response, and the lowest dose that achieves this response should be cho- sen. Lower doses are appropriate for patients who are also being treated with diuretics and are water and sodium depleted. Dosing adjustment for renal impairment: Creatinine clearance (Cl ) 10 to 50mL/min/1. Monitoring for blood pressure effect should focus on the period 1 to 3 hours after dosing. Adverse Effects Cardiovascular: hypotension, tachycardia Respiratory: cough, dyspnea. The risk of neutropenia is increased by approximately 15-fold in patients with renal dysfunction Cutaneous/peripheral: rash, angioedema Other: fever, anaphylactoid reaction Precautions Dosing should be adjusted downward in patients with renal impairment, col- lagen vascular disease, or obstruction to systemic arterial flow (e. Monitor renal function closely in patients with known renal impairment, low cardiac output, or volume depletion (e. Drug-Drug Interactions In patients who are also receiving potassium supplements or a potassium-sparing diuretic (e. Compatible Diluents/Administration Captopril is only available for oral/enteral administration. Administer via an infusion over 5 minutes Infants/children: Oral, enalapril: initial or “test” dose 0. Administer via an infusion over 5 minutes Adults: Oral, enalapril: initial or “test” dose 2. Maximum dose, 5 mg/dose every 6 hours (20 mg/day) Note: Dosing for all age groups should be titrated to an individual patient’s response, and the lowest dose that achieves this response should be cho- sen. For additional dosing precautions in neonates, see “Poisoning Information” Dosing adjustment for renal impairment: Cl 10 to 50 mL/min/1. Moni- toring for blood pressure effect should focus on the period 1 to 3 hours (enal- april) or 15 to 60 minutes (enalaprilat) after dosing. Adverse Effects Cardiovascular: hypotension, tachycardia, syncope Respiratory: cough, dyspnea, eosinophilic pneumonitis. Central nervous system: fatigue, vertigo, dizziness, headache, insomnia Gastrointestinal: nausea, diarrhea, loss of taste perception Hepatic: cholestatic jaundice, fulminant hepatic necrosis (rare, but poten- tially fatal) Renal: diminished renal function Genitourinary: impotence Neuromuscular and skeletal: muscle cramps Endocrine/metabolic: hypoglycemia, hyperkalemia Hematological: agranulocytosis, neutropenia, anemia Cutaneous/peripheral: rash, angioedema. The risk of angioedema is higher in the first 30 days of use and for enalapril and lisinopril as compared with captopril Drug-Drug Interactions In patients who are also receiving potassium supplements or a potassium- sparing diuretic (e. Poisoning Information Enalaprilat contains benzyl alcohol (9 mg/mL), which may cause allergic reac- tions and a potentially fatal toxicity in neonates, called “gasping syndrome” at high doses (≥ 99mg/kg/d). Gasping syndrome is manifested by metabolic acidosis, respiratory distress with gasping respirations, central nervous system dysfunction (seizures, hemorrhage), hypotension, and cardiovascular collapse. Therefore, enalaprilat should be used with caution and close monitoring in neonates. Compatible Diluents/Administration Enalapril is available for oral/enteral administration. Enalaprilat can be administered undi- luted or diluted with normal saline; infuse over 5 minutes. Dosing Neonates (premature and full term), infants, and children younger than 6 years: no dosing information is available; because of this, the manufacturer recommends not using lisinopril in patients younger than 6 years of age Children older than 6 years: initial or “test” dose 0. Increase dose by at most 10mg/dose by at least 2-week intervals based on clinical response. Maximum dose is 40 mg/day Note: Dosing for all age groups should be titrated to an individual patient’s response, and the lowest dose that achieves this response should be cho- sen. For additional dosing precautions in neonates, see “Poisoning Information” Dosing adjustment for renal impairment: Cl greater than 30 mL/min/1. Monitoring for blood pressure should be conducted with knowledge that the maximum effect is 6 to 8 hours after dosing. The risk of neutropenia is increased in patients with renal dysfunction Cutaneous/peripheral: rash, angioedema. The risk of angioedema is higher in the first 30 days of use and is greater for lisinopril and enalapril than captopril Other: anaphylactoid reactions Precautions Note: Dosing for all age groups should be titrated to an individual patient’s response, and the lowest dose that achieves this response chosen.
Diabetes mellitus and metabolic syndrome are widely-spread problems of the modern society advair diskus 500 mcg cheap asthma symptoms and joint pain. As the patients are becoming more interested in traditional herbal medicines buy advair diskus with amex asthma uri, the verification of their effects is needed cheap advair diskus 100mcg line asthma symptoms joint. Phytotherapy in the most cases is supplementary, but it may augment the efficacy of the commonly used antihyperglycemic drugs. Goutweed is a perennial herb of the Apiaceae family that has been used in folk medicine for a long time. Goutweed tincture renders protective activity in alloxan-induced diabetic mice, the tincture shows hypoglycemic properties under the conditions of metabolic disorders induced by fructose and hydrochlorothiazide in rats. Oral glucose tolerance test was performed after the treatment of the animals with metformin, goutweed tincture or their combination. The total area under the blood glucose curve was calculated using the trapezoidal method, the average glycemia value was also calculated. Given that glucose and lipid metabolism disorders are interrelated in the pathogenesis of metabolic syndrome and other ―disease of civilization,‖ the same test was also performed in dyslipidemic animals. In dexamethasone treated rats, goutweed tincture combined with the respectively low dose of metformin increased the effect on the latter on the basal glycemia. In the oral glucose tolerance test the lowest area under glucose curve and average glycemia value were seen in these group. The efficacy of the investigated combination was also partially manifested in dyslipidemic animals (the reduction in area under glucose curve). Goutweed tincture is able to partially increase the efficacy of metformin in dexamethasone treated and dyslipidemic rats. Nosocomial infections involving Staphylococcus aureus and methicillin-resistant S. One strategy to combat these infections is to develop novel and effective anti-infective agents. The data from the literature search and study of new antibiotics, clinical trial information. A new group of drugs was discovered recently: Pentaalkylcyclopentadienyl (Cp * g) of 1,2-diamine complexes of transition metals. There were synthesized a series of compounds differing in the structure of the radical in the ligand. Hemolytic activities of the transition metal-complexes as well as toxicity toward Vero cells were also measured. The transition metal complex of Cp*R Ir with cis-1,2-diaminocyclohexane, had strong antibiotic activity against S. A cyclopentadienylcobalt complex of cis-1,2- diaminocyclohexane also showed significant anti-microbial activity against both S. Conclusions: The transition metal complexes described here show specific activity against S. In addition, the specificity of the complexes that show activity indicates that there are specific structure/activity relationships that must be met. The combination of high and specific activity for certain complexes, the low cytotoxicity as tested with Vero cells and the low hemolytic activity all suggest that this transition metal platform may prove to be useful in overcoming antibiotic resistance in S. The imidazole nucleus is a known structural fragment of many natural physiologically active compounds and effective synthetic medicinal products, which are characterized by a wide range of pharmacological properties, among which the antioxidant activity deserves special attention. But despite the considerable synthetic and biological potential of the imidazole nucleus the methods of synthesis and the properties of this heterocyclic type had not been adequately studied yet. The search of new biologically active compounds with antioxidant activity among the imidazole derivatives functionalized with the carboxymethylthiol fragment. Previously in the department of medical and pharmaceutical chemistry we synthesized a number of imidazole derivatives functionalized in the position 4 with carboxymethylthiol fragment, and in the position 5 – with the formyl group, [(1-aryl-5-formyl-1Н-imidazole-4-yl)thio]acetic(propanoic) acids and [(1-arylimidazole-5-yl)methylthio]alkane carboxylic acids in particular. The content of malonaldehyde in the samples was determined by the reaction with the thiobarbituric acid. The results of the study have shown that in the in vitro system all of the -1 -3 studied original compounds in the range of concentrations 10 -10 mol/L inhibit the 2+ Fe -ascorbate induced free radical oxidation of lipids and demonstrate a pronounced antioxidant activity. The highest antioxidant activity in vitro was shown by the [(1- phenyl-5-formyl-1H-imidazole-4-yl)thio]acetic acid. At the same time it was determined that the increase of methylene groups‘ quantity in the carboxyalkylthiol fragment does not significantly influence the antioxidant activity of the synthesized compounds. The [(1-phenyl-5-formyl-1H-imidazole-4-yl)thio]acetic acid is the most promising compound for the further research of antioxidant activity in the wider range of concentrations in vitro and in the in vivo system. Stress is the attempt of organism to regenerate the balance, to recover from unusual events, to keep stability of organism internal parameters (homeostasis) against the influence of bad agents. Nowadays the amount of information is increasing, the temp of life is speeding up, long intellectual and mental load has a big influence on people. Using modern complicated technology and machinery very often causes small and big catastrophes, traffic delays, electric power breaks, connection cessations. It is known that 72-80% of car crashes and 70% air crashes happen because of guiltiness of human. The aim of our research was to analyse the cause and sequence of psychoemotional and phycosocial stress by using literature sources. Negative emotional reactions are caused by long conflict situations, difference between expectation and reality, sometimes by responsibility of making a decision. Psychological multiple manifestations can be low self-appraisal, which in future can overgrow into depression, state of anxiety and terror. This is a complicated emotional state, important component of neural and psychical changings. Neurosis is the neuropsychic dysfunction which appears as the attempt of organism to go round stressful situation instead of comprehension of the problem and finding the solution. At the same time men oftener find way out in abuse the alcohol, drugs, absence from work. There are two types of depression: reactive (as manifestation of heavy psychoemotional stress and it is curable) and endogenic (depends on psyche asthenia and sometimes cannot be treated). Physical and behaviour manifestations of psychoemotional stress are headache (migraine), backache, insomnia, muscle contraction, stomach dysfunctions (diarrhea), dysmenorrhea, amenorrhea, perspirations, tachycardia, raised arterial tension, overeating (bulimia) or anorexia (absence of appetite). In the second World War in blockade Leningrad frequency of hypertonic decease grew up in five times compere to pre-war times mainly because of psychical 68 stress. Ulcer of stomach almost disappeared among inhabitants of Leningrad during the blockade. According to preset analysis of American scientists stress at work is one of the heaviest. In table 1 it is presented information which shows the degree of stress in provisional units due to the influence of psychoemotional and phycosocial stress in different situations. It was analysed the cause and sequence of psychoemotional and phycosocial stress by using literature sources and discovered that character and stage of organism reactions for influence of external facts depend on the nature and power of factors, original functionary stage of organism, level of its reserve abilities, daily and season variation of functionary stage.
Most diuretcs increase urine volume by inhibitng the reab- sorpton of Sodium and chloride ions in the renal tubule; they also modify renal handling of potassium discount 100mcg advair diskus mastercard asthma treatment nz, calcium generic 100mcg advair diskus with mastercard asthma 2014 trailer, magnesium and urate discount 500 mcg advair diskus free shipping asthma inhalers over the counter. Osmotc diuretcs act diferently; they cause an increase in urine volume by an osmotc efect. Although loop diuretcs are the most potent their duraton of acton is relatvely short, whilst thiazide diuretcs are moder- ately potent but produce diuresis for a longer period. Carbonic anhydrase inhibitors are weak diuretcs which are rarely, used for their diuretc efect and are principally used to lower intraocular pressure in glaucoma. Electrolyte Imbalance: The adverse efects of diuretc therapy are mainly due to the fuid and electrolyte imbalance induced by the drugs. The risk of hypoka- laemia, which may occur with both thiazide and loop diuretcs, depends more on the duraton of acton than on potency and is thus greater with thiazides than with loop diuretcs (when given in equipotent doses). Other electrolyte disturbances include hypercalcaemia (thiazides), hypocalcaemia (loop diuretcs) and hypomagnesaemia (thiazide and loop diuretcs). Symptoms of fuid and electrolyte imbalance include dry mouth, thirst, gastrointestnal disturbances (including nausea, vomitng), weakness, lethargy, drowsiness, restlessness, seizures, confusion, headache, muscle pains or cramps, hypo- tension (including postural hypotension), oliguria, arrhyth- mias. Elderly: The elderly are more susceptble to electrolyte imbalance than younger patents. Treatment should begin with a lower inital dose of the diuretc (commonly about 50% of the adult dose) and then adjusted carefully according to renal functon, plasma electrolytes and diuretc response. They produce diuresis within 1-2 h of oral administraton and most have a duraton of acton of 12-24 h. Thiazide diuretcs are used in the management of oedema associated with mild to moderate congestve heart failure, renal dysfuncton or hepatc disease; however, thiazides are not efectve in patents with poor renal functon (creatnine clear- ance of less than 30 ml per min). In hypertension, a thiazide diuretc is used at a low dose to lower blood pressure with very litle biochemical disturbance; the max. Higher doses should not be used because they do not neces- sarily increase the hypotensive response but may cause marked changes in plasma potassium, magnesium, uric acid, glucose and lipids. If a thiazide alone does not lower blood pressure adequately, it may be used in combinaton with another ant- hypertensive such as a beta-adrenoceptor antagonist. Urinary excreton of calcium is reduced by thiazide diuretcs and this property is occasionally utlized in the treatment of idiopathic hypercalciuria in patents with calcium-containing calculi. Paradoxically, thiazide diuretcs are used in the treat- ment of diabetes insipidus, since in this disease they reduce urine volume. Thiazide diuretcs, especially in high doses, produce a marked increase in potassium excreton which may cause hypoka- laemia; this is dangerous in patents with severe coronary artery disease and those being treated with cardiac glyco- sides. In hepatc failure hypokalaemia can precipitate enceph- alopathy, partcularly in alcoholic cirrhosis. Potassium-sparing diuretcs are used as a more efectve alternatve to potas- sium supplements for preventon of hypokalaemia induced by thiazide diuretcs; however supplementaton with potas- sium in any form is seldom necessary with the smaller doses of diuretcs used to treat hypertension. Loop Diuretcs: Loop diuretcs, or high-ceiling diuretcs, such as furosemide, are the most potent and rapidly produce an intense dose-de- pendent diuresis of relatvely short duraton. Oral furosemide produces diuresis within 30-60 min of administraton, with the max. They are also used to treat oedema associated with renal and hepatc disorders and are used in high doses in the management of oliguria due to chronic renal insufciency. Because of their shorter duraton of acton, the risk of hypoka- laemia may be less with loop diuretcs than with thiazide diuretcs; if required, potassium-sparing diuretcs may be used for preventon of hypokalaemia. Loop diuretcs may cause hypovolaemia and excessive use can produce severe dehydraton with the possibility of circulatory collapse. Rapid high-dose injecton or infusion of furosemide may cause tnnitus and even permanent deafness. Potassium-Sparing Diuretcs: Potassium-sparing diuretcs include amiloride and spironolac- tone; they are weak diuretcs and reduce potassium excreton and increase Sodium excreton in the distal tubule. Amiloride acts about 2 h afer oral administraton, reaching a peak in 6-10 h and persistng for about 24 h. Spironolactone, which acts by antagonising aldosterone, has a relatvely slow onset of acton requiring 2-3 days to achieve max. Amiloride may be used alone, but its principal use is in combi- naton with a thiazide or a loop diuretc to conserve potassium during treatment of congestve heart failure or hepatc cirrhosis with ascites. Spironolactone is used in the treatment of refractory oedema due to heart failure, hepatc cirrhosis (with or without ascites), nephrotc syndrome and ascites associated with malignancy. It is frequently given with a thiazide or a loop diuretc, helping to conserve potassium in those at risk from hypokalaemia. Spironolactone is used in the diagnosis and treat- ment of primary hyperaldosteronism; presumptve evidence for diagnosis is provided by correcton of hypokalaemia and of hypertension. The most dangerous adverse efect of potassium-sparing diuretcs, such as amiloride or spironolactone, is hyperka- laemia, which can be life-threatening. Osmotc Diuretcs: Osmotc diuretcs, such as mannitol, are administered in suf- ciently large doses to raise the osmolarity of plasma and renal tubular fuid. Osmotc diuretcs are used to reduce or prevent cerebral oedema, to reduce raised intraocular pressure or to treat disequilibrium syndrome. Mannitol is also used to control intraocular pressure during acute atacks of glaucoma. Reduc- ton of cerebrospinal and intraocular fuid pressure occurs within 15 min of the start of infusion and lasts for 3-8 h afer the infusion has been discontnued; diuresis occurs afer 1-3 h. Circulatory overload due to expansion of extracellular fuid is a serious adverse efect of mannitol; as a consequence, pulmo- nary oedema can be precipitated in patents with diminished cardiac reserve, and acute water intoxicaton may occur in patents with inadequate urine fow. Amiloride Pregnancy Category-B Schedule H Indicatons Oedema associated with heart failure or hepatc cirrhosis (with ascites), usually with thiazide or loop diuretc; hypertension. Dose Oral Oedema: used alone initally 10 mg daily in 1 or 2 divided doses, adjusted according to response (max. Combined with a thiazide or a loop diuretc: initally 5 mg daily, increasing to 10 mg if necessary (max. Precautons Monitor electrolytes; partcularly potassium; hypocholeremia, hepatc cirrhosis, renal impairment (Appendix 7d); diabetes mellitus; elderly (reduce dose); lactaton; interactons (Appendix 6b, 6c); pregnancy (Appendix 7c). Adverse Efects Hyperkalaemia;hyponatreamia(forsymptoms of fuid and electrolyte imbalance see introductory notes); diarrhoea; constpaton; anorexia; paraesthesia; dizziness; minor psychiatric or visual disturbances; rash; pruritus; rise in blood urea nitrogen; headache; abdominal pain, fatulence. Dose Oral Adult- Oedema: initally 40 mg daily on waking up; maintenance dose 20 to 40 mg daily; may be increased to 80 mg daily or more in resistant oedema. Contraindicatons Renal failure with anuria; precomatose states associated with liver cirrhosis; hypersensitvity. Precautons Monitor electrolytes partcularly potassium and Sodium; hypotension; asymptomatc hyperuricaemia, systemic lupus erythmatosus, elderly (reduce dose); pregnancy (Appendix 7c); lactaton; correct hypovolaemia before using in oliguria; renal impairment; hepatc impairment (Appendix 7a); prostatc enlargement; porphyria; interactons (Appendix 6b, 6c). Adverse Efects Hypokalaemia; hypomagnesaemia; hyponatraemia; hypochloraemic alkalosis (for symptoms of fuid and electrolyte im- balance; see introductory notes); increased calcium excreton; hypovolaemia; hyperg- lycaemia (but less ofen than with thiazide diuretcs); temporary increase in plasma cholesterol and triglyceride concentraton; less commonly hyperuricaemia and gout; rarely, rash; photosensitvity; bone marrow depression (withdraw treatment); pancrea- tts (with large parenteral doses); tnnitus and deafness (with rapid administraton of large parenteral doses and in renal impair- ment; deafness may be permanent if other ototoxic drugs taken); hepatc encephalopa- thy, anorexia, orthostatc hypotension. Severe oedema in patents unable to tolerate loop diuretcs: up to 100 mg either daily or on alternate days (max. Adverse Efects Hypokalaemia; hypomagnesaemia; hyponat- raemia; hypochloraemic alkalosis (for symp- toms of fuid and electrolyte imbalance see introductory notes); hypercalcaemia; hyperg- lycaemia; hyperuricaemia; gout; rash; photo- sensitvity; altered plasma lipid concentraton; rarely, impotence (reversible); blood disorders (including neutropenia; thrombocytopenia); pancreatts; intrahepatc cholestasis and hy- persensitvity reactons (including pneumoni- ts; pulmonary oedema; severe skin reactons) also reported; acute renal failure. Mannitol* Pregnancy Category-C Indicatons Cerebral edema, impending acute renal failure, acute poisonings, raised intraocular pressure (emergency treatment or before surgery). Dose Test dose (if patent is oliguric or if renal functon is inadequate), By intravenous infusion as a 20% soluton infused over 3–5 minutes, Adult and Child- 200 mg/kg; repeat test dose if urine output is less than 30–50 ml/h; if response is inadequate afer a second test dose, re-evaluate the patent.
Epidural analgesia is ideal for labour and delivery buy generic advair diskus 500 mcg on line asthma zenhale, but should only be undertaken by experienced practitioners in a unit properly equipped for resuscitation and with facilities available for urgent operative delivery discount generic advair diskus canada asthma symptoms yahoo answers. Management will include preventing further seizures buy advair diskus with amex asthma definition 5 1, controlling the blood pressure, referral to a high-care unit and delivery of the baby if not already post-delivery. To prevent eclamptic seizures, magnesium sulphate is recommended for patients with severe pre-eclampsia, including imminent eclampsia. When used for prevention of eclampsia, magnesium sulphate is administered for 24 hours, and then stopped. Stop magnesium sulphate if knee reflexes absent or if urine output < 100 mL/ 4 hours or respiratory rate <16 breaths/minute. Notify the person who will resuscitate the newborn that a benzodiazepine and/or magnesium has been given to the mother. Women should be advised that there’s an increased risk of congenital abnormalities if these drugs were taken during pregnancy. Decisions about postpartum contraceptive use and method of infant feeding must be made in the antenatal period. Note: If mother has received <3 doses, the baby should be treated for congenital syphilis. For penicillin sensitive patients, the penicillin desensitisation regimen is an option. If penicillin is not used, the baby must be regarded as inadequately treated and given penicillin after delivery. Retreat mother with doxycycline once she has stopped breast feeding • Doxycycline, oral, 100 mg 12 hourly for 28 days. Pregnancy-specific causes include: » intrahepatic cholestasis of pregnancy, » acute fatty liver of pregnancy (acute yellow atrophy of the liver), » severe pre-eclampsia or eclampsia, and » hyperemesis gravidarum. Preterm labour confirmed by regular uterine contractions with progressive cervical changes. If gestation <30 weeks and where nifedipine contra-indicated: • Indomethacin, oral, 50 mg immediately then 25 mg 4 hourly for up to 48 hours. Note: Indomethacin may cause oligohydramnios, and its use is associated with a risk of premature closure of the ductus arteriosis. Note: Corticosteroids are maximally effective if the complete course is administered at least 24 hours before delivery. Antibiotic therapy Indicated routinely for ruptured membranes and selectively for preterm labour with intact membranes at high risk of infection. Cervix unfavourable Extra-amniotic saline infusion: recommended if attempts at ripening the cervix with prostaglandins fail. Most women will experience adequate contractions at a dose of 12 milliunits/minute. If uterine hyperstimulation syndrome develops (>5 contractions in 10 minutes with fetal heart rate abnormalities), stop the oxytocin infusion and administer salbutamol as above. Note: Perform a non-stress test (cardiotocography) within an hour of each dinoprostone insertion, to evaluate the fetal condition during labour induction. Oral misoprostol may be given as freshly made-up solution of one 200 mcg tablet in 200 mL water, i. Misoprostol and other prostaglandins are contraindicated in women with previous Caesarean sections and in grand multiparous women. Misoprostol in larger doses than indicated here for labour induction at term, may cause uterine rupture. The need for analgesics may be reduced by keeping the woman informed about the progress of labour, providing reassurance and carefully explaining the procedures performed. Perineal analgesia: • Lidocaine, 1 or 2%, infiltration, locally or by a pudendal block. Postpartum and post-episiotomy pain • Paracetamol, oral, 1 g 4–6 hourly when required to a maximum of 4 doses per 24 hours. Compress the abdominal aorta in situations where bleeding is not responsive to above measures when transferring or waiting for definitive treatment. During pregnancy, give prophylactic anti-D immunoglobulin to the mother within 72 hours of a potentially sensitising event. Rh positive, Coomb’s positive: In these cases the mother will also have antibodies. Chronic kidney disease can be entirely asymptomatic until over 75% of kidney function is lost. Staging of kidney disease Stage/ Description Action glomerular Includes actions from filtration preceding stages rate 2 (mL/minute/1. Proteinuria reduction Determine the amount of proteinuria with a spot urine specimen. Achievement of these targets must be balanced against side-effects such as hypotension and hypoglycaemia. Diabetes mellitus In diabetics with kidney disease there is an increased risk of hypoglycaemia. Hypocalcaemia and hyperphosphataemia The aim is to lower phosphate levels and maintain normal calcium levels to ensure calcium phosphate product (i. Where facilities are available, investigation and management is usually done with guidance or referral to a specialist. Management should be carried out or guided by a nephrologist according to the biopsy result. Postural blood pressure for monitoring fluid loss and to prevent excessive diuresis. Common complications of acute renal failure include: » fluid overload and pulmonary oedema, » hyperkalaemia, » bleeding, » acidosis, and » encephalopathy. Both haemodialysis and peritoneal dialysis are acceptable modalities of therapy in the acute setting. For long-term or chronic, non-urgent need for potassium removal: • Sodium polystyrene sulfonate, oral, 15 g with 15 mL lactulose, 6 hourly. Hyperphosphataemia To decrease absorption of phosphate in acute renal failure: • Aluminium hydroxide 300 mg/5 mL, oral, 10 mL 8 hourly. Do not administer aluminium hydroxide and sodium polystyrene sulfonate simultaneously as this may potentiate aluminium toxicity. Alkalinising agents are not advised as many antibiotics require a lower urinary pH. For pregnant women: • Amoxicillin/clavulanic acid, oral, 875/125 mg 12 hourly for 7 days. If there is a poor response, perform an ultrasound on all hospitalised patients urgently as in-patients or electively as out-patients. Duration of antibiotic therapy: » fluoroquinolones 7 days » other antibiotics 14 days. Longer courses of therapy, 2–3 weeks, should be given for complicated pyelonephritis. Switch to oral therapy as soon as the patient is able to take oral fluids: • Ciprofloxacin, oral, 500 mg 12 hourly for 7 days. Switch to oral therapy as soon as the patient is able to take oral fluids: • Ciprofloxacin, oral, 500 mg 12 hourly for 7 days.
Drug interactions Because they produce vasoconstriction buy advair diskus 100mcg with amex asthma causes, which reduces drug ab- sorption buy advair diskus 100 mcg lowest price asthma symptoms in 12 month old, topical decongestants seldom produce drug interactions buy cheap advair diskus 250 mcg on line asthma treatment 1930s. Adverse reactions to decongestants Most adverse reactions to deconges- Systemic decongestants exacerbate Other reactions include: tants result from central nervous system hypertension, hyperthyroidism, diabetes, • burning and stinging of the nasal mu- stimulation and include: benign prostatic hypertrophy, glaucoma, cosa • nervousness and heart disease. They’re also secreted • sneezing • restlessness in breast milk in a breast-feeding • mucosal dryness or ulceration. Issue of sensitivity • nausea Topical decongestants The patient who’s hypersensitive to other • palpitations The most common adverse reaction as- sympathomimetic amines may also be • tachycardia sociated with prolonged use (more than hypersensitive to decongestants. Which adverse reaction can occur if guaifenesin is taken in larger doses than necessary? Which adverse reaction most commonly occurs with a decon- gestant, such as tetrahydrozoline, especially if it’s taken more of- ten than recommended? Rebound nasal congestion commonly occurs when Great job on tetrahydrozoline is taken more frequently than recommended. Scoring ✰✰✰ If you answered all four items correctly, you’re slicker than a mu- colytic in action! I help tions are to digest food and absorb nutrients and fluids and ex- digest food and crete metabolic waste. Antiulcer drugs A peptic ulcer is a circumscribed lesion that develops in the mu- cous membranes of the lower esophagus, stomach, duodenum, or jejunum. These drugs include: • systemic antibiotics • antacids • Histamine-2 (H2) receptor antagonists • proton pump inhibitors • other peptic ulcer drugs, such as misoprostol and sucralfate. Teamwork is a must Successful treatment involves the use of two or more antibiotics in combination with other drugs such as acid suppressants. Distribution and excretion All of these antibiotics are distributed widely and are excreted pri- marily in urine. They’re usually combined with an H2-receptor antagonist or a proton pump in- hibitor to decrease stomach acid and further promote healing. For this reason they may be used in conjunction with other medications such as proton pump inhibitors. Successful strategy Successful treatment plans use at least two antibiotics and a pro- ton pump inhibitor for 14 days and then use a proton pump in- hibitor for 6 more weeks to help reduce acid in patients with a Warning! Adverse Drug interactions reactions to Tetracycline and metronidazole can interact with many other med- ications. They include: metronidazole may also • aluminum carbonate gel produce abnormal • calcium carbonate tastes. Pharmacotherapeutics Antacids are primarily prescribed to relieve pain and are used ad- junctively in peptic ulcer disease. Antacids can interfere with the Fighting phosphate absorption of Antacids may be used to control hyperphosphatemia (elevated other orally blood phosphate levels) in kidney failure. Drug interactions All antacids can interfere with the absorption of oral drugs given at the same time. Absorption of digoxin, phenytoin, ketoconazole, iron salts, isoniazid, quinolones, and tetracyclines may be reduced if taken within 2 hours of antacids. Distribution, metabolism, and excretion H2-receptor antagonists are distributed widely throughout the body, metabolized by the liver, and excreted primarily in urine. Pharmacodynamics H2-receptor antagonists block histamine from stimulating the acid- secreting parietal cells of the stomach. The acid test Acid secretion in the stomach depends on the binding of gastrin, acetylcholine, and histamine to receptors on the parietal cells. The H2-receptor antagonists, by binding with H2 recep- tors, block the action of histamine in the stomach and reduce acid secretion. Drug interactions H2-receptor antagonists may interact with antacids and other drugs. How H -receptor antagonists work 2 These illustrations show how histamine-2 (H2) receptor antagonists reduce the release of gastric acid. To stimulate gastric acid secretion, certain endogenous sub- stances—primarily histamine, but also acetylcholine and gas- trin—attach to receptors on the surface of parietal cells. The pump catalyzes the exchange of extracellular potas- sium (K) ions for intracellular hydrogen (H) ions. H2-receptor • Cimetidine taken with carmustine increases the risk of bone antagonists marrow toxicity. They include: dine may produce • esomeprazole headache, dizziness, • lansoprazole malaise, muscle pain, • omeprazole nausea, diarrhea or con- • pantoprazole stipation, rash, itching, • rabeprazole. Pharmacokinetics • Famotidine and nizati- Proton pump inhibitors are given orally in enteric-coated formulas dine produce few ad- to bypass the stomach because they’re highly unstable in acid. These medications are highly protein-bound and are extensively metabolized by the liver to inactive compounds and then eliminat- ed in urine. Pharmacodynamics Proton pump inhibitors block the last step in the secretion of gas- tric acid by combining with hydrogen, potassium, and adenosine triphosphate in the parietal cells of the stomach. Two other drugs currently in use are: • misoprostol (a synthetic form of prostaglandin E1) • sucralfate. Absorption, metabolism, and excretion After an oral dose, misoprostol is absorbed extensively and rapid- ly. It’s metabolized to misoprostol acid, which is clinically active, meaning that it can produce a pharmacologic effect. Safe and sound Dangers of misoprostol use during pregnancy Adverse reactions to Use of misoprostol during pregnancy can lead can cause uterine rupture as well. Misopros- to premature birth, birth defects, or fetal abor- tol-induced abortions may be incomplete. When used after the 8th week of preg- these reasons, the drug is contraindicated for ulcer drugs nancy to induce labor or abortion, misoprostol gastric ulcer prevention during pregnancy. Misoprostol • Diarrhea (common and usually dose-related) Protective paste • Abdominal pain Sucralfate works locally in the stomach, rapidly reacting with hy- • Gas drochloric acid to form a thick, pastelike substance that adheres • Indigestion to the gastric mucosa and, especially, to ulcers. By binding to the • Nausea and vomiting ulcer site, sucralfate actually protects the ulcer from the damaging effects of acid and pepsin to promote healing. Adsorbent drugs Natural and synthetic adsorbents are prescribed as antidotes for the ingestion of toxins, substances that can lead to poisoning or overdose. Charcoal sketch The most commonly used clinical adsorbent is activated charcoal, a black powder residue obtained from the distillation of various organic materials. Pharmacokinetics Activated charcoal must be administered soon after toxic inges- Don’t worry. After initial absorption, some poisons move back into the in- testines, where they’re reabsorbed. Absorption, metabolism, and excretion Activated charcoal, which isn’t absorbed or metabolized by the body, is excreted unchanged in stool. However, this binding doesn’t change toxic effects caused by earlier absorp- tion of the poison. Pharmacotherapeutics Activated charcoal is a general-purpose antidote used for many types of acute oral poisoning. Adverse reactions to Drug interactions activated Activated charcoal can decrease absorption of oral medications; charcoal therefore, medications (other than those used to treat the ingested toxin) shouldn’t be taken orally within 2 hours of taking the acti- Activated charcoal turns vated charcoal.
This flux makes it more difficult to calculate the apparent volume in which a drug distributes order discount advair diskus line asthma treatment rajiv dixit. One way to calculate the apparent volume of drug distribution in the body is to measure the plasma concentration immediately after intravenous administration before elimination has had a significant effect buy genuine advair diskus line asthma treatment early 20th century. The concentration just after intravenous administration (at time zero order advair diskus visa asthma in kids, t0) is abbreviated as C0 (Figure 2-1). The volume of distribution can be calculated using the equation: (See Equation 1-1. If two concentrations have been determined, a line containing the two values and extending through the y-axis can be drawn on semilog paper. Both the direct measurement and back-extrapolation approaches assume that the drug distributes instantaneously into a single homogeneous compartment. The volume of distribution is an important parameter for determining proper drug dosing regimens. Often referred to as the apparent volume of distribution, it does not have an exact physiologic significance, but it can indicate the extent of drug distribution and aid in determination of dosage requirements. For example: the larger the volume of distribution, the larger a dose must be to achieve a desired target concentration. To understand how distribution occurs, you must have a basic understanding of body fluids and tissues (Figure 2-2). The fluid portion (water) in an adult makes up approximately 60% of total body weight and is composed of intracellular fluid (35%) and extracellular fluid (25%). If a drug has a volume of distribution of approximately 15-18 L in a 70-kg person, we might assume that its distribution is limited to extracellular fluid, as that is the approximate volume of extracellular fluid in the body. If a drug has a volume of distribution of about 40 L, the drug may be distributing into all body water, because a 70-kg person has approximately 40 L of body water (70 kg × 60%). If the volume of distribution is much greater than 40-50 L, the drug probably is being concentrated in tissue outside the plasma and interstitial fluid. If a drug distributes extensively into tissues, the volume of distribution calculated from plasma concentrations could be much higher than the actual physiologic volume in which it distributes. For example, by measuring plasma concentrations, it appears that digoxin distributes in approximately 440 L in an adult. Because digoxin binds extensively to muscle tissue, plasma levels are fairly low relative to concentrations in muscle tissue. For other drugs, tissue concentrations may not be as high as the plasma concentration, so it may appear that these drugs distribute into a relatively small volume. Blood refers to the fluid portion in combination with formed elements (white cells, red cells, and platelets). Plasma refers only to the fluid portion of blood (including soluble proteins but not formed elements). When the soluble protein fibrinogen is removed from plasma, the remaining product is serum (Figure 2-3). These differences in biologic fluids must be recognized when considering reported drug concentrations. The plasma concentration of a drug may be much less than the whole blood concentration if the drug is preferentially sequestered by red blood cells. Clinical Correlate Most drug concentrations are measured using plasma or serum that usually generate similar values. It is more relevant to use plasma or serum than whole blood measurements to estimate drug concentrations at the site of effect. However, some drugs such as antimalarials are extensively taken up by red blood cells. In these situations, whole blood concentrations would be more relevant, although they are not commonly used in clinical practice. Concentration resulting immediately after an intravenous injection of a drug is referred to as C0. Plasma drug concentrations are affected by the rate at which drug is administered, the volume in which it distributes, and its clearance. Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It indicates the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time period. In Figure 2-4, the amount of drug (the number of dots) decreases but fills the same volume, resulting in a lower concentration. Another way of viewing the same decrease would be to calculate the volume that would be drug-free if the concentration were held constant. Drugs can be cleared from the body by many different mechanisms, pathways, or organs, including hepatic biotransformation and renal and biliary excretion. Total body clearance of a drug is the sum of all the clearances by various mechanisms. For an agent removed primarily by the kidneys, renal clearance (Clr) makes up most of the total body clearance. For a drug primarily metabolized by the liver, hepatic clearance (Clm) is most important. A good way to understand clearance is to consider a single well-perfused organ that eliminates drug. Blood flow through the organ is referred to as Q (mL/minute) as seen in Figure 2-6, where Cin is the drug concentration in the blood entering the organ and Cout is the drug concentration in the exiting blood. Organs that are very efficient at eliminating a drug will have an extraction ratio approaching one (i. The drug clearance of any organ is determined by blood flow and the extraction ratio: organ clearance = blood flow × extraction ratio or: 2-2 If an organ is very efficient in removing drug (i. The equations noted previously are not used routinely in clinical drug monitoring, but they describe the concept of drug clearance. Examination of a single well-perfused organ to understand clearance is a noncompartmental approach; no assumptions about the number of compartments have to be made. Clearance also can be related to the model-dependent parameters volume of distribution and elimination rate (discussed in Lesson 3). Clearance can also be a useful parameter for constructing dosage recommendations in clinical situations. Therefore, clearance is approximately equal to liver blood flow (Cl = Q × E: when E ~ 1. One indication of the high extraction ratio is the relatively high oral dose of propranolol compared with the intravenous dose; an oral dose is 10-20 times the equivalent intravenous dose. The difference reflects the amount of drug removed by first-pass metabolism after absorption from the gastrointestinal tract and before entry into the general circulation. These values can vary considerably between individuals and may be altered by disease. Clearance may be viewed as the volume of plasma from which drug is totally removed over a specified period. Distribution and equilibration to all tissues and fluids occurs instantaneously, so a one- compartment model applies. Most drugs are eliminated by a first-order process, and the concept of first-order elimination must be understood.