Dissolve the parabens and Lutrol F 127 in water water discount famciclovir 250 mg free shipping, cool to 5°–10°C buy famciclovir 250 mg on line, dissolve Lutrol F 127 generic famciclovir 250 mg mastercard, heated to about 80 C. Each gram contains neomycin sulfate equivalent to 400 bacitracin units, and white petrolatum, q. Nicotine Polymer Gel Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 66. Nitrofurazone Cream Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 0. In a separate vessel, heat two thirds of item 9 to 50°C and dissolve item 8 in it. Add and mix item 1 with item 5 (balance) and vessel after passing it through a stainless steel add to step 2. Formulations of Semisolid Drugs 215 Nystatin Ointment Bill of Materials Scale mg/g Item Material Name Quantity/kg (g) 21. Homogenize twice to make a smooth disper- temperature 45°C, mixer speed 10–12 rpm, and sion. Disperse item 4 in the clear solution of gramicidin–propylene glycol by Formulations of Semisolid Drugs 217 Nystatin, Neomycin Sulfate, Gramicidin, and Triamcinolone Acetonide Ointment Bill of Materials Scale (mg/g) Item Material Name Quantity/kg (g) 22. Mix until the temperature of the ointment (gap setting 1) to make smooth dispersion and reaches 28°–30°C. Octyl Methoxycinnamate, Octyl Salicylate, and Oxybenzone Gel The active ingredients in octyl methoxycinnamate, octyl glyceryl monostearate, propylene glycol, petrolatum, dia- salicylate, and oxybenzone gel are octyl methoxycin- zolidinyl urea, triethanolamine, disodium ethylene namate 7. Weighed quantity of emulsifying ointment is melted in another vessel, and propylparaben 1. The lumps (1 kg) are powdered in an edge der and methylparaben is also heated to the runner mill for 30 minutes. Weighed quantity of the powder is dispersed in banum powder is added to the molten emulsi- appropriate quantity of water, along with fying ointment, and the mixture is stirred methylparaben (0. Both formulations mg oxiconazole per gram of lotion in a white to off-white, are for topical dermatologic use only. Formulations of Semisolid Drugs 219 Oxytetracycline Ointment Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 3. Panthenol and Chlorhexidine Lotion Bill of Materials Scale (mg/mL) Item Material Name Quantity/1000 Tablets (g) 25. Place into kettle and heat to 70°C while stirring; transfer the melted fatty mass under vacuum 1. After the addition, evacuate again at 80°C with stirring to keep the fatty phase at to −0. Transfer the ointment in a mixer and mix for 5 by pouring and then rinsing it with hot deion- minutes with electric mixture. Each gram of cream contains 10 mg penciclovir puriﬁed water, and white petrolatum. Formulations of Semisolid Drugs 221 Peppermint Cream Bill of Materials Scale (mg/g) Item Material Name Quantity/kg (g) 25. Permethrin Cream and Lotion Permethrin cream 5% is a topical scabicidal agent for the polyoxyethylene cetyl ethers, puriﬁed water, and sodium treatment of infestation with Sarcoptes scabiei (scabies). Petrolatum and Lanolin Ointment Active ingredients in petrolatum and lanolin ointment are fragrance, light mineral oil, microcrystalline wax, and par- petrolatum 53. The suppositories 222 Handbook of Pharmaceutical Manufacturing Formulations: Semisolid Products Piroxicam Ointment Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 1. All items are blended uniformly together to pro- duce an ointment formulation having a pH of 7. Piroxicam and Dexpanthenol Gel Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 0. Dissolve piroxicam in propylene glycol, dexpan- glycol and dexpanthenol at 70–80°C. Stir the highly viscous mixture, add 50% of to about 5°C and mix with the piroxicam the hot water (70°C). Maintain the cool temperature until the air perature when the air bubbles escape, and bubbles escape. Formulations of Semisolid Drugs 223 Polymyxin, Bacitracin, Hydrocortisone, and Zinc Ointment Bill of Materials Scale (g/100 g) Item Material Name Quantity/kg (g) 18. Povidone-Iodine and Lidocain Gel Bill of Materials Scale (mg/g) Item Material Name Quantity/kg (g) 100. Dissolve items 1–3 in item 6, cool to about 6°C, dissolve item 4, and adjust the pH value (4. Prepare a basic cream from the emulsifying agents and the fatty substances, items 4–8. Povidone-Iodine Cream Bill of Materials Scale (mg/g) Item Material Name Quantity/kg (g) 100. Mix items 2–6 by heating, stir the solution in the previous mixture, and cool by stirring. Formulations of Semisolid Drugs 225 Povidone-Iodine Gel Bill of Materials Scale (mg/g) Item Material Name Quantity/kg (g) 100. Dissolve item 1 in a solution of items 2–4, mix with item 5, and dissolve item 6 at about 20°C. Povidone-Iodine Gel Bill of Materials Scale (mg/g) Item Material Name Quantity/kg (g) 100. Prepare solution of items 1–4, heat to about 60°C, incorporate item 6, stir very well, and cool to room temperature. Povidone-Iodine Glucose Ointment Bill of Materials Scale (mg/g) Item Material Name Quantity/kg (g) 20. Dissolve Lutrol E 4000 in the hot mixture of glycerol and water and add the glucose warmed to 60°–80°C. Formulations of Semisolid Drugs 227 Povidone-Iodine Vaginal Ovules Bill of Materials Scale (mg/ovule) Item Material Name Quantity/1000 Tablets (g) 100. Preheat a suitable jacketed stainless steel batch 166 mL of puriﬁed water and raise the temper- tank to 60°–65°C. Add the pramoxine hydro- the batch tank, maintaining temperature at chloride (item 8) and mix until dissolved. Rinse through 3) into a suitable jacketed stainless steel tank with 12 mL of puriﬁed water. Adjust the water rate to prevent air entrainment and commence temperature to 80°–90°C and add methylpara- cooling to 32°–36°C. Stir should maintain cooling water at 10°C below until dissolved, ensuring that no solids are batch temperature until 45°C, switching then to entrained in the bottom valve. The Formulations of Semisolid Drugs 229 Pramoxine Suppositories Bill of Materials Scale (mg/suppository) Item Material Name Quantity/1000 Suppositories (g) 1782. Slowly add the ted with a turno mixer/emulsiﬁer, premelt pramoxine and mix for 15 minutes. After melting, adjust the mixer/emulsiﬁer in mill into a jacketed stainless steel batching a batching tank containing the premelted tank ﬁtted with a suitable homogenizer. Homog- cool to 35°–36°C, always maintaining the enize the contents of the batch tank at high whole mass under agitation. Add the balance of the premelted Witepsol maintain the blending until the batch is ﬁlled. Pramoxine Suppositories Bill of Materials Scale (mg/suppository) Item Material Name Quantity/1000 Suppositories (g) 1781. Verify that witepsol W-32 from step 2 is com- pletely melted and is below 50°C, then add the This formula is less irritating and preferred. In a suitable stainless steel tank ﬁtted with an ® maintaining temperature below 50°C. Slowly add pramoxine hydrochloride to step 3 and with constant recirculation or mixing through- premix using homomixer or similar. Make certain that pramoxine hydrochloride is completely dispersed and the mixture is free of lumps.
Intravenous infusion Emergency control of atrial fbrillaton buy 250 mg famciclovir mastercard, over at least 2 h: 0 purchase famciclovir 250 mg with amex. Note: Infusion dose may need to be reduced if digoxin or other cardiac glycoside given in previous 2 weeks 250 mg famciclovir with amex. Contraindicatons Hypertrophic obstructve cardiomyopathy (unless also atrial fbrillaton and heart failure); ventricular tachycardia; hypokalaemia; digitalis toxicity; arrhythmias; Wolf-Parkinson-White syndrome or other accessory pathway, partcularly if accompanied by atrial fbrillaton; intermitent complete heart block; second- degree atrioventricular block. Precautons Recent myocardial infarcton; sick sinus syndrome; severe pulmonary disease; thyroid disease; congestve cardiac myopathy; hypercalcaemia; aortc valve disease, heart block, cardiac dysrrythmias; elderly (reduce dose); renal impairment (Appendix 7d); avoid hypokalaemia; avoid rapid intravenous administraton (nausea and risk of arrhythmias); lactaton; interactons (Appendix 6c, 6d); pregnancy (Appendix 7c). Dose Intravenous infusion Usually with a range of 50 to 200 µg/kg body weight/min under strict professional supervision of cardiologist. The Cardiovascular Society of Medicine has advised that beta-blockers, including those considered to be cardioselectve, should not be given to patents with a history of asthma or bronchospasm. However, in rare situatons where there is no alternatve a cardioselectve beta-blocker is given to these patents with extreme cauton and under specialist supervision. Adverse Efects Gastro-intestnal disturbances; bradycardia, heart failure, hypotension, conducton disorders, peripheral vasoconstricton (including exacerbaton of intermitent claudicaton and Raynaud’s phenomenon); bronchospasm, dyspnoea; headache, fatgue, sleep disturbances, paraesthesia, dizziness, vertgo, psychoses; sexual dysfuncton; purpura, thrombocytopenia; visual disturbances; exacerbaton of psoriasis, alopecia; rarely, rashes and dry eyes (reversible on withdrawal); on infusion venous irritaton and thrombophlebits; asthenia. Isoprenaline Pregnancy Category-C Schedule H Indicatons Severe bradycardia, unresponsive to atropine; short-term emergency treatment of heart block; ventricular arrhythmias secondary to atrio-ventricular nodal block. Dose Slow intravenous injecton 2 mg/ml injecton under strict professional supervision of cardiologist. Precautons Ischaemic heart disease, diabetes mellitus or hyperthyroidism; pregnancy (Appendix 7c). Adverse Efects Arrhythmias, hypotension, sweatng, tremor, headache, palpitatons, tachycardia, nervousness, excitability, insomnia. Note: Following intravenous injecton, lidocaine has a short duraton of acton (of 15 to 20 min). If it cannot be given by intravenous infusion immediately, the inital intravenous injecton of 50 to 100 mg can be repeated if necessary once or twice at intervals of not less than 10 min. Contraindicatons Sino-atrial disorder; any grade of atrioventricular block or any other type of conducton disturbances, severe myocardial depression, acute porphyria or hypovolaemia, bradycardia, cardiac decompensaton. Adverse Efects Dizziness; paraesthesia; drowsiness, confusion; apnoea, respiratory depression; coma; seizures and convulsions; hypotension, arrhythmias, heart block; cardiovascular collapse and bradycardia (may lead to cardiac arrest); nystagmus ofen an early sign of lidocaine overdosage; blurred vision, disorientaton. Dose Oral Inital dose; 400 to 600 mg, followed by 200 to 250 mg afer 2 h, 3 to 4 tmes a day. Contraindicatons Sinus node dysfuncton; hepatc dysfuncton; cardiogenic shock, myocardial infarcton. Precautons Hepatc; cardiac or renal failure; hypotension, bradycardia; interactons (Appendix 6d); pregnancy (Appendix 7c). Adverse Efects Dizziness; confusion; ataxia; bradycardia, hypotension, nausea; vomitng; constpaton; palpitatons; jaundice; hepatts; dysarthria. Procainamide * Pregnancy Category-C Schedule H Indicatons Severe ventricular arrhythmias, especially those resistant to lidocaine or those appearing afer myocardial infarcton; atrial tachycardia, atrial fbrillaton; maintenance of sinus rhythm afer cardioversion of atrial fbrillaton. Dose Oral Adult- Ventricular arrhythmias: up to 50 mg/kg daily in divided doses every 3 to 6 h, preferably controlled by monitoring plasma- procainamide concentraton (therapeutc concentraton usually within range of 3 to 10 µg/ml). Contraindicatons Asymptomatc ventricular premature contractons; torsades de pointes; systemic lupus erythematosus; heart block, heart failure, hypotension; lactaton; children; myasthenia gravis. Adverse Efects Nausea, vomitng, diarrhoea, anorexia, rashes, pruritus, urtcaria, fushing, fever, myocardial depression, heart failure, angioedema, depression, dizziness, psychosis; blood disorders include leukopenia, haemolytc anaemia and agranulocytosis afer prolonged treatment; lupus erythematosus-like syndrome; high plasma procainamide concentraton may impair cardiac conducton; hypotension, heart block; hallucinatons. Quinidine Pregnancy Category-C Schedule H Indicatons Suppression of supraventricular arrhythmias and ventricular arrhythmias; maintenance of sinus rhythm afer cardioversion of atrial fbrillaton. Precautons Partal heart block, extreme care in uncompensated heart failure, myocardits, severe myocardial damage; myasthenia gravis; acute infectons or fever (symptoms may mask hypersensitvity reacton to quinidine); lactaton (Appendix 7b); pregnancy (Appendix 7c). Adverse Efects Hypersensitvity reactons, nausea, vomitng, diarrhoea, rashes, anaphylaxis, purpura, pruritus, urtcaria, fever, thrombocytopenia, agranulocytosis afer prolonged treatment, psychosis, angioedema, hepatotoxicity, respiratory difcultes; cardiac efects include myocardial depression, heart failure, ventricular arrhythmias and hypotension; cinchonism including tnnitus, impaired hearing, vertgo, headache, visual disturbances, abdominal pain and confusion; lupus erythematosus-like syndrome. Hypertension was formerly classifed as mild, moderate or severe, but a grading system is now preferred. Grade 1 hypertension is defned as 140-159 mmHg systolic blood pressure and 90-99 mmHg diastolic blood pressure, Grade 2 hypertension 160-179 mmHg systolic and 100-109 mmHg diastolic and Grade 3 hypertension more than 180 mmHg systolic and more than 110 mmHg diastolic. Lifestyle changes should be introduced for all patents; they include weight reducton, reducton in alcohol intake, reduc- ton of dietary Sodium, stopping tobacco smoking and reduc- ton in saturated fat intake. The patent should eat a healthy nutritous diet including adequate fruit and vegetables and should exercise regularly. These measures alone may be suf- cient in mild hypertension, but patents with moderate to severe hypertension will also require specifc anthypertensive therapy. Thiazide diuretcs, such as hydrochlorothiazide, have been used as frst-line anthypertensive therapy and are partcularly indicated in the elderly. They have few adverse efects in low doses, but in large doses they may cause a variety of unwanted metabolic efects (principally potassium depleton), reduced glucose tolerance, ventricular ectopic beats and impotence; they should be avoided in gout. These efects can be reduced by keeping the dose as low as possible; higher doses do not produce an increased reducton in blood pressure. Thiazides are inexpensive and, when used in combinaton, can enhance the efectveness of many other classes of anthypertensive drugs. They can be used in heart failure, lef ventricular dysfuncton and diabetc nephropathy, but should be avoided in renovascular disease and in pregnancy. Dihydropyridine calcium-channel blockers such as nifedipine are useful for isolated systolic hypertension, in populatons unresponsive to other anthypertensives (e. Short-actng formu- latons of nifedipine should be avoided as they may evoke refex tachycardia and cause large variatons in blood pressure. In partcular, methyldopa is efectve in the treatment of hypertension in pregnancy. A single anthypertensive drug is ofen not adequate and other anthypertensive drugs are usually added in a stepwise manner untl blood pressure is controlled. Hypertensive Emergencies In situatons where immediate reducton of blood pressure is essental and treatment by mouth is not possible, intravenous infusion of Sodium nitroprusside is efectve. Over-rapid reduc- ton in blood pressure is hazardous and can lead to reduced organ perfusion and cerebral infarcton. Hypertension in Pregnancy This is defned as a sustained diastolic blood pressure of 90 mmHg or more. If diastolic blood pressure is greater than 95 mmHg, methyldopa is the safest drug. Beta- blockers should be used with cauton in early pregnancy, since they may retard fetal growth; they are efectve and safe in the third trimester. Women who are taking these drugs and become pregnant should have their anthyperten- sive therapy changed immediately. Pre-eclampsia and eclampsia: If pre-eclampsia or severe hyper- tension occurs beyond the 36th week of pregnancy, delivery is the treatment of choice. For acute severe hypertension in pre- eclampsia or eclampsia, intravenous hydralazine can be used. Magnesium sulphate is the treatment of choice to prevent eclamptc convulsions in eclampsia and severe pre-eclampsia. Contraindicatons Signifcant aortc stenosis, sinoatrial node disease, hypersensitvity to dihydropyridines, cardiogenic shock, unstable angina; interactons (Appendix 6d). Precautons Hypotension, myocardial infarcton, impaired renal functon sick-sinus syndrome, severe ventricular dysfuncton, hypertrophic cardiomyopathy, severe aortc stenosis, eld- erly, children, pregnancy (Appendix 7c); lac- taton; hepatc impairment (Appendix 7a). Adverse efects Arrhythmias, postural hypotension; dizziness, ankle edema, hypoesthesia, fatulence, dizziness, blurred vision, facial fushing, dyspnoea, asthenia, muscle cramps, conducton system delay, abdominal pain, headache; sleep disturbances, fatgue. Dose Oral Adult-75 to 225 µg/day in two divided doses, increase gradually every two weeks. Precautons Depressive illness; concurrent anthypertensive therapy, cerebrovascular disease; porphyria; interactons (Appendix 6a, 6c); pregnancy (Appendix 7c). Adverse Efects Dry mouth; sedaton; dizziness; nausea; nocturnal restlessness; occasionally rashes; cardiac arrhythmias; systemic lupus erythmatosus; anxiety; constpaton; abdominal pain; hallucinaton; impotence and depression. Enalapril* Pregnancy Category-D Schedule H Indicatons Heart failure (with a diuretc); preventon of symptomatc heart failure and preventon of coronary ischaemic events in patents with lef ventricular dysfuncton; hypertension; renal hypertension. Dose Oral Adult- Hypertension: initally 5 mg once daily; if used in additon to diuretc.
Verapamil administration may worsen myasthenia gravis and may decrease neuromuscular transmission in patients with Duch- enne’s muscular dystrophy generic 250 mg famciclovir amex. Verapamil may increase serum concentrations of digoxin buy famciclovir 250 mg on-line, quinidine cyclosporine famciclovir 250mg free shipping, and carbamazepine. Confusion, stu- por, nausea, vomiting, metabolic acidosis, and hyperglycemia may also be observed. Continu- ous infusion, initiate infusion of 10mg/h and increase by 5mg/h to 15 mg/h. When increasing the infusion dose, administer for less than 24 hours at a rate of less than 15 mg/h Conversion from I. Contraindications Severe hypotension, second- or third-degree heart block or sinus node dys- function, and acute myocardial infarction with pulmonary congestion are con- traindications for diltiazem use. Dubin Precautions/Warnings Use of diltiazem with β-blockers or digoxin can result in conduction abnor- malities. Drug-Drug Interactions Cimetidine use may increase diltiazem serum concentrations. The risk of bradycardia or heart block is increased with β-blocker or digoxin use. Diltiazem may decrease metabolism of cyclosporine, carbamazepine, digoxin, lovastatin, midazolam, and quinidine. Noncardiac symptoms include confusion, stupor, nausea, vomiting, metabolic acidosis, and hyperglycemia. Compatible Diluents/Administration The final concentration for infusion of diltiazem should be 1 mg/mL. Antiarrhythmic Medications 183 Mechanism of Action Adenosine is an endogenous purinergic agent. Contraindications Second- or third-degree heart block or sinus node dysfunction, unless a pace- maker is in place, are contraindications for adenosine use. The initial dose of adenosine should be decreased in patients receiving dipyridamole. Atropine has a half-life in children younger than 2 years of 7 hours; in children older than 2 years, of 2. Precautions/Warnings Psychosis can occur with atropine use in sensitive individuals. Drug-Drug Interactions Atropine has additive effects when administered with other anticholinergic drugs. Dubin Mechanism of Action Magnesium sulfate suppresses early after-depolarizations that can trigger tor- sade de pointes. Contraindications Heart block, serious renal impairment, and coma are contraindications for magnesium sulfate use. Precautions/Warnings Use magnesium sulfate with caution in patients with renal dysfunction and those receiving digoxin. Compatible Diluents/Administration Magnesium sulfate is incompatible when mixed with fat emulsions, calcium gluceptate, clindamycin, dobutamine, hydrocortisone, polymyxin B, procaine hydrochloride, nafcillin, tetracyclines, and thiopental. Effect of acetyla- tor phenotype on the rate at which procainamide induces antinuclear antibodies and the lupus syndrome. Mexiletine: an effective antiarrhythmic drug for treatment of ventricular arrhythmias in congenital heart disease. Control of late post- operative ventricular arrhythmias with phenytoin in young patients. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. Proarrhythmia, cardiac arrest and death in young patients receiving encainide and flecainide. Usefulness of propafenone for supraven- tricular arrhythmias in infants and children. Intravenous esmolol for the treatment of supraventricular tachyarrhythmia: results of a multicenter, baseline-controlled safety and efficacy study in 160 patients. Double-blind titrated-dose comparison of metoprolol and pro- pranolol in the treatment of angina pectoris. Efficacy and safety of intravenous and oral nadolol for supraventricular tachycardia in children. Intravenous amiodarone for life-threatening tachyarrhythmias in children and young adults. Amiodarone in the treatment of cardiac arrhythmias in children: one hundred thirty-five cases. Pediatric use of intravenous amiodarone: efficacy and safety in critically ill patients from a multicenter protocol. Bretylium tosylate: a newly available antiarrhythmic drug for ventricular arrhythmias. Cardiac decompensation following verapamil ther- apy in infants with supraventricular tachycardia. Acute conversion of paroxysmal supraventricular tachycardia with intravenous diltiazem. The addition of these agents reduces early acute rejection events and may improve long-term graft and patient outcomes. The most controversial issue is whether corticos- teroids should be routinely added to form a “triple therapy. Finally, there is no agreement on whether intravenous anti- body induction therapy should be routinely used. A summary of the options for induction and maintenance therapy is shown in Table 8-1. It should be noted that there have been no large-scale randomized controlled tri- als of any immunosuppressive therapy in pediatric thoracic transplantation. Corticosteroids (Methylprednisolone and Prednisone) Indication Corticosteroids have broad immunosuppressive and anti-inflammatory effects. Many pediatric heart transplant centers are using steroid-avoidance regimens or early steroid withdrawal to avoid the many side effects and complications associated with long-term steroid use in children. High-dose steroids remain the standard therapy for treatment of acute rejection episodes. Mechanism of Action Corticosteroids decrease inflammation through the suppression of the migration of polymorphonuclear leukocytes and the reversal of increased 8. Corticosteroids prevent immune activation by inhibiting antigen presentation, cytokine production, and proliferation of lymphocytes. Some centers use moderate-dose oral steroids for less severe episodes of acute rejection (e. Maintenance Therapy Those centers that use long-term maintenance therapy typically use prednisone in doses of 0. Webber prednisone indefinitely, whereas others wean to discontinuation in the first few months if the rejection history is benign. Increasing evidence suggests that complete steroid avoidance beyond the intraoperative period is possible in many children, especially infants. Pharmacokinetics The peak and duration are dependent on the route of administration of the drug. Oral: peak effect occurs within 1 to 2 hours, and the duration is 30 to 36 hours Intramuscular: peak effect is 4 to 8 days, and the duration is 1 to 4 weeks Corticosteroids are metabolized in the liver to inactive glucuronide and sulfate metabolites. Monitoring Parameters Blood pressure, weight, height, serum electrolytes, and glucose should be monitored. Phenytoin, phenobarbital, and rifampin increase clearance of methylpred- nisolone; potassium-depleting diuretics (furosemide) enhance potassium depletion. Permanent diabetes mellitus may be precipitated when corticosteroids are used in combination with cyclosporine or tacrolimus. Cyclosporine was the most commonly used agent 5 years ago, but, currently, almost half of pediatric heart transplant recipients are receiving tacrolimus. Cyclosporine and tacrolimus have not been compared in large randomized tri- als in children after transplantation of thoracic organs. One small (26 children), single-center randomized trial in pediatric heart transplantation has been per- formed but was not powered to identify differences between immunosuppres- sive regimens. In the presence of intracellular calcium and calmodulin, the cyclosporine-cyclo- philin complex binds to an active site on calcineurin. Webber Dosing The oral dosage for cyclosporine is approximately three times the I. The bioavailability of Sandimmune® capsules and the oral solution are equivalent, and the bioavailability of the oral solution is approximately 30% of the I.
This may minimize the development of dry mouth buy 250mg famciclovir with visa, hoarseness cheap famciclovir 250 mg mastercard, and oral fungal infection buy cheap famciclovir 250 mg on-line. Adverse reactions • Common: nasal irritation, cough, pharyngitis, sneezing attacks. Parameters to monitor • Signs and symptoms of acute adrenal insufficiency, particu- larly in response to stress. If these occur, the dose of systemic steroid should be increased followed by slower withdrawal. However, there is considerable controversy with respect to the beneficial use of higher than recommended inhalation doses of these drugs. Adjustment of dosage • Kidney disease: Creatinine clearance <30 mL/min: initial dose 5 mg/d. Warnings/precautions • Use with caution in patients with the following conditions: kidney disease, especially renal artery stenosis, drugs that cause bone marrow depression, hypovolemia, hyponatremia, cardiac or cerebral insufficiency, collagen vascular disease, lupus ery- thematosus, scleroderma, patients undergoing dialysis. Clinically important drug interactions • Drugs that increase effects/toxicity of benazepril: potassium- sparing drugs, other diuretics, guanethidine. Nearly every large randomized clinical trial examining their use has been favorable. Treatment with this class of drugs is the gold standard in patients with left ventricular systolic dys- function. As drugs in this class are vasodilators, orthostasis is another potential problem. Mechanism of action: Inhibits sodium resorption in distal tubule, resulting in increased urinary excretion of sodium, potasssium, and water. Onset of Action Peak Effect Duration 1–2 h 4 h 6–24 h Food: Should be taken with food. Hydrochlorothiazide (another thi- azide diuretic) is considered compatible with breastfeeding by the American Academy of Pediatrics. Editorial comments • Do not coadminister with allopurinol as the combination may lead to severe hypersensitivity vasculitis. Mechanism of action: Blocks acetylcholine effects at muscarinic receptors throughout the body. Adverse reactions • Common: dry mouth, blurred vision (decreased accommoda- tion), drowsiness, tachycardia, urinary hesitancy, dry skin, con- stipation. Parameters to monitor • Signs and symptoms of severe toxicity: tachycardia, supraven- tricular arrythmias, delirium, seizures, agitation, hyperthermia. Mechanism of action: Inhibits migration of polymorphonuclear leukocytes; stabilizes lysomal membranes; inhibits production of products of arachidonic acid cascade. These should be individualized according to the disease being treated and the response of the patient. Contraindications: Systemic use: fungal, viral, or bacterial infec- tions, Cushing’s syndrome. Topical use: hypersensitivity to cor- ticosteroids, markedly impaired circulation, occlusive dressing if primary skin infection is present, monotherapy in primary bac- terial infections, eg, impetigo, cellulitis, rosacea, ophthalmic use, plaque psoriasis (widespread). Warnings/precautions • Use with caution in patients with the following conditions: diabetes mellitus, cardiovascular disease, hypertension, throm- bophlebitis, renal or hepatic insufficiency. Topical agent: Use with caution in patients with primary skin infections and those receiving other immunosuppressant drugs. When every-other-day therapy is initiated, twice the daily dose should be administered on alternate days in the morning. Adverse reactions • Common: dyspepsia, appetite stimulation, insomnia, anxiety, fluid retension, cushinoid facies. Children: Growth suppression, pseudotumor cerebri (reversible papilledema, visual loss, nerve paralysis [abducens or oculomotor]), vascular bone necrosis, pan- creatitis. Editorial comments: Corticoid treatment remains challeng- ing for clinicians due to commonly occurring short-term and long-term side effects. The agents produce accelerated bone resorption as well as decreased bone formation, result- ing in overall bone loss with chronic use. Ongoing monitor- ing is suggested and treatment with bisphosphonates or calcitonin is suggested when decreased bone mineral density occurs. Mechanism of action: Competitive blocker of β-adrenergic receptors in heart, blood vessels, and eyes. If necessary to dis- continue, taper as follows: Reduce dose and reassess after 1–2 weeks. Advice to patient • Avoid driving and other activities requiring mental alertness or that are potentially dangerous until response to drug is known. Clinically important drug interactions • Drugs that increase effects/toxicity of β blockers: reserpine, bretylium, calcium channel blockers. If hypotension occurs despite correction of bradycardia, administer vasopressor (norephinephrine, dopamine, or dobuta- mine). Stop therapy and administer large doses of β-adrenergic bronchodilator, eg, albuterol, terbutaline, or amino- phylline. Some advocate discontinuing the drug 48 hours before surgery; others recommend withdrawal for a considerably longer time. These are drugs of first choice for chronic stable angina, used in conjunction with nitroglycerin. Warnings/precautions • Use with caution in patients with the following conditions: epilepsy, hyperthyroidism. Advice to patient: Change position slowly, in particular from recumbent to upright, to minimize orthostatic hypotension. Sit at the edge of the bed for several minutes before standing and lie down if feeling faint or dizzy. Male patients with orthostatic hypoten- sion may be safer urinating while seated on the toilet rather than standing. Parameters to monitor • Intake of fluids and urinary and other fluid output to minimize renal toxicity. Effectiveness of treatment is indicated by reduction in abdominal distention and decreased bowel activity. Editorial comments: Because of the potential for life-threatening complications from this drug, the editors recommend adminis- tration only by experienced practitioners. Mechanism of action: Relaxes smooth muscles of the bronchi- oles by stimulating β2-adrenergic receptors. Contraindications: Hypersensitivity to adrenergic compounds, tachycardia (idiopathic or from digitalis). Editorial comments • This agent appears to cause tremor and palpitations more fre- quently than isoproterenol. Adjustment of dosage • Kidney disease: creatinine clearance 10–50 mL/min: reduce dose by 25%; creatinine clearance <10 mL/min: reduce dose by 50%. Warnings/precautions • Use caution in patients with kidney impairment, compromised pulmonary function. Advice to patient • Use two forms of birth control including hormonal and barrier methods. Adverse reactions • Common: Raynaud’s phenomenon, febrile allergic reactions, nausea, vomiting, anorexia, stomatitis, thickening bronchial secretions, alopecia, dermatologic changes (erythema, peeling, hyperkeratosis, induration in 50% of patients). Severe idiosyncratic reaction: mental confusion, fever, hypotension, particularly in lymphoma patients. Clinically important drug interactions • Drugs that increase effects/toxicity of bleomycin: cisplatin. Treat with peroxide, tea, top- ical anesthetics such as benzocaine, lidocaine, or antifungal drug. Editorial comment • Use latex gloves and safety glasses when handling this med- ication; avoid contact with skin as well as inhalation. Corticosteroids are sometimes helpful in treating this problem, but it may also be fatal. Mechanism of action: Depletes adrenergic nerve terminals of norepinephrine; this decreases adrenergic stimulation of the myocardium. Adjustment of dosage • Kidney disease: creatinine clearance 10–60 mL/min; reduce dose by 50–75%; creatinine clearance<10 mL/min: reduce dose by 75%. For treatment of ventricular fibrillation or life-threatening refractory ventricular arrhythmias, there is no con- traindication to using bretylium. Warnings/precautions • Use with caution in patients with the following conditions: hypotension, pulmonary hypertension, aortic stenosis.
An drugs methoxypenicillin buy famciclovir 250mg low price, and compliance (pass/fail) with aqueous formulation of injectable tetracycline assay standards of the British procaine benzylpenicillin showed Pharmacopoeia purchase famciclovir 250 mg online. Drug stability moderate instability with 4% was measured by comparing (1% to 6%) loss after 4 trusted 250mg famciclovir. However, four (31%) were (rifampicin and pyrazinamide) substandard, including two (15%) content of active ingredient with low rifampicin content, one (8%) with excessive rifampicin and one (8%) with excessive pyrazinamide. The found to be bioequivalent to the implications for tuberculosis reference administered as loose programs are extremely serious (separate) formulations. Drug quality was Poor initial quality accounted for Reduced level of active Not reported Hogerzeil of 26 benzylpenicillin, measured by level of active problems in injectable ampicillin ingredient (1998) brands of amoxicillin, ampicillin, ingredient as percentage (2/10 central samples failed, 13 essential doxycycline, phenyl- of stated content and by with 87% and 91% content). An drugs methoxypenicillin, and compliance (pass/fail) with aqueous formulation of injectable tetracycline assay standards of the British procaine benzylpenicillin showed Pharmacopoeia. Drug stability moderate instability with 4% was measured by comparing (1% to 6%) loss after 4. Ten brands deliberately kept below the of ampicillin were found to be required levels. This was also true of the two brands of co-trimoxazole suspension found to be substandard. Ten other Decomposition is not likely samples outside the British to be a major factor (no large Pharmacopoeia’s range had at amounts of decomposition least 90% or up to 126%. The bioavailability tetracycline content the pharmacopoeia prescribed of substandard product as standards. The power content determined from 48 h urinary of four brands was well below tetracycline excretion was the labeled amount of the signifcantly lower when standard drug. Comparative compared with standard analysis of bioavailability of product both in well-nourished substandard versus standard and in undernourished product indicates that the use subjects. Kelesidis and colleagues use the term counterfeit broadly, the way this report uses the term falsifed. Ten brands deliberately kept below the of ampicillin were found to be required levels. This was also true of the two brands of co-trimoxazole suspension found to be substandard. Ten other Decomposition is not likely samples outside the British to be a major factor (no large Pharmacopoeia’s range had at amounts of decomposition least 90% or up to 126%. The bioavailability tetracycline content the pharmacopoeia prescribed of substandard product as standards. The power content determined from 48 h urinary of four brands was well below tetracycline excretion was the labeled amount of the signifcantly lower when standard drug. Comparative compared with standard analysis of bioavailability of product both in well-nourished substandard versus standard and in undernourished product indicates that the use subjects. Cameroon 2001 Chloroquine, Colorimetric Private Convenience 284 112/284 (39%) Not tested 49/284 (18%) (2004) quinine, test, thin layer pharmacies sampling sulfadoxine- chromatography only from various pyrimethamine vendors Amin et al. Cameroon 2001 Chloroquine, Colorimetric Private Convenience 284 112/284 (39%) Not tested 49/284 (18%) (2004) quinine, test, thin layer pharmacies sampling sulfadoxine- chromatography only from various pyrimethamine vendors Amin et al. Burkina Faso 2006 Artesunate, Packaging Private Convenience 77 32/77 (42%); 28/77 (38%) 29/77 (38%) (2008) artemether analysis, and public 1/32 (3%)† lumefantrine, disintegration pharmacies or quinine, analysis, outlets chloroquine, colorimetric sulfadoxine- tests, thin layer pyrimethamine, chromatography, amodiaquine ultraviolet-visible spectroscopy U. Burkina Faso 2006 Artesunate, Packaging Private Convenience 77 32/77 (42%); 28/77 (38%) 29/77 (38%) (2008) artemether analysis, and public 1/32 (3%)† lumefantrine, disintegration pharmacies or quinine, analysis, outlets chloroquine, colorimetric sulfadoxine- tests, thin layer pyrimethamine, chromatography, amodiaquine ultraviolet-visible spectroscopy U. Congo choroquine, Pharmacopeia private 1/16 (6%)† (2007) sulfadoxine- standards, pharmacies pyrimethamine, uniformity of mass, and outlets mefoquine disintegration analysis Aina et al. Congo choroquine, Pharmacopeia private 1/16 (6%)† (2007) sulfadoxine- standards, pharmacies pyrimethamine, uniformity of mass, and outlets mefoquine disintegration analysis Aina et al. Congo, Ghana, dihydroartemisinin- pollen analysis, private Kenya, Nigeria, piperaquine X-ray difraction, and public Rwanda, Senegal artemether- packaging analysis pharmacies lumefantrine, artemether- amodiaquine, amodiaquine, halofantrine ‡ 115 samples from Laos were randomly selected. The quality of sulphadoxine- pyrimethamine and amodiaquine products in the Kenyan retail sector. Anti-infective medicine quality: Analysis of basic product quality by approval status and country of manufacture. Medicine registration and medicine quality: A pre- liminary analysis of key cities in emerging markets. The global threat of counterfeit drugs: Why industry and governments must communicate the dan- gers. Quality of anti-malarials collected in the private and informal sectors in Guyana and Suriname. Interpol launches global campaign against fake medicines with powerful Af- rican voices. Ensuring safe foods and medical products through stronger regulatory systems abroad. A nationwide survey of the quality of antimalarials in retail outlets in Tanzania. Counterfeit or substandard antimicrobial drugs: A review of the scientifc evidence. Transactions of the Royal Society of Tropical Medicine and Hygiene 100(11):1019-1024. Quality of anti-malarial drugs provided by public and private healthcare providers in south-east Nigeria. Presentation to the committee on understanding the global public health implications of substandard, falsifed, and counterfeit medical products: Meeting 1, March 13. Poor-quality medi- cal products: Time to address substandards, not only counterfeits. The need for better data about counterfeit drugs in developing countries: A proposed standard research methodology tested in Chennai, India. Uterotonic drug quality: An assessment of the potency of injectable uterotonic drugs purchased by simulated clients in three districts in Ghana. Survey of the quality of selected antimalarial medicines circulating in six countries of sub-Saharan Africa. New global mechanism to combat substandard/spurious/falsely-labelled/ falsifed/counterfeit medical products. Counterfeit and substandard drugs in Myanmar and Viet Nam: Report of a study carried out in cooperation with the governments of Myanmar and Viet Nam. Countering the Problem of Falsified and Substandard Drugs 4 Causes of Falsifed and Substandard Drugs The committee recognizes that the factors that encourage the prolifera- tion of substandard and falsifed medicines are different but overlapping. In general, neglect of good manufacturing practices, both accidental and deliberate, drives the circulation of substandard drugs, while falsifcation of medicines has its roots in crime and corruption. Both types of products circulate because of the erratic supply and constant demand for medicines and weaknesses in the regulatory system. An inaccurate or inadequate understanding of the problem among health workers and the public con- tributes to the problem. Substandard medicines may, for example, be made in such a way that they do not dissolve properly; they may be of incorrect hardness or osmolarity; they may contain im- proper doses of the active ingredients; or be made from impure or unstable ingredients. Uneven Manufacturing Quality Any company can make mistakes, but adherence to good manufactur- ing practices makes mistakes less likely and easier to correct. There are many exemplary manufacturers in de- veloping countries that observe international best practices. There are also many that do not, but they operate anyway, either because the regulatory authority is unaware of the problem, or because regulators are under pres- sure to ignore it in the name of promoting industry. Quality control is a part of good manufacturing practices sometimes neglected in developing countries. The majority of the pharmaceutical industry in the poorest countries only formulates and re- Copyright © National Academy of Sciences. Confrming the quality control measures used by suppliers, who are often in other countries, is particularly diffcult for these frms. Formulation companies have about a 6-month lag between placing an order for an active ingredient and selling a fnished drug (Bumpas and Betsch, 2009). This delay can be even longer for frms in landlocked countries or places where customs clearance and transportation from the port of entry are slow or unpredictable (McCabe, 2009).
By V. Yugul. California State University, Fresno.
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