By P. Kamak. Saybrook Graduate School and Research Center.

Precautons Adrenal suppression during prolonged treatment which persists for years afer stopping treatment (see notes above); ensure patents understand importance of compliance with dosage and have guidance on precautons to reduce risks; monitor weight order 50 mg kamagra overnight delivery erectile dysfunction doctor in philadelphia, blood pressure buy kamagra 50mg overnight delivery erectile dysfunction causes prescription drugs, fuid and electrolyte balance and blood glucose levels throughout prolonged treatment; infectons (greater susceptbility cheap 100mg kamagra overnight delivery erectile dysfunction from smoking, symptoms may be masked untl advanced stage); clinical presentaton may be atypical; risk of chickenpox and measles increased (see notes above); quiescent tuberculosis- chemoprophylactc therapy during prolonged cortcosteroid treatment; elderly; children and adolescents (growth retardaton possibly irreversible); hypertension buy kamagra 100mg with mastercard erectile dysfunction vitamin shoppe, recent myocardial infarcton (rupture reported), congestve heart failure, liver failure, renal impairment, diabetes mellitus including family history, osteoporosis (may be manifested as back pain, postmenopausal women at special risk), glaucoma including family history, epilepsy, psoriasis, peptc ulcer, hypothyroidism, history of steroid myopathy; lactaton (Appendix 7b); interactons (Appendix 6c); pregnancy (Appendix 7c). Dose Oral Adult-20 to 30 mg daily in divided doses (usually 20 mg in the morning and 10 mg in early evening). Slow intravenous injecton or intravenous infusion Adult- Acute adrenocortcal insufciency: 100 to 500 mg, 3 to 4 tmes in 24 h or as required. Contraindicatons See notes above; systemic infecton (unless life-threatening or specifc antmicrobial therapy given); avoid live virus vaccines in those receiving immunosuppressive doses (serum antbody response diminished); ulcers. Precautons Refer cortcosteroids; lactaton (Appendix 7b); interactons (Appendix 6b, 6c, 6d); pregnancy (Appendix 7c). Methyl Prednisolone* Pregnancy Category-C Schedule H Indicatons Cortcosteroid responsive conditons such as severe allergic rhinits, asthma, rheumatoid arthrits, osteoarthrits, collagen disease, dermatoses. Dose should be regulated in accordance with severity of conditon; large joints- 20 to 80 mg; medium joints- 10 to 40 mg; small joints- 4 to 10 mg directly in bursae. Contraindicatons Systemic fungal infecton (unless specifc antmicrobial therapy given); avoid live virus vaccines in those receiving immunosuppressive doses (serum antbody response diminished); hypersensitvity. Precautons Refer notes above; interactons (Appendix 6c, 6d); pregnancy (Appendix 7c). Dose Oral Adult- Suppression of infammatory and allergic disorders: initally up to 10 to 20 mg daily (severe disease, up to 60 mg daily), preferably taken in the morning afer breakfast; dose can ofen be reduced within a few days, but may need to be contnued for several weeks or months. Myasthenia gravis: initally 10 mg on alternate days, increased in steps of 10 mg on alternate days to 1-1. Child- Fractons of adult dose may be used (At 1 year: 25% of adult dose; at 7 years: 50%; and at 12 years: 75%) but clinical factors must be given due weight. Contraindicatons See notes above; systemic infecton (unless life-threatening or specifc antmicrobial therapy given); avoid live virus vaccines in those receiving immunosuppressive doses (serum antbody response diminished). Precautons Refer notes above; hepatc impairment (Appendix 7a); lactaton (Appendix 7b); interactons (Appendix 6c, 6d); pregnancy (Appendix 7c). In the male, they are respon- sible for the development and maintenance of the sex organs and the secondary sexual characteristcs, normal reproduc- tve functon, and sexual performance ability in additon to stmulatng the growth and development of the skeleton and skeletal muscle during puberty. At high doses in the normal male androgens inhibit pituitary gonadotrophin secreton and depress spermatogenesis. Testosterone is used as replacement therapy in those who are hypogonadal due to either pitui- tary (secondary hypogonadism) or testcular disease (primary hypogonadism). Androgens are useless as a treatment of impo- tence and impaired spermatogenesis unless there is associated hypogonadism; they should not be given untl the hypogo- nadism has been properly investgated and treatment should always be under expert supervision. When given to patents with hypopituitarism they can lead to normal sexual develop- ment and potency but not fertlity. If fertlity is desired, the usual treatment is with gonadotrophins or pulsatle gonado- trophin-releasing hormone which will stmulate spermatogen- esis as well as androgen producton. Cauton should be used in treatng boys with delayed puberty with excessive doses of testosterone since the fusion of epiphyses is hastened and may result in short stature. Androgens, including testosterone have also been used in postmenopausal women for the pallia- tve treatment of androgen-responsive, advanced, metastatc breast cancer; care is required to prevent masculinizing efects. Danazol* Pregnancy Category-X Schedule H Indicatons Endometriosis, fbrocystc mastts,hereditary angioedema, menorrhagia, gynaecomasta, precocious puberty. Contraindicatons Hepatc dysfuncton; undiagnosed vaginal bleeding; porphyria; thromboembolic complicaton; hypersensitvity; pregnancy (Appendix 7c), lactaton. Precautons Use with cauton in patents with migraine, headache, heart, liver or kidney disease. History of seizures; abnormal bleeding; previous strokes; severe hypertension; diabetes mellitus, polycythaemia; interactons (Appendix 6c). Adverse efects Androgen like efects including weight gain, acne, deepening of voice; seborrhoea; edema; hair loss; amenorrhoea; hirsutsm; benign intracranial hypertension; dizziness. Testosterone* Pregnancy Category-X Schedule H Indicatons Hypogonadism; palliatve treatment of advanced breast cancer in women. Dose Slow intramuscular injecton Adult- Hypogonadism: initally 200 to 250 mg every 2 to 3 weeks; maintenance dose 200 to 250 mg every 3 to 6 weeks. Contraindicatons Breast cancer in men; prostate cancer; hypercalcaemia; pregnancy (Appendix 7c), lactaton (Appendix 7b); nephrosis; history of primary liver tumours. Precautons Cardiac, renal or hepatc impairment (Appendix 7a), elderly; ischaemic heart disease; hypertension, epilepsy; migraine; diabetes mellitus; skeletal metastases (risk of hypercalcaemia); regular examinaton of prostate during treatment; prepubertal boys; breathing disturbance. Dose 50 mg about 1 hour before sexual intercourse, maximum 100 mg per dose and not more than once in 24 hours. Precautons Liver or kidney disease; peptc ulcer; bleeding disorder; leukemia, sickle cell anaemia, myloma predisposing priapism; recent history of stroke, myocardial infarcton, arrthymias, unstable angina; anatomical deformaton of penis; interactons (Appendix 6c); pregnancy (Appendix 7c). Type-1 diabetes or insulin-dependent diabetes mellitus is due to a defciency of insulin caused by autoimmune destructon of pancreatc β-cells. Type-2 diabetes or non-insulin dependent diabetes mellitus is due to reduced secreton of insulin or to peripheral resistance to the acton of insulin. Patents may be controlled by diet alone, but ofen require administraton of oral antdiabetc drugs or insulin. The energy and carbohydrate intake must be adequate but obesity should be avoided. In type 2 diabetes, obesity is one of the factors associated with insulin resistance. The aim of treatment is to achieve the best possible control of plasma glucose concentraton and prevent or minimize compli- catons including microvascular complicatons (retnopathy, albuminuria, neuropathy). Diabetes mellitus is a strong risk factor for cardiovascular disease; other risk factors such as smoking, hypertension, obesity and hyperlipidaemia should also be addressed. Insulin requirements may be afected by variatons in lifestyle (diet and exercise)-drugs such as cortcosteroids, infectons, stress, accidental or surgical trauma, puberty and pregnancy (second and third trimesters) may increase insulin requirements; renal or hepatc impairment and some endocrine disorders (for example Addison’s disease, hypopituitarism) or coelic disease may reduce requirements. If possible patents should monitor their own blood-glucose concentraton using blood glucose strips. Since blood-glucose concentraton varies throughout the day, patents should aim to maintain blood-glucose concentraton between 4 and 9 mmol/litre (4-7 mmol/L before meals, <9 mmol/L) for most of the day while acceptng that on occasions it will be higher; strenuous eforts should be made to prevent blood-glucose concentratons falling below 4 mmol/litre because of the risk of hypoglycaemia. Patents should be advised to look for troughs and peaks of blood glucose and to adjust their insulin dosage only once or twice a week. In the absence of blood-glucose monitoring strips, urine-glu- cose monitoring strips can be used; in fact this is the method of personal choice for many patents with Type 2 diabetes mellitus. Hypoglycaemia is a potental complicaton in all patents treated with insulin or oral hypoglycaemic agents. The consequences of hypoglycaemia include confusion, seizures, coma and cerebral infarcton. Loss of warning of hypoglycaemia is common among insulin- treated patents and can be a serious hazard especially for drivers and those in dangerous occupatons. Very tght control lowers the blood glucose concentraton needed to trigger hypoglycaemic symptoms; increase in the frequency of hypogly- caemic episodes reduces the warning symptoms experienced by patents. Some patents report loss of hypogly- caemic warning afer transfer to human insulin. Clinical studies do not confrm that human insulin decreases hypoglycaemic awareness. If a patent believes that human insulin is responsible for loss of warning it is reasonable to revert to animal insulin. To restore warning signs, episodes of hypoglycaemia must be reduced to a minimum; this involves appropriate adjustment of insulin dose and frequency, and suitable tming and quantty of meals and snacks. They should check their blood-glucose concentraton before driving and, on long journeys, at intervals of approximately two hour; they should ensure that a supply of sugar is always readily available. If hypoglycaemia occurs, the driver should stop the vehicle in a safe place, ingest a suitable sugar supply and wait untl recovery is complete (may be 15 min or longer). For sporadic physical actvity, extra carbohydrate may need to be taken to avert hypoglycaemia. Hypoglycaemia can develop in patents taking oral antdiabetcs, notably the sulfo- nylureas, but this is uncommon and usually indicates excessive dosage. Sulfonylurea-induced hypoglycaemia may persist for several hour and must be treated in hospital. Diabetc ketoacidosis is characterized by hyperglycaemia, hyperketo- naemia and acidaemia with dehydraton and electrolyte distur- bances. It is essental that soluble insulin (and intravenous fuids) is readily available for its treatment. Infectons are more likely to develop in patents with poorly controlled diabetes mellitus. Surgery: Partcular atenton should be paid to insulin require- ments when a patent with diabetes undergoes surgery that is likely to need an intravenous infusion of insulin for longer than 12 h. Soluble insulin should be given in intravenous infu- sion of glucose and potassium chloride (provided the patent is not hyperkalaemic), and adjusted to provide a blood-glucose concentraton of between 7 and 12 mmol/litre. The duraton of acton of intravenous insulin is only a few min therefore the infusion must not be stopped unless the patent becomes frankly hypoglycaemic. For non-insulin dependent diabetcs, insulin treatment is almost always required during surgery (oral hypoglycaemic drugs having been omited). Insulin must be given by injecton because it is inactvated by gastrointestnal enzymes. Generally, insulin is given by subcu- taneous injecton into the upper arms, thighs, butocks, or abdomen. There may be increased absorpton from a limb, if the limb is used in strenuous exercise following the injecton. It is essental to use only syringes calibrated for the partcular concentraton of insulin administered. There are three main types of insulin preparatons, classifed according to duraton of acton afer subcutaneous injecton: • those of short duraton which have a relatvely rapid onset of acton, for example soluble or neutral insulin; • those with an intermediate acton, for example isophane insulin and insulin zinc suspension; • those with a relatvely slow onset and long duraton of acton, for example crystalline insulin zinc suspension. Soluble insulin, when injected subcutaneously, has a rapid onset of acton (afer 30-60 min), a peak acton between 2 and 4 h, and a duraton of acton up to 8 h.

What are the two major types of ‘errors’ invariably encountered in pharmaceutical analysis? Discuss the various means of minimising ‘systemic errors’ with respect to the following aspects : (i) Calibration of instruments and apparatus (ii) Parallel control determination (iii) Blank determination (iv) Verifying results by different methods of analysis (v) Method of standard deviation (vi) Method of internal standards buy kamagra visa erectile dysfunction treatment patanjali. Elaborate the following statistical methods with suitable examples : (i) Students t-test (ii) F-test (Variance-Ratio Test) generic 50mg kamagra with visa erectile dysfunction shake ingredients. What are the various recommendations a ‘pharmaceutical analyst’ shall propose for rejecting an observation kamagra 100 mg with mastercard erectile dysfunction medication contraindications. Kaufman purchase kamagra 50mg online erectile dysfunction pump implant video, ‘Evaluation and Optimisation of Laboratory Methods and Ana- lytical Procedures’, Amsterdam, Elsevier, 1978. Caulcutt, R, and R, Boddy, ‘Statistics for Analytical Chemists’, London, Chapman and Hall, 1983. However, these definitions have two serious short-comings, they are : (a) they lack explanation of the behaviour of acids and bases in non-aqueous media, and (b) acidity is associated withhydrogen ion—a relatively simple particle ; whereas,basicity is associated with hydroxyl ion—a relatively complex entity. According to Lowry and Bronsted’s theory—‘an acid is a substance capable of yielding a proton (hydrogen ion), while a base is a substance capable of accepting a proton’. Thus, a complementary relationship exists between an acid and a base that may be expressed in a generalized fashion as below : A H+ + B acid base 4. Conjugate Acid-Base Pair The pair of substances which by virtue of their mutual ability either gain or lose a proton is called a conjugate acid-base pair. Sometimes, such a reaction is termed as protolytic reaction or protolysis, where A1 and B1 make the first conjugate acid-base pair and A2 and B2 the other pair. According to Lewis—‘an acid is an electron pair acceptor, whereas a base is an electron pair donor’. Therefore, it is obvious that whenever any neutralization occurs the formation of an altogether new coordinate covalent bond between the electron pair donor and acceptor atoms take place. Thus, Lewis’s definition is a much broader definition that includes coordination compound formation as acid-base reactions, besides Arrhenius and Lowry-Bronsted acids and bases. F H F H Boron trifluoride Ammonia (acid) (base) The reaction of borontrifluoride (acid) with ammonia (base) results into a stable octet configuration between mutual sharing of a pair of electrons of latter (donor) and former (acceptor). H M P N H Q 2 Electron Electron Acceptor Donor (acid) (base) The reaction of ammonia (base) with Ag+ (acid) results into a stable configuration due to the mutual sharing of a pair of electrons of latter (donor) and former (acceptor). According to him : Acid : It is a chemical species that reacts with a base thereby giving up cations or accepting anions or electrons. Base : It is a chemical species that reacts with an acid thereby giving up anions or electrons or combines with cations. Unlike Arrhenius, Lowry-Bronsted and Lewis acids and bases, the Usanovich’s concept in a much broader sense includes all the oxidizing agents as acids and the reducing agents as bases, e. According to the Lux-Flood concept—‘an acid is the oxide-ion acceptor while a base is the oxide donor’. Examples : (a) Organic substances : urea, sodium salicylate, diphenhydramine, emetine hydrochloride, meprobamate, paramethadione, pyrazinamide etc. The two methods, namely : direct titration method and residual titration method are briefly discussed as under : 4. In usual practice, the residual titration is accomplished by allowing to dissolve the substance under estimation in an accurately measured quantity of a standard solution of known strength present in excess and subsequently titrating the excess of the latter with another previously standardized solution. A good number of examples of this particular method shall be discussed in subsequent exercises. Cool and titrate with 1 N sulphuric acid using phenolphthalein solution as indicator. When the pink colour of the solution is discharged record the volume of acid solution required. Hence, each millili- tre of the total amount of 1 N sulphuric acid consumed is equivalent to 40. After complete dissolution, add methyl orange and titrate the excess of sulphuric acid with 1 N sodium hydoxide. Hence, each millilitre of 1 N sulphuric acid, 1 meq neautralized by the ZnO, is equivalent to 40. Thus, the percentage of zinc oxide present in the sample may be calculated as follows : (ml1 N) (ml2 N) meq. Cognate Assays Calamine ; Ephedrine ; Lithium carbonate ; Milk of Magnesia ; Magnesium stearate ; Sodium lactate Injection. However, two methods are generally adopted for the assay of acidic substances, namely : (a) Direct Titration Methods : It is accomplished by directly titrating an exact quantity of the acid, acid salt or other acidic substance with standard alkali solutions. As a general principle, the following guidelines may be observed carefully, namely : (i) the normality of the solution obtained by dissolving the acidic substance must be approximately the same as that of the titrant, (ii) the liquid acidic substance to be titrated must be brought to room temperature (25°C) before titration, because many indicators offer different values at different temperatures, and (iii) the quantity of acid to be taken should be calculated in such a manner that approximately 30 to 40 ml of the previously standardized base shall be utilized for the assay. Inorganic Acids—for these either methyl red or phenolphthalein may be employed as indicators and the alkali must be standardized with the particular indicator used. Procedure : Place 2 g of previously dried and accurately weighed sample of tartaric acid in a conical flask. Thus, the percentage of tartaric acid present in the sample is given by : ml l 0 07504. Thus, the percentage of busulphan present in the sample may be calculated as under : ml 0. Great care should be taken to avoid inhaling the particles of busulphan or exposing the skin to it. Cognate Assays Benzoic acid ; cellulose acetate phthalate ; chlorpropamide ; ibuprofen ; indomethacin ; nicotinic acid ; oxyphenbutazone ; phosphoric acid ; phenylbutazone and salicylic acid. In practice this method applies to such substances that normally react too slowly with the titrant because of their poor solubility which may be accomplished either by a heating process or by a precipitation method so as to convert the substance capable for reaction with the standard base. Repeat the operation without the substance being examined, the difference between the titrations represents the amount of 0. Describe the theory of ‘Acids and Bases’ with respect to the following aspects : (a) Lowry-Bronsted’s Theory (b) Lewi’s Theory (c) Usanovich Theory (d) Lux-Flood Concept. What do you understand by ‘direct titration method’ in the context of Aqueous Titrations? Discuss in details the procedure involved in the assay of : (a) Sodium carbonate (b) Sodium salicylate tablets. Justify the statement with the help of assay of the following pharmaceutical substances : (a) Zine Oxide (b) Milk of Magnesia. Rosenthal, D, and P Zuman, ‘Acid-Base Equilibria, Buffers and Titration in Water’, In Treatise on Analytical Chemistry, ed. Ahuja, S, Impurities Evaluation of Pharmaceuticals, Marcel Dekker, New York, 1988. Evidently, these compounds posed two vital problems of quality control, both in pure and dosage forms by virtue of their inherent characteristics, namely : (a) poor solubility, and (b) weak reactivity in aqueous medium. Initially, the above two problems were usually circumvented in the following manner : Example 1 : Amine salts—It is first changed to the water-soluble free base, extracted with an appro- priate organic solvent and treated with an excess volume of standard acid ; subsequently, the solvent was evaporated, and the remaining acid determined with a standard base. Example 2 : Sodium salts—It is first acidified to release the water-insoluble organic acid, extracted with a suitable organic solvent, the solvent was removed and the residue was subsequently dried and weighed. Example 3 : Nitrogen containing compounds—They are estimated by micro Kjeldahl’s Method. Nevertheless, such specific quantitative methods gave rise to certain serious anomalies and draw- backs. In order to overcome these shortcomings the non-aqueous titrations were introduced. The reason being that in aqueous medium and at higher Kb values (> 10–6) the solvent water competes progressively with the basic species in solution for the proton of the solvent. Hence, from the above definitions it may be implied that : (a) an acid : could be either an electrically neutral molecule e. H+ + A – Acid Basic Solvated Conjugate solvent proton base of acid Perchloric acid displays more strongly acidic characteristics than a weak acid, for instance : acetic acid when dissolved in a weakly basic solvent. Perchloric Acid : It is a very strong acid and when it is made to dissolve in acetic acid, the latter can behave as a base and forms an ‘onium ion’ after combining with protons donated by the perchloric acid. Pyridine, a weak base, when dissolved in acetic acid, the latter exerts its levelling effect and subsequently increases the basic characteristics of the pyridine. Therefore, it is practically feasible to titrate a solution of a weak base in acetic acid against a mixture of perchloric acid in acetic acid. Thus, a sharp end point is achieved which otherwise cannot be obtained when the titration is performed in an aqueous medium. In short, it is possible to titrate mixtures of two or three components selectively with a single titration by wisdom of the right choice of solvent for the non-aqueous titrations. Now add 30 ml acetic anhydride and make up the volume to 1 litre with glacial acetic acid and allow to stand for 24 hours before use. It usually undergoes a spontaneous explosive decomposition and, therefore, it is available always in the form of a solution. Add 25 ml of glacial acetic acid and attach a reflux condenser fitted with a silica-gel drying tube. It is, however, necessary to mention here that the same indicator must be used throughout for carrying out the standardiza- tion, titration and neutralization of mercuric acetate solution. Hence, it is always advisable to carry out standardization and titration preferably at the same temperature. In a situation where these temperature parameters cannot be achieved, the volume of titrant may be corrected by the application of the following formula : Vc = V [1 + 0. For the sake of convenience these typical titrations can be catego- rized into two broad groups, namely : (a) Acidimetry in Non-aqueous Titrations—It can be further sub-divided into two heads, namely : (i) Titration of primary, secondary and tertiary amines, and (ii) Titration of halogen acid salts of bases. Methlyldopa In general, the reaction taking place between a primary amine and perchloric acid may be expressed as follows : R. Calculations : The percentage of methyldopa present in the sample is given by : ml 0.

Because of prominent anticholinergic effects discount kamagra 50mg free shipping erectile dysfunction pump hcpcs, extrapyramidal symptoms are less frequent than for high-potency dopaminergic blocking agents such as haloperidol buy generic kamagra impotence pump medicare. Dose is best administered before breakfast or order generic kamagra erectile dysfunction drugs buy, if taken twice a day purchase kamagra 100 mg fast delivery erectile dysfunction medicine, before the evening meal. Contraindications: Hypersensitivity to chlorpropamide diabetes complicated by ketoacidosis. Editorial comments • Adisulfirsam-like reaction may occur when chlorpropamide is combined with alcohol. Because of the long half-life, pro- longed hypoglycemia is an important potential adverse effect of chlorpropamide. 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 Diuretic: 2 h 2–6 h 24–48 h Food: Should be taken with food. Contraindications: Anuria, hypersensitivity to thiazides or sulfonamide-derived drugs. May cause decreased absorption of fat- soluble vitamins with potential adverse fetal effects. Warnings/precautions • Use with caution in patients with the following conditions: con- stipation, phenylketonuria (Prevalite contains phenylalanine). Clinically important drug interactions Cholestyramine decreases effects/toxicity of following drugs: acetaminophen, amiodarone, cardiac glycosides, furosemide, cor- ticosteroids, thyroid preparations, propranolol, estrogens, metho- trexate, oral anticoagulants, penicillin G, phenobarbital, thiazide diuretics. Parameters to monitor • Levels of digitalis and other drugs to ensure appropriate drug levels. Editorial comments • Cholestyramine has procarcinogenic effects in laboratory ani- mals, but this effect has not been demonstrated in humans. Mechanism of action: Competitively blocks H2 receptors on parietal cells, thereby blocking gastric acid secretion. Adjustment of dosage • Kidney: Creatinine clearance <30 mL/min: use half recom- mended dose. Warnings/precautions • Use with caution in the elderly, patients with hepatic or liver disease, immunocompromised patients. Advice to patient • Avoid driving and other activities requiring mental alertness or that are potentially dangerous until response to drug is known. Parameters to monitor • Presence of Helicobacter pylori: This is a standard approach in patients with peptic ulcer disease. Editorial comments • Current management of peptic ulcer disease includes diagno- sis and treatment of H. Adjustment of dosage • Kidney disease: Creatinine clearance >30 mL/min: usual dosages; creatinine clearance 5–29 mL/min: 200–400 q18–24h. Contraindications: Hypersensitivity to fluoroquinolone antibi- otics or quinolone antibiotics, eg, cinoxacin, nalidixic acid. Advice to patient • Limit intake of caffeinated products including coffee, tea and colas. Clinically important drug interactions • Drugs that increase effects/toxicity of fluoroquinolones: cyclo- sporine, probenecid. Parameters to monitor • Renal, hepatic, and hemopoietic systems should be monitored periodically during prolonged therapy. As with quino-lones, ciprofloxacin is not appropriate monotherapy for community- acquired pneumonia because of poor activity against Strepto- coccus pneumoniae. Mechanism of action: Releases acetycholine within myenteric plexus; agonist at serotonin receptors. Onset of Action Duration 30–60 min No data Food: Generally taken 15 minutes to 1 hour before meals and at bedtime. 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 cisapride and are con- traindicated in combination: ketoconazole, fluconazole, itra- conazole, erythromycin, clarithromycin, troleandomycin, protease inhibitors, nefazodone. Parameters to monitor • Relief of heartburn, relief of gastroporesis, ie, reduction of nausea and vomiting. Editorial comments • Use of cisapride has been markedly restricted due to cardiac toxicity and is now only available in very special circum- stances. See Clinically Important Drug Interactions for drugs that should not be administered with cisapride. Dose is dependent on creati- nine clearance, body surface area; laboratory parameters required prior to subsequent treatment (see Parameters to Monitor). Adjustment of dosage • Kidney disease: Creatinine clearance 10–50 mL/min: 50% of dose; creatinine clearance <10 mL/min: do not use. Warnings/precautions • Patient must be well hydrated prior to and for 24 hours after treatment. It may be necessary to administer a diuretic to ensure good urine output (>100 mL/h), eg, mannitol or furosemide. Advice to patient: Use two forms of birth control including hor- monal and barrier methods. Adverse reactions • Common: hyperuricemia, tinnitus (9%), nausea and vomiting (76–100%) (antiemetics should always be administered with cisplatin). Clinically important drug interactions: • Drugs that increase effects/toxicity of cisplatin: aminoglyco- sides, loop diuretics. Warnings/precautions • Use with caution in patients with the following conditions: dia- betes mellitus, seizures, liver, kidney disease. Advice to patient • Avoid driving and other activities requiring mental alertness or that are potentially dangerous until response to drug is known. Adverse reactions • Common: insomnia, drowsiness, nausea, dry mouth, excessive sweating. Warnings/precautions • Use with caution in patients with the following conditions: kidney disease, active infection. Advice to patient: Use two forms of birth control including hor- monal and barrier methods. Adverse reactions • Common: fever (66%), rash, nausea, pain at injection site, fatigue, headache. Editorial comments • Fever with temperature greater than 100°F occurs in about two thirds of patients in the first month of therapy. Susceptible organisms in vivo: Similar to erythromycin but more effective against gram-negative organisms and more active against Hemophilus influenzae. Contraindications: Hypersensitivity to macrolide antibiotics, concomitant administration of pimozide. Warnings/precautions: Use with caution in patients with liver or kidney dysfunction. Clinically important drug interactions • Drugs that decrease effects/toxicity of macrolides: rifampin, aluminum, magnesium containing antacids. Parameters to monitor • Signs and symptoms of superinfection, in particular pseudomem- branous colitis. Editorial comments • In general, clarithromycin has no major clinical advantages over azithromycin except in the treatment of pneumonia because of better S. Mechanism of action: Inhibits hepatic lipoprotein release, pos- sibly potentiates lipoprotein lipase. Adjustment of dosage • Kidney disease: Creatinine clearance >50 mL/min: dose q6–12h; creatinine clearance 10–50 mL/min: dose q12–18h; creatinine clearance <10 mL/min: avoid. Contraindications: Severe renal or hepatic dysfunction, primary biliary cirrhosis, hypersensitivity to clofibrate, pregnancy. Warnings/precautions • Use with caution in patients with the following conditions: gout, peptic ulcer. Clinically important drugs interactions • Drug that increases effects/toxicity of clofibrate: probenicid. Editorial comment: Use an alternative agent whenever possi- ble as this drug is potentially carcinogenic and has not been shown to lessen cardiovascular mortality in hyperlipemic patients. Contraindications: hypersensitivity, pregnancy, abnormal uter- ine bleeding, liver disease, ovarian cysts, uncontrolled thyroid or adrenal dysfunction, organic intracranial lesion such as pitu- itary tumor. Advice to patient • If visual disturbances occur (eg, blurred vision, spots), report to physician immediately for ophthalmologic evaluation. Editorial comments • This drug is listed without details in the Physician’s Desk Reference, 54th edition, 2000. Adjustment of dosage • Kidney disease: creatinine clearance <10 mL/min: 50–75% of normal initial dose. Onset of Action Peak Effect Duration Oral 30–60 min 2–4 h 12–24 h Transdermal 2–3 d No data 7 d Food: No restriction. Advice to patient • Do not stop taking drug abruptly as this may precipitate a with- drawal reaction (eg, hypertensive crisis). Sit at the edge of the bed for several minutes before standing, and lie down if feeling faint or dizzy. Male patients with orthostatic hypotension may be safer urinating while seated on the toilet rather than standing. Clinically important drug interactions • Drugs that decrease effects/toxicity of clonidine: tricyclic anti- depressants. Parameters to monitor • Signs and symptoms of depression, particularly in patient who has a history of this condition. American Academy of Pediatrics expresses concern about breast- feeding while taking benzodiazepines. Warnings/precautions • Use with caution in patients with the following conditions: his- tory of drug abuse, severe renal and hepatic impairment, elderly, neonates, infants. If suddenly withdrawn, there may be recurrence of the original anxiety or insomnia. A full-blown withdrawal symptom may occur consisting of vomiting, insomnia, tremor, sweating, muscle spasms.