By W. Trano. University of Puerto Rico, Mayaguez. 2019.
The drug Troxevasin® buy buspar 5mg free shipping, Actavis Group order 5mg buspar with visa, Iceland in gel form takes the leading position on the phlebotropic drugs market in physical terms of sales (annual sales of more than 2 buy buspar 10mg online. The drug Detralex®, Servier, France takes the leading position in sales on monetary indicators (annual sales about 74. This is due the fact that this market segment has a lot of large players with significant market shares. The phlebotropic drugs market potential in Ukraine is formed under the influence of many factors of general and specific character. At the Ukrainian pharmaceutical market there is a wide range of phlebotropic drugs. The group C05C A «Bioflavonoids», in particular foreign products Troxevasin® and Detralex® plays a leading role in the formation of market potential. We assessed the degree of monopolization of the market and described the specific factors influencing the phlebotropic drugs market potential. One of the symptoms of a cold is rhinitis — inflammation of the mucous membrane of the nasal cavity. There is evidence that in economically developed countries 15-20% of the population suffer from rhinitis. Despite the fact that this disease does not require hospitalization of the patient and does not lead to disability and death, it has a significant negative impact on social life of patients. They are interested in most of the population during the season of colds and epidemics. Studies have shown that sympathomimetics (drugs) on the basis of Oxymetazoline (Nazivin®, Noxprey, Nazol®), Xylometazoline (Galazolin®, Pharmaton®, Elcatonin®, Aqua) and naphazoline (Naphazoline®, Sanorin) have the greatest demand among nasal drugs. In connection with significant growth of fungal diseases, owing to broad application in medical practice of antibiotics of a broad spectrum of activity, immunodepressants and other groups of medicines, a significant segment of the pharmaceutical market are antifungals, which are widely used at treatment of mycoses of various etiologies. In the course of research were used methods systemic, comparative and content analysis. Research was conducted with use of the given "State Register of medicines and products of medical prescription" N20 for 2016. Out of 109 foreign preparations the greatest number was registered by the Indian producers (46 preparations), 7 preparations producers of France, by 6 preparations – producers have registered of China and Turkey, by the 5 preparations – the Netherlands, the Czech Republic, Romania, by 4 and 3 preparations – producers of Germany and Bangladesh respectively, 2 preparations – producers of Spain, Poland, Belgium, Switzerland, Austria, Italy and Great Britain. Other producers (Bulgaria, Egypt, Hungary, Brazil, Jordan, the United Arab Emirates, Slovenia and Pakistan) have registered by one preparation. The consumer value of medicine along with its clinical efficiency was defined by convenience of its application that is provided with optimum selection of a dosage form and dosage. Along with specialized shops beauty products are also distributed on the pharmaceutical market. Given in attention an annual sales increase of cosmetic products, sales of those products in pharmacies are also increased. Also there are a pharmacy network expansion and an pharmacies quantity growth, especially those who have an open form of trade. Increasing a range of cosmetic products is economically profitable for pharmacy networks because of increased goods turnover, which leads to higher sales and increases pharmacy profitability. Since cosmetics does not treated as medications, the government has not set a maximum value added tax for these kind of products, so cosmetic products are profitable for pharmaceutical organizations. Goal of this work is to provide study about cosmetic products range on the market. The general cosmetic products characteristic on the market are made during the study. In the course of our work desk research was conducted at the Department of Pharmaceutical Marketing and Management, National University of Pharmacy, in parallel carried out field research in pharmacies. As a result, on the basis of these studies was carried out a comparative analysis of the range of cosmetics and cosmetic products in the pharmaceutical markets of Ukraine and abroad. Medical and cosmetic products development trends and market development prospects was made. The medical and cosmetic goods comparative range analysis for Ukrainian and foreign markets was made. As a result of study established that the Ukrainian market has a various cosmetic goods positions, from which 42% of positions are local products, and 58% are foreign products. Cosmetic products volume is higher on the foreign markets in pharmacies and in stock at all. Cosmetic products is very popular among consumers because it occupies an important place in their lives. The number of objects of investigation (cases) and the number of features that characterize these objects may be very large. These tasks are the segmentation of the market, the construction of a typology of countries over a sufficiently large number of indicators, forecasting market conditions of certain goods, the definition of competitive capacity of the goods. For these tasks, important applications are cluster analysis methods — multivariate statistical procedures, data collection, containing information on a sample of objects, and then organize the objects in a relatively homogeneous group. The aim of this study is to investigate the possibility of using the method of principal component analysis to solve clustering problems in marketing research. Cluster analysis unlike most mathematical and statistical methods does not impose any restrictions on the form of these objects, and allows you to treat a variety of source data almost arbitrary nature. This is important, for example, to predict the conditions when the figures have varied views, difficult to use traditional econometric approaches. If clustering objects are represented as a point in n-dimensional feature space (n – number of features that characterize the objects), the similarity between objects is determined by the concept of distance between the points, since it is intuitively clear that the smaller the distance between objects, so they are similar. The method of calculating the distance between objects and groups of objects reflects the specificity solve applied problems. For example, the euclidean distance can be set in the case of continuous variables: 2 = ( − ) =1 178 here Xij – the value of the i-th factor in the j-th observation. Despite much research in the cluster analysis, there are a number of current problems in this area. These include, in particular, multicollinearity is often present in these marketers. The questionnaires in conducting marketing research, as a rule, contain related issues, and the data is usually multicollinearity.
Invasive amoebiasis is more likely in malnutriton discount 5mg buspar with mastercard, immu- nosuppression and pregnancy buy buspar 5 mg on-line. Amoebic dysentery may take a fulminatng course in late pregnancy and the puer- perium; treatment with metronidazole may be life saving purchase 5 mg buspar with visa. In less severe infecton, metronidazole should, if possible, be avoided in the frst trimester. All patents with invasive amoebiasis require treatment with a systemically actve compound such as metronidazole, ornidazole and tnidazole followed by a luminal amoebicide in order to eliminate any surviving organisms in the colon. In severe cases of amoebic dysentery, tetracycline given in combinaton with a systemic amoebicide lessens the risk of superinfecton, intestnal perforaton and peritonits. Giardiasis: Giardiasis is caused by Giardia intestnalis and is acquired by oral ingeston of Giardia cysts. Larger epidemics are difcult to eradicate because of the high proporton of sympto mless carriers and because excreted cysts can survive for long periods outside the human host. Trichomoniasis: Trichomoniasis is an infecton of the genito-urinary tract caused by Trichomonas vaginalis and transmission is usually sexual. Patents and their sexual partners should be treated with metronidazole or other nitroimidazole. Diloxanide Furoate* Schedule H Indicatons Amoebiasis (asymptomatc carriers in non- endemic areas; eradicaton of residual luminal amoebae afer treatment of invasive disease with other drugs). Adverse Efects Flatulence; occasionally vomitng, pruritus and urtcaria; furred tongue. Child- 35 to 50 mg/kg body weight in amoebiasis and 10 to 15 mg/kg body weight in giardiasis. Contraindicatons Chronic alcohol dependence; neurological disease, blood dyscrasias, frst trimester of pregnancy. Precautons Disulfram-like reacton with alcohol; hepatc impairment and hepatc encephalopathy (Appendix 7a); pregnancy (Appendix 7c); see also notes above); lactaton (Appendix 7b); clinical and laboratory monitoring in courses lastng longer than 10 days; interactons (Appendix 6a, 6c, 6d); prolonged use may result in fungal or bacterial superinfecton, phenobarbitones, history of seizure disorder. Adverse Efects Nausea, vomitng, unpleasant metallic taste, furred tongue and gastrointestnal distur- bances; rarely, headache, drowsiness, dizzi- ness, ataxia, darkening of urine, erythema multforme, pruritus, urtcaria, angioedema and anaphylaxis; abnormal liver functon tests, hepatts, jaundice; thrombocytope- nia, aplastc anaemia; myalgia, arthralgia; peripheral neuropathy, epileptform seizures; leukopenia on prolonged or high dosage reg- imens; anorexia, glossits, dryness of mouth. Tinidazole Pregnancy Category-C Schedule H Indicatons Amoebiasis, trichomoniasis and giardiasis, anaerobic infectons, necrotsing ulceratve gingivits, bacterial vaginosis, H. Parenteral Bacterial vaginosis and ulceratve gingivits: Adult- 2g as a single dose parenterally. Contraindicatons Hypersensitvity to nitroimidazole derivatves, frst trimester of pregnancy (Appendix 7c), lactaton, blood dyscrasias, porphyria; interactons (Appendix 6a). Benzylpenicillin and phenoxymethylpenicillin are actve against susceptble strains of Gram-positve bacteria and Gram-negatve bacteria, spirochaetes and actnomycetes, but are inactvated by penicillinase and other beta-lactamases. Benzathine benzylpenicillin and procaine benzylpenicillin are long-actng preparatons which slowly release benzylpenicillin on injecton. A range of penicillins with improved stability to gastric acid and penicillinases have been produced by substtuton of the 6-amino positon of 6-aminopenicillanic acid. Cloxacillin is an isoxazoyl penicillin which is resistant to staphylococcal penicillinase. Broad-spectrum penicillins such as ampicillin are acid-stable and actve against Gram-positve and Gram-negatve bacteria, but are inactvated by penicil- linase. Beta-lactamase inhibitors such as clavulanic acid are ofen necessary to provide actvity against beta-lactamases produced by a wide range of both Gram-negatve and Gram- positve bacteria. Cephalosporins are classifed by generaton, with the frst generaton agents having Gram-positve and some Gram- negatve actvity; the second generaton drugs have improved Gram-negatve actvity and the third generaton cephalosporin have a wider spectrum of actvity, although may be less actve against Gram-positve bacteria than frst generaton drugs, but they are actve against Gram-negatve Enterobacteriaceae and Pseudomonas aeruginosa. This rare, but serious adverse efect may result from very high doses or in severe renal failure. Penicillins should not be given by intrathecal injecton because they can cause encephalopathy which may be fatal. Hypersensitvity: The most important adverse efect of penicillins is hypersensi- tvity which causes rashes and, occasionally anaphylaxis, which can be fatal. Allergic reactons to penicillins occur in 1-10% of exposed individuals, while anaphylactc reactons occur in fewer than 0. Individuals with a history of anaphylaxis, urtcaria or rash immediately afer peni- cllin administraton are at risk of immediate hypersensitvity to penicillin. These individuals should not receive penicillin, rather a cephalosporins or another beta-lactam antbiotc may be used. Patents who are allergic to one penicillin will be allergic to them all because the hypersensitvity is related to the basic penicillin structure and about 10% of penicillin-sensitve patents will be allergic to cephalosporins and other beta-lactams. Individuals with a history of a minor rash (a non-confuent rash restricted to a small area of the body) or a rash occurring more than 72 h afer penicillin administraton are possibly not allergic to peni- cillin and in these individuals a penicillin should not be withheld unnecessarily for a serious infecton; however, the possibility of an allergic reacton should be borne in mind and facilites should be available for treatng anaphylaxis. Ampicillin, Amoxycillin, Amoxycillin with Clavulanic Acid and Cloxacillin: Ampicillin is actve against certain Gram-positve and Gram- negatve organisms. It is used to treat a wide range of infec- tons including otts media, respiratory-tract and urinary- tract infectons and gonorrhoea due to susceptble bacteria. However, ampicillin is inactvated by penicillinases including those produced by Staphylococcus aureus and by common Gram-negatve bacilli such as Escherichia coli; many strains of Haemophilus infuenzae, Moraxella catarrhalis, Neisseria gonorrhoeae and Salmonella and Shigella spp. There are geographical variatons in the incidence of resistance and an awareness of local paterns is important. In some areas, oral use should be restricted to treatment of Shigella infectons; it is given in an oral dose of 1g every 6 h for 7-10 days. Amoxycillin has a similar spectrum of actvity to ampicillin, but is also inactvated by penicillinases. However, it is beter absorbed afer oral administraton than ampicillin and higher plasma and tssue levels are achieved. Amoxycillin is preferred to ampicillin for the treatment of some infectons including otts media and respiratory-tract and urinary-tract infectons. It has no signif- cant antbacterial actvity but in combinaton with Amoxycillin widens Amoxycillin’s spectrum of actvity and allows its use against Amoxycillin-resistant strains of bacteria. It is used in respiratory-tract, genito-urinary and abdominal infectons, cellulits, animal bites and dental infectons. These antbiotcs may also be administered with an aminogly- coside to increase their spectrums of actvity. The penicillin and aminoglycoside should not be mixed before or during administraton, because loss of aminoglycoside actvity can occur on mixing. Benzylpenicillin and Phenoxymethylpenicillin: Benzylpenicillin remains an important and useful antbiotc but it is inactvated by bacterial beta-lactamases.
The equation describing elimination after an intravenous bolus dose of a drug characterized by a two-compartment model requires two exponential terms buy buspar 10 mg amex. A patient is given a 500-mg dose of drug by intravenous injection and the following plasma concentrations result buspar 5mg with amex. K12 represents the rate constant for drug transfer from compartment 1 (central) to compartment 2 (peripheral) generic buspar 5 mg on line. The y-intercept associated with the residual portion of the curve (which has a slope of -α) is A. One for distribution phase and the other for elimination or post- distribution phase. Describe situations for which it would be better to use a two-compartment model rather than a one-compartment model. What is the minimum number of plasma-concentration data points needed to calculate parameters for a two-compartment model? Definitions of symbols and key equations are provided here: K = elimination rate constant C0 = plasma drug concentration just after a single intravenous injection e = base for the natural log function = 2. Forty-eight hours after beginning the infusion, the plasma concentration is 12 mg/L. If we assume that this concentration is at steady state, what is the theophylline clearance? As we know V and K, what would the plasma concentration be 10 hours after beginning the infusion? If the infusion is continued for 3 days and then discontinued, what would the plasma concentration be 12 hours after stopping the infusion? If the infusion is continued for 3 days at 40 mg/hour and the steady-state plasma concentration is 12 mg/L, what rate of drug infusion would likely result in a concentration of 18 mg/L? After the increased infusion rate above is begun, how long would it take to reach a plasma concentration of 18 mg/L? If this patient is assumed to have an "average" V of 15 L and a normal half-life of 3 hours, what will be the peak plasma concentration at steady state? After the fifth dose, a peak plasma concentration (drawn at the end of the infusion) is 5 mg/L and the trough concentration (drawn right before the sixth dose) is 0. For this patient, what dose should be administered to reach a new steady-state peak gentamicin concentration of 8 mg/L? To calculate the plasma concentration with a continuous infusion before steady state is reached, the following equation can be used: where t = 10 hr. If the continuous intravenous infusion is continued for 3 days, steady state would have been reached, so the plasma concentration would be 12 mg/L. When the infusion is stopped, the declining drug concentration can be described just as after an intravenous injection: -Kt Ct = Csse where: Ct = plasma concentration after infusion has been stopped for t hour, Css = steady-state plasma concentrations from continuous infusion, and K = elimination rate constant. Then remember that at steady state: Css = K0/Clt or, rearranged: Css × Cl =t K0 If the desired Css equals 18 mg/L, then: k0 = 18 mg/L × 3. Whenever the infusion rate is changed to a new rate (increased or decreased), it will take approximately five half-lives to achieve a new steady state. First, recall that the multiple-dose infusion equation should be used: where: K0 = 80 mg/1 hour (because the dose is given over 1 hour). Recall that there are two concentrations on a straight line, where K is the slope of the line. To calculate V, the multiple-doseinfusion equation can be used, where: and: Cpeak = 5 mg/L K0 = 80 mg/hour -1 K = 0. To calculate a new dose, we would use the same equation as above but would now include the known V and desired Cpeak and then solve for K0: So, in practical terms, a 125-mg dose would be infused over 1 hour to attain a peak of approximately 8 mg/L. Describe the pharmacokinetic differences and clinical utility of controlled-release products and the several techniques used in formulating controlled-release drugs. Calculate dose and clearance of controlled-release products given plasma concentration, volume of distribution, and elimination rate constant. The drug enters the body by some route of administration and is subjected to processes such as absorption, distribution, metabolism, and excretion (Figure 7-1). The concepts used in pharmacokinetics enable us to understand what happens to a drug when it enters the body. Unless a drug is given intravenously or is absorbed cutaneously, it must be absorbed into the systemic circulation to exert its effect. After entering the systemic circulation, the drug is distributed to various tissues and fluids. Plasma and tissue protein binding affect the volume of distribution, transport to and from sites of action or metabolism, and elimination. While the drug is distributing into tissues and producing an effect, the body is working to eliminate the drug and terminate its effect. For an orally administered drug, the absorption process depends on the drug dissociating from its dosage form, dissolving in body fluids, and then diffusing across the biologic membrane barriers of the gut wall into the systemic circulation (Figure 7-2). Different drugs or different formulations of the same drug can vary considerably in both the rate and extent of absorption. The difference in absorption rates of drugs has important therapeutic implications. Assuming that concentration correlates with effect, if one drug is absorbed at a faster rate than another similar drug, the first drug may produce a higher peak concentration, which may lead to a clinical effect sooner than the second drug (Figure 7-3). When drug absorption is delayed (usually through manipulation of the rate of drug release from the formulation), a prolonged or sustained effect can be produced. The amount of the drug dose that reaches the systemic circulation determines its bioavailability. Therefore, overall oral bioavailability can be described by the following equation, which shows the combination of all these factors: Foral = Fabs × Fgut × Fhepatic where F is a fraction. A product with poor bioavailability is not completely absorbed into the systemic circulation or is eliminated by the liver before it reaches the systemic circulation. Differences in bioavailability may be evident between two products (A and B) containing the same drug but producing different plasma concentrations (Figure 7-4).
Contraindicatons Inability to maintain airway; hypersensitvity to barbiturates; cardiovascular disease; dyspnoea or obstructve respiratory disease; porphyria; hypotension or shock; Addison’s disease; hepatc or renal dysfuncton; increased blood urea; severe anaemia; asthma; myasthenia gravis purchase buspar 5 mg online. Precautons Local extravasaton can result in extensive tssue necrosis and sloughing; intra-arterial injecton causes intense pain and may result in arteriospasm; hepatc impairment (Appendix 7a); interactons (Appendix 6a); pregnancy (Appendix 7c); patents with advanced cardiac disease; increased intracranial pressure; asthma; myasthenia gravis; endocrine insufciency buy 10mg buspar. Warn patent not to perform skilled tasks; for example operatng machinery; driving for 24 h and also to avoid alcohol for 24 h buy 10mg buspar free shipping. Adverse Efects Respiratory depression; myocardial depres- sion; cardiac arrhythmias; somnolence; bronchospasm; urtcaria; vasodilaton; apnoea; emergence delirium; headache; nausea; oedema. Local anaesthetcs are used very widely in dental practce; for brief and superfcial inter- ventons; for obstetric procedures and for specialized tech- niques of regional anaesthesia calling for highly developed skills. Local anaesthetc injectons should be given slowly in order to detect inadvertent intra- vascular injecton. Hypersensitvity testng should be done in all patents before administratons of local anaesthetcs. Local Infltraton Many simple surgical procedures that neither involve the body cavites nor require muscle relaxaton can be performed under local infltraton anaesthesia. Lower-segment caesarean secton can also be performed under local infltraton anaes- thesia. No more than 4 mg/kg of plain lidocaine or 7 mg/kg of lidocaine with epinephrine should be administered on any one occasion. The additon of epine- phrine (adrenaline) diminishes local blood fow; slows the rate of absorpton of the local anaesthetc and prolongs its efect. Care is necessary when using epinephrine for this purpose since; in excess; it may produce ischaemic necrosis. Surface Anaesthesia Topical preparatons of lidocaine are available and topical eye drop solutons of tetracaine (chapter 19. Regional Block A regional nerve block can provide safe and efectve anaes- thesia but its executon requires considerable training and practce. Nevertheless; where the necessary skills are avail- able; techniques such as axillary or ankle blocks can be invalu- able. Spinal Anaesthesia This is one of the most useful of all anaesthetc techniques and can be used widely for surgery of the abdomen and the lower limbs. Contraindicatons Adjacent skin infecton; infamed skin; concomitant antcoagulant therapy; severe anaemia or heart disease; spinal or epidural anaesthesia in dehydrated or hypovolaemic patent. Precautons Respiratory impairment; hepatc impairment (Appendix 7a); epilepsy; porphyria; myasthenia gravis; lactaton; interactons (Appendix 6c); pregnancy (Appendix 7c). Adverse Efects With excessive dosage or following intravascular injecton; light-headedness; dizziness; blurred vision; restlessness; tremors and occasionally convulsions rapidly followed by drowsiness; unconsciousness and respiratory failure; cardiovascular toxicity includes hypotension; heart block and cardiac arrest; hypersensitvity and allergic reactons also occur; epidural anaesthesia occasionally complicated by urinary retenton; faecal incontnence; headache; backache or loss of perineal sensaton; transient paraesthesia and paraplegia very rare. Dose Inducton of anaesthesia: By injecton according to patent weight and nature of procedure. Contraindicatons Adjacent skin infecton; infamed skin; concomitant antcoagulant therapy; severe anaemia or heart disease; spinal or epidural anaesthesia in dehydrated or hypovolaemic patent; hypersensitvity. Precautons Respiratory impairment; hepatc impairment (Appendix 7a); epilepsy; porphyria; myasthenia gravis; avoid (or use with great care) solutons containing epinephrine (adrenaline) for ring block of digits or appendages (risk of ischaemic necrosis); lactaton; pregnancy (Appendix 7c); interactons (Appendix 6c). Promethazine; which has anthista- minic and antemetc propertes as well as a sedatve efect; is of partcular value in children. A potent analgesic such as morphine should be administered preoperatvely to patents in severe pain or for analgesia during and afer surgery. Antcholinergic (more correctly antmuscarinic) drugs such as atropine are also used before general anaesthesia. They inhibit excessive bronchial and salivary secretons induced; in partcular; by ether and ketamine. Intramuscular administra- ton is most efectve; but oral administraton is more conven- ient in children. Intramuscular route or subcutaneous Premedicaton (30 to 60 min before inducton of anaesthesia): 300 to 600 µg. Precautons Down syndrome; children; elderly; ulceratve colits; diarrhoea; hyperthyroidism; heart failure; hypertension; patents with atrial fbrillaton or futer; lactaton (Appendix 7b); interactons (Appendix 6a); pregnancy (Appendix 7c). Since atropine has a shorter duraton of acton than neostgmine; late unopposed bradycardia may result; close monitoring of the patent is necessary. Adverse Efects Dry mouth; blurred vision; photophobia; fushing and dryness of skin; rash; difculty in micturiton; less commonly arrhythmias; tachycardia; palpitatons; confusion (partcularly in elderly); heat prostraton and convulsions; ventricular fbrillaton; hallucinatons; dilated pupils; psychosis. Dose Oral Adult- 5 mg on night before surgery or minor procedure; thereafer 5 mg for 2h before procedures. Precautons Respiratory disease; muscle weakness; history of alcohol or drug abuse; marked personality disorder; elderly or debilitated patents (adverse efects more common in these groups); hepatc impairment (Appendix 7a) or renal failure; lactaton (monitoring for adverse efcts required Appendix 7b); porphyria; interactons (Appendix 6a, 6c); organic cerebral changes; epileptc patents. Warn patent not to perform skilled tasks; for example operatng machinery; driving for 24 h. Adverse Efects Central nervous system efects common and include drowsiness; sedaton; confusion; amnesia; vertgo and ataxia; hypotension; bradycardia; or cardiac arrest; partcularly in elderly or severely ill patents; also paradoxical reactons; including irritability; excitability; hallucinatons; sleep disturbances; pain and thromboembolism on intravenous injecton. Dose Slow intravenous injecton Adult- Conscious sedaton: approximately 2 mg/min; 5 to 10 min before procedure; initally 2 to 2. Intramuscular injecton Adult- Sedaton in combined anaesthesia: 30 to 100 µg/kg repeated as required by contnuous intravenous infusion 30 to 100 µg/ kg/h (lower doses in elderly). Contraindicatons Acute narrow angle glaucoma; comatose patents; shock; acute alcohol intoxicaton; for intrathecal and epidural use; acute pulmonary insufciency; myasthenia gravis. Precautons Chronic renal failure; cardiac disease; open angle glaucoma; respiratory disorders; neonates; prolonged use and abrupt withdrawal should be avoided; hepatc impairment; pregnancy (Appendix 7c) and lactaton; interactons (Appendix 6a, 6c). Dose Subcutaneous or intramuscular injecton Adult- Preoperatve medicaton before procedure: up to 10 mg; 60 to 90 min before procedure; 20 to 30 mg per 12 h depending on patent weight. Child- (By intramuscular injecton) Preopera- tve medicaton before procedure: 150 µg/kg. Postoperatve analgesia: 8 to10 mg over 30 min (slow intravenous infusion); then 2 to 2. Child- Intra-operatve analgesia: 100 µg/kg; repeated every 40 to 60 min as required. Contraindicatons Patents with acute respiratory depression and when there is risk of paralytc ileus; conditons associated with raised intracranial pressure and in head injury (they interfere with pupilary responses vital for neurological assessment); comatose patents; acute asthma; acute liver disease; acute alcoholism; pulmonary oedema; interactons (Appendix 6a, 6c, 6d); lactaton (Appendix 7b); hepatc impairment (Appendix 7a). Precautons Patents with impaired respiratory functon (avoid in chronic obstructve pulmonary disease) and asthma (avoid during an acute atack); hypotension; myasthenia gravis; prostatc hypertrophy and hyperplasia; obstructve or infammatory bowel disorders; disease of the biliary tract and convulsive disorders; pancreatts; cardiac arrhythmias; hypothyroidism; head injury; circulatory shock; lactaton; pregnancy (Appendix 7c). Adverse Efects Nausea and vomitng (partcularly in inital stages); constpaton; dry mouth and biliary spasm; larger doses produce muscle rigidity; hypotension and respiratory depression; bradycardia; paralytc ileus; abdominal pain; anorexia; dyspepsia; exacerbaton of pancreatts; taste disturbance; hypertension; hypothermia; syncope; bronchospasm; inhibiton of cough refex; restlessness; seizures; paraesthesis; asthenia; malaise; disorientaton; excitaton; agitaton; delirium; raised intracranial pressure; amenorrhoea; myoclonus; muscle fasciculaton and rhabdomyolysis.