By S. Givess. Ferris State University.
In a rat study buy cheap pariet 20 mg on line gastritis unusual symptoms, the frequency of craniofacial and skeletal malformations was increased among fetuses exposed to meclizine during embryogenesis (King cheap pariet 20 mg line gastritis diet óêð, 1963) discount pariet 20mg fast delivery gastritis flare up diet. No birth defects were found in the offspring of monkeys who received 10 times the usual human dose of meclizine during embryogenesis (Courtney and Valerio purchase pariet 20 mg overnight delivery gastritis pylori symptoms, 1968; Wilson and Gavan, 1967). Phenindamine No animal or human studies regarding congenital anomalies and the use of phenin- damine in pregnant women have been published. However, it is closely related to chlor- pheniramine which has been studied during pregnancy and found not to increase the risk for birth defects (Table 11. Guaifenesin use dur- ing the first trimester in more than 1000 human pregnancies was not associated with an increased risk of congenital anomalies (Aselton, 1985; Heinonen et al. Other mucolytic agents or drugs that act as an expectorant include potassium iodide or iodinated glycerol. It is well known that iodine-containing agents cross the pla- centa freely and may result in fetal goiter. Therefore, iodide-containing agents are con- traindicated for use during pregnancy. It was used by 300 pregnant women during the first trimester and the frequency of congenital anomalies was not Expectorants and antitussives 213 Table 11. Numerous narcotics are used in cough preparations, including codeine, hydrocodone, and hydromorphone. Chronic use of narcotic agents may result in neonatal addiction, withdrawal, and respiratory depression. However, narcotics are not associated with an increased frequency of congenital anomalies. Also, acute use of narcotic antitussives is not associated with neonatal addiction or congenital anomalies. Benzonatate (Tessalon) is a local anesthetic-like compound and acts as an antitussive by anesthetizing the stretch receptors in the respiratory passage. No human studies are available on which to base an evaluation of adverse fetal effects. Case reports of fetal alcohol syndrome have been published in which the mother abused cough preparations during pregnancy. If symptomatic therapy is indicated, pregnant women with the common cold can be treated with acetaminophen, in combination with a decongestant and an antihis- tamine, and a combination of an antitussive and expectorant. Pseudoephedrine and chlorpheniramine are the preferred treatments (Hornby and Abrahams, 1996). If a nasal spray is deemed necessary, agents containing oxymetazoline, xylometazoline, or napha- zoline are reasonable, since minimal systemic absorption occurs. Other, noniodinated prepara- tions offer equally effective alternative medication (Tables 11. Allergic rhinitis/sinusitis Chlorpheniramine compounds are preferable for first-line use in pregnant women because they are better studied. The histamine H -receptor antagonist astemizole1 (Hismanal) and terfenadine (Seldane) have been studied in the first trimester in pregnant women (Table 11. Pruritis/urticaria Diphenhydramine is well studied during pregnancy and is a safe agent to use (Table 11. Its oxytocic effects do not appear to be as pronounced as dimenhydrinate (Hara et al. Other medications found to be safe and effective in the treatment of pruritus are hydroxyzine or dexchlorpheniramine (Drugs and Pregnancy Study Group, 1994) (Table 11. Motion sickness/vertigo Dimenhydrinate is a commonly used agent, although it may have some oxytocic proper- ties. It has been studied during the first trimester of human pregnancy and was not asso- ciated with an increased frequency of congenital anomalies (Czeizel and Vargha, 2005). Drug-induced dyskinesia The antimuscarinic and sedative effects of diphenhydramine make it the ideal agent for the treatment of drug-induced dyskinesia in the pregnant patient. Its use during pregnancy has been studied extensively, and there were no apparent untoward effects (Table 11. A caseâ€“control study of congenital abnormality and dimenhydrinate usage during pregnancy. Prenatal vitamin supplements are usually given, but there is no clear consensus that they are needed. Iron is the only nutrient for which supplementation during pregnancy is invari- ably required. Calories required during pregnancy increase (approximately 300â€“500 calories per day) only mar- ginally above the needs of nonpregnant women (2100 calories daily). Gravidas who follow a veg- etarian diet or are otherwise nutritionally restricted (e. When considering the gravid vegetarian, it is extremely important to distinguish between the strictly vegetarian (e. Nonlacto-ovo vegetarians eat only plant-derived foods and are Vitamins 217 Table 12. Special action from the clinician to ensure an adequate intake of the essential amino acids and folate must be taken. A pro- fessional nutritionist should be involved to help manage meal plans during pregnancy for the strict vegetarian. Nonlacto-ovo vegetarians may also suffer from various other nutri- ent deficiencies, specifically of vitamins of the A and B group. However, megadoses of vitamin A, taken by some individuals for undocumented health advantages, are often encountered in practice. No data to support large-dose vitamin A are published in the scientific literature. Other vitamin A supplements (retinoic acid, discussed above) are fat soluble, and usu- ally fish liver derived. Beta-carotene vitamin A probably has a higher clearance rate than retinoic acid because it is water soluble. Beta-carotene presumably poses much less, if any, teratogenic risk compared to similar amounts of retinoid acid-derived vitamin A (or Retinol). Anecdotal data (case reports) support the hypothesized association of birth defects with high-dose retinoic acid-derived vitamin A. Findings among infants whose moth- ers used megadoses of vitamin A analogs (isotretinoin, etretinate) support the existence of a retinoic acid embryopathy (see Chapter 14). As with human case reports, anomalies in animal studies were also hetero- geneous (brain, cardiac, eye, and craniofacial anomalies) and not consistent with a syndrome. Despite the purely anecdotal nature of direct information on large doses of vitamin A during early pregnancy, an increased risk of congenital anomalies seems highly likely. On balance, the negative information regarding the association of birth defects and high-dose vitamin A is the apparent lack of a pattern of congenital anomalies observed (highly heterogeneous collection of defects). The high frequency of congenital anomalies with isotretinoin and etretinate â€“ vitamin A congeners â€“ exposure during embryogene- sis offers evidence that vitamin A megadoses during pregnancy increase the risk of con- genital anomalies (see Chapter 14). Vitamin D Vitamin D is produced by skin exposed to ultraviolet light and is integral to normal cal- cium metabolism. Skeletal anomalies comparable to rickets in humans were found in rats born to mothers who were vitamin D deficient during gestation (Warkany, 1943). Defects with high-dose vitamin D parallel those seen in Williams syndrome â€“ supravalvular aortic stenosis, unusual facies, and infantile hypercalcemia â€“ in the human (Chan et al. Williams syndrome was speculated to be caused by the use of megadoses of vitamin D during pregnancy (Friedman, 1968), but the available data do not support this (Forbes, 1979; Warkany, 1943). No studies have been pub- lished of congenital anomalies among infants born to mothers who took niacin during the first trimester.
Membrane vesicles are typically formed from intact cells and require some skill for their preparation cheap pariet 20mg overnight delivery gastritis diet and recipes. Given this relative limitation 20 mg pariet for sale gastritis diet ñèíîïòèê, the use of membrane vesicles as a rapid screen for P-gp efflux activity has not been extensive and has proven a better tool for studying the microscopic aspects of P-gp-mediated efflux discount 20 mg pariet amex gastritis otc. Additionally buy pariet 20mg cheap gastritis diet àâèòî, these vesicles have been used to study microscopic aspects of P-gp-mediated efflux, such as the relationship of P-gp function to the membrane fluidity (137). In the intestinal segment study, the intestine is removed and either mounted in a diffusion apparatus (Ussing chamber) or everted to make an everted sac (234,414â€“416). The transport characteristics of verapamil were determined for each region of the intestine as well as the colon with this model system. The duodenum and jejunum showed the most P-gp activity followed by lower activity in the colon and, surprisingly, none in the ileum (416). Polarized transport of quinidine due to P-gp efflux was demonstrated by using intestinal segments mounted in Ussing chambers (414). Further studies using everted sacs showed that P-gp inhibition by quinidine caused an altered drug absorption of digoxin and explained the interaction seen with coadministration of these agents (234). Metabolism and P-gp-mediated efflux of the macrolide antibiotic tacrolimus were studied in perfusion studies and in everted sacs (415). It was shown that inhibiting P-gp with miconazole (a P-gp inhibitor) greatly increased the amount of tacrolimus in the tissue (415). The results of these experiments provided evidence that P-gp is active in limiting tissue exposure to drugs and also that the intestinal metabolism of certain compounds can be significant. P-gp, expressed in these in vitro systems, is thought to function normally (analogous to function seen in in vivo systems) even though the former lacks glycosylation at N-terminal. Despite the normal functional activity of P-gp, researchers found it difficult to use P-gp expressed in E. To solve this problem, Beja and Bibi developed a method to express P-gp in â€˜â€˜leakyâ€™â€™ E. The results of these assays may be significantly different than those obtained in studies performed with 400 Troutman et al. A membrane product pre- pared from baculovirus infected insect cells containing this activity is now commercially available from Gentest Corp. By determination of inorganic phosphate liberated in the reaction containing a P-gp preparation and a test compound, in the presence and absence of vanadate, one can determine if the test compound is a substrate/inhibitor of P-gp (123,422). In Situ and In Vivo Models Whereas in vitro models are the tool of choice to identify P-gp substrates and to specifically study molecular aspects of P-gp-mediated efflux activity, extrapolation of these data to predict relevance in vivo can sometimes be difficult. Indeed, P-gp-mediated efflux activity is often one of a multitude of parameters that ultimately combine to confer substrate disposition; these exact relationships between key parameters are complex and remain to be resolved. For these reasons, models with greater complexity, more specifically those in which more key factors are present such as in situ and in vivo models, are essential to gain insight into the overall relevance of P-gp efflux for substrate disposition. The following section summarizes the respective strengths and weaknesses of in situ and in vivo models currently used to study P-gp efflux. In Situ Studies and Models Some efforts have been made to determine the effect P-gp has on its substrates by use of in situ perfusion methods, including intestinal perfusion, liver perfu- sion, kidney perfusion, and brain perfusion. These experiments allow the researcher to study the transport of compounds in a physiologically relevant environment in which the integrity of the organ is preserved with regards to cell polarity and representation of all cell types seen in the organ. Furthermore, the reduction in complexity of in situ models versus in vivo studies facilitates the conduct of complex studies and allows more definitive conclusions to be made regarding the role P-gp may play in disposition. In situ intestinal perfusion studies are typically done with live animals in which a perfusion loop has been inserted into the intestine (233,424). Depending on the experimental protocol, the system can offer a relatively unbiased view of The Role of P-Glycoprotein in Drug Disposition 401 intestinal transport with respect to normal expression of transporters in healthy animals. One limitation of this protocol is that the disappearance rather than the appearance of a compound is often determined (appearance can be determined by collection of blood in the vessels perfusing the section of intestine studied, a process requiring significant surgical skill). Estimates of the polarity of transport imparted by P-gp are difficult to assess and typically can only be determined by using an inhibitor or antibody to P-gp. Often the animal is anesthetized, and the anesthetizing agent can further affect the results (altered membrane fluidity, possible inhibitory effects on P-gp-mediated efflux activity) (187). Using the intact intestine adds more levels of complexity that can further confound studies meant to elucidate the role of transporters, which act on the cellular level. However, this complexity can be a strength to the role P-gp plays in concert with other key factors that influence absorption and can be studied in parallel. It is possible that results will differ for intestinal region and also due to the presence of Peyerâ€™s patches that have different physiological roles from enterocytes (414,416). Furthermore, these studies suffer from an interspecies variability (rats are typically the test subjects). Despite certain disadvantages, if these studies are con- ducted with appropriate controls involving known P-gp substrates, it can provide valuable insights on how to correlate the effectofP-gpobservedincellulartransport studies to that expressed in the absorption of drugs in vivo. By measuring the intestinal absorption from small intestine of rat in situ, Saitoh et al. Compared with prednisolone and hydrocortisone, meth- ylprednisolone absorption was significantly retarded in jejunum and ileum by an intestinal efflux system. In the presence of verapamil and quinidine, the attenua- tion in the absorption of methylprednisolone was reversed, suggesting that P-gp is responsible for the unique features of methylprednisolone absorption. This study provides a good example of the usefulness of an intestinal perfusion experiment in further determining the regional differences in intestinal drug absorption modu- lated by P-gp that would otherwise be difficult to deduce in experiments per- formed with cell culture models or performed with whole animal systems. The isolated perfused rat liver has been extensively used because of the minimal surgical manipulation needed due to its size and because the organ is less than 25 g, the perfusate used can be hemoglobin-free while ensuring ade- quate oxygen delivery at the flow rates used in these experiments (425). The isolated perfused liver system provides an excellent model for studying the hep- atobiliary disposition of compounds without confounding influences that may be seen in vivo, such as influences on hepatic metabolism and additional metabolism or excretion by other organs of clearance (270,425). The isolated perfused rat liver can be used to study biochemical regulation of hepatic metabolism, synthetic function of liver, and mechanism of bile formation and secretion (270). In a similar study on the hepatic elimination of other P-gp substrates, including vincristine and daunorubicin, it was reported that canalicular P-gp plays a significant role in the biliary secretion of these com- pounds (428,429). Because of the kidneyâ€™s involvement in the excretion of hydrophilic compounds and because most of the substrates of P-gp are hydrophobic com- pounds that are likely to be cleared mainly by biliary excretion or intestinal secretion, comparably fewer studies have been performed with the isolated perfused kidney. The isolated perfused rat kidney model was used to demonstrate that digoxin is actively secreted by P-gp located on the luminal membrane of renal tubular epithelial cells and that clinically important interactions with qui- nidine and verapamil are caused by the inhibition of P-gp activity in the kidney (332). One major advantage this technique has over an in vivo experiment involves the perfusion fluid used in the experiment. The composition of the solution can be controlled with respect to test compounds, plasma proteins, nutrients, and met- abolic cofactors (432). However, the use of a perfusate solution can also be a disadvantage as it may not be possible to provide all the necessary nutrients or metabolic cofactors that would be present in vivo and, thus, may lead to incorrect conclusions (430). The major disadvantages of the model with respect to in vitro models include the lack of control of the extracellular fluid concentration for studies of drug efflux from the brain and a greater complexity that the brain matrix provides. As with other perfusion systems, this technique requires anes- thesia and thereby may act to confound results. These in situ techniques can be powerful tools to gauge the actual extent of P-gp efflux that can be expected in vivo. There are confounding factors that must be addressed when interpreting data obtained from these studies, and as with all biological models, the appropriate controls must be used to ensure that the observed effect appears to be due to P-gp-mediated efflux activity. In Vivo Models The major advantages to in vivo models are that they provide a method to understand relevance on an organism level and that these models have been used successfully to predict outcomes in humans. The obvious disadvantages of these models are their limitations with regards to study designs and sampling, reduced ability to deconvolute complex processes, and the need for animal experimenta- tion. For that reason, the in vivo model is a tool more suitable for aiding the understanding of the ramifications of P-gp efflux liability for gross disposition processes. A great deal of understanding around how P-gp affects disposition has come from in vivo models.
All alterations to the settings of an infusion pump must be made by healthcare professionals who have been assessed as competent in using the device discount pariet 20mg without prescription gastritis complications. Infusion pumps must be cleaned by the practitioner disconnecting and removing the empty or unwanted infusion container after each patient discount pariet 20mg line gastritis symptoms blood. Infusion pumps should be kept plugged in to the mains when in use to ensure the backup battery is charged discount pariet 20 mg gastritis flare up symptoms. If an infusion pump is involvedin an adverse incident thenurseinchargeand the Medical Devices department must be informed immediately purchase pariet 20mg online gastritis diet fruit. The following actions must be taken: Appendix 8 Infusion devices | 893 * Close the roller clamp on the administration set. A ppendix 9 Syringe drivers Syringe drivers are portable, battery-operated pumps delivering drugs at a predetermined rate by continuous subcutaneous infusion. The most common clinical use for the syringe driver is in palliative care when the oral route may not be available and other routes, e. Typical indications for their use are:1 * Dysphagia * Unconsciousness * Intractable nausea and vomiting * Intestinal obstruction * Malabsorption * Intolerability of the oral route. Common infusion sites used are the upper chest wall, the upper arm or thigh, the abdomen and occasionally the back. Sites to be avoided include oedematous areas (due to poor absorption), adjacency of bony prominences or joints, inflamed or infected sites, the upper abdomen if there is an enlarged liver, the upper chest wall if the patient is very cachexic, and previously irradiated skin (within the last 8 weeks). One delivers medication by the hour and the other delivers medication by the day (or 24-hour period). Practitioners should check with their Medical Devices department which type is used in their organisation. The British National Formulary also carries some limited information about compatibilities in the section â€˜Prescribing in palliative careâ€™. If it is not possible for a practitioner to verify whether a particular combination of drugs is compatible, options include: * For a given indication, seeking alternate drugs for which compatibility has been validated * Using a second driver at a different site * Administering some drugs as subcutaneous injections, e. Check that the driver is in full working order, and does not require a new battery. Calculate the volume of drugs to be given (before dilution) and pick an appropriate size of syringe to hold the final volume. Consideration should be given to the order in which the drugs are introduced into the Appendix 9 Syringe drivers | 895 syringe because of possible incompatibilities during the preparation process. The syringe should be labelled with the patientâ€™s name, the time and date of preparation and the drugs and doses contained. The label should not totally obscure the fluid in the barrel as this requires subsequent measurement. The infusion set can then be primed if necessary with the infusion fluid to expel all the air from the tubing. This length is dialled into the driver to set the rate of movement of the plunger over the next 24 hours. Theskin isreleased and the butterfly is secured in position with a clear film dressing. The start button can now be pressed, the transparent cover placed on the driver and the device placed in a safe, convenient place next to the patient. A fabric bag with a drawstring opening is often used to conceal the driver in a discreet fashion. The driver should also be checked to ensure that it is functioning correctly and there is no sign of precipitation in the syringe. Because of minor variations the accuracy of syringe driver infusion rates, the driver should be checked at least 1 hour before the anticipated finish of the infusion to check that a replacement is not required. Drivers should be cleaned after each use with a disposable cloth dampened with a mild detergent. Troubleshooting If the infusion has finished early this may indicate that:1 * The rate was incorrectly set. If the infusion finishes late this may indicate that: * The rate was incorrectly set. Protocol for the use of Graseby syringe drivers for subcu- taneous use in palliative care. The drug might therefore accumulate in the body, potentially resulting in serious adverse effects. In order to prevent this, the dose should be adjusted or the drug avoided altogether if necessary. The monographs in this book give some guidance on this but specialist texts such as The Renal Drug Handbook should be consulted if necessary. F Ã‚Ã°140Ã€ageÃžÃ‚weight Ã°kgÃž* Creatinine clearance Ã°mL=minuteÃžÂ¼ Serum creatinine Ã°micromol=LÃž where FÂ¼1. Appendix 10 Ideal bodyweight, dosing in patients with renal or hepatic impairment | 897 Dose adjustment in impaired liver function Drugs metabolised or excreted by the liver may accumulate in the body if liver function is impaired. The monographs in this book give some guidance on this, but determining the degree of hepatic impairment is much more difficult than with renal function. Several methods exist but the most commonly used is the Child--Pugh classification,4 which has been developed as a prognostic tool in chronic liver disease. For the Child--Pugh classification, five clinical measures of liver disease are given scores of 1, 2 or 3 points in increasing severity as shown in Table A10. The scores for each parameter are added together and the degree of hepatic impairment is categorised as Child--Pugh class A to C as follows: * 5--6 points Class A * 7--9 points Class B * 10--15 points Class C Table A10. For the purposes of certain monographs this classification is all that may be needed. As a prog- nostic tool, however, the classification is used by clinicians to determine the survival chances of apatient. The risk scores are presented as a grid displaying pictorial icons for theindividual risk category and the score is the summation of these categories. The eight risk categories are: Therapeutic risk: where there is a significant risk of patient harm if the injectable medicine is not used as intended. Use of a concentrate: where further dilution after reconstitution is required before use, i. Complex calculation: any calculation with more than one step required for prep- aration and/or administration, e. Complex method: where more than five non-touch manipulations are involved, or other steps including syringe-to-syringe transfer, preparation of a burette, the use of a filter. Reconstitution of powder in a vial: where a dry powder has to be reconstituted with a liquid. Use of a part vial or ampoule, or use of more than one vial or ampoule is required: e. This risk is symbolised by showing more than one vial with the second vial only half used. Use of a pump or syringe driver: all pumps and syringe drivers require some element of calculation and therefore have potential for error; and the potential risk is considered less significant than the risks associated with not using a pump when indicated. Appendix 11 Risk ratings | 899 Use of non-standard giving set/device required: examples include light-pro- tected products, low adsorption, use of an in-line filter or air inlet. This risk is symbo- lised by a square peg in a round hole to indicate something of a non-standard nature. Itispossible thattheriskscoremayvarydependingonthemethodofadministration;for example, a direct intravenous injection may score lower than an infusion as there is no further dilution involved and therefore one less risk factor. In these scenarios the risk rating at the end of each monograph is always for the highest rated assessment unless otherwise stated. It is vital that a local risk assessment accounts for method of administration in any given clinical area, so the risk score may be moderated to reflect local practice. In all areas, appropriate competence is essential for healthcare professionals working with injectable medicines to give assurance of safety.
Crystallisation orturbidity preparation may develop at any time; inspect during infusion and discard if present 20mg pariet for sale gastritis diet treatment inflammation. Monitoring Measure Frequency Rationale Plasma At intervals of * In samples taken 12 hours after administration order pariet 20 mg amex gastritis diet ìóëüòôèëüìû, if the concentration of 2--3 days in renal sulfamethoxazole concentration exceeds 150 sulfamethoxazole impairment micrograms/mL then interrupt treatment until the value falls below 120 micrograms/mL order pariet 20 mg otc gastritis from alcohol. Renal function and Periodically buy discount pariet 20 mg on line gastritis eating out, but * Contraindicated in severe renal insufficiency where serum Na and K more frequently repeated measurements of the plasma concentration if known renal cannot be performed. Action in case of Symptoms to watch for: Nausea, vomiting, dizziness and confusion. Counselling The development of rash, sore throat, fever, pallor, arthralgia, cough, shortness of breath, purpura, or jaundice may be an early sign of a serious adverse reaction. This assessment is based on the full range of preparation and administration options described in the monograph. Cyanocobalam in (vitam in B12) 1mg/mL solution in ampoules * Vitamin B12, a water-soluble vitamin, occurs in the body in various forms including cyanocobal- amin. Deficiency may occur in strict vegetarians, in patients with malabsorption syndromes or metabolic disorders, or in patients following gastrectomy or extensive ileal resection. Deficiency results in megaloblastic anaemias, demyelination and other neurological damage. Onlyhydroxocobalaminisusedtotreat tobacco amblyopia and Leberâ€™s optic atrophy (use of cyanocobalamin may allow these optic atro- phies to degenerate further). Pre-treatment checks * Do not use for the treatment of megaloblastic anaemia of pregnancy unless a definite diagnosis of vitamin B12 deficiency has been established. Biochemical and other tests Electrolytes: serum K (cardiac arrhythmias secondary to #K during initial therapy have been reported -- correct if necessary). A baseline assessment of neurological function is useful to assess impact of treatment in cases of vitamin B12 deficiency anaemia with neurological complications. Prophylaxis of macrocytic anaemias associated with vitamin B12 deficiency: 250 micro- grams--1mg monthly. Technical information Incompatible with Not relevant Compatible with Not relevant pH 4. Monitoring Measure Frequency Rationale Serum K Daily for first 48 hours, * If #K occurs, correct potassium levels, consider then consider 2--3 times withdrawing cyanocobalamin and monitor weekly during acute cardiac function. Reticulocyte and * Generation of new reticulocytes and erythrocyte count erythrocytes supports a diagnosis and treatment of vitamin B12 deficiency anaemia. Additional information Commonandserious Hypersensitivity reactions (rash, pruritus, rarely anaphylaxis); pyrexia; chills; hot undesirable effects flushes; dizziness; malaise; nausea; diarrhoea; acneiform and bullous eruptions. Significant Vitamin B12 assay: anti-metabolites and most antibiotics invalidate vitamin B12 interactions assays by microbiological techniques. This assessment is based on the full range of preparation and administration options described in the monograph. Cyclizine | 193 Cyclizine 50mg/mL solution in 1-mL ampoules * Cyclizine lactate is an antihistamine with antimuscarinic activity and mild sedative effects. It may also be used to treat vomiting and attacks of vertigo associated with Meniereâ€™s disease and other vestibular disturbances. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Monitoring Measure Frequency Rationale Improvement in nausea and Periodically * For signs of clinical vomiting or dizziness improvement. Additional information Common and serious Immediate: Anaphylaxis and other hypersensitivity reactions have undesirable effects been reported. Injection/infusion-related: * Too rapid administration: Transient paralysis has been reported. Other: Drowsiness, urticaria, rash, headache, dryness of the mouth, nose and throat, blurred vision, "pulse, urinary retention, constipation, restlessness, nervousness, insomnia and auditory and visual hallucinations. Significant interactions * Cyclizine may "sedative effect of opioid analgesics and other sedating medicines. Action in case of overdose Stop administration and give supportive therapy as appropriate. This assessment is based on the full range of preparation and administration options described in the monograph. Pre-treatment checks * Avoid in acute bacterial endocarditis, major bleeding or high risk of uncontrolled haemorrhage including recent haemorrhagic stroke. If treatment is required beyond 8 days, reduce the dose to either 5000 units (women <80kg, men <70kg) or 7500 units (women! For treatment doses either monitor anti-Factor Xa levels or use unfractionated heparin. For treatment doses either monitor anti-Factor Xa levels or use unfractionated heparin. Dose in hepatic impairment: the manufacturer advises to avoid in severe hepatic impairment. Pinch up a skin fold on the abdominal wall between the thumb and forefinger and hold through- out the injection. Dalteparin sodium | 199 Intravenous infusion via a syringe pump (haemodialysis only) Preparation and administration 1. Technical information Incompatible with No information Compatible with Flush: NaCl 0. In use: Vials should be stored below 30 C and contents used within 14 days of first use. Stability after From a microbiological point of view, prepared infusions should be used preparation immediately; however, the preparation is known to be stable at room temperature for up to 24 hours. Monitoring Measure Frequency Rationale Platelets Alternate days from * Thrombocytopenia can occur in this period of therapy. Serum K After 7 days * Heparins #secretion of aldosterone and so may cause "K (especially in chronic kidney disease). Bleeding Throughout treatment * Low bodyweight: In women <45kg and men <57kg there is a higher risk of bleeding with prophylactic dalteparin doses. Anti-Xa activity If indicated * Not required routinely but may be considered in patients at "risk of bleeding or actively bleeding. Other: Risk of bleeding with organic lesions, invasive procedures, asymptomatic thrombocytopenia during the first days of therapy, clinically significant "K in patients with diabetes or chronic renal failure. This assessment is based on the full range of preparation and administration options described in the monograph. Danaparoid should be started preoperatively; thelast preoperative dose being given a minimum of 1--4 hours before surgery. Pinch up a skin fold on the abdominal wall between the thumb and forefinger and hold through- out the injection. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Intravenous infusion via a syringe pump Preparation of a 200 anti-Factor Xa units/mL infusion with a total volume of 22. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Technical information Incompatible with No information Compatible with Flush: NaCl 0. Monitoring Measure Frequency Rationale Platelet count (patients Daily * To rule out cross-reactivity (#platelets). Signs and symptoms Continuously * If danaparoid is administered in the context of of neurologic peridural or spinal anaesthesia, extreme vigilance impairment (peridural and frequent monitoring must be exercised to or spinal anaesthesia) detect any signs and symptoms of neurologic impairment, such as back pain, sensory and motor deficits (numbness and weakness in lower limbs) and bowel or bladder dysfunction. The risk is increased by the prolonged use of these routes, by the concomitant use of drugs affecting haemostasis, e.