By V. Zarkos. University of Wisconsin-Madison.
This dis- order may take a chronic generic xalatan 2.5 ml online, indolent course or progress into a true medical emergency characterized by an ‘Addisonian crisis’ – severe nausea and vomiting order 2.5 ml xalatan amex, diarrhea generic 2.5 ml xalatan with visa, abdom- inal pain purchase xalatan 2.5 ml, and hypotension. Pregnancy may exacerbate the course of Addison’s disease; however, the spontaneous abortion rate, prematurity rate, and neonatal outcome are apparently not affected by the disease (Brent, 1950; Satterfield and Williamson, 1976). Chronic adrenal insufficiency requires adequate adrenal replacement in the form of cortisone acetate or prednisone and 9-alpha-fluoro-hydrocortisone. During labor, deliv- ery, and the first few days postpartum, the mother should be monitored closely, ensur- ing a good state of hydration with normal saline and adequate cortisol hemisuccinate 88 Endocrine disorders, contraception, and hormone therapy during pregnancy replacement. It is common for women with adrenal insufficiency to be diagnosed for the first time during the puerperium when they develop adrenal crisis (Brent, 1950). Treatment involves replacement steroids during an Addisonian crisis including cortisol hemisuccinate (Solu-Cortef), with fluid replacement as isotonic saline, and glucose administration. It is used for replacement therapy and to treat allergic and inflammatory diseases. The Collaborative Perinatal Project included 34 pregnancies exposed during the first trimester to cortisone, and the frequency of congenital anomalies among the exposed pregnancies was no greater than expected (Heinonen et al. Prednisone and prednisolone Prednisone and prednisolone are synthetic glucocorticoids. Prednisone is biologically inert but is metabolized in the liver to prednisolone, a biologically active compound. Prednisone and prednisolone are used for replacement therapy and to treat a variety of allergic and inflammatory conditions. Among infants born to 43 and 204 women who had been treated with prednisone/prednisolone during the first trimester of pregnancy, the frequency of malformation was not increased (Heinonen et al. Perinatal death does not appear to be excessively frequent in most series of infants born to women treated with prednisone or prednisolone, but the incidence of fetal growth retardation may be increased (Reinisch et al. No such effect was apparent in two smaller studies, one of which also involved women treated throughout pregnancy (Lee et al. Newborn infants of women who take prednisone throughout pregnancy usually have normal adrenocortical reserves and no symptoms of adrenal suppression (Arad and Landau, 1984). Dose-related fetal growth retardation, cleft palate, genital anomalies, and behavioral alterations occur in the offspring of mice treated in pregnancy with prednisone or prednisolone in doses within or above the human therapeutic range (Ballard et al. Increased frequen- cies of cleft palate are also observed among the offspring of pregnant hamsters treated during pregnancy with prednisolone in doses 80–240 times that used in humans (Shah and Kilistoff, 1976). Corticosteroids in general In one study of 631 whose mothers used therapeutic corticosteroids during the first trimester, the risk of non-syndromic cleft palate was increased more than sixfold (Rodriguez-Pinilla and Martinez-Frias, 1998). However, given the prevalence of the use of these drugs and of cleft palate, the absolute risk is probably less than 1 percent in pregnancies exposed to corticosteroids in the first trimester (Shepard et al. Genital virilization is common in female infants, and both sexes manifest elec- trolyte imbalance and hypotension that can be life-threatening if not promptly treated by steroid hormone replacement. Currently, all known heterozygotes are treated with high-dose glucocorticoids until chorionic villus sampling occurs. If a female fetus is present, treatment is continued because virilization of affected females can be prevented. Medications used to treat congenital adrenal hyperplasia include prednisone, fludro- cortisone (see the section on Medications for Addison’s disease), and dexamethasone. If exposure to oral contraceptives during embryogenesis increases the risk of birth defects, the increase is small compared to the risk of malformations in the general pop- ulation (3. Congenital anomalies were not increased in frequency among more than 500 infants born to women who took oral contraceptives during the first trimester (Harlap and Eldor, 1980; Heinonen et al. A slight increase of congenital anomalies was associated with use of oral con- traceptives in the first trimester in several studies, but it is generally accepted that the risk is not real, or extremely small. No epidemiologic studies have been published regarding malformations in the off- spring of women who became pregnant with a Norplant system in place. Levonorgestrel is the progestin component in many oral contraceptive preparations. When the device is removed or expelled spontaneously, spontaneous abortion is reduced to approximately 20–30 percent, which is much closer to the rates of miscarriage in the general population (Alvior, 1973; Tatum et al. Spermicidal agents (nonoxynols) Spermicidal intravaginal sponges, foams, creams, and suppositories contain nonoxynols, surfactants that are extremely toxic to sperm. The risk of congenital anomalies was not increased in frequency among more than 1200 infants whose mothers used nonoxynol spermicides during embryogenesis (Heinonen et al. Similar results were found in large studies of the frequency of congenital anomalies among infants whose mothers used a multiagent spermicide that contained nonoxynol (Huggins et al. The frequency of heterogenous anomalies (chromosomal abnormalities, hypospadias, limb reduction defects, neoplasms) was statistically increased in more than 700 infants born to women who had used any vaginal spermicide within 10 months of conception (Jick et al. However, method- ological flaws in that study (Cordero and Layde, 1983), combined with simple data errors in classification of spermicidal exposures in the cases, cast doubt on the meaning of this study. It is now widely accepted that neither nonoxynols nor other spermicides are associated with an increased risk for chromosomal abnormalities and congenital anom- alies (Bracken, 1985). A case–control study of the use of topical contraceptives among mothers of infants with chromosomal abnormalities or limb reduction defects found no General hormonal therapy 91 difference in the frequency of spermicide use around the time of conception between the case and the normal control groups (Cordero and Layde, 1983). Women using clomiphene should be cautioned that pregnancy is to be excluded before each new course of the drug. Malformations were not increased in frequency among 1500 infants of women who had clomiphene preconceptionally (Barrat and Leger, 1979; Harlap, 1976; Kurachi et al. Multiple case–control studies of neural tube defects failed to find a signifi- cant association with artificial induction of ovulation and risk of a congenital anomaly (Cornel et al. In a well-designed, case–control study, the frequency of clomiphene usage was not increased among more than 500 women who delivered children with a neural tube defect compared with a sim- ilar number of normal controls (Mills et al. In summary, clomiphene is not asso- ciated with an increased risk of congenital anomalies. It is administered by intramuscular injection and is used to stimulate multiple ovarian follicular development in ovulation induction cycles. No epidemiologic studies have been reported regarding malformations in the offspring of women exposed to Pergonal or Metrodin before or during pregnancy. However, the risk does not appear to be high, although a very small risk cannot be excluded. Leuprolide acetate (Lupron) is an agent that is frequently used for these conditions. Although no epidemiological studies are published of infants born following Lupon therapy, it is 92 Endocrine disorders, contraception, and hormone therapy during pregnancy unlikely that the risk of congenital anomalies is high following exposure to this drug during pregnancy (Friedman and Polifka, 2006). Typically, administration is begun in the luteal phase of the cycle, when a patient may be in the early stage of a pregnancy. No epidemiologic studies are published on the risk malformations in the offspring of women treated with this drug during pregnancy. Congenital anomalies were not increased in frequency among infants born to women given ethinyl estradiol during embryogenesis or at any time during pregnancy (Heinonen et al. Results from two other studies of ethinyl estradiol use during pregnancy showed that it was not associated with an increased risk of congenital anomalies (Kullander and Kallen, 1976; Spira et al. Congenital anomalies were not increased in frequency in teratology studies of three species of nonhuman primates given large doses of ethinyl estradiol during pregnancy (Hendrickx et al. An increased frequency of intrauterine deaths was observed at doses that were also mater- nally lethal in one monkey species studied. Miscarriages occurred more frequently among monkeys given approximately 100 times the amount of ethinyl estradiol included in oral contraceptive dose regimens (Prahalada and Hendrickx, 1983). In rodent teratol- ogy studies, no increase in the frequency of congenital anomalies after embryonic treat- ment was found, but early intrauterine deaths were increased in frequency at the high- est doses (Chemnitius et al. Among 614 infants born to women who used estrogenic compounds during gestation, an increase in certain congenital anomalies was found – cardiovascular, eye and ear defects, and Down’s syndrome (Heinonen et al. However, this association was reevaluated in another report, and the link between estrogens and cardiac malformations was not borne out (Wiseman and Dodds- Smith, 1984). The malignancy was diagnosed among females 7–30 years old, with a median age of 19 years. Nonmalignant abnormalities, especially adenosis, are common among the daughters of pregnant women who were treated with diethylstilbestrol. Gross structural abnormal- ities of the cervix or vagina are identified in about one quarter and abnormalities of the vaginal epithelium in one-third to one-half of women whose mothers took diethylstilbe- strol during gestation (Bibbo, 1979; Herbst et al.
The idea for such a book grew out from some of the entries in our sister book Clinical Pharmacy Pocket Companion xalatan 2.5 ml visa, which buy xalatan 2.5 ml amex, as well as covering many clinical topics such as electrolyte disturbances and perioperative management of medicines generic xalatan 2.5 ml overnight delivery, also deals with a number of medicines requiring therapeutic monitoring buy discount xalatan online. It became apparent that the benefits of such an approach could be rolled out to a greater number of medicines. This requires organisations to risk assess individual parenteral drugs and put procedures in place to allow them to be handled more safely. The Injectable Drugs Guide is a handbook supporting the risk assessment process (each drug has a risk rating). It also provides a holistic approach to injectable medicines to meet the needs of the many disciplines involved in the clinical use of injectables and also those providing advice about injectable drug use. There are a number of appendices giving further guidance on specific aspects of injectable therapy and additional clinical information (the full list of these is found on the Contents page). This is because there are tight controls around the use of these agents in clinical practice. Their handling in clinical settings is highly protocol driven and locality specific; use by inexperienced individuals is inappropriate. Alistair Gray Jane Wright Vince Goodey Lynn Bruce November 2010 H ow to use the Injectable rugs uide m onographs Each monograph is presented in a format that sequences the information as needed by healthcare professionals from contemplation of treatment, through preparation and administration, to the monitoring that may be required during and after therapy. Monographs are generally presented in the following order: Drug name and form(s) of the preparation(s) Background information about each medicine including, * Type of drug * What it is used to treat (licensed and unlicensed indications and routes) * Additional miscellany of interest to the user * If appropriate, how doses of the drug are usually expressed Pre-treatment checks including, * Contraindications and cautions to be considered prior to use * Any measures and/or tests that should be undertaken before commencing therapy. In some cases these tests are mandatory; in others they are dependent on the circum- stances in which the drug is being used. Dose including indication-specific information and any adjustments required in renal or hepatic impairment. Unless otherwise stated, doses are for adults (child and neonatal doses have not been included). Routes of administration * A series of headings outline the route(s) by which a particular drug may be given; the specifics of preparation and administration are provided for each route. In some cases the individual heading indicates the circumstances in which a particular route is appropriate. However, some monographs use the phrase ‘dilute in a suitable volume of compatible infusion fluid’. In this case the prescriber should choose a volume and fluid that is appropriate to the patient’s needs and clinical condition (compatibility data are given further down the monograph in the Technical Information table). How to use the Injectable Drugs Guide monographs | xi Technical information includes details of: * Incompatibilities with fluids, other drugs by Y-site administration and also some- times with materials * Compatibilities with infusion fluids and also drugs where co-administration and concentrations are likely to be used in practice. Drugs for which compatibility is concentration-specific are not included in this list. This is not provided so that infusions can be prepared significantly prior to use in a clinical area, but rather to indicate how long a preparation is stable if it is not possible to administer it immediately. Monitoring includes the measures required to ensure the medicine is used safely throughout therapy, the clinical outcome and other parameters that need consider- ation, e. The frequency of monitoring of each parameter is stated and the rationale for monitoring. Additional information includes Common and serious undesirable effects including: * Immediate adverse reactions or those that may occur shortly after administration * Injection- or infusion-related adverse events, either due to rapid administration or those which are injection-site related * Other adverse reactions Pharmacokinetics in the main provides an indication of the elimination half-life of the drug, which can be useful in determining duration of effect. Some monographs provide information on other pharmacokinetic or pharmacodynamic parameters where these might be helpful. Significant interactions drugs are grouped together under subheadings to give an indication of likely effect of the interaction. These lists are not comprehensive and more detailed sources such as Stockley’s Drug Interactions2 should be used if required. Action in case of overdose gives guidance on managing therapeutic overdose of the drug and in most cases lists general supportive measures required. For the management of significant overdose an on-line source such as Toxbase3 should always be consulted. Counselling points are intended to provide a prompt for healthcare professionals as they speak to patients about their therapy. Any other reference source used is stated in the normal way using the Vancouver system of referencing. Feedback Feedback on any aspect of the book would be welcome via the e-mail address pharmpresseditorial@rpharms. Hospital clinical pharmacy beckoned her back to secondary care in 2002: she is now Pharmacy Team Leader on the Medical Assessment Unit at the Royal Blackburn Hospital. Lynn is married and, when she’s not writing pharmacy books, loves studying wildlife and travelling and is addicted to puzzles of all types. Vince Goodey graduated in 1985 from the London School of Pharmacy, and has since worked primarily in the hospital sector in clinical and managerial roles. He studied pharmacy at Sunderland Polytechnic, graduating in 1988 with first-class honours, and then completed his pre-registration year with Boots in Newcastle-upon-Tyne. He continued working for Boots in a variety of pharmacy and store management positions in the North West of England. In 2002 he changed disciplines and became Community Services pharmacist at Queens Park Hospital in Blackburn. He follows Formula One motor racing closely, enjoys reading, eating out, going to the movies, playing guitar and songwriting. Jane Wright, after working for 18 years in the Civil Service, attended the University of Manchester to study pharmacy. Jane graduated in 1994 and did her pre-registration year at the Royal Preston Hospital. For the next ten years Jane worked in Blackburn hospitals in a variety of clinical roles, her last being Clinical Services Manager with responsibility for education and training. In 1999 she obtained a Diploma in Clinical & Health Services Pharmacy at the University of Manchester. Jane is married and in her spare time enjoys playing with Molly and Polly (two very lively dogs). A cknow ledgem ents All the authors would like to thank Cat, Katie, Joanna and Kevin (our contributors) for all their time, expertise and patience. The advice and assistance provided by the National Extravasation Information Service in producing Appendix 6 is gratefully acknowledged. Thanks also to Bruce Burnett who put the original draft of Appendix 6 and Appendix 7 together for the Clinical Pharmacy Pocket Companion. Alistair thanks Rachel, Amelia and Imogen for all their support throughout the creation of this publication. Jane thanks Steve for his tolerance, and apologies to Molly and Polly for all the missed walkies opportunities. Vince thanks Joanne and Josh for their support and Marm for all her well- intentioned but aberrant key padding. Finally we would like to thank everyone at the Pharmaceutical Press who has had a hand in this publication, particularly Christina De Bono, Louise McIndoe, Rebecca Perry and Linda Paulus. Dose in renal impairment: use with caution in severe impairment: "risk of bleeding. Inspect visually for particulate matter or discolor- ation before administration and discard if present. Continuous intravenous infusion Preparation and administration *Filter either at the preparation or at the administration stage. Inspect visually for particulate matter or discolor- ation before administration and discard if present. Giveatthecalculated rate via avolumetricinfusiondevicethrough anin-linenon-pyrogeniclow- protein-binding 0. Technical information Incompatible with No information Compatible with Flush:NaCl0. Stability after From a microbiological point of view, should be used immediately; however, preparation prepared infusions may be stored at 2--8 C and infused (at room temperature) within 24 hours. If platelets drop to: and at 24 hours * 60000 cells/mm3 (60Â109/L), heparin and aspirin should be stopped. Pharmacokinetics Initial elimination half-life is 10 minutes, followed by a second phase of about 30 minutes. Significant * The following may "abciximab levels or effect (or "side-effects): interactions thrombolytics, coumarin anticoagulants, antiplatelet drugs.
Extravasation: where dispersal rather than localisation is indicated order xalatan american express, 1500 units infiltrated into affected area (as soon as possible after extravasation is noticed) cheap xalatan online visa. With subcutaneous infusions Care should be taken to control the speed and total volume of fluid administered and to avoid over-hydration generic xalatan 2.5 ml free shipping, especially in renal impairment order xalatan 2.5 ml on line. Alternatively, it may be injected into the tubing of the infusion set (about 2cm back from the needle) at the start of the infusion. Dissolve 1500 units directly in the solution to be injected (check compatibility). Technical information Incompatible with Benzodiazepines, furosemide, heparin sodium, phenytoin. Monitoring Measure Frequency Rationale Infusion site When the bag is changed or * The site should be moved if pain is more frequently for solutions experienced at the infusion site, if the other than NaCl 0. Additional information Common and serious Immediate: Anaphylaxis has been reported rarely. This assessment is based on the full range of preparation and administration options described in the monograph. The injection is used in management of hypertension with renal complications and hypertensive emergencies particularly those associated with pre-eclampsia and toxaemia of pregnancy. Pre-treatment checks * Avoid in patients with idiopathic systemic lupus erythematosus, severe "pulse, high output heart failure, myocardial insufficiency due to mechanical obstruction, cor pulmonale, dissecting aortic aneurysm; acute porphyria. The rate should be titrated to response and maintenance rate is usually within 50--150 micrograms/minute. Dose in renal impairment: if CrCl < 30mL/minute, the dose or dose interval should be adjusted according to clinical response. Hydralazine hydrochloride | 421 Dose in hepatic impairment: the dose or dose interval should be adjusted according to clinical response. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Continuous intravenous infusion (large-volume infusion) Preparation and administration 1. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Continuous intravenous infusion via a syringe pump Preparation and administration 1. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Technical information Incompatible with Hydralazine is incompatible with glucose solutions. Additional information Common and serious Injection/infusion-related: Local: Pain. Pharmacokinetics Elimination half-life is 2--3 hours but is up to 16 hours in severe renal failure (CrCl <20mL/minute) and shortened to <1 hour in rapid acetylators. Antidote: No known antidote; 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. Hydrocortisone acetate 25mg/mL aqueous suspension in 1-mL ampoules * Hydrocortisone acetate is a corticosteroid formulated for local use only. Monitoring Measure Frequency Rationale Symptoms of septic Following * Marked "pain accompanied by local swelling, arthritis intra-articular further restriction of joint motion, fever, and injection malaise are suggestive of septic arthritis. Additional information Common and serious Injection-related: Intra-articular: Temporary local exacerbation with increased undesirable effects pain and swelling. Pharmacokinetics Absorption after local injection is very slow and is usually completed 24--48 hours after intra-articular injection. Significant A small number of local injections are unlikely to have any significant interactions interactions typical of corticosteroids. This assessment is based on the full range of preparation and administration options described in the monograph. Hydrocortisone sodium phosphate 100mg/mL solution in 1-mL and 5-mL ampoules * Hydrocortisone sodium phosphate is a corticosteroid with both glucocorticoid and, to a lesser extent, mineralocorticoid activity. Pre-treatment checks * Avoid where systemic infection is present (unless specific therapy is given). The dose may be repeated 3--4 times in 24 hours as determined by the patient’s response. Injection into soft tissues: 100--200mg daily; may be repeated on 2--3 occasions depending upon the patient’s response. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. 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. Hydrocortisone sodium phosphate | 427 Monitoring Measure Frequency Rationale Serum Na, K, Ca Throughout treatment * May cause fluid and electrolyte disturbances. Withdrawal During withdrawal and * During prolonged therapy with corticosteroids, symptoms and signs after stopping treatment adrenal atrophy develops and can persist for years after stopping. Signs of infection During treatment * Prolonged courses "susceptibility to infections and severity of infections. Signs of chickenpox * Unless they have had chickenpox, patients receiving corticosteroids for purposes other than replacement should be regarded as being at risk of severe chickenpox. Exposure to measles * Patients should be advised to take particular care to avoid exposure to measles and to seek immediate medical advice if exposure occurs. Significant * The following may #corticosteroid levels or effect: barbiturates, interactions carbamazepine, phenytoin, primidone, rifabutin, rifampicin. Following chronic overdose the possibility of adrenal suppression should be considered. Counselling Patients on long-term corticosteroid treatment should read and carry a Steroid Treatment Card. This assessment is based on the full range of preparation and administration options described in the monograph. Hydrocortisone sodium succinate 100-mg dry powder vials * Hydrocortisone sodium succinate is a corticosteroid with both glucocorticoid and, to a lesser extent, mineralocorticoid activity. Pre-treatment checks * Avoid where systemic infection is present (unless specific therapy given). The dose depends on the severity of the condition and may be repeated at intervals of 2, 4 or 6 hours as indicated by the patient’s response and clinical condition. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Withdraw the required dose and add to a minimum of 100mL of compatible infusion fluid. Inspect visually for particulate matter or discolor- ation prior to administration and discard if present. Technical information Incompatible with Ciprofloxacin, diazepam, midazolam, pantoprazole, phenytoin. Monitoring Measure Frequency Rationale Serum Na, K, Ca Throughout treatment * May cause fluid and electrolyte disturbances. Withdrawal During withdrawal * During prolonged therapy with corticosteroids, symptoms and signs and after stopping adrenalatrophydevelopsandcanpersistforyears treatment after stopping. Signs of infection During treatment * Prolonged courses "susceptibility to infections and severity of infections. Signs of chickenpox * Unless they have had chickenpox, patients receiving corticosteroids for purposes other than replacementshouldberegardedasbeing atriskof severe chickenpox. Exposure to measles * Patients should be advised to take particular care to avoid exposure to measles and to seek immediate medical advice if exposure occurs. Additional information Common and serious Immediate: Anaphylaxis and other hypersensitivity reactions have been undesirable effects reported.