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Clinical symptoms of intoxication may include thirst cheap liv 52 60 ml on line treatment using drugs, nausea purchase liv 52 200 ml medicine website, vomiting order 100 ml liv 52 fast delivery symptoms dust mites, constipation, polyuria, abdominal pain, mus- cle weakness, mental disturbances, and, in severe cases, cardiac arrhythmia and coma. Inotropic and Vasoactive Drugs 65 or even withdraw the drug and treat symptomatically (significant individual variability). In severe cases, it is recommended to monitor calcium, potas- sium, and magnesium blood levels carefully, to rehydrate the patient with a 0. In cases of extravasation, local administration of phentolamine or papaverine should be considered. Compatible Diluents Calcium chloride may be administered undiluted or diluted in dextrose or in sodium chloride. Concentrations as high as 100mg/mL have been infused through a central line in some institutions. It is incompatible with bicarbonates, sulfates, and phosphates, as well as with some antibiotics (tetracyclines). It must be slowly administered into a central vein, except and in urgent scenarios (at lower concentrations), with an infusion device allowing proper and reliable titration. Liothyronine Indication Liothyronine, also called T3 or L-triiodothyronine, is a thyroid product used for replacement or supplemental therapy of hypothyroidism and chronic thyroiditis. Adult patients who undergo open-heart surgery and receive thyroid hormone supplementation have demonstrated a dose-dependent increase in cardiac output, which has been associated with an improved clinical outcome. However, at present, there is a lack of evidence concerning the effects of triiodothyronine supplementation in infants undergoing cardiac surgery, and further randomized, controlled studies are required. This chapter will primarily discuss the properties of this drug when administered parenterally for the last indication. However, it is known that T3 is involved with the metabolism of almost all body organs. It increases basal metabolic rate, oxygen consumption, and metabolism of carbohydrates, lipids, and proteins. Its use in the perioperative course of pediatric cardiac surgery has been based on the theory that cardiopulmonary bypass suppresses circu- lating thyroid hormone levels, particularly in newborn patients121. Rimensberger Dosing Liothyronine may be used in the perioperative course of pediatric cardiac surgery via parenteral administration as a bolus. Pharmacokinetics Onset of action: a few hours Maximum effect: 48 to 72 hours Duration: up to 72 hours Protein binding: almost nil, which makes it readily available to tissues Metabolism: in the liver to inactive compounds Elimination: 75 to 85% in urine Drug Interactions Liothyronine increases the effect of oral anticoagulants and decreases the action of digoxin and theophylline. Adverse Effects Cardiovascular: palpitations, sinus tachycardia, cardiac arrhythmias, hypertension, angina, congestive heart failure, chest pain. Liothyronine should be used cautiously in patients with ischemic disease Central nervous system: headache, fever, nervousness, agitation, insomnia Gastrointestinal: abdominal cramps, diarrhea, vomiting, increased appetite Cutaneous: alopecia, dermatitis herpetiformis, phlebitis at the site of infusion or injection Neuromuscular and skeletal: tremor Metabolic: use with caution in patients with diabetes mellitus or insipidus, thyroid dysfunction, adrenal insufficiency Other: diaphoresis, heat intolerance, weight loss, fever Poisoning Information Adverse effects caused by excessive doses or altered pharmacokinetics of liothyronine may be observed. In these circumstances, it is recommended to decrease temporarily or even withdraw the drug and treat symptomatically (with significant individual variability). Inotropic and Vasoactive Drugs 67 Compatible Diluents For parenteral administration, it is recommended to dilute a vial of liothyro- nine in 2mL of normal saline, shake it until a clear solution is obtained, and draw the required dose. Levosimendan Indication Levosimendan is a new inodilator used in the treatment of decompensated car- diac failure122–129 and as an elective drug in patients with perioperative risk of ventricular failure23, 130–134. It has also been used in the rescue therapy of patients who have difficulty weaning from cardiopulmonary bypass or from mechani- cal circulatory support126, 135. It has been shown to exert a potent positive ino- tropic and systemic vasodilator effect, thereby significantly increasing cardiac output and decreasing ventricular filling pressures. There are also reports documenting its favorable effect in reducing pulmonary vascular resistance and endothelin-1 levels and in improving right ventricular failure126, 136. Lastly, levosimendan seems to induce a sustained lowering of atrial natriuretic pep- tide, and it has not shown either an arrhythmogenic effect or a drug-mediated increase in neurohormone levels. Pediatric experience is limited to a few stud- ies to date, but the overall reports are very encouraging. It may be used with conventional inotropic support, has a simple dosing regimen, does not alter diastolic function (neutral or positive lusitropic effect), and demonstrates minimal hemodynamic side effects. Mechanisms of Action Levosimendan is a pyridazinone-dinitrate that belongs to a new class of drugs, the calcium sensitizers. In contrast with other inotropic agents, levosimendan is deemed to improve myocardial contractility without increasing intracellular calcium. It acts by binding to myocardial troponin C, causing a conFiguration change in tropomyosin that exposes actin and myosin elements, allowing for a more effective contraction. It offers the advantage of increasing systolic force without compromising coronary perfusion. Rimensberger Neonates, infants, and children: loading dose of 12µg/kg over 1 hour, fol- lowed by a continuous infusion of 0. Adverse Effects Cardiovascular: palpitations, flushing, symptomatic hypotension (very rare) Central nervous system: headache, dizziness, vertigo Gastrointestinal: nausea Cutaneous: irritation at the injection site Poisoning Information Significant adverse effects caused by excessive doses or altered pharmacoki- netics of levosimendan have not been described. In case of any adverse reac- tions, it is recommended to decrease temporarily or even withdraw the drug and treat symptomatically (significant individual variability). Compatible Diluents Levosimendan may be diluted in normal saline or in dextrose solutions and administered ideally in a reliable central catheter, except in an emergency situation. Cardiac performance and mortality early after intracardiac surgery in infants and young children. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants: a comparison of low- flow cardiopulmonary bypass and circulatory arrest. Efficacy and safety of milrinone in pre- venting low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Summary proceedings from the cardiology group on cardiovascular instability in preterm infants. Right ventricular injury in young swine: effects of catecholamines on right ventricular function and pulmonary vascular mechanics. Assessment of splanchnic perfusion with gastric tonometry in the immediate postoperative period of cardiac surgery in children. Single daily dose of digoxin for maintenance therapy of infants and children with cardiac disease: is it reliable? The effect of digoxin on mortality and morbidity in patients with heart failure: N Engl J Med 1997; 336: 525–533. Effect of digoxin on contractility and symptoms in infants with a large ventricular septal defect. Effects of digoxin in infants with congestive circulatory state due to a ventricular septal defect. Further evidence suggesting a limited role of digitalis in infants with circulatory congestion secondary to large ventricular septal defect. Hemodynamic effects of levosimendan compared with dobutamine in patients with low cardiac output after cardiac surgery. Dobutamine compensates deleterious hemodynamic and metabolic effects of vasopressin in the splanchnic region in endo- toxin shock.

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If the malingerer does not immediately agree that he suffers with that symptom order 120 ml liv 52 with amex professional english medicine, he may show up with it at the next interview buy cheap liv 52 60 ml online treatment 2 degree burns. Cases are reported in the literature where the malingerer picked up the most outlandish and unusual suggestions made by the examiner and displayed that bizarre behavior shortly after the interview cheap liv 52 120 ml visa medicine 44390. This may consist of any number of devices, including drugs, electroshock, or hypnosis. In the malingerer the suggested potency of a therepeutic maneuver may shake his confidence and lead to his dropping the symptom. There is much in the literature to indicate that suggestibility is increased when the situation is ambiguous, unstructured, or difficult, and the person has few guideposts on which to rely. Under such -287- circumstances, he seems to be greatly influenced by the attitudes and perceptions of peers and authorities. On the other hand, studies by Spohn (81) and Didato (20) indicate that schizophrenics may be less susceptible to social pressures to conform. They may therefore be less susceptible to suggestions made by an interviewer regarding their improvement or symptoms. The success reported for the Rorschach in detecting malingering seems to follow from the same principles. The malingerer is confronted with an unstructured stimulus, and there is very little in his background or experience which would indicate to him the responses to the Rorschach which would be consistent with the illness he is simulating. Thus, once again, the malingerer would be hampered by inadequate role expectations and an unsatisfactory frame of reference. Whether or not a Rorschach can be changed enough to fool an experienced psychologist is still undetermined. Fosberg (24, 25) asked his subjects to give two Rorschachs, a good impression one and a bad impression one, and when he found high correlations between the scoring categories on the two Rorschachs, he concluded that the Rorschach cannot be manipulated, at least with regard to its formal scoring categories. Carp and Shavzin (16) also asked their subjects to fake the Rorschach, and using a somewhat different method of ordering the data, found correlations between the good impression and bad impression Rorschachs ranging from. The authors state that no attempt was made to determine whether the subjects were successful in altering their responses in the desired direction. In each of these studies, the malingerer is described as constricted, evasive, suspicious, reluctant to respond, and determined not to give himself away. He may appeal for clues on how to respond, show increased reaction times, and may very often attempt to reject a particular card or the entire procedure. The malingerer must deal with the unexpected when he is presented with the Rorschach, and very often he seems to err by giving an extremely poor or wildly bizarre Wechsler and then a constricted, evasive but "good" Rorschach. Thus, there may be inconsistencies not only on the Rorschach but throughout the battery of tests. Ganser Syndrome Before turning to the simulation of mental deficiency and amnesia, it is necessary to mention a pathological state which resembles malingering and resembles psychosis, but which may be neither. In this condition, the person appears to be psychotic, but his behavior is strikingly similar to that of the person who is simulating psychosis. The symptoms are an imperfect representation of the condition they resemble and correspond to the mental picture that the patient might be expected to have of psychosis (32, 53, 86). MacDonald (58) reports that such a patient may enter a room and stand on his head, wear his clothes inside out, eat the skin instead of the banana, and try to light his cigarette with the wrong end of the match. Instead he gives an approximate answer, one which is not too far wrong and is obviously related to the question, but is wrong nevertheless. This has been called "vorbeireden," or talking past the point, and it was first described by Ganser (26). An example of this would be the patient who says that 2 + 2 equals 5, 5 times 5 equals 24, a cat has three ears, and that there are eleven months in the year. These responses are usually given after great deliberation and concentration, and the patient does not appear to be upset or irritated when he is told he is wrong. Almost all authors agree that this peculiar mental state arises when the patient is faced with a crisis and when irresponsibility would help mitigate the crisis. It is differentiated from malingering in that malin- -289- gering is a deliberate pose, whereas the patient is unaware of the driving forces which lead him into the Ganser syndrome (53, 58, 68, 89). Historically it has been considered a hysterical twilight state, characterized by vorbeireden, clouding of consciousness, excitement or stupor, and bizarre behavior (26, 49). More recently it has been considered a last ditch attempt to ward off a real psychosis (54), a prodromal sign of psychosis (53), or an acute epidose superimposed on an actual psychotic condition (2, 8, 61, 82). Golden and MacDonald (32) as well as Tyndel (86) see it as occupying a position intermediate between malingering and hysterical fugue states. Weiner and Braiman (89) feel that it occurs in a setting of hysteria or psychosis, and interpret it as a reaction to intolerable stress in a person who fells utterly helpless and who wishes to throw off his identity and responsibility. They argue that it is not malingering because of the uniformity seen among patients with regard to clouding of consciousness, amnesia, and approximate answers. Although the Ganser state may not result from purposive deception, the overt behavior is similar enough to malingering to make differential diagnosis an extremely difficult problem. Indeed, the examples given of the Ganser state are sometimes indistinguishable from those given for simulation, and the same inconsistencies which establish a diagnosis of Ganser syndrome are on other pages proof positive of malingering. However, Weiner and Braiman (89) point out that the Ganser patient rarely if ever offers a peculiar or approximate answer unless it is solicited, whereas the malingerer is anxious to display his peculiarities. Two differences between schizophrenia and the Ganser state have been noted: (a) the schizophrenic differs in that his responses are given explosively and impulsively rather than with great concentration and thought, and (b) the answers are often irrelevant rather than approximate (53, 58, 89). The Ganser patient also differs from the schizophrenic by being able to adapt himself to the ward situation and to carry out the tasks of the day in a manner which would be inconceivable if he had as advanced a dementia as examination seems to indicate (53). Golden and MacDonald (32) and Tyndel (86) report success in using electroshock therapy with Ganser patients, with only a few courses being necessary. However, the same treatment might be effective with the malingerer for other reasons, and therefore this is not a crucial diagnostic test. The Ganser state may clear fairly quickly with alleviation of pressures, sympathy, and psychotherapy, which can also be the case in malingering. Mental deficiency usually entails a reduced scope of awareness of the environment, failure to discriminate between the consequential and the inconsequential, difficulty in forming concepts and using symbols, and sometimes poor memory. Although low intelligence would not preclude a source from being able to supply some useful information, it might lead an interrogator to reject such a person in favor of a more intelligent source. Although a source may play dumb with regard to certain areas of discussion, it probably is not too likely that he will play dumb in general, or to the degree that he will be classified as defective. His role as a soldier suggests that he has some capacity for training and learning, and if he is a commissioned or noncommissioned officer, the odds are very much against an extremely low level of intelligence. Almost all the studies relating to the simulation of mental deficiency have employed standard psychometric tests of intelligence. In one of the earliest of these (43), naval recruits were asked to behave as if they were defectives, and then their performances were compared with those of true mental defectives. Hunt and Older found that the simulators did not act dumb enough, and as a group, their scores were higher than those attained by true mental defectives. However, more recently, Pollaczek (70) asked college males and naval recruits to simulate feeblemindedness on the comprehension, vocabulary, and similarities subtests of the Wechsler-Bellevue Intelligence Scale (Form I), and found that their mean scores did not differ significantly from the mean scores of the mentally defective control group. However, all -291- these authors would agree that simulated mental deficiency cannot be identified on the basis of total score alone unless that total score is extremely low and there is contradictory information available.

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This system also puts wholesale buying in the hands of a purchaser qualifed to judge product quality order liv 52 200 ml otc 68w medications. The purchaser’s frequent large orders command a collective buying power that controls costs quality 60 ml liv 52 symptoms queasy stomach and headache. Customer loyalty to the CareShop franchise grew quickly in the pro- gram’s frst 4 years (Segrè and Tran liv 52 120 ml lowest price schedule 6 medications, 2008). With 270 outlets, CareShop is one of the largest drug store franchises in Africa (Segrè and Tran, 2008). Drug seller accreditation requires making the best use of the shopkeepers already selling medicines. Part of the project’s success came from its training of motivated drug shopkeepers. Pharmaceutical Task Shifting Training and credentialing of drug shop staff must accompany any successful accreditation program. Task shifting, delegating responsibilities from doctors, nurses, and pharmacists to less specialized lay health work- ers, is a way to improve the shortage of health professionals in developing countries (Fulton et al. There is international sup- port for task shifting in pharmacy, especially in the training of pharmacy technicians, which is often a kind of post–high school vocational training in dispensing medicines (Bureau of Labor Statistics, 2012; Hawthorne and Anderson, 2009). They can, however, help ministries of education and national pharmacy councils identify the competencies a vocational pharmacy worker would need in their coun- try. Their efforts in-country should aim to identify the competencies and Copyright © National Academy of Sciences. Apreku worked on her family farm prior to saving enough money to start her own licensed chemical shop. Apreku explained that the CareShop franchise drastically improved her business in several ways. First, she is able to advise her customers more confdently on the nature and appropriate treatment of their afictions. Second, she is able to ofer her patients better customer service through complementary selling techniques. Apreku’s sales are fve times higher than they were prior to conversion, and she runs the store from 7 am to 10 pm every day with the help of Adams, her son (also pictured)” (Segrè and Tran, 2008, p. Asiam inherited his chemical shop, a converted space attached to his home, from his father and was a licensed chemical seller for nearly 20 years prior to his conversion to CareShop. Commenting on the difer- ence between his business before and after conversion, Mr. Asiam spent roughly $200 on improvements, which include ceiling fans, a refrigerator, and glass display cases. They might also consider developing chains of supervision wherein minimally educated staff manage stock and then report their needs up to someone who is qualifed to identify good-quality wholesalers and buy from them. The committee believes that national pharmacy councils are best able to articulate what the proper reporting chain should be in their country and what minimum qualifcations their countries’ patients will accept. The minimum training for a drug dispenser or pharmacy technician in rural Canada will be dif- ferent from what is suitable to rural Nepal. In any case, there should be emphasis on vocational training to credential medicine shopkeepers and include them in the health system. There is evidence that task shifting can alleviate the pharmacist short- age in developing countries. In Malawi, an emergency training and cre- dentialing program for health workers increased the number of pharmacy technicians by 84 percent between 2004 and 2009 (O’Neil et al. Malawian pharmacy technicians supervise pharmacy attendants, the lower- level staff who stock and dispense drugs, allowing the technician more time for stock management and other more complicated tasks (Shulman et al. Because of task shifting, pharmacy technicians monitor adherence to antiretroviral treatment in Zambia and tuberculosis treatment in urban Uganda (Bolton-Moore et al. Training and task shifting programs that recruit minimally educated shopkeepers are also promising. For example, Kilif, Kenya, is a rural area of 70,000 people with 15 licensed dispensaries and pharmacies and 316 general stores that sell medicine (Marsh et al. A training program for Kilif shopkeepers more than doubled the proportion of antimalarials sold in adequate dosage (Marsh et al. A similar Kenyan program trained mobile wholesalers or wholesaler counter attendants to teach drug retailers about correct malaria drug dosing (Tavrow and Shabahang, 2002). After 6 months, mystery shoppers were nine times more likely to receive the correct drugs in the correct dose from retailers who had participated in the program (Tavrow and Shabahang, 2002). Giving Incentives to Pharmaceutical Personnel Using workers more effciently could do much to remedy chaotic drug retail in low- and middle-income countries, but there is also a problem of retaining trained staff in underserved posts. Even minimal technical train- ing confers a competitive advantage in the labor market, especially in poor countries (Attanasio et al. Newly minted pharmacy technicians or drug dispensers can easily leave their rural Copyright © National Academy of Sciences. This pattern can undermine the best efforts to improve rural-urban equity and should be discouraged, while respecting the individual right to emigrate. Governments should reward service in underserved areas and attempt to mitigate the hardships of these posts. Scholarships for the children of pharmacy staff in underserved areas could assuage fears that a rural posting puts their children at a disadvantage. Efforts to guarantee good schooling for children, possibly through boarding schools or scholarships, could remove a barrier to rural service (Rao et al. Health workers also have concerns about quality of life and physical hardships in rural posts (Rao et al. Subsidized housing or provi- sion of modern living quarters could help in places where this is a common concern. It is also possible to recruit pharmacy technicians and pharmacy assistants from underserved communities. Training students from rural and remote areas is a known way to reduce attrition in these posts (Rabinowitz et al. The Australian Rural and Remote Pharmacy program has successfully increased service to rural and isolated communities, in part through giving scholarships to students from rural backgrounds (see Box 5-4). Internet Pharmacies in Middle- and High-Income Countries Disorganized medicines retail is not confned to developing countries. The previous section describes the large gray market for medicines in ba- zaars and unlicensed drug shops in low- and middle-income countries. The internet serves the same purpose, but mostly in middle- and high-income countries. Illegitimate internet pharmacies are similar to unlicensed drug shops both in the quality of the products they stock, which is poor, and in the lack of offcial oversight of their operations (Crawford, 2003). And, because the internet facilitates easy international sales, online drug stores have spread the problem of falsifed and substandard drugs “from small, unproftable, markets in developing nations to the [drug] industry’s most lucrative markets” (Lybecker, 2007, p. The program aims to improve access to pharmacy services in rural or remote regions and includes a variety of initiatives to improve recruitment and retention of rural pharmacists. The program also increases pharmacy students’ exposure to rural work during their training.

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Permeability The vagina demonstrates a relatively high permeability to many drugs buy generic liv 52 100 ml on-line medications zolpidem, particularly during the late luteal and early follicular phases of the menstrual cycle order 60 ml liv 52 free shipping medications or therapy. Ease of administration Intravaginal dosage forms are relatively easy to administer and offer the feasibility of self-administration buy liv 52 60 ml without prescription treatment 7th march. Patient compliance is generally good, particularly if no leakage or staining occurs. Prolonged retention Prolonged retention of the drug is possible, if the appropriate delivery system such as vaginal silicone ring is used, thereby allowing a reduction in the dosing frequency. Alternative when the oral route is unfeasible The vaginal route may be appropriate in certain situations where the oral route is unfeasible, such as: • patients with nausea and vomiting; • patients with swallowing difficulties; • drugs that cause gastric irritation; • drugs that are unstable in the gastrointestinal fluids; • drugs that undergo extensive first-pass effects in the gut wall or liver. Zero-order controlled release Vaginal drug delivery offers the potential to achieve zero-order controlled release over a controlled period. Adverse effects The relatively low amount of fluids bathing the vaginal mucous membranes means the tissue is prone to adverse reactions, such as local irritation, caused by vaginal devices. Similarly, locally irritating or sensitizing drugs must be used with caution in this route. Furthermore, materials used in vaginal preparations should be sterilized and not act as a growth medium for the proliferation of pathogenic microorganisms, bacteria, fungi, and protozoa. Hormone-dependent changes Cyclic changes in the reproductive system mean that large fluctuations in vaginal bioavilability can occur. Cyclical changes in the vaginal epithelium include changes in the thickness and porosity of the vaginal epithelium, the amount and pH of the vaginal fluids and the degree of enzymatic activity present. Furthermore, estrogen therapy and steroidal contraceptives influence the vaginal fluid, epithelial thickness and vascularity, which also contributes to a lack of reproducibility in the vaginal absorption of drugs. This lack of reproducibility constitutes a major problem associated with vaginal drug delivery and, for drugs with a narrow therapeutic index, such variations may be unacceptable. Leakage The bulbocavernosus muscles which surround the orifice of the vagina are not usually strong enough to retain vaginal preparations in the same way as the anal sphincter retains rectal suppositories. Slipping-out or leakage may occur, particularly in the case of preparations involving a relatively large volume of liquid or semisolid. Life-cycle constraints The vagina is the final part of the internal female genitalia, the parturient canal, and also serves as a passage for the outflow of cervical fluids and the menstrual flow. Menstruation, intercourse, pregnancy and delivery, and other anatomical or physiological changes in the life cycle of women must also be taken into account when the timing and effectiveness of drug application are being considered. Applicability constraints No matter what degree of optimization can actually be achieved via this route, it must be remembered that vaginal delivery is only applicable to approximately 50% of the population. Thus it may be that the true potential of this route lies in the treatment of female-specific conditions, such as in the treatment of climacteric symptoms of the menopause etc. However more recently, the vaginal delivery of estrogens, progesterones and prostaglandins has been considered in term of their systemic, as opposed to merely local, delivery. Current technologies in vaginal drug delivery are increasingly concerned with the systemic delivery of these agents and commercial preparations are now available: 11. This risk can be eliminated by treatment with a progestational agent for up to 14 days a month. These limitations can be overcome by the vaginal administration (tablets, suppositories, gels) of progesterone. Vaginal administration gives higher plasma levels than the oral route and levels are sustained for a longer time (Figure 11. Estrogens are also subject to extensive first-pass effects (it has been shown that these first-pass effects occur predominantly in the intestinal wall, rather than in the liver) after oral administration. Again, vaginal administration of estradiol results in higher bioavailability than via the oral route (Figure 11. A number of different types of vaginal rings containing various progesterones and estrogens have been investigated as a steroidal contraceptive since the mid-1970s, the most successful being a Silastic toroidal- shaped ring. This is designed for insertion into the vagina and positioned around the cervix for 21 days, in order to achieve a constant plasma progestin level and cyclic intravaginal contraception. Although the device is successful in achieving the prolonged release of levonorgestrel, irregular bleeding is a major drawback associated with its use. In postmenopausal women with symptoms of urogenital aging, the vaginal ring gives significantly better, or equal, improvements of vaginal mucosal maturation value and restoration of vaginal pH levels than estradiol—containing vaginal pessaries or conjugated estrogen vaginal creams and is significantly more acceptable. Vaginal administration of progesterone is associated with a “first-uterine-pass effect”, i. Using a human ex vivo uterine perfusion model, the vaginal administration of radioactive progesterone was shown to result in the progressive migration of [ H]3 progesterone into the uterus, where it reached high concentrations in both the endometrium and the myometrium. Furthermore, vaginal administration of micronized progesterone has been shown to enhance progesterone delivery to the uterus by about 10-fold in comparison to im injection, despite the markedly higher (about 7- fold) circulating drug concentration achieved with im injection. Uterine selectivity after vaginal 288 administration has further been observed for both danazol and the β-agonist terbutaline and the vaginal-to- uterine delivery of misoprostol is currently being investigated for the reliable termination of early pregnancy (see below). Hence considerable evidence has accumulated demonstrating that the vaginal route permits targeted drug delivery to the uterus. This phenomenon opens new therapeutic options for the administration of compounds whose primary site of action is the uterus, thereby maximizing the desired effects, while minimizing the potential for adverse systemic effects. The retrieval system comprises a Dacron polyester net which proximally surrounds the insert and has a long ribbon end. The insert is placed in the posterior fornix of the vagina; insertion is performed digitally, thereby obviating the need for speculum examination. The system is effective in producing cervical ripening at term by releasing a small amount of the drug over a prolonged period. Furthermore, the system allows the obstetrician to control the dose administered and to terminate drug delivery by removal of the device, if uterine hyperstimulation or abnormal fetal heart rate changes should occur during the ripening process. Thus the system offers particular advantages in cases where there is concern about fetal condition or a risk of uterine over-activity. Misoprostol The most widely used medical method of terminating second-trimester pregnancy for fetal malformations or previous fetal death is the intravaginal use of prostaglandins; in particular, clinical interest is growing in the use of a synthetic prostaglandin E1 analog, misoprostol. The bioavailability of vaginally administered misoprostol is 3 times higher than that of orally administered misoprostol, which may explain why intravaginal misoprostol has been reported to be more effective than oral misoprostol for medical abortion. Recently, there has been renewed interest in the possibility of delivering therapeutic peptides and proteins via the vaginal epithelium. However, in this investigation, the analog was applied selectively at the early and mid-follicular phases, when the vaginal epithelium is thick and cohesive; greater bioavailability is to be expected during the luteal phase of the cycle, when the epithelium is porous and thin. The uptake of leuprorelin via a variety of routes (iv, sc, rectal, nasal, oral, and vaginal) has been compared in diestrous rats. Insulin Rapid dose-related changes in the plasma glucose and insulin levels have been demonstrated in alloxan- induced diabetic rats and rabbits, after vaginal administration of insulin suspended in a poly(acrylate) aqueous gel (0. However, the hypoglycemic effect was less than that achieved using the rectal route in the same base, or using the ip route. Penetration enhancers may be used to promote peptide absorption across the vaginal epithelium. However, less extensive investigations on the use of penetration enhancers for the vaginal route have been carried out in comparison to other routes, such as intranasal and transdermal (see Sections 9. The mechanism of enhancement of vaginal absorption of peptides by organic acids has been attributed to their acidifying and chelating abilities.

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