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By K. Pakwan. Gordon-Conwell Theological Seminary.

The adherent group consisted of 20 (25%) participants (score of 9) and the nonadherent group consisted of 60 (75%) participants (score 10-36) cheap nicotinell 52.5 mg on line quit smoking 6 months ago how should i feel. Both groups were analyzed in relation to antihypertensive medication adherence or nonadherence and background variables associated with adherence nicotinell 35 mg amex quit smoking 40 days ago. The Shapiro-Wilk test was used to assess normality (Norusis safe nicotinell 52.5mg quit smoking 36 hours, 2008) of independent variables discount nicotinell 17.5 mg without a prescription quit smoking encouraging words. In addition, calculated means, ranges, standard deviations, frequencies, skewness, kurtosis, and graphic plots were analyzed on all continuous data to assess distributions. This was suggestive of a normal distribution allowing use of the independent sample t-test (Gliner & Morgan, 2000; Polit, 1996) to determine if there was a significant difference between the adherent and nonadherent antihypertensive medication groups. Because there was evidence of nonnormality, a two-tailed Mann-Whitney U-test (Gliner & Morgan, 2000) was used to investigate differences between the adherent and nonadherent groups. The Fisher‘s exact test was used to examine the significance of association (contingency) between background and dynamic variables on medication adherence. The procedure follows a hypergeometric distribution under the null hypothesis of independence with fixed margins and is frequently used in place of a phi correlation coefficient when data are sparse (Bower, 2003; Huck, 2008). Fisher‘s exact test does not rely on normality assumptions and uses the exact distribution instead of a normal approximation (Polit, 1996). Variables not previously categorized were divided into quartiles (Q) prior to statistical analysis. Quartile derivations is advantageous because it limits outlier influence (Mertler & Vannatta, 2010; Vogt, 2005). In addition, Fisher‘s exact test could test the significance of the difference in proportions of background and dynamic variables on medication adherence when some of the expected cell frequencies fell below 5 (Polit, 1996). The results displayed in Table 7 show counts and frequencies of all variables as related to the outcome variable medication adherence and provide results of the Fisher‘s exact test. However, the lack of a statistically significant association in a simple contingency table analysis does not rule out ordinal effects or trends that may predict outcome. Influence of Background and Dynamic Variables on Medication Adherence Compliant Compliant Compliant Compliant None of Some of Most of All of Characteristics the time the time the time the time (>14) (13-14) (10-12) (9) Fisher‘s n(%) n(%) n(%) n(%) Exact Test Income Q1 <20,000 7 (37) 7 (33) 7 (35) 8 (40) Q2 ≥20,000- <35,000 1 (5) 7 (33) 7 (35) 3 (15) Q3 ≥35,000- <55,000 6 (32) 4 (19) 2 (10) 6 (30) Q4 ≥55,000 5 (26) 3 (14) 4 (20) 3 (15) 0. This is a semi-parametric regression procedure that examines the association between a set of predictor variables and an ordinal scale outcome variable. The higher scores represent the importance of the dimension (LeBreton & Tonidandel, 2008; Sachdev & Verma, 2004). Conditional maximum likelihood parameter estimates were determined iteratively using an integral approximation (Gail, Lubin, & Rubinstein, 1981). Model fit was assessed using standard regression deviance-based diagnostic plots (Pregibon, 1981). Continuous variables were categorized into quartiles based on the distribution among referent 133 participants. An ―optimal predictive model‖ was identified by retaining variables in a multivariable analysis only if, for at least for one level, p<0. The univariable background variables that predicted medication adherence were participant age and number of medications (see Table 8). In contrast participants who reported taking five to seven medications (Q3) were 3. However, participants who manifested major depressive symptoms were less likely to be adherent to antihypertensive medications as observed by a significant linear trend (P for trend=0. Variables retained in the ―optimal predictive model‖ included participant age, number of medications, and trust in health care provider (see Table 8). However, similar to the univariable case, a significant linear trend was not observed for ―number of medications. In summary, participant age was the only background variable that independently predicted nonadherence to antihypertensive medications in our ―optimal predictive model. Univariable predictors and the optimal predictive model for medication adherence are listed in Table 8. Spearman‘s rho was used to determine the correlation between therapeutic reactance and medication adherence. Based on the results of the Shapiro-Wilk test, there was no significant difference in the verbal subscale (p=. Because the sample size was not equal, Levene‘s test (Polit, 1996) for homogeneity of variance was conducted, and there was no significant difference in the variance of the adherent group and the nonadherent group for the mean verbal subscale (F=. The independent sample t-test revealed no significant difference in the verbal subscale for the adherent (M=29. The basic assumption of the M-C 1[10] is that participants who answer in a socially desirable manner are highly likely to answer in a similar manner on all self-report measures. Low scores on the M-C 1[10] scale reflect socially undesirable or honest answers, high scores reflect socially desirable or dishonest answers, and middle scores reflect a combination of both ("Social desirability scale"). Of all the participants, 63% (n=51) scored in the middle range (4-7) while 19% (n=15) scored in the low range (0-3), and 18% (n=14) scored in the high range (8-10). Participants who engaged in significant amounts of socially desirable responding were not discarded from the study. These data were used to provide a measure to gauge the likelihood that participants were providing honest responses to the self-report measure. Marlowe-Crowne Social Desirability (M-C 1[10] scale was significantly associated with three of the instruments used in this study (see Table 9). A weak negative association was noted with the verbal subscale and total scale of the Therapeutic Reactance Scale. This correlation implies that participants who demonstrated higher verbal and total scale reactance scores tend to be honest. These data imply that participants who reported nonadherence to medication-taking and those who 140 reported depressive symptoms were truthful. Participants were mostly single or married, with a mean age of 48 years and employed full-time. Cardiovascular disease risk factors such as physical inactivity, overweight/obese, and a history of smoking were prevalent in the sample. In the optimal predictive model, only age and trust in health care provider significantly predicted medication adherence. In addition, this study explored the relationship between reactant behaviors and medication adherence. This chapter provides an interpretation of the findings and implications for nursing practice. Element of Health Outcome: Adherence to the Recommended Health Regimen Medication adherence. In the current study, one-fourth of the sample reported total adherence to their antihypertensive medication regimen as indicated by a perfect adherence score (9) on the medication subscale of the Hill-Bone Compliance to High Blood Pressure Therapy Scale. In comparison, almost half of the nonadherent group reported they were not faithful in taking their antihypertensive medications consistently. In addition to adherence issues, the appropriateness of pharmacological management should be evaluated. However, in the optimal predictive model, only age and trust in health care provider significantly predicted medication adherence. Each of these predictors is discussed in more detail under the elements of client singularity. If we use these guidelines for Black women, almost one-third of the participants in this study would meet this criterion.

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One cannot ignore the enormous importance of Fischerisms Howard Fabing and Ray Marr () early detection of an appendix which may burst purchase 17.5 mg nicotinell with amex quit smoking florida free patches. Lecture to Boston Medical Society generic nicotinell 17.5 mg amex quit smoking florida free patches, June () When he lacks mental balance without the pneumonia generic 17.5mg nicotinell with mastercard quit smoking using hypnosis, he is pronounced insane by all smart doctors purchase nicotinell 35mg on line quit smoking encouraging words. Fischerisms Howard Fabing and Ray Marr () The Crack-up ‘Sleeping and Walking’ An insane man is a sick man. Sir Alexander Fleming – Fischerisms Howard Fabing and Ray Marr () British microbiologist A man who cannot work without his A good gulp of hot whisky at bedtime – it’s not hypodermic needle is a poor doctor. Fischerisms Howard Fabing and Ray Marr () Where there is sunshine no doctors are wanted. English lexicographer and translator System einer vollständigen medizinischen Polizei Vol ii () Patience is the best medicine. French anatomist Poor Richard’s Almanack () In vain we shall penetrate more and more deeply the secrets of the structure of the human body, we A ship under sail and a big-bellied woman, shall not dupe nature; we shall die as usual. Are the handsomest two things that can be seen Dialogues des Morts Dialogue V common. We anatomists are like the porters in Paris, who Poor Richard’s Almanack () are acquainted with the narrowest and most In general, mankind, since the improvement in distant streets, but who know nothing of what cookery, eats twice as much as nature requires. Poor Richard’s Almanack () Attributed Nothing is more fatal to Health, than an over Care Sir John Forbes – of it. Scottish physician and editor Poor Richard’s Almanack () In a large proportion of cases treated by He’s the best physician that knows the physicians, the disease is cured by nature, not by worthlessness of the most medicines. Poor Richard’s Almanack () Cyclopaedia of Practical Medicine Be temperate in wine, in eating, girls, and sloth, or Henry Ford – the Gout will seize you and plague you both. If you are healthy, you don’t The patient may well be safer with a physician need it: if you are sick, you shouldn’t take it. Poor Richard’s Almanack () The trouble with the human body as compared with the car is that the exhaust is too near the He that lives upon hope will die fasting. The Way to Wealth Attributed Quacks are the greatest liars in the world except Nicholas J. Contemporary Lecturer in Sociology, Department of Attributed General Practice, University of Sheffield Three elements of surgery define it as different Girolamo Frascastoro – from almost all other clinical specialties: the Italian physician, Verona degree of invasiveness, the use of anaesthetic techniques and its emphasis on sterility. Mothers and fathers, peasants and rulers, children The Social Meaning of Surgery p. Open University Press and greybeards, stood mingled together; all () tortured in soul and foul in body, with scabby skin from which matter oozed. He is the individual Frederick the Great – servant of his individual patient basing his King of Prussia decisions always on their individual interest. Letter to Voltaire () We shall have to learn to refrain from doing things merely because we know how to do them. Men are born with an indelible character Lancet :  () Letter to d’Lembert ()    · . The minute study of the process of rationalization He who is master of his thirst is master of his is perhaps the most significant contribution of health. It requires the most intense love L’amour de la médicine fait le savant; on the mother’s side, yet this very love must help L’amour du malade fait le médicin. Professor of History, Oxford, England Poems, ‘Tobacco’ Wild animals never kill for sport. Man is the only one to whom the torture and death of his fellow- creatures is amusing in itself. Commonly physicians, like beer, are best when Bartlett’s Unfamiliar Quotations Leonard Louis Levinson they are old, and lawyers, like bread, when they The true believer is in a high degree protected are young and new. Gaddum – physician is bound to take up the position of British professor of physiology teacher and mentor, but it must be done with great caution, and the patient should be educated Patients may recover in spite of drugs or because to liberate and to fulfill his own nature and not to of them. Laurence, Churchill Livingstone, Edinburgh (), Frontispiece The poets and philosophers before me have discovered the unconscious; I have discovered the Gaelic proverb scientific method with which the unconscious can be studied. The Dispensary Of Protecting the Health Bk  Dear gentlemen, let me die a natural death. Most physicians are like athletes who aspire to Brewer’s Dictionary of Phrase and Fable (centenary edition), victory in the Olympic Games without doing revised by Ivor Evans () anything to deserve it; for they praise Hippocrates as first in the art of healing but make no attempt John Gay – to resemble him. The silent doctor shook his head, Attributed And took his leave, with signs of sorrow, All who drink of this remedy recover in a short Despairing of his fee tomorrow. Sir Auckland Geddes – Attributed British surgeon and politician Employment is nature’s physician, and is essential So many come to the sickroom thinking of to human happiness. We must be daring and search after Truth; even if The Practitioner we do not succeed in finding her, we shall at least come closer than we are at present. To justify that trust, we as a Sir Francis Galton – profession have a duty to maintain a good British scientist and explorer standard of practice and care and to show respect The conditions that direct the order of the whole for human life. Inquiries Into Human Faculty and Its Development ‘The Doctors should take part regularly in educational Observed Order of Events’ activities which develop their competence. In addition, they should respond constructively to Mahatma Gandhi – appraisals of their competence and performance. Doctors cruelly and needlessly prolong the lives of For the Prevention of Hereditarily Diseased Offspring  July, the dying (for reasons) of avarice and passion for () technology. Archives of Internal Medicine : – () German proverbs A half doctor near is better than a whole one far Sir William S. Paul Gill Contemporary British anthropologist and nurse When the boy is growing he has a wolf in his belly. Brain death may very well be a distinct, Man without woman is head without body; physiological entity but this concept of death is woman without man is body without head. Care of the Critically Ill :  () The garden is the poor man’s apothecary. Sir Harold Gillies – Edward Gibbon – Plastic and burn surgeon English historian It is terrifying to think what will happen when the That salutary and lucrative profession. Anybody would be able to go into his local organ bank and, for a not insurmountable sum, Kahlil Gibran – trade in a weak heart or a feeble brain for a better Syrian writer and painter one, or a cirrhotic liver for a healthier one. You may give them your love but not your In Principles and Art of Plastic Surgery with Ralph Millard () thoughts. There is no better training for a surgeon than to be taught observation by a physician. You may house their bodies but not their souls, In Principles and Art of Plastic Surgery with Ralph Millard For their souls dwell in the house of tomorrow, Vol. The great ignominy to the plastic surgeon is his The Prophet ‘On Children’ inability to remove a scar without leaving another one. André Gide – In Principles and Art of Plastic Surgery with Ralph Millard French writer Vol. Hospitals tend to weaken the family tie by awesome and to some terrifying powers over life separating the sick from their homes and their and death—must continue to earn that public relatives, who are often too ready to relieve trust by being absolutely clear that the law as it themselves of the burden of the sick. But when all usefulness is over, when Medicine absorbs the physician’s whole being one is assured of an unavoidable and imminent because it is concerned with the entire human death, it is the simplest of human rights to choose organism. No skill or art is needed to grow old; the trick is to Note written before her suicide,  August () endure it. Attributed The medical student is likely to be one son of the family too weak to labour on the farm, too Oliver St. John Gogarty – indolent to do any exercise, too stupid for the bar and too immoral for the pulpit.

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What is the primary pathogenic process buy nicotinell 17.5mg low cost quit smoking patches, and has it progressed to a secondary process? Infancy and early childhood is the haven for congenital and nicotinell 17.5mg with amex quit smoking vapor sticks, to a lesser degree discount nicotinell 17.5mg on-line quit smoking and weight gain, infectious diseases buy 17.5mg nicotinell mastercard quit smoking 51, while, in the aged, neoplastic and degen- erative cardiovascular diseases predominate. Young and middle-aged adults are more likely to exhibit the consequences of substance abuse, alcoholism, sexually transmitted diseases, and trauma. Preex- isting chronic diseases and medications used for their management may predispose the patient to certain disorders, as do certain occupa- tional, dietary, and behavioral practices. The subjective (S) and objective (O) data obtained from the history, physical examination, and laboratory studies are integrated to reach an initial assessment (A) of the clinical problem. This is the working or initial diagnosis from which a reasoned management plan (P) can be formulated. If the initial assessment is that a surgi- cally treatable, catastrophic, life-threatening emergency is present, an immediate surgical intervention is indicated. Catastrophic Surgical Abdominal Emergencies Major Intraabdominal Bleeding Aneurysmal disease of major arteries is the most common etiology for nontraumatic severe intraabdominal bleeding. To avoid the high mortality of aortic aneurysm rupture associated with shock no matter how treated, a prompt diagnosis based on a high level of suspicion is required. The temptation to transport the patient to the radiology depart- ment for confirmatory imaging studies or attempts at prolonged preop- erative resuscitation should be avoided. Recognition and treatment of a worrisome aneurysm before it ruptures is clearly the best course. Other potential sources of intraabdominal bleeding are iliac and vis- ceral aneurysms, notably of the hepatic and splenic arteries, the latter often rupturing during pregnancy. Still other sources of intraabdominal apoplexy are ruptured ectopic pregnancy; spontaneous rupture of the spleen; hemorrhage into and from necrosing neoplastic lesions of the liver, kidneys, and adrenal glands; and hemorrhagic pancreatitis. Spontaneous intra- and retroperitoneal bleeding also may occur after minimal, often unrecognized, trauma in patients with coagulopathies. Wise Acute thromboembolic occlusion of major mesenteric arteries with intestinal infarction is a dramatic event with rapidly progressive life- threatening consequences. The initial abdominal pain is sudden, severe, and diffuse, with an associated transient hyperperistaltic response. Typically, the pain remains constant and quite severe, in con- trast to the few, if any, abdominal physical findings. This acute embolic syndrome requires prompt diagnosis, laparotomy, and, where indicated, embolec- tomy and/or resection of necrotic bowel. Thrombotic occlusion of mesenteric arteries and veins also can be associated with heart failure, hypoperfusion, or shock. Case Discussion The patient in Case 1 requires resuscitation and, most likely, operative treatment. His irregular heart rate and medication list lead one to believe that he has an atrial fibrillation. In addition, his recent myocar- dial infarction and coronary artery bypass procedure highlight under- lying cardiac disease. Performing an angiogram and thrombolitic therapy is an option if he does not develop peritonitis and his overall clinical picture improves with fluid resuscitation; however, he is at great risk for transmural ischemia that will require resection in the operating room. Gastrointestinal Perforation and Generalized Peritonitis Another disastrous scenario is generalized peritonitis due to a free perforation of a hollow viscus containing noxious or infectious mate- rial. Duodenal and gastric ulcers are the most common cause of per- foration of the gastrointestinal tract in adults. Although many of these patients have a history of ulcer or at least have experienced several days of epigastric discomfort prior to a perforation, it is not unusual for acute perforation to occur unexpectedly. The perforation is heralded by the sudden onset of severe general- ized abdominal pain and anterior wall muscle guarding. The wide- spread spill produces inflammation of all of the peritoneal surfaces, sequestration of fluid, cessation of intestinal motor activity, and dra- matic incapacitation of the patient. Colonic perforation may occur at the site of diverticular disease, severe transmural inflammation as in toxic dilatation of ulcerative colitis, or transmural cancer. The consequences of colonic rupture usually are more serious because of the large inoculum of fecal bacteria. Small-bowel perforation is relatively rare, but it may be encountered as a complication of small-bowel obstruction or severe necrotizing enterocolitis in infants. With rare exceptions, surgical management is required in cases of free perforation. The Acute Surgical Abdomen Intraabdominal conditions producing localized or regional peritoneal signs often are accompanied by a systemic inflammatory response that characterizes the acute surgical abdomen. The majority of these conditions arise from infections of obstructed ducts or diverticular outpouchings of the gastrointestinal tract and, less often, the genitourinary tract. Appendicitis Appendicitis is the most common of the intraabdominal inflam- matory disorders, occurring in both genders and in all age groups. It is most common in older children and young adults, but it does occur in the extremes of age when it is more difficult to diagnose and treat. In the early stages of the process, the inflammatory edema and dis- tention are confined to the appendix, and the patient perceives visceral pain in the periumbilical area. Appendicitis Psoas abscess Bowel obstruction Pyelonephritis Inflammatory bowel disease Ureteral calculi Mesenteric adenitis Abdominal wall hematoma Cholecystitis Ectopic pregnancy Diverticulitis Ovarian cyst or torsion Leaking aneurysm Endometriosis Perforated ulcer Salpingitis Hernia Mittelschmerz inflammation can proceed to suppuration and, finally, to gangrene of the appendix. Perforation usually leads to local abscess formation; however, in some circumstances, such as in infants with a poorly devel- oped omentum, walling off is inadequate and generalized peritonitis may occur. Signs and symptoms may be confusing when an inflamed appendix is in an atypical location. A retrocecal location may mask anterior abdominal signs and produce pain in the back or flank. A high-riding cecum, with the appendix in the subhepatic area, can mimic acute cholecystitis, while a pelvic location mimics acute salpingitis and pro- duces signs most prominent on rectal and pelvic examination. Other conditions to consider in the differential diagnosis of right lower quadrant pain include mesenteric adenitis in children, cecal or Meckel’s diverticulitis, sigmoid diverticulitis when a redundant sigmoid falls toward the right lower quadrant, acute regional ileitis, and a partially contained duodenal ulcer perforation with contents tracking down the right gutter to the right lower quadrant. In the older age group, cecal carcinoma may cause appendicitis by blocking the appendiceal orifice or may mimic appendicitis when it penetrates the full thickness of the cecal wall. Extraintestinal conditions in the dif- ferential diagnosis are any of the many inflammatory and hemorrhagic conditions of the internal female genital tract and urinary tract dis- orders, such as ureteral colic, pyelonephritis, perinephric abscess, and renal carcinoma (tumors that outgrow their blood supply necrose cen- trally and bleed). Diverticulitis Ureteral calculi Bowel obstruction Abdominal wall hematoma Inflammatory bowel disease Ectopic pregnancy Appendicitis Ovarian cyst or torsion Leaking aneurysm Endometriosis Hernia Salpingitis Psoas abscess Mittelschmerz Pyelonephritis 21. Abdominal Pain 391 Case Discussion The young man portrayed in Case 2 presented to the infirmary with typical signs and symptoms of appendicitis. After waiting long enough to ensure an empty stomach and after the infusion of intravenous electrolyte solution and antibiotics, an appendectomy is performed through a small, lower right muscle-splitting incision. An edematous and hyperemic appendix is found and removed, and there is no evi- dence of perforation or pus in the area. The patient makes an unevent- ful recovery and is discharged from the hospital on the second postoperative day. This is a classic example of the progression of a visceral, pathologic process and its associated pain to a process affecting the parietal peritoneal sur- faces and changing into somatic pain. Most older adults in the United States have some colonic diverticula, and diverticulitis of the descending and sigmoid colon is not unusual. The gamut runs from mild attacks treated in the ambulatory setting with bowel rest and oral antibiotics to severe trans- mural and pericolonic infection. Free perforations and fecal peritonitis may occur occasionally, but most perforations are localized and Figure 21. A 14- year-old boy is brought to the emergency department by anxious parents because he has been vomiting and has abdominal pain. Laparotomy Laparoscopy Shorter time in operating room Diagnosis of other conditions Lesser cost of operation Decreased wound infection Overall lesser cost of hospital stay Minimal decrease in hospital stay Possibly less risk of intraabdominal Possible decrease in time for abscess in perforated cases convalescence and return to work or normal activity Source: Based on meta-analysis and reviews of prior prospective controlled randomized trials (level I evidence), including Br J Surg 1997;84:1045–1050, Dis Colon Rectum 1998;41:398–403, J Am Coll Surg 1998;186:545–553. Small intestinal diverticuli are less common, but these do occur in the distal duodenum and the periampullary region.

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Poor drug bioavailability may thus be expected from an absorption site in which enzyme activity is high 17.5mg nicotinell sale quit smoking journals, such as the gastrointestinal tract generic nicotinell 35mg overnight delivery quit smoking 6 weeks pregnant. Furthermore discount nicotinell 17.5mg visa quit smoking meds, drugs which are orally absorbed must first pass through the intestinal wall and the liver cheap 35 mg nicotinell with mastercard quit smoking using laser therapy, prior to reaching the systemic circulation. Contact time As described above, the length of time the drug is in contact with the absorbing tissue will influence the amount of drug which crosses the mucosa. Materials administered to different sites of the body are removed from the site of administration by a variety of natural clearance mechanisms. For example, intestinal motility moves material in the stomach or small intestine distally towards the large intestine; it has been estimated that in some cases residence of a drug in the small intestine can be in the order of minutes. In the nasal cavity and the upper and central lungs, an efficient self-cleansing mechanism referred to as the “mucociliary escalator” is in place to remove any foreign material, including undissolved drug particles. Particulates entering the airways are entrapped within a mucus blanket and ciliary action propels the mucus along the airways, to the Table 3. Typical vaginal delivery systems such as foams, gels and tablets are removed in a relatively short period of time by the self-cleansing action of the vaginal tract. In the eye, materials are diluted by tears and removed via the lachrymal drainage system. Blood supply Adequate blood flow from the absorption site is required to carry the drug to the site of action post- absorption and also to ensure that “sink” conditions are maintained (see Section 1. Accessibility Certain absorption sites, for example the alveolar region of the lungs, are not readily accessible and thus may require quite complex delivery devices to ensure the drug reaches the absorption site. Lack of variability Lack of variability is essential to ensure reproducible drug delivery. This is a particularly important criterion for the delivery of highly potent drugs with a narrow therapeutic window. Due to such factors as extremes of pH, enzyme activity, intestinal motility, presence of food/fluid etc. Similarly, diseases such as the common cold and hayfever are recognized to alter the physiological conditions of the nose, contributing to the variability of this site. The presence of disease can also severely compromise the reproducibility of drug delivery in the lungs. Cyclic changes in the female menstrual cycle mean that large fluctuations in vaginal bioavailability can occur. Permeability A more permeable epithelium obviously facilitates greater absorption. For example, the skin is an extremely impermeable barrier, whereas the permeability of the lung membranes towards many compounds is much higher than the skin and is also higher than that of the small intestine and other mucosal routes. The vaginal epithelium is relatively permeable, particularly at certain stages of the menstrual cycle. Parenteral drug delivery The main clinical role of parenteral therapy is to administer drugs that cannot be given by the oral route, either because of their poor absorption properties, or propensity to degrade in the gastrointestinal tract. Injections are unpleasant and patient acceptance and compliance via this route are low. Intravenous injections may only be given by qualified medical professionals, making this route expensive and inconvenient. Intramuscular and subcutaneous preparations are self-injectable; however, patients dislike them. In addition, elderly, infirm and pediatric patients cannot administer their own injections and require assistance, thereby increasing inconvenience to these patients and the cost of their therapy. Increased medical complications can result from the poor compliance associated with the parenteral route. There has always been a need for injectable formulations that could offer a prolongation of action similar to that achievable by the oral route. Novel sophisticated implant devices have been developed which can adequately control drug dosage and provide a prolonged duration of effect. Implants are available as biodegradable and non- biodegradable polymeric devices and as mini-pumps, and are described in detail in Chapter 4; new- generation implantable technologies, such as bioresponsive implants, are discussed in Chapter 16. The other major thrust of research in the parenteral field involves the delivery of drugs to specific targets in the body. Parenteral drug delivery and targeting systems are discussed in detail in Chapter 5. Oral drug delivery It is estimated that 90% of all medicines usage is in oral forms and oral products consistently comprise more than half the annual drug delivery market. It is the preferred route of administration, being convenient, controlled by the patient and needs no skilled medical intervention. Considerable success has been achieved with various types of controlled-release systems for peroral delivery, which are used to prolong drug effects. For example, the oral route is highly variable, so that there is considerable potential for bio-inequivalence amongst orally administered drugs. The route is also characterized by adverse environmental conditions, including extremes of pH, intestinal motility, mucus barriers, the presence of p-glycoprotein efflux systems, high metabolic activity and a relatively impermeable epithelium. Buccal and sub-lingual drug delivery 67 Although currently a minor route for drug delivery, the oral cavity is associated with many advantages as site for drug delivery (Table 3. The sub-lingual route is characterized by a relatively permeable epithelium, and is suited to the delivery of low molecular-weight lipophilic drugs, when a rapid onset of action is required. Advanced drug delivery systems such as buccal adhesive patches are now being developed in order to provide prolonged mucosal adhesion and sustained delivery of drugs. Transdermal drug delivery The transdermal route, discussed in Chapter 8, has emerged as a viable alternative route to the parenteral and oral routes, in order to achieve the systemic delivery of drug molecules. Although the skin provides a highly effective barrier against external damage and desiccation, transdermal technology has been developed to overcome this resistance and now several systemically active drugs are delivered transdermally. Advanced delivery systems include transdermal patches, which are now well established and accepted by patients. Technologies under development include, for example, iontophoresis, which uses a small electric current to propel the drug through the skin. Drug delivery via iontophoresis occurs at enhanced rates and amounts in comparison to patch technology, which uses simple passive diffusion. The development of safe, non-toxic absorption enhancers to facilitate transdermal absorption is a further focus of current research. Nasal drug delivery Nasal sprays are commercially available for the systemic delivery of various peptide drugs, including buserelin, desmopressin, oxytocin and calcitonin. Although currently a relatively small market, the nasal route possesses many properties of an “ideal” delivery site (Table 3. New technologies in nasal delivery are primarily concerned with strategies to increase the rate of systemic drug absorption, in particular, in developing absorption promoters with minimal toxicity. Pulmonary drug delivery Drug delivery by inhalation has a long history and is an obvious way of administering agents that act on the respiratory system. A more recent advance has been the investigation of this route for systemic drug delivery, although the morphology of the lungs makes drug access to the airways difficult. Furthermore, particles that gain access to the upper airways may subsequently be cleared by mucociliary clearance mechanisms. Pulmonary drug delivery research is addressing factors such as the use of optimized drug delivery devices and novel drug delivery systems, such as liposomes. Systemic drug delivery via the lungs has largely focused on nebulization procedures, which are the most efficient at delivering the emitted dose to the peripheral lung. Vaginal drug delivery The vaginal route, discussed in Chapter 11, constitutes another mucosal route of emerging importance for systemic drug delivery. As with other mucosal routes, a major challenge lies in the development of safe, non-toxic absorption enhancers, to potentiate drug absorption. Furthermore, the route is only applicable to approximately 50% of the population, so that it may be that the future of this route lies in the treatment of diseases specific or more common to the female population.

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