By R. Renwik. University of New Orleans.
However order 20mg levitra professional free shipping, the effective surface area for absorption is influenced by the type of dosage form from which the drug is administered discount levitra professional 20mg online, as described below purchase levitra professional 20 mg without a prescription. Molecules (% loss) Degradation 0–15 0–5 Clearance a 0–30 20–50 Deposition (anterior loss) 10–20 10–20 Health status and environment 10–20 10–40 Membrane permeability ab 0–30 20–50 Mucus layer <1 <1 adepends on excipients bdepends on physicochemical characteristics of the drug, e. This property facilitates its physiological role in heat exchange and also potentially, drug absorption. The rich blood supply means that drugs absorbed via the nasal route have a rapid onset of action, which can be exploited for therapeutic gain. In the nasal cavity this is influenced by the rate at which the drug is cleared from the absorption site by mucociliary clearance and by metabolism. While the mucociliary clearance of deposited particles is advantageous if the particles are likely to be hazardous, the clearance of a deposited drug is clearly not beneficial if it prevents absorption. The site of deposition in the nasal cavity profoundly affects the rate of mucociliary clearance of a drug moiety: • Particles deposited on ciliated regions (for example, the turbinates) of the mucosa are immediately available for clearance. As described above, clearance of the bulk of the mucus from the nose to the nasopharynx occurs over 10–20 minutes. This is probably because most of the spray has deposited on non-ciliated regions of the nasal cavity. Deposition site; □ Turbinates; ▲ Nasopharynx ● The implications of this for drug absorption are that administration of a drug as drops may only be suitable if the drug molecule is rapidly absorbed. Those drug molecules which diffuse across the nasal epithelium more slowly will need a longer contact time and may be better administered as sprays. The absorption rate of certain drugs may be so slow that therapeutically active plasma levels are not attained. Such conditions include rhinitis, the common cold, hayfever, sinusitis, asthma, nasal polyposis, Sjogren’s and Kartagener’s syndromes. In addition, environmental factors such as humidity, temperature and pollution can also affect the rate of nasal clearance. The common cold consists of two distinct phases: mucus hypersecretion, followed by nasal congestion. It has been shown that during the former phase, less than 10% of a dose administered as a nasal spray will remain in the nasal cavity after 25 minutes. In contrast, almost all the administered dose will still be present at the site of deposition up to 90 minutes after administration during the nasal congestion phase. This would clearly lead to unpredictable absorption of an administered drug which would be unacceptable for a potent drug with a narrow therapeutic window. The inclusion of a vasoconstrictor such as oxymetazoline in the formulation might relieve such symptoms and provide more reproducible drug absorption. This would be likely to affect drug absorption but not necessarily in a reproducible manner. It has been suggested that the low bioavailabilities of some nasally administered peptides results from their enzymatic degradation in the nasal cavity. The nasal mucosa and fluids have been shown to possess a variety of exopeptidases and endopeptidases (see Section 1. The actions of intracellular enzymes will not be significant if the peptide is absorbed by the paracellular route (see Section 9. Small peptides are relatively resistant to the action of endopeptidases but their activity is significant for large peptides. Although enzymatic activity is present in the nasal cavity, this activity is generally lower than the enzymatic activity of the gastrointestinal tract, making this route an attractive alternative to the oral delivery of enzymatically labile drugs such as therapeutic peptides and proteins. These enzymes are capable of metabolizing inhaled pollutants into reactive metabolites which may induce nasal tumors. Antibodies are secreted in the nasal cavity and may be found in high concentrations in the mucus layer where they are able to neutralize antigens presented to the nasal mucosa. Foreign proteins delivered to the body are capable of eliciting an immune response and indeed antibodies have been detected in nasal secretions in response to the intranasal administration of insulin. Clearly this situation is undesirable since the therapeutic molecule will undergo degradation and the patient is likely to suffer with symptoms associated with allergic diseases such as hayfever. It is possible that pharmaceutical excipients which cause inflammation of the nasal cavity might exacerbate such reactions. One method by which mucus protects the nasal epithelium is by acting as a physical barrier and respiratory mucus has been reported to retard the diffusion of water and a range of β-lactam antibiotics used to treat respiratory infections. However, other studies have shown that antibodies (150–970 kDa) are able to diffuse through cervical mucus relatively unimpeded; these latter studies tend to suggest that the diffusion barrier presented by mucus in the nasal cavity would be insignificant. Positively charged drug molecules can bind to mucus glycoproteins via electrostatic interactions with the large number of negatively charged sialic acid and sulfate ester residues. Such residues have low pKa values and are thus ionized under most physiological conditions. Hydrogen-bonding is also possible, between drugs and the hydroxyl groups on the sugars and other O- and N-containing groups on the protein backbone. Hydrophobic interactions between drugs and a globular protein region of the glycoprotein molecule can also occur. Tetracycline has been shown to bind to gastrointestinal mucus by hydrogen-bonding and via electrostatic and hydrophobic interactions. It has been suggested that cephaloridine and gentamicin bind intestinal mucin via ionic interactions. As has been stressed for all the transepithelial routes in this book, it is important to remember that although a drug molecule may be predominantly absorbed via one particular route/mechanism, it is also likely that sub-optimal transport will occur via alternative routes and mechanisms. Passive diffusion between the cells is driven by a concentration gradient, with the rate of absorption governed by Fick’s first law of diffusion (see Section 1. Again, movement occurs down a concentration gradient, according to Fick’s first law of diffusion (see Section 1. The degree of ionization of a drug species is an important property for absorption via passive transcellular diffusion (see Section 1. Carrier-mediated processes Active transport mechanisms for di- and tri-peptides, as well as L-amino acids, have been demonstrated in the nasal epithelium. Endocytic processes Most compounds of interest for nasal delivery have a molecular weight in excess of 1,000 Da and until recently were thought to cross the cells endocytically. These factors influence the mechanism and rate of drug absorption through the nasal epithelium.
With the advent of laparoscopic and endoscopic techniques in the 1990s generic 20mg levitra professional with mastercard, the management plan becomes more complex generic 20 mg levitra professional free shipping. Individual hospital and physician abilities may inﬂuence the choice and timing of procedures buy 20mg levitra professional amex. The condition results from an imbalance among levels of bile acid, lecithin, and cholesterol in the gallbladder. There are several scenarios in which patients with asymptomatic cholelithiasis should consider prophylactic cholecystec- tomy. These include patients with hematologic disorders, such as sickle cell disease or hereditary spherocytosis. Chole- cystectomy in diabetic patients formerly was thought to require pro- phylactic surgery due to the high rate of gangrenous cholecystitis. Patients with a porcelain gallbladder have a high rate of harboring gallbladder cancer and should have surgery. The majority of otherwise normal patients with asymptomatic cholelithiasis will not suffer an episode of cholecystitis. Jaundice 439 Patients with mildly symptomatic cholecystitis can be managed safely in most cases with laparoscopic cholecystectomy. Although shock-wave lithotripsy, bile acids, and gallbladder perfusion with sol- vents all have been tried to dissolve gallstones, surgery remains the main form of therapy. In elective cases, the rate of conversion to open cholecystectomy is under 5%, and the rate of bile duct injury (a rare but extremely serious complication) is about 3 per 1000 cases. The gallbladder always should be inspected at the time of removal to eval- uate for the rare case of unsuspected gallbladder cancer. Gallbladder cancer is seen in about 1 of 200 cholecystectomy speci- mens and is the ﬁfth most common gastrointestinal tract cancer in the United States. Stage I gallbladder cancer (conﬁned to the mucosa) is treated with simple cholecystectomy. Patients with suspected acute cholecystitis are managed best with intravenous hydration, antibiotics, and cholecystectomy within 24 to 48 hours. The practice of “cooling down” the patient and scheduling elective cholecystectomy at a later date is less desirable than early cholecystectomy. Originally, acute cholecystitis was felt to be a contraindication to laparoscopic cholecystectomy. The majority of patients today can undergo laparoscopic cholecystectomy in the setting of acute cholecystitis if an experienced surgeon is available. Pancreatic adenocarcinoma Cholangiocarcinoma of distal common bile duct Ampullary cancer Duodenal cancer transcystic duct approach or via a choledochotomy. The patient also could be managed primarily with an open cholecystectomy with intraoperative cholangiogram. Ultimately, the experience of the surgical team and gastroen- terologist and the availability of specialized equipment inﬂuence the exact management algorithm at a particular institution. The history of insidious onset of jaundice with weight loss strongly suggests a malignancy. The dilated gallbladder locates the patient’s obstruction at a point distal to the junction of the common hepatic duct with the cystic duct. His laboratory proﬁle, with elevated bilirubin and alkaline phosphatase, would be similar to that of the ﬁrst patient. In addition, metastases can be identiﬁed and surgical resectability often can be predicted based on local involvement of the superior mesenteric artery and vein. Periampullary cancer usually occurs from one of the four causes listed in Table 24. This patient has an ampullary cancer, one of the rarer causes of periampullary obstruction. The silver streaks in the gray stools represent intermittent bleeding into the lumen of the duodenum. Usually, pancreatic adenocarcinoma is the cause of malignant periampullary obstruction. Patients without signs of distant metastases and without signs of local unresectability are candidates for pancreaticoduodenec- tomy—a Whipple procedure. Survival from bile duct, ampullary, and duodenal cancers is slightly better then for pancreatic adenocarcinoma. Most experienced pancreatic surgeons prefer direct referral without any other interventional studies. There is no convincing evidence that preoperative biliary decompression provides any advantage to patients with resectable lesions, and it may be harmful. Jaundice 443 biopsy often can provide a diagnosis, and the patient can receive palliative systemic therapy without requiring an operation. When obstruction occurs in the distal common bile duct, the patient is managed as a patient with periampullary cancer. Intrahepatic cholangiocarcinoma usually does not cause jaundice, since a portion of the liver remains unobstructed. Cholangiocarcinoma in the common hepatic duct or at the bifurcation of the right and left hepatic duct (Klatskin’s tumor) represents the most common site of extrahepatic cholangiocarcinoma. Patients present with obstructive jaundice, but they typically do not have a dilated gallbladder. Ultrasound reveals dilated intrahepatic ducts, but it also reveals a collapsed extrahepatic system and gallbladder. If the tumor is local- ized and there are no distant metastases, resection is indicated. The entire extrahepatic biliary system is removed, and biliary drainage is reestablished with a Roux-en-Y hepaticojejunostomy. Occasionally a partial hepatectomy is required to provide a negative margin of resec- tion. Aggressive surgical resection of hilar bile duct cancer can produce cure (5-year survival) in about 20% of patients. Uncommon Causes There are other rare causes of biliary obstruction that are not related to cancer but that are not secondary to gallstone disease either (Table 24. Patients often are managed initially with endoscopic balloon dilation and stent place- ment. Long-term success usually requires deﬁnitive surgical excision, with reconstruction similar to malignant biliary strictures. The other cause of benign biliary stricture that must be mentioned is sclerosing cholangitis: an inﬂammatory narrowing of the biliary ducts usually Table 24.
State regulations may estab- lish a minimum abstinence period before an Flexibility in thinking generic 20mg levitra professional mastercard, behavior order 20mg levitra professional with amex, and attitudes buy 20 mg levitra professional mastercard. Staff biases, are not judgmental, and do not have members who are in recovery and their col- punitive attitudes toward patients (Bell 2000). At least Staff Retention one study has associated such attitudes with Retaining staff is important for several reasons: lower rates of patient retention and poorer patient outcomes (Caplehorn et al. Staff members can experience permitting staff members to attend offsite burnout when they work in isolation with training during work hours. Managers should take concrete steps ï Encourage professional development by to retain staff, including the following: supporting staff certifications. Even the most ï Offer routine praise and recognition for staff professional, committed counselor struggles contributions and achievements. Staff members usually feel less isolated and overwhelmed Training when a team makes treatment decisions. W hen a lack of cohesion exists, staff members Training should be offered for all staff mem- risk burnout, disillusionment, or cynicism. A bers, including secretaries, nurses, counselors, well-coordinated team also reduces the level supervisors, and managers, to ensure a strong of intrastaff disagreements about patient care knowledge base so that staff members do their and decreases the likelihood of ìstaff split- best and to affirm that all staff members are ting,î when patients pit staff members against valued members of the treatment team. Managers should sional staff members acquire education credits hold regular staff meetings. Staff cooperation to maintain their licensure by offering onsite also can be fostered through training and training, collaborating with other agencies for retreats. The program director or manager reciprocal training, or paying for educational should mediate disputes among staff members. One way to address negative staff Federal and State attitudes is to include successful patients in agencies and profes- training (Bell 2000). Training should ensure that staff events and resource dards require members are knowledgeable about drug materials abuse trends in the community. Staff members should have allow staff from access to generic skills training such as crisis smaller programs to attend their sessions. The importance ing organizations, such as the Association for of emphasizing sensitivity to patient needs Addiction Professionals, and professional should be reviewed periodically. A program physician might members, often the first to speak with patients, educate staff members about the etiology play an important role. A random-callback policy Control Plans avoids patient complaints of being unfairly Federal opioid treatment standards state that ìpicked onî by staff members. All scheduled that patients can substances should be accounted for rigorously the possibility of store medications and inventoried continuously. All from receipt through dispensing and measured take-home medica- at the beginning and end of each workday. W ithin the dispensary, remains misunderstood even among some employees should open the safe or work with health care professionals. Some treatment Transition in Federal oversight of substance providers have overcome community opposi- abuse treatment from the U. Having ade- Children and Family Services, Joint quate onsite staff is equally important in avoid- Commission on Accreditation of Healthcare ing and resolving community problems. Glezen Organizations, National Commission for and Lowery (1999) provide other practical Correctional Health Care, State of Missouri guidelines for addressing community concerns Department of Mental Health Division of about substance abuse treatment facilities. Alcohol and Drug Abuse, and W ashington Community opposition can be triggered when State Department of Social and Health Services community groups believe that they have been Division of Alcohol and Substance Abuseó informed or consulted insufficiently. The relations with the payer community (Edmunds availability of public transportation is impor- et al. Adding designed, and operated in accordance with alternative care models and longer acting accreditation standards, Federal guidelines, pharmacotherapies to the services continuum and State and local licensing, approval, and can decrease loitering, illicit transactions, ille- operating requirements. Staff and patients from the parent organizationís community should be part of a multifaceted, proactive effort relations department. Although program contacts w ith com m unity activities differ in specificity and scope, a Personal contact with community leaders per- community relations plan should address the mits open dialog, information sharing, and dis- following: cussion of community developments, needs, and problems. Occasional becoming increasingly instrumental in empow- press releases can ering patients as active participants in public community notify the public relations, community outreach, and program about specific support initiatives and in local, State, and services demon- services, activities, national community education efforts. Staff members with community improvement and and the general development expertise can support other public. A program organizations in advocacy, promotional, and counter negative support efforts. Consenting patients and staff can professional journals, sponsoring or research organize projects such as community cleanups institutions, provider coalitions, advocacy and neighborhood patrols. Such affilia- Improvement Exchange tions augment community relations efforts ï W hite House Office of National Drug Control through increased professional education and Policy (www. These forums also may present patient advisory committees, patient family 234 Chapter 14 community relations models that can be adapt- an outgrowth of providing service to the public. These patrols should features have been produced, providing impor- emphasize observation, not intervention. Logs tant, accurate information to the public about summarizing observations should be main- the science and policy of opioid addiction and tained. Media outreach can demystify treat- ment programs to provide increased treatment ment, counteract stigma, and improve fairness intensity. Communications should be logged, and staff participation in community events should be Decisions to discharge patients for loitering summarized. Letters and communications should balance consequences for the individual substantiating community complaints and the patient and public health against the need to programís followup should be on file. Confidentiality Medicine hold national and regional confer- remains paramount, so this relationship should ences that bring together treatment providers, be delineated carefully. A database explain how to improve their current treatment should be developed and updated (e. Other number and nature of community complaints sessions may focus on improving staff attitudes 236 Chapter 14 and the treatment system regarding implemen- opportunities of those stigmatized. For example, one application of commercial marketing conference, Blending Clinical Practice and technologies to programs to change social atti- ResearchóForging Partnerships To Enhance tudes. This publication proposed a unique Drug Addiction Treatment, held in April 2002 national approach to reducing stigma that (National Institute on Drug Abuse 2002), incorporates science-based marketing research, incorporated a special forum focused on the a social marketing plan, facilitation and sup- mediaís role in presenting addiction treatment port of grassroots efforts by the recovery and research issues in the context of science community, and promotion of the dignity of reporting. Performance outcome evaluation atic use of prescription drugs focuses on results, for example, patient ï reducing or eliminating associated criminal progress. Process evaluation focuses on how activities results were achievedóthe active ingredients ï reducing behaviors contributing to the spread of treatment.