The benefts accrued from implementing them are likely to considerably outweigh the upfront investment needed and have the potential to fundamentally change the course of the epidemic order levitra visa goal of erectile dysfunction treatment. It is essential to design strategies to mitigate such events so that continued service delivery can be assured cheap 10mg levitra with visa erectile dysfunction treatment dallas texas, especially for those most in need (20) buy generic levitra 10 mg on-line erectile dysfunction patient.co.uk doctor. Such considerations should not determine whether a particular recommendation is included or excluded from national guidelines but can be used as a tool to understand the impact of a recommendation and how best to adapt it and mobilize resources for its implementation. An implementation plan should clearly defne the set of activities required in a specifed period of time to achieve targeted outcomes, with a clear division of labour among all stakeholders involved in implementing programmes. Robust procurement and supply management systems are needed to ensure the continued availability of all necessary drugs, diagnostics and other commodities across the various levels of the health system. Pooled or joint procurement can be used to secure lower costs through economies of scale, and careful demand forecasting is key to minimizing waste. Fixed-dose combinations and once-daily therapy should be used whenever possible to support adherence and make treatment as convenient as possible for the people receiving therapy and their caregivers. Laboratory capacity must also be reviewed and services should be strengthened to cope with higher demand, and nationally standardized health information systems and patient monitoring tools should be used in all settings. Stronger interventions are also needed to maximize treatment adherence and retention across the continuum of care. Specifc interventions may be needed in particular settings, such as postpartum follow- up of mother–infant pairs. The quality of health care is a critical dimension to consider in the planning and adaptation process. The implementation of new guidelines provides an opportunity to comprehensively review and address such gaps. Critically, this requires effective monitoring and evaluation systems (see Chapter 11). A key component of sound quality assurance mechanisms is a clear delineation of roles and responsibilities for the delivery of the various functions and inputs (such as leadership, fnancing, supply chain management, human resources, monitoring and evaluation needed for effectively providing services at the national, regional, district, facility and individual clinician levels). Planning should also take into account the variety of providers involved in health service delivery, including public, private and not-for-proft organizations. Community involvement and peer outreach strategies are key to improve programme design, promote its sustainability and maximize coverage. Communication, leadership and advocacy Has it been determined who will be responsible for updating currently existing materials, including service delivery guidelines, protocols, clinical and laboratory standard operating procedures, monitoring and evaluation tools, patient monitoring mechanisms or systems, reference manuals, health worker training materials, job aids, supervisory checklists and materials for public information, education and communication? Has it been agreed who will take overall responsibility for advocacy with stakeholders such as political leaders, health personnel and the mass media? Staffing and human resources Has it been determined how many additional workers are required to implement new recommendations? Which cadres of health workers (physicians, health officers, nurses, midwifes, community health workers and laboratory assistants) are needed and how they can be recruited? Can task shifting and sharing be employed to optimize available human resources and expand service delivery? Has it been determined what systems are required for forecasting needs and procuring medicines and other commodities at the best possible prices? Has a transition plan been developed to phase out old medicines (such as d4T) and introduce new ones? Do supply management systems – especially at the peripheral level – need to be strengthened to manage increased demand? Is a regulatory process in place to approve and register new medicines and diagnostics in a timely manner? Are laboratory quality control and external quality assurance systems in place and fully functional? Do national laws allow for the purchase and importation of all necessary commodities? Do services need to be decentralized and/or integrated to support policy implementation? Infrastructure Has the necessary physical infrastructure (such as warehouses, meeting rooms, consultation space, laboratories, pharmacies, administration areas and equipment) and transport infrastructure (such as vehicles) needed to support implementation been identified? Is additional communication infrastructure needed, including between health facilities, health workers, laboratories and clients? Costs Has the total annual investment of implementing new recommendations, including ancillary and other services, been estimated? Can potential cost-savings be achieved through economies of scale or synergies with other interventions and programmes? Monitoring and evaluation Does the monitoring and evaluation plan clearly identify the facility- and programme- level indicators needed to adequately monitor the coverage of interventions and impact of new recommendations? Have the human resources, equipment and infrastructure requirements been identified? Are monitoring and evaluation systems interoperable (between the local and central levels and among various donors) to avoid duplication and ensure consistency? Have the necessary quality control, quality assurance and quality improvement systems been identified and put in place to optimize service delivery? What interventions to promote and reinforce adherence will be implemented for these people? Programme managers need to consider the optimal choice in light of multiple factors, such as the availability of existing infrastructure and the number of people receiving services at different levels of care (such as centralized versus peripheral sites). Review the use of viral load monitoring in the context of alternative patient monitoring strategies. People whose viral load remains detectable following adherence support have probably developed drug resistance and may need to switch regimens. Centralized systems should be enrolled in external quality assurance programmes, while new quality assurance approaches are needed for decentralized and point-of-care systems. Countries may consider a phased approach with an early learning phase before full scale-up. Adherence to therapy and retention in care of mother–baby pairs may be especially difficult in the postpartum breastfeeding period. What process and strategies will be put in place at the policy and service delivery levels to address such possible disparities? Programmes should determine which clinical and laboratory services will be available at what level of the health care delivery system. All health workers, including community health workers, need to be trained regularly, mentored and supervised to ensure high-quality care and implementation of updated national recommendations. Programme managers should support the development and implementation of policies to create a suitable environment for recruiting, retaining and motivating personnel in rural or remote areas, where health worker turnover and attrition may be considerably higher than in urban settings. An effcient division of responsibilities among levels of the health system (national, provincial or regional and district) is crucial to minimize duplication and to optimize the use of resources.
Although a smaller drop may be retained longer in the conjunctival sac order levitra master card impotence australia, the instilled volume less than 8 μl is not recommended due to the difficulty in making up a suitable concentration for the eyedrop discount levitra uk impotence pronunciation. The process of passive diffusion initially involves partition of a drug between the aqueous fluid at the site of the application and the lipoidal cell membrane order genuine levitra online erectile dysfunction causes natural cures. The drug in solution in the membrane then diffuses across the membrane followed by a second partition of drug between the membrane and the aqueous fluids within the site of absorption. Two approaches can be used to enhance corneal drug permeability: • modify integrity of the corneal epithelium transiently; • modify the chemical structure of the drug. Flow from the lacrimal gland dilutes the concentration of drug in the tear film pulled up from the lower marginal strip The first approach can be accomplished by exposing the eye to compounds such as chelating agents and surfactants, but it has hardly been explored due to the sensitivity of this particular tissue. The second approach commonly focuses on changing the physicochemical properties of the drug, such as lipophilicity, solubility and pKa. Physicochemical factors associated with the drug moiety The physicochemical properties of a molecule which affect its absorption across the cornea are broadly the same as those affecting transepithelial absorption at any site and have been discussed extensively in Chapter 1 (Section 1. These factors influence the mechanism and rate of drug absorption through the cornea. This is well illustrated by efforts in developing topically effective carbonic anhydrase inhibitors such as dorzolamide through significant alternations in chemical structure. Prodrug approach In ophthalmic research, a prodrug is designed to be inactive with some degree of biphasic solubility as the cornea is a biphasic tissue in structure. It will be transformed into the active drug by either an enzymatic or a chemical processes in the eye. Due to its increased lipophilicity, 308 dipivefrin penetrates the corneal epithelium 10 times more readily than epinephrine. The higher penetration of the drug results in a smaller dose being required, thus reducing systemic side-effects. For potent drugs such as timolol, which has the potential to cause serious systemic side-effects, such a corresponding reduction would be clinically valuable. By other routes, this can be achieved by adhering a reservoir of drug as a membrane-controlled patch or osmotic pump on the epithelium (see Chapters 4 and 8). However, the function of the eye as a visual apparatus limits the possibility of such an attachment of these dosage forms to the cornea. To optimize ocular drug bioavailability by increasing concentration gradient of the drug, considerable efforts have been devoted to minimize solution drainage. This would improve drug residence time on the sclera and cornea, thereby modifying the drug pulse entry characteristics. Other techniques include the use of novel formulations allowing drugs to be delivered in a controlled manner over a long period. A suitable placement of an eyedrop and a reduced instilled volume also contribute to the improved ocular bioavailability. Viscous systems A popular approach to improve ocular drug bioavailability is to incorporate soluble polymers into an aqueous solution to extend the drug residence time in the cul-de-sac. It is reasoned that the solution viscosity would be increased and hence solution drainage would be reduced. They have common properties: • a wide range of viscosity (400 to 15,000 cps); • compatibility with many topically applied drugs; • increased stability of the lacrimal film. Bioadhesives Bioadhesion is an interfacial phenomenon in which a synthetic or natural polymer becomes attached to a biological substrate by means of interfacial forces. If it involves mucin or mucous-covered membrane, the narrow term mucoadhesion is employed. Bioadhesion has been used to enhance bioavailability of drugs via various other routes including oral (Section 6. Bioadhesion may offer several unique features: 309 • localizing a dosage form within a particular region, increasing drug bioavailability; • promoting contact with the absorbing surface, permitting modification of tissue permeability in a restricted region; • prolonging residence time and reducing dosing frequency. The presence of mucin in the eye allows bioadhesive polymers to thicken the tear film in the front of eye. The hydrophilic groups on mucoadhesive polymers and the large amount of water associated with mucin present two possible adhesion mechanisms: (i) hydrogen bonding and (ii) interpenetration of a swollen gel network with hydrated mucin. Many methods have been used for the assessment of bioadhesive properties, including fluorescent techniques and tensile tests. By using these methods, a number of natural and synthetic polymers have been discovered possessing mucoadhesive properties. Natural polymers Sodium hyaluronate is a high molecular weight polymer extracted by a patented process from sources including chicken coxcombs. It consists of a linear, unbranched, non-sulphated, polyanionic glycosaminoglycan, composed of one repeating disaccharide unit of D-sodium glucuronate and N-acetyl-D- glucosamine. Products based on hyaluronates are widely used in intraocular surgery as a substitute for vitreous humor and as an adjuvant to promote tissue repair. Hyaluronates show a topical protective effect for the corneal endothelium and other delicate tissues from mechanical damage through providing a stabilized hydrogel. Sodium hyaluronate with its unusual rheological quality, producing a rapid transformation from a liquid to a solid character with increasing stress frequency, appears to be beneficial for topical vehicles. The pseudoplastic behavior of hyaluronate solutions, where viscosity is higher at the resting phase, provides a thickened tear film, slow drainage and an improved distribution on the cornea during blinking. Furthermore, the carboxyl groups of hyaluronate form hydrogen bonds with sugar hydroxyl groups of mucin when sodium hyaluronate is applied in the eye, producing an intimate contact with the cornea. These unique properties give hyaluronates great potential in ocular drug delivery. Chondroitin sulphate is another polysaccharide derivative (glycosaminoglycan) with a repeat unit containing β-D-glucoronic acid and D-N-acetyl galactosamine, very similar to hyaluronic acid except for modification of the position of a hydroxyl group and the addition of sulphate groups to the galactosamine residue. Chondroitin sulphate has a good affinity to the corneal surface, preventing premature breakup of the tear film between blinks. Formulations containing chondroitin have been used for the treatment of dry eye and showed superiority to hyaluronic acid in treating severe cases of keratoconjunctivitis sicca. Synthetic polymers Carbomers are poly (acrylic acid) polymers widely used in the pharmaceutical and cosmetic industries. They have several advantages, including high viscosities at low concentrations, strong adhesion to mucosa without irritation, thickening properties, compatibility with many active ingredients, good patient acceptability and low toxicity profiles. These properties have made carbomers very valuable in the field of ophthalmic formulations. Artificial tear products and novel drug delivery systems based on carbomers have been extensively formulated. A recent scintigraphic study on Geltears (a Carbopol 940 based product) showed that the precorneal residence is significantly prolonged by carbomer gel when compared to the saline control. Phase transition systems The introduction in the early 1980s of the concept of in situ gel systems demonstrated that a considerable prolongation in duration of action could be obtained. In situ gelling systems have unique properties, which can make a liquid change phase to a gel or solid phase in the culde-sac upon its instillation into the eye. Three methods have been employed to induce phase transition on the eye surface: change in pH and temperature as well as activation by ions. Cellulose acetate phthalate forms a pH-triggered phase transition system, which shows a very low viscosity up to pH 5. The half-life of residence on the rabbit corneal surface was approximately 400 seconds compared to 40 seconds for saline.
T. Pranck. Cardinal Stritch University. 2019.