By V. Silvio. University of Wisconsin-Green Bay.

Dependence syndrome A cluster of behavioural discount 250mg biaxin visa gastritis alcohol, cognitive discount 500 mg biaxin visa gastritis symptoms treatment mayo clinic, and physiological phenomena that may develop after repeated Substance use. Typically, these phenomena include a strong desire to take the Drug, impaired control over its use, persistent use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased Tolerance, and a physical withdrawal reaction when Drug use is discontinued (Withdrawal syndrome). Dependence syndrome may relate to a specific substance (eg heroin), a class of substances (eg opioids), or a wider range of pharmacologically different substances. Detoxification A controlled process of providing symptomatic relief to assist patients to complete withdrawal from a Drug, while minimising the associated adverse effects. In the context of Illicit drug use, the aim of detoxification is to reverse or reduce Dependence on and Tolerance to a Psychoactive drug. Diversion From a medical perspective, diversion is the inappropriate use of a Drug by those for whom it has been prescribed, or use by a person for whom the medication was not prescribed. The term may be used to describe diversion of a shipment of drugs out of legal channels at wholesale level or, for example, to describe the sale of prescription methadone to, and use by, an individual for whom it was not prescribed. The term diversion is also used in a criminal justice context to refer to measures that take an arrestee out of the criminal justice system and into education, medical management or another type of intervention. In medicine, it refers to any substance with the potential to prevent or cure disease or enhance physical or mental welfare, and in pharmacology it refers to any chemical agent that alters the biochemical or physiological processes of tissues or organisms. In common usage, the term often refers specifically to Psychoactive drugs, and often, even more specifically, to Illicit drugs, of which there is non-medical use in addition to any medical use. Professional formulations (eg ‘alcohol and other drugs’) often seek to make the point that caffeine, tobacco, alcohol and other substances in common non-medical use are also drugs in the sense of being taken, at least in part, for their psychoactive effects. In other contexts, abuse has referred to non-medical or unsanctioned patterns of use, irrespective of consequences. Drug control The regulation, by a system of laws and agencies, of the production, distribution, sale and use of specific Psychoactive drugs (Controlled substances) locally, nationally or internationally. Drug misuse Use of a substance for a purpose that is not consistent with legal or medical guidelines, as in the non-medical use of prescription medications. This term is often preferred to Drug abuse, as it is perceived to be less judgemental. Drug poisoning A state of major disturbance of consciousness level, vital functions, and behaviour following the administration in excessive dosage (deliberately or accidentally) of a Psychoactive substance. In the field of toxicology, the term poisoning is used more broadly to denote a state resulting from the administration of excessive amounts of any pharmacological agent, psychoactive or not. In the context of Illicit drug use, poisoning may occur as a result of adulterants in the drug. Drug policy In the context of Psychoactive drugs, the aggregate of policies designed to affect the supply and/or demand for Illicit drugs, locally or nationally, including education, treatment, control and other programmes and polices to reduce the harms related to illicit drug use. In this context, ‘drug policy’ often does not include pharmaceutical policy (except with regard to diversion to non-medical use), or tobacco or alcohol policy. Drug-related problem Any of the range of adverse accompaniments of Drug use, particularly Illicit drug use. The term was coined by analogy with alcohol-related problems but is less used, since it is Drug use itself, rather than the consequence, that tends to be defined as the problem. This term has been used throughout this book rather than Drug abuse or Drug misuse, as it is non-judgemental. Gateway drug An Illicit or Licit drug, use of which is regarded as opening the way to the use of another drug, usually one that is viewed as more problematic. Harmful use A pattern of Psychoactive Substance use that is causing damage to health. The damage may be physical (eg hepatitis following injection of drugs) or mental (eg depressive episodes secondary to heroin use). Harmful use commonly, but not invariably, has adverse social consequences but social consequences are not necessary to justify a diagnosis of harmful use. Harm reduction In the context of alcohol or other drugs, harm reduction describes policies or programmes that focus directly on reducing the harm resulting from the use of alcohol or other drugs. The term is used particularly of policies or programmes that aim to reduce the harm without necessarily affecting the underlying Drug use; examples include Maintenance treatment in Opioid Dependence and needle/syringe exchanges to counteract needle sharing among heroin users. Harm reduction can be used either to refer to goals (focusing on the harm rather than on use per se) or to means (eg needle exchanges, Opioid Substitution Therapy etc); in the latter sense, it is often contrasted to the dichotomy of supply reduction and demand reduction. Hazardous use A pattern of substance use that increases the risk of harmful consequences for the user. Some would limit the consequences to physical and mental health (as in Harmful use); some would also include social consequences. In contrast to Harmful use, hazardous use refers to patterns of use that are of public health significance, despite the absence of any current disorder in the individual user. It is also commonly used for Licit drugs, such as alcohol, which allows comparison between the pattern of use of these drugs and the harm related to their use. These substances cause dopamine to be released rapidly and in huge quantities when compared to usual brain levels, which leads to the intense feelings of pleasure. Illicit drug A Psychoactive substance, the possession, production, sale or use of which is prohibited. Strictly speaking, it is not the Drug that is illicit, but its possession, production, sale or use in particular circumstances in a given jurisdiction.

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Under normal conditions the human tear volume is about 7–9 μl and it is relatively constant biaxin 250mg sale gastritis gerd diet. The maximum amount of fluid that can be held in the lower eyelid sack is 25–30 μl purchase 250mg biaxin free shipping extreme gastritis diet, but only 3 μl of a solution can be incorporated in the precorneal film without causing it to destabilize. When eyedrops are administered, the tear volume is suddenly increased which can cause rapid reflex blinking. Most of the eyedrop is pumped through the lacrimal drainage system into the nasolacrimal duct, and some is spilled on the cheeks and splashed on the eyelashes. The drainage rate of the solution is related to the instilled volume; the smaller the volume the slower the drainage rate. However, the typical volumes delivered by commercial eyedroppers are in the range of 35–56 μl. Formulations often disappear from the cul-de-sac within 5 to 10 minutes following instillation in rabbits and 1 to 2 minutes in humans. Severe systemic side-effects may be result from absorption of some drugs through the mucous membrane of the nasolacrimal duct. It is lowest on awakening as a result of acid by-products associated with relatively anaerobic conditions in prolonged lid closure and increases because of loss of carbon dioxide as the eyes open. The tears are more acid in contact-lens wearers due to the impediment of the efflux of carbon dioxide, and more alkaline in the case of diseases such as dry eye, severe ocular rosacea and lacrimal stenosis. When an ophthalmic solution is instilled onto the eye surface, it is mixed with the tears present in the conjunctival sac and with the precorneal tear film. Tears have a weak buffering capacity and therefore the pH of the mixture is mainly determined by the pH of the instilled solution. The exposure of the eye surface to an acid fluid may cause damage to the ocular tissues resulting from a reaction with cellular proteins, forming insoluble complexes. Alkalinization of the tear film tends to produce an interaction of the hydroxyl ions with the cell membranes. At a high pH the lipids in the cell membranes will be saponified causing disruption of the structural integrity of the cells. The damage is dependent on the concentration of hydrogen and hydroxyl ions and on the exposure time. To avoid reflex lachrimation and to prolong the retention of a drug at the eye surface, it is desirable that the ophthalmic solution has a pH between 7. Some drugs are unstable in this pH range, and therefore need to be formulated at other pH values, but it is preferred that little or no buffering is employed. The instillation of a solution containing drugs or adjuvants that lower the surface tension may disrupt the outmost lipid of the tear film into numerous oily droplets, which become solubilized. The protective effect of the oily film against evaporation of the tear film aqueous layer disappears and dry spots will be formed. The dry spots are painful and irritant and elicit reflex blinks to eliminate the material. In many cases it appears 30 minutes to 1 hour following the application and is dependent on the substance and on its concentration. The tear film is destabilized when the surface tension of the instilled solution is much lower than the surface tension of the lacrimal fluid. The normal osmolality of tears varies from 290 to 310 mOsmkg−1, which is almost equivalent to that of normal saline solution. Variations in osmotic pressure between 100– 640 mOsmkg−1 appear to be well tolerated by the eye; beyond these values irritation takes place, eliciting reflex tears and reflex blinking. When the eye surface is covered with a hypotonic solution the permeability of the epithelium is increased considerably and water flows into the cornea. The corneal tissues swell, increasing the pressure on the nerves and causing an anesthetizing action on the cornea. In the case where the eye surface is covered with hypertonic solution, water flows from the aqueous layer through the cornea to the eye surface. A desquamation of superficial cells is also observed after instillation of hypertonic solution in rabbits. Although the instillation of a non-isotonic solution will cause a change in tear osmolality, it will regain the original value within 1 to 2 minutes following dosing. In general, however, hypotonic solutions are well tolerated in the eye and can lead to better corneal absorption of the drug due to a concentration effect on the formulation and increased permeability of the cornea (both by virtue of uptake of water from the formulation by the corneal tissue). Conjunctival absorption is nonproductive and constitutes an additional loss following instillation of a topical dose. Most drugs cross this membrane into the intraocular tissues by either intercellular or transcellular diffusion. Lipophilic drugs are transported via the transcellular route, and hydrophilic drugs penetrate mainly through the intercellular 305 Figure 12. There is little evidence that ophthalmic drugs penetrate into ocular compartments by active transport.

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In sub-Saharan Africa trusted 250 mg biaxin chronic gastritis symptoms stress, a government-owned-and-operated central medical store manages the distri- bution of drugs buy biaxin 250 mg on line gastritis symptoms child, transporting goods around the country in a government- owned feet. Donors and developing-country governments favor this system, wherein the central store manager can neither hire people with business experience nor fre incompetent workers (Yadav, 2010). Ineffcient supply chain management directly drives up costs and causes drug stock-outs in Copyright © National Academy of Sciences. Despite its many stops along the way, only at one of the fnal destinations did a volunteer doctor notice fungal spores contaminating the product (Caudron et al. The infusions had been distributed so widely and haphazardly that, despite a product recall, only 15 per- cent were ever collected (Caudron et al. Such problems are not uncommon during emergencies, when quality control throughout long supply chains becomes difcult. The dangers of poorly regulated drugs lead some bodies, such as the European Commission’s Directorate-General for Humanitarian Aid, to stipulate that quality-assurance guidelines not be relaxed during emer- gencies, even though quality-assurance steps can slow down response (Pomatto and Schuftan, 2006). After the tsunami in Sri Lanka, only 50 percent of the drugs donated had expiration dates on them; of that half, 5 percent had already expired or would expire within days; 62 percent of the medication labels were not in English, the language of the Sri Lankan health system (Mahmood et al. Such inappropriate drug donations cause serious problems because disposing of such drugs, especially in large quantities, is a lengthy and expensive project (Pomatto and Schuftan, 2006). After the 2000 foods in Venezuela, 70 percent of the drugs donated for humani- tarian assistance needed to be destroyed, requiring the government to pay $16,000 to cover the extra personnel needed to sort the donations (Hechmann and Dune-Birouste, 2007). During emergencies, little about patients, their diagnoses, or medi- cal history is collected at most health facilities. Drug quality signals can be difcult to spot when infrastructure is disrupted: Patients are seen quickly and only minimal information is recorded. The World Health Organization published its “Guidelines for Drug Donations” in 1996 after particularly problematic donations during the Bosnian War (Berckmans et al. At times the guidelines are followed closely; for example, humani- tarian emergencies in East Timor and Gujarat State saw few inappropri- ate donations (van Dijk et al. As Chapter 4 explained, this drug scarcity in turn creates a vacuum for poor-quality products to fll. Of course, donor demands alone do not drive the costs of supply chain management in developing countries. In India, for example, nearly 70 percent of the population lives in rural areas, where the health posts may be few and lacking in staff, electricity, and supplies (Langer and Kelkar, 2008). The costs of drug distribution in India are two to three times greater than in the United States or the European Union, despite vastly lower labor costs (Langer and Kelkar, 2008). Supply chain managers are always concerned with the last-mile problem: the disproportionately expensive and ineffcient fnal leg on the distribution chain. Managing the drug distribution system in developing countries means containing the costs of the last mile, moving medicines to patients quickly, and keeping records of all transactions between the manufacturer and the consumer. Around the world, drug wholesale is a common point of vulnerability to falsifed and substandard medicines. In some countries, including the United States, there are also large regional wholesalers (Fein, 2012; White and Bothma, 2009). They often serve independent pharmacies or hospitals and may have strong distribution networks (Levy, 2006). As Figure 5-1 suggests, the distinction between the primary and second- ary wholesalers is not always clear. Primary wholesalers may, for example, buy products from secondary wholesalers as well as manufacturers (Ziance, 2008). The back-and-forth sales are common among drug wholesalers, who buy and sell medicines to accommodate market demand. That is, when they see a medicine is scarce in one region, they can buy the same medicine from other wholesalers that may be fush with it. Sometimes secondary wholesalers fll a void; they supply to rural phar- macies or markets that national or regional wholesalers do not reach. But they choose stock based on demand forecasts, price, margin, and their customers’ willingness to pay (Yadav, 2009). There are three major national wholesalers, a few regional wholesalers, and thousands of secondary wholesalers. In wholesale repackaging, illegitimate products can gain authentic packaging, and clean, authentic packag- ing is removed and not always destroyed. Unscru- pulous wholesalers seek out states with the most lenient requirements and move from state to state when caught in violations. Wholesalers may sell and resell medicines repeatedly among themselves before flling a pharmacy order.

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