By O. Dudley. Loyola College, Baltimore.
Therefore buy 5 mg medex fast delivery, it is of utmost importance to describe the pharmacological basis of therapeutics in order to maximize the benefits and minimize the risks of drugs to recipients buy 5 mg medex with amex. This lecture note on pharmacology is primarily a note for undergraduate health science students such as health officer purchase 5 mg medex visa, nursing, midwifery and laboratory technology students. However, other health professionals whose career involves drug therapy or related aspects should also find much of the material relevant. The goal is to empower the practitioner through an understanding of the fundamental scientific principles of pharmacology. The effects of prototypical drugs on physiological and pathophysiological processes are clearly explained to promote understanding. The selection of the drugs is based on the national drugs list for Ethiopia and on the accumulated experience of teaching pharmacology to many health profession students. The chapters open with a list of objectives to guide the reader, and most end with questions which challenge the reader’s understanding of the concepts covered with in the chapter. Most sections have an introduction that provides an overview of the material to be covered. Readers are encouraged to refer the references mentioned for further information and we hope that this material will be a valuable companion in our pursuit of a fundamental understanding in a most fascinating area of clinical knowledge, pharmacology. Understand theoritical pharmacokinetics like half-life, order of kinetics, steady state plasma concentration. Understand drug safety and effectiveness like factors affecting drug action and adverse drug reactions. Pharmacology: Pharmacology is the study of interaction of drugs with living organisms. It also includes history, source, physicochemical properties, dosage forms, methods of administration, absorption, distribution mechanism of action, biotransformation, excretion, clinical uses and adverse effects of drugs. Clinical Pharmacology: It evaluate the pharmacological action of drug preferred route of administration and safe dosage range in human by clinical trails. Drugs are generally given for the diagnosis, prevention, control or cure of disease. Pharmacy: It is the science of identification, selection, preservation, standardisation, compounding and dispensing of medical substances. Pharmacodynamics: The study of the biological and therapeutic effects of drugs (i. Pharmacotherapeutics: It deals with the proper selection and use of drugs for the prevention and treatment of disease. Poisons are substances that cause harmful, dangerous or fatal symptoms in living substances. Chemotherapy: It’s the effect of drugs upon microorganisms, parasites and neoplastic cells living and multiplying in living organisms. Pharmacopoeia: An official code containing a selected list of the established drugs and medical preparations with descriptions of their physical properties and tests for their identity, purity and potency e. Out of all the above sources, majority of the drugs currently used in therapeutics are from synthetic source. Pharmacodynamics Involves how the drugs act on target cells to alter cellular function. Receptor and non-receptor mechanisms: Most of the drugs act by interacting with a cellular component called receptor. Some drugs act through simple physical or chemical reactions without interacting with any receptor. Many drugs are similar to or have similar chemical groups to the naturally occurring chemical and have the ability to bind onto a receptor where one of two things can happen- either the receptor will respond or it will be blocked. A drug, which is able to fit onto a receptor, is said to have affinity for that receptor. An agonist has both an affinity and efficacy whereas antagonist has affinity but not efficacy or intrinsic activity. When a drug is able to stimulate a receptor, it is known as an agonist and therefore mimics the endogenous transmitter. When the drug blocks a receptor, it is known as antagonist and therefore blocks the action of the endogenous transmitter (i. However, as most drug binding is reversible, there will be competition between the drug and the natural stimulus to the receptor. The forces that attract the drug to its receptor are termed chemical bonds and they are (a) hydrogen bond (b) ionic bond (c) covalent bond (d) Vander waals force. Covalent bond is the strongest bond and the drug-receptor complex is usually irreversible. Dose Response relationship The exact relationship between the dose and the response depends on the biological object under observation and the drug employed. When a logarithm of dose as abscissa and responses as ordinate are constructed graphically, the “S” shaped or sigmoid type curve is obtained. The lowest concentration of a drug that elicits a response is minimal dose, and the largest concentration after which further increase in concentration will not change the response is the maximal dose. Graded dose effect: As the dose administered to a single subject or tissue increases, the pharmacological response also increases in graded fashion up to ceiling effect. Quantal dose effect: It is all or none response, the sensitive objects give response to small doses of a drug while some will be resistant and need very large doses. The quantal dose- effect curve is often characterized by stating the median effective dose and the median lethal dose. Penicillin has a very high therapeutic index, while it is much smaller for the digitalis preparation. Structural activity relationship The activity of a drug is intimately related to its chemical structure. Knowledge about the chemical structure of a drug is useful for: (i) Synthesis of new compounds with more specific actions and fewer adverse reactions (ii) Synthesis of competitive antagonist and (iii) Understanding the mechanism of drug action. Slight modification of structure of the compound can change the effect completely. Pharmacokinetics Pharmacokinetics deals with the absorption, distribution, metabolism and excretion drugs in the body. Biotransport of drug: It is translocation of a solute from one side of the biological barrier to the other. Structure of biological membrane: The outer surface of the cell covered by a very thin structure known as plasma membrane. The 5 membrane proteins have many functions like (a) contributing structure to the membrane (b) acting as enzyme (c) acting as carrier for transport of substances (d) acting as receptors. The plasma membrane is a semipermeable membrane allowing certain chemical substances to pass freely e. Drug absorption: Absorption is the process by which the drug enters in to the systemic circulation from the site of administration through biological barrier. In case of intravenous or intra-arterial administration the drug bypasses absorption processes and it enters into the circulation directly.
However buy 5mg medex visa, the ability to breathe—to have air enter the lungs during inspiration and air leave the lungs during expiration—is dependent on the air pressure of the atmosphere and the air pressure within the lungs buy cheap medex 1 mg on-line. Pressure Relationships Inspiration (or inhalation) and expiration (or exhalation) are dependent on the differences in pressure between the atmosphere and the lungs buy 1 mg medex visa. For example, a certain number of gas molecules in a two-liter container has more room than the same number of gas molecules This OpenStax book is available for free at http://cnx. In this case, the force exerted by the movement of the gas molecules against the walls of the two-liter container is lower than the force exerted by the gas molecules in the one-liter container. At a constant temperature, changing the volume occupied by the gas changes the pressure, as does changing the number of gas molecules. Boyle’s law describes the relationship between volume and pressure in a gas at a constant temperature. Boyle discovered that the pressure of a gas is inversely proportional to its volume: If volume increases, pressure decreases. Therefore, the pressure in the one-liter container (one-half the volume of the two-liter container) would be twice the pressure in the two-liter container. Boyle’s law is expressed by the following formula: P1 V1 = P2 V2 In this formula, P1 represents the initial pressure and V1 represents the initial volume, whereas the final pressure and volume are represented by P2 and V2, respectively. If the two- and one-liter containers were connected by a tube and the volume of one of the containers were changed, then the gases would move from higher pressure (lower volume) to lower pressure (higher volume). Pulmonary ventilation is dependent on three types of pressure: atmospheric, intra-alveolar, and intrapleural. Atmospheric pressure is the amount of force that is exerted by gases in the air surrounding any given surface, such as the body. Atmospheric pressure can be expressed in terms of the unit atmosphere, abbreviated atm, or in millimeters of mercury (mm Hg). Therefore, negative pressure is pressure lower than the atmospheric pressure, whereas positive pressure is pressure that it is greater than the atmospheric pressure. Intra-alveolar pressure (intrapulmonary pressure) is the pressure of the air within the alveoli, which changes during the different phases of breathing (Figure 22. Because the alveoli are connected to the atmosphere via the tubing of the airways (similar to the two- and one-liter containers in the example above), the intrapulmonary pressure of the alveoli always equalizes with the atmospheric pressure. Intrapleural pressure is the pressure of the air within the pleural cavity, between the visceral and parietal pleurae. Similar to intra-alveolar pressure, intrapleural pressure also changes during the different phases of breathing. However, due to certain characteristics of the lungs, the intrapleural pressure is always lower than, or negative to, the intra-alveolar pressure (and therefore also to atmospheric pressure). Although it fluctuates during inspiration and expiration, intrapleural pressure remains approximately –4 mm Hg throughout the breathing cycle. One of these forces relates to the elasticity of the lungs themselves—elastic tissue pulls the lungs inward, away from the thoracic wall. Surface tension of alveolar fluid, which is mostly water, also creates an inward pull of the lung tissue. This inward tension from the lungs is countered by opposing forces from the pleural fluid and thoracic wall. Too much or too little pleural fluid would hinder the creation of the negative intrapleural pressure; therefore, the level must be closely monitored by the mesothelial cells and drained by the lymphatic system. Since the parietal pleura is attached to the thoracic wall, the natural elasticity of the chest wall opposes the inward pull of the lungs. Ultimately, the outward pull is slightly greater than the inward pull, creating the –4 mm Hg intrapleural pressure relative to the intra- alveolar pressure. Transpulmonary pressure is the difference between the intrapleural and intra-alveolar pressures, and it determines the size of the lungs. Physical Factors Affecting Ventilation In addition to the differences in pressures, breathing is also dependent upon the contraction and relaxation of muscle fibers of both the diaphragm and thorax. The lungs themselves are passive during breathing, meaning they are not involved in creating the movement that helps inspiration and expiration. This is because of the adhesive nature of the pleural fluid, which allows the lungs to be pulled outward when the thoracic wall moves during inspiration. Contraction and relaxation of the diaphragm and intercostals muscles (found between the ribs) cause most of the pressure changes that result in inspiration and expiration. These muscle movements and subsequent pressure changes cause air to either rush in or be forced out of the lungs. A small tubular diameter forces air through a smaller space, causing more collisions of air molecules with the walls of the airways. The following formula helps to describe the relationship between airway resistance and pressure changes: F = ∆ P / R This OpenStax book is available for free at http://cnx. If the tissues of the thoracic wall are not very compliant, it will be difficult to expand the thorax to increase the size of the lungs. Pulmonary Ventilation The difference in pressures drives pulmonary ventilation because air flows down a pressure gradient, that is, air flows from an area of higher pressure to an area of lower pressure. Air flows into the lungs largely due to a difference in pressure; atmospheric pressure is greater than intra-alveolar pressure, and intra-alveolar pressure is greater than intrapleural pressure. Air flows out of the lungs during expiration based on the same principle; pressure within the lungs becomes greater than the atmospheric pressure. Inspiration is the process that causes air to enter the lungs, and expiration is the process that causes air to leave the lungs (Figure 22. In general, two muscle groups are used during normal inspiration: the diaphragm and the external intercostal muscles. When the diaphragm contracts, it moves inferiorly toward the abdominal cavity, creating a larger thoracic cavity and more space for the lungs. Contraction of the external intercostal muscles moves the ribs upward and outward, causing the rib cage to expand, which increases the volume of the thoracic cavity. Due to the adhesive force of the pleural fluid, the expansion of the thoracic cavity forces the lungs to stretch and expand as well. This increase in volume leads to a decrease in intra-alveolar pressure, creating a pressure lower than atmospheric pressure. The process of normal expiration is passive, meaning that energy is not required to push air out of the lungs. Instead, the elasticity of the lung tissue causes the lung to recoil, as the diaphragm and intercostal muscles relax following inspiration. In turn, the thoracic cavity and lungs decrease in volume, causing an increase in intrapulmonary pressure. The intrapulmonary pressure rises above atmospheric pressure, creating a pressure gradient that causes air to leave the lungs.
Several settings reported a small number of cases tested (1–19 cases in 6 settings 1mg medex mastercard; 20–49 cases in 14 settings medex 1 mg line; 50–99 cases in 11 settings) buy cheap medex 5 mg on line. There was no resistance reported in the Gambia, Iceland, Malta and Luxembourg, where the number of previously treated cases was very small. In contrast, Kazakhstan and Karakalpakstan, Uzbekistan, showed tremendously high prevalences of any resistance – 82. Twelve settings reported no resistance to three or four drugs (Belgrade, Finland, the Gambia, Iceland, Ireland, Luxembourg, Malta, New Zealand, Norway, Sweden, Switzerland, and Zambia). The highest prevalences of resistance to three or four drugs were reported in Orel Oblast, Russian Federation (52. Full details of drug resistance prevalence among combined cases for the period 1999–2002 are given in Annex 5 and Annex 6. Any resistance among combined cases The overall prevalence of drug resistance ranged from 0% (Andorra, Iceland and Malta) to 63. Figure 9 shows the ten countries/settings with combined prevalence of any resistance higher than 30%. Resistance to three or four drugs was less than 2% in almost two-thirds of the settings, with a median of 1. Any resistance among combined cases by individual drug Annex 6 shows the prevalence of any resistance to each of the four drugs among combined cases. The highest prevalence of resistance to all four drugs was observed in Kazakhstan. The distribution of the prevalence of resistance to each individual drug is illustrated in figure 11. Exceptionally high prevalences and outliers were found in many countries/ settings. However the range of resistance prevalence varied considerably within regions (Figure 12). The ranges in the Western Pacific Region and especially in the European region were much wider than for the other regions. The range of any resistance to each of the four drugs was by far the widest in the European region. The ranges of values for the African Region and the Americas were quite narrow, those of the Western Pacific Region wider, while the widest are observed in the European Region, reflecting the diversity of the resistance prevalence. The median prevalences of any resistance in the Regions of Africa, the Americas and Europe were around 20%, while the median prevalence in the Western Pacific Region reached 32. This was also true for the prevalence of resistance to 3 or 4 drugs, where Kazakhstan was an outlier (62. The Puerto Rico outlier (25%) is an artefact caused by the small sample size (n = 4). For most of the parameters the African Region had the lowest medians as well as the smallest ranges. We therefore explored stratification in three geographical subregions – Western, Central and Eastern Europe (Table 3). This was also true for the ranges of the parameters – narrow for Central Europe, somewhat wider for Western Europe, and widest for the Eastern European subregion. A high rate of immigration from areas with a higher prevalence of resistance, such as countries of the former Soviet Union, is one possible reason. The following analysis includes data from the three global reports, as well as data provided between the publication of reports. The present report examines time trends for resistance in new cases in 46 settings: 20 settings provided two data points and 26 three or more data points (Table 4). Twelve showed only slight variations in prevalence, while significant changes were observed in five settings: Poland, Peru, Argentina,b Henan Province (China),c and Thailand. In three of these settings (Argentina, Henan (China), and Thailand) the decrease was significant. Seven settings showed an increase over time, of which only Poland and Ivanovo Oblast were significant. New Zealand and Norway reported a doubling and Botswana a tripling of the prevalence. Figure 17 depicts the trend of prevalence of any resistance among new cases in Botswana. Tomsk Oblast (Russian Federation) showed a steady and significant increase, reaching a level of resistance 1. Tomsk Oblast, Russian Federation, and Slovakia both reported significant increases. Regarding any resistance among previously treated cases (Figure 20), a significant decrease was observed in Argentina, Ivanovo Oblast, Russian Federation, Peru and the Republic of Korea. There are only two significant decreases (Argentina and the Republic of Korea) and one significant increase (Nepal). All other settings showed variations with large confidence intervals; the upper limit for Belgrade, Serbia and Montenegro, reached 27. Three settings showed a significant increase; Estonia, Lithuania, and Tomsk Oblast (Russian Federation). Surveillance data from nine settings are displayed in Figure 23 and Figure 24, which show the prevalence ratios and 95% confidence intervals. As these data had to be adjusted, no confidence intervals could be calculated and, consequently, the level of significance of any increase or decrease could not be determined. Dynamics in settings reporting two data points Figure 23: Prevalence ratios of any resistance among combined cases, 1994–2002 With regard to prevalence of any resistance (Figure 23) only one setting, Belgium, showed a significant decrease over time. No other survey settings reported statistically significant changes over two data points. A borderline significant increase was observed in Ivanovo Oblast (Russian Federation). An initial decrease followed by a stabilization of prevalence was seen in Latvia (Figure 26). The following patient-related factors were retained: level of education67 and purchasing power. Preferences for the private sector could not be included as a factor, as no aggregate data were available. The human poverty index67 and the out-of-pocket expenditure,68 as a percentage of total health expenditure, measure the purchasing power. Although the model included the fairness indexa,72 (the responsiveness of the health system relative to people’s expectationsb) as a measurement of functionality, it could not be included in the final analysis. However, given the preliminary nature of the available data, this factor has been omitted in the multivariate analysis a The fairness concept implies that the health system responds equally well to everyone, without discrimination.
Examples of day surgery processes amenable to audit that have some measurable outcomes are shown in Table 2 1mg medex sale. A robust database is helpful generic medex 5mg line; however cheap 1 mg medex with visa, the best databases fail to effect change unless the information is clearly displayed and freely disseminated to the day surgery users. Monthly graphs and ﬁgures detailing all outcomes and trends should be disseminated to everyone, particularly to key individuals empowered to inﬂuence change. However, formal day surgery training programmes for anaesthetic (and surgical) trainees are rare. It is essential to design a well-structured module that provides training in anaesthesia for all aspects of day surgery and exposure to the organisational challenges of running a day surgery unit. To facilitate this, it is recommended that advanced training should take place in a dedicated day surgery unit, yet few such units exist. It is important to remember that high quality day surgery requires the experience of senior anaesthetists (and surgeons) and that although the day surgery unit is an ideal environment for training junior medical staff, relying on them to deliver the service results in poorer quality patient outcomes and reduced efﬁciency [51, 52]. A list of topics that might be included in a day surgery module is shown in Appendix 5. The day surgery unit is an excellent environment for surgical and nursing training and many of the aspects covered above are equally applicable to surgical and nursing colleagues. Day surgery in special environments A number of complex and highly specialist procedures are beginning to enter the day surgery arena. In the interventional X-ray suite, uterine artery embolisation is a day case procedure, whereas endovascular aneurysm stents and several other procedures are appropriate for a short stay approach. Optimal care for these procedures should be developed by those with expertise in day and short stay surgery, working in collaboration with specialists in the management of the speciﬁc procedure. Many of these procedures are undertaken in challenging environments, such as X-ray departments. Introducing new procedures to day surgery The successful introduction of new procedures to day surgery depends on many factors, including the procedure itself and surgical, nursing and anaesthetic colleagues. It is important to evaluate the procedure while still performing it as an overnight stay and identify any steps in the process that require modiﬁcation to enable it to be performed as a day case, e. A multidis- ciplinary visit to another unit where the procedure is performed successfully as a day case can be very helpful. Initially limiting the procedure to a few colleagues (surgeons and anaesthetists) allows an opportunity to evaluate and optimise techniques and to implement step changes so that the patient can be discharged safely and with good analgesia. Once the procedure has been successfully moved to the Ó 2011 The Authors Anaesthesia Ó 2011 The Association of Anaesthetists of Great Britain and Ireland 15 Guidelines: Day case and short stay surgery. Clear clinical protocols help to ensure that all the lessons learned during the evaluation phase are clearly passed on to colleagues. Currently, there is no set absolute minimum distance between any stand-alone unit and the nearest acute or associated hospital, although large distances are uncommon. The commissioning of any new isolated stand-alone unit requires analysis of its suitability for the provision of intended services. These facilities may or may not be purpose-built and the Clinical Lead must be aware of this in managing any risk. Remoteness is a factor to be considered in the delivery of a safe and efﬁcient service. On-call commitments must be taken into account so as to avoid accidents and fatigue either in theatre or when travelling. This list is not meant to be exhaustive but gives guidance to some of the important areas that require consideration. Short stay surgery and enhanced recovery New approaches to the assessment and management of patients undergoing more complex surgery are being used to improve the quality of recovery, reduce the incidence of postoperative complications and reduce lengths of stay. Many of these techniques are based on the wider application of well- established day surgery principles and are aimed at improving the quality of recovery so that the patient is well enough to go home sooner. These strategies are variously called enhanced recovery, fast-track, accelerated or rapid recovery. Increasing numbers of hospitals are focusing on the short stay pathway and plan to manage the majority of their elective patients with stays of fewer than 72 h. To achieve the maximum beneﬁt from this, hospitals are developing 24-h stay facilities (some as part of their existing day units) and are embracing these principles. Principles of enhanced recovery Enhanced recovery is the outcome of applying a range of multimodal strategies that are designed to prepare and optimise patients before, during and after surgery, ensuring prompt recovery and discharge. Most of these principles are already well established in day surgery, which can be considered the ultimate example of enhanced recovery. Anaesthetic departments should play a major role in this as they can contribute extensively to all phases of the patients’ management. Pre-operative factors Pre-operative preparation of the patient plays a crucial role and identiﬁes additional risk factors and ensures that their medical condition is optimised. Cardiopulmonary exercise testing provides further information to enable anaesthetists to discuss these risks with their patients and ensure that high-risk patients are counselled appropriately. An appropriate level of intensive or high dependency care can also be put in place if necessary. Patients and their carers should receive a careful explanation about the procedure and what will happen to them at every stage of the peri-operative pathway. This includes resumption of food, drink, mobilisation and information about discharge and when this is likely Ó 2011 The Authors Anaesthesia Ó 2011 The Association of Anaesthetists of Great Britain and Ireland 17 Guidelines: Day case and short stay surgery. Patients should usually be admitted on the day of surgery with minimal starvation times (i. Intra-operative factors Minimally invasive surgery should be combined with use of regional anaesthesia where possible. Thoracic epidurals or other regional anaesthetic techniques should normally be used for abdominal surgery in patients likely to require more than oral analgesia postoperatively. Intra-operative ﬂuid therapy should be goal directed to avoid sodium ⁄ ﬂuid overload and attention should be paid to maintaining normothermia. Anaesthetic techniques are otherwise similar to day surgery with the expectation that patients will mobilise and eat ⁄ drink later in the day. For more invasive procedures, epidural analgesia should be maintained in the postoperative period. They should be aware and encouraged to meet milestones for mobilisation, drinking and eating. This requires active involvement from both the medical and nursing teams in the immediate postoperative period. The provision of a speciﬁed dining room, with access to high calorie drinks and where meals can be taken, encourages the patient to mobilise. There should be a target discharge date set for which the staff, patients and relatives should aim, and as in day surgery the discharge should be a nurse-led process and not dependent on consultant review. The patient’s perspective A Mayo Clinic study in 2006 showed that patients want their doctors to be conﬁdent, empathetic, humane, personal, forthright, respectful and thor- ough.
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