Comparison of unusual administration methods of morphine

Comparison of unusual administration methods of morphine Morphine is a widely used analgesic. Its clinical use and the high dependency factor (morphine and heroin have proven to be the most addictive opiates) brought up the need to investigate the classic routes of administration (oral, rectal, iv, sc) and compare them with some not so well established routes (nebulised, intrathecal, transdermal, sublingual etc). Introduction Morphine is a strong opioid derived from the opium poppy, Papaver somniferum1. It is used for the management of moderate and severe pain. It acts directly to central nervous system exhibiting a quick time of action. Along with pain relief, it causes the sense of well being (euphoria). It can also produce a series of other central and peripheral effects such as sedation, cough suppression, nausea, constipation and might cause histamine release2. It is used during surgeries for anaesthesia and as a pain reliever after the operation. It is a drug of choice for terminal care and it is really useful for pain management in cancer patients3. Morphine is available at several formulations and different drug administration routes. The selection of the appropriate administration route is dependent on the extent of pain control required. For instance, parenteral morphine is used for acute severe pain, while oral morphine is used for the treatment of temporary pain. The location of the pain will also determine if it is necessary to apply topical preparations or not. Table 1 Pharmacokinetic Properties of three opioid analgesics Pharmacokinetic Parameters Half life Volume of Distribution Clearance Morphine (iv) 2-3 hours   3-5 litre/kg 15 -20ml/min/kg Fentanyl (iv) 3.5-3.8 hours 5-6 litre/kg 21-29ml/min/kg Diamorphine(iv) 2-3 minutes 25litre/kg Use morphine values Source: Clarkes analysis of drugs and poisons4 Moreover, pharmacokinetic parameters such as bioavailability, half life and clearance and other characteristics of the drug (table 1) like side effects, ADRs and interactions must be taken into account before choosing the appropriate drug route. Patients preference (or fear) for a specific drug route and other psychosocial factors might also affect the choice of the formulation and patients compliance and finally medicines effectiveness. Discussion Oral route Regarding oral route, morphine comes as a solution and as immediate or controlled (systained) release tablets and capsules(fig 2). Fig 2. Oral formulations of morphine Oral Suspension Morphine solutions come in different strengths. Oral solutions can be prescribed by writing the formula Morphine HCl 5mg and Chloroform water to 5ml but the proportion can be altered. Morphine Sulphate solutions (Oramorph) are available at 10mg/5ml and as concentrated solutions of 100mg/5ml3. Other excipients include: ethanol (96%- morphine is slightly soluble in ethanol), corn syrup, sucrose, methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216) and purified water. Due to the high content of alcohol this drug is not recommended to alcohol misusers. Normal adult dose is 10-20mg every four hours although when prescribed in palliative care dosage varies higher or lower according to the severity of the pain and kidney function respectively3. As this formulation is not readily absorbed from GI tract, in order to produce same effects as iv dose a 50%-100% increase in dose must be considered. Overdose risk is high and can cause hypotension, respiratory depression and in some cases death. Naloxone which is an opiate antagonist is the first line treatment in case of overdosing5. Tablets and Capsules Solid dosage forms contain morphine in form of salt e.g Morphine Sulphate and Morphine hydrochlorate. Theses salts in the body will be available as morphine bases. Tablets are available in two preparations immediate release and modified release. The short acting tablets come in 10mg, 20mg and 50mg3. They are given every 2-4 hours to control and stabilise breakthrough pain. These tablets are a way of determining the amount of morphine needed to manage pain. Once the quantity of morphine is established the patient can take slow-release tablets and capsules. These formulations contain enough morphine to control pain for 12 or 24 hours. The starting dose varies and from 10-20mg every 12hours if the patient has not taken any other painkiller previously, to 20-30 mg every 12 hours in cases of replacement weak analgesics3. Note only the dose can increase whereas the frequency must remain the same i.e. every 12 hours. It can take up to 48 hours for the morphine to reach the required plasma levels meaning that it is important to be taken regularly otherwise they lose their effectiveness5. If the patience experience pain between doses an additional dose must be given and the GP should decide if it is necessary to increase the daily dose. Oral morphine is a well established drug delivery method however; problems such as the first pass metabolism, the slow onset and the risk of overdose have raised questions on whether other novel administration routes can be used. Intravenous This route is used only in hospitals and in managing emergency pain symptoms. The bolus administration provides almost instant onset with a short effect. Iv morphine is used when sc route is not tolerated. A popular application of this method is in Patient Controlled analgesia (PCA) where the opioid is delivered using a Hospiral infusion device. The patient can control the morphine intake and establish an acceptable level of analgesia6. Morphine is available in 50 and 100ml vials with strength 1mg/ml3. It is used post operatively especially after transplants surgeries and in the management of chronic pain of malignancy. Although this method is useful for the management of severe pain there are many drawbacks. First of all, most of the pumps are bulky and invasive. Their installation is complicated as they require mains attachment and the patient has limited mobility .There is a high risk of overdose therefore supervision is needed. Side effects such as hypotension and respiratory dep ression might develop while convulsions due to high dosage are likely to occur. fig3. PCA infusion device vs syringe driver Subcutaneous Subcutaneous method is an excellent alternative to oral administration method. It is safe and effective method which is widely used both in palliative care and severe pain management. It is used for patients that present conditions such as gastrointestinal disturbances including indigestion, palindromic motility and obstruction5. A prime characteristic of the sc method is the syringe driver. The driver employs simple syringes and bears a flow rate setting option usually ml/hr which enables accurate dosing over a specific period of time. Unlike PCA infusion devices, it is battery powered, so patients mobility is not an issue (fig 3). The risk of overdose is lower compared to iv route as there is a constant stable administration schedule6. There is no need for continuous strict supervision as the driver is easy to use. Often, the subcutaneous route can cause some skin site problems. Irritation might appear especially when there are high concentrations of morphine or when it is combined with other drugs which are not fully compatible3. This problem can be treated either by diluting the dose or by choosing alternative more compatible drugs. Also some patients might experience needle allergic reactions and action must be taken e.g introduce an alternative Teflon cannula. Patients might feel discomfort, especially those who lack of subcutaneous tissue16. Sometimes, possible leakage of subcutaneous site might be observed. Finally, the sc method is not recommended for palliative care patients with acute vascular conditions. Rectal This drug administration route is quite popular and is used for short term management of acute pain. Also in terminal cancer patients modified release morphine sulphate is administered via this route6. Although the absorption rate varies for each individual, it is estimated that around 300-330 mg of morphine are absorbed rectally every four hours, indicating a sufficient analgesic effect. Studies have shown that for the patients who have never taken morphine, rectal morphine is more effective than the oral administered one5. Rectal morphine is available in the form of suppositories at different strengths (10, 15, 20 and 30 mg) 3. Prescribers must specify both the strength and the morphine salt (morphine hydrochloride or morphine sulphate) that suppositories should contain. Evidence shows two deaths15 after consequent doses of rectal morphine should raise awareness and the need of monitoring the dosing regimen and frequency. Rectal route is not avoiding completely the first pass metabolism; therefore the bioavailability might be influenced. Non conventional routes Apart from the conventional drug routes mentioned before, it is necessary to look into other not so popular ones such as the transmucosal, transdermal, sublingual, intrathecal and nebulised routes of administration and try to compare them. Transdermal- Transmucosal Transdermal route is a relatively painless method. The drug absorption is rapidly. Patches are easy to use and not quite expensive. Although this method is usually tolerated from the patients skin irritation and rashes might appear. Transdermal morphine is not popular as there are questions about the efficacy of this method. However, fentanyl another opioid is the drug of choice. More specifically, fentanyl patches are more effective in managing chronic pain compared to modified release oral morphine9. Also, transdermal fentanyl causes reduced constipation and drowsiness14. Another administration route which fentanyl is again preferred than morphine is the transmucosal route by a buccal tablet. The main reason is that fentanyl is a lipophilic drug while morphine has a limited lipid solubility. More specifically, when fentanyl is placed in saliva it is 80% non-ionized  and it usually takes 20-30 minutes for the analgesic effect to reach its peak14. Note transmucosal morphine is also available but the bioavailability is low and analgesic effect is not significant. Sublingual route This route utilises soluble immediate release tablets and it is recommended to patients that have swallowing difficulties. Morphine enters into bloodstream via sublingual mucosa. Investigations have shown that the absorption of morphine is the same (and in a few cases faster) compared with the oral route7. Same studies have shown that there is no significant difference in the extent and duration of analgesic effect when is compared with oral administered morphine3. Nebulised morphine Nebulised morphine utilises the airways to deliver the drug into pulmonary circulation. It can be used for COPD patients in the management of acute thoracic pain11. Through this route, the effect of hepatic metabolism is avoided and a rapid absorption is noted. However, the plasma drug levels are unpredictable indicating the necessity of further clinical investigations. Studies showed that inhaled morphine was as effective as intravenous PCA morphine without causing strong sedating symptoms8. Although nebulised morphine is well accepted, patients who are not used to opioids might experience nausea and vomiting and in rare cases respiratory depression. Other common side effects include constipation and histamine induced broncho-constriction. Another drawback of nebulised morphine is the high cost of the equipment (nebuliser, injectable vials, etc). It is not a simple method and some patients might find it difficult to use the nebuliser. Studies show a wide range of bioavailability in subjects; relating the bioavailability of the drug with the patients ability to use the nebuliser in the right way10. Epidural/intrathecal Both epidural and intrathecal routes are used mostly in the hospital clinical environment. The bioavailability is high so spinal administered morphine can provide extended analgesic effect at lower doses (compared to the conventional drug routes)12. Although epidural and intrathecal morphine can relieve both acute and chronic pain; studies suggest that these routes should be used only for pain which cannot be controlled by the classic established methods13. For instance, these routes are effective in managing lower body pain. Note that only 1% of the daily iv dose must be used intrathecally and only 10% epidurally5. An implanted infusion pump may be used to deliver intrathecal morphine at a continuous rate. A disadvantage of these methods is the high risk of infection and overdose as the staff must be trained and careful when dosing for breakthrough pains. Studies have reported a number of patients experiencing side effects such as sedation, dyspnoea, nausea and vomiting after spinal administration12. Spinal morphine is not usually preferred while diamorphine is the drug of choice due to its high solubility manner. Conclusion As it was mentioned before, morphine can be administered via different routes. However, it is vital each time to consider the risk- benefit ratio for each method and choose the most effective and safe one. Moreover, before establishing unconventional methods such as nebulised and spinal morphine it is important to further investigate their suitability and ways to improve the drug delivery and minimise side effects. Finally, if it is necessary to choose other opiates (such as fentanyl and diamorphine), which might be more efficient than morphine.

Australia’s Economic Objective of Resource Allocation Essay

The objective of efficient resource allocation refers to an economy’s ability to meet its obligations in ensuring that all social and economic objectives are met without waste, for example to allocate resources so that they are distributed efficiently to improve the standard or living. This is the only way that we can ensure that we will be able to maximize the number of goods and services that we are able to provide. In addition, we will also be more likely to guarantee the long term availability of the resources that are currently available to us. The current target for efficiency target concerning labor is 1.5-2% per year or more. Thus, the economic objective of efficiency in resource allocation exists when our productive inputs are used to create the highest possible value of national output (ie GDP is at its highest level). In turn, having more G&S available helps to ensure the maximum satisfaction of our society’s needs and wants. In Economics, we distinguish between four different types of efficiency:1.Productive (or Technical) efficiency: Is about firms producing G&S using the least-cost method and by minimizing the quantity of resources used. This is perhaps the easiest type of efficiency to understand. In this instance, we are interested in ensuring that any time we produce a good or service we are able to do so by using the smallest number of resources. If I use a tree to make four cricket bats, and you can produce five cricket bats from a tree of the same size, then your productive efficiency is better than mine. Another example is also sometimes a higher level of investment spending by firms on new equipment rather than simply employing more staff is the cheapest way to lift output per worker. 2.Allocative efficiency: ensures that resources are only used to make those particular types of G&S that best satisfy society’s needs and wants. That is, we want to produce those things most desired by the community first. This is a problem experienced by many of the world’s poorer countries,  especially those which suffer from poor governance. Corrupt leaders will often use a countries scarce resources to provide elaborate palaces, rather than ensuring that their people have access to clean drinking water. This is very poor allocative efficiency. 3.Dynamic efficiency: entails that firms are able to respond quickly to changing economic circumstances. To be dynamically efficient means that firms are aware of the changing circumstances, and they are able to adapt to meet those new needs and tastes of customers. For example, as technology has improved, many businesses have elected to adopt computers. This has involved buying the hardware, choosing the correct software and training the staff. In going through this process, the firm is demonstrating their dynamic efficiency. 4.Inter-temporal efficiency: means that there is a suitable balance between resources being allocated towards current consumption and saving that becomes available to finance future investment. Causes of efficiency of resource allocation:Cyclical changes in domestic economic activity resulting from changes in demand side conditions that affect efficiency in resource allocation. Supply side structural causes of changes in labor in lobular and capital productivity. Demand Side CYCLICAL FactorsIf levels of AD and EA slow leading to a recession (due to weak demand-side conditions like drops in business confidence/consumer), labor efficiency can suffer for at least 4 reasons. 1.Firms are reluctant to sack experienced staff during a slowdown of sales, as they hope that recovery is not far away and thus save them the cost of hiring and training new staff. This leads to over staffing which lowers the level of output per hour worked. 2.Prolonged or severe cyclical recessions in EA causes higher cyclical  unemployment as staff are cut in numbers, slowing down efficiency rates because more of labor resources are idle. 3.Business confidence about sales and profits, once down, can partly cause recession. This causes the firm to cut investment on new P&E with new technology, consequently productivity slows. 4.Cyclical slowdown in domestic productivity sometimes follows trends in the level of EA and productivity overseas. Productivity also slows when there is an inflationary boom following cyclical rises in the level of domestic economic activity. This is true when the growth in AD exceeds the economoy’s productive capacity. Productivity may slow down in this situation. 1. Workers may not work as hard as they feel secure in the jobs when the economy is stretched to its capacity. Abseentisms can rise, along with strikes and industrial unrest, cutting efficiency. 2. When the economy is at its full capacity, there can be diminishing returns resulting from equipment breakdowns, labor shortages, leading to less efficient natural, labor and capital resources. 3. Rapid inflation can undermine business confidence, leading to reduced investment in new technology and equipment, slowing efficiency. 4. Investment used for expanding the business through plant & equipment can be pumped into less productive or more speculative areas (eg real estate and stock market activities.) This is a mis allocation of resources that slows down productivity. So, when EA is weak due to reduced level of AD, productivity falls due to pessimism, reduced investment, unemployed resources, and labor hoarding. However, at the opposite extreme, excessively strong spending and EA means that productivity suffers from the above reasons. Productivity is likely to be maximized when AD and domestic EA are at ideal levels and demand side conditions are positive but are neither too weak nor too strong. Business Confidence – Optimism of business (eg ^ consumer confidence, ^ household disposable incomes) has a cyclical impact on efficiency. This results in the business investing in new equipment with latest technology, leading to the worker having a greater value/amount of machinery to use in the production process than previously (capital deepening), thus raises theh level of GDP per hour worked. Interest Rates – Higher business overdraft means that firms are more reluctant to borrow in order to purchase new, more efficient plant equipment due to increased repayments. Investment thus is reduced and productivity slows. Company Tax Rates – Impacts the level of the firm’s investment spending. Reduced tax rates increased investment spending and better productivity. Supply Side Structural FactorsSupply factors are far more significant than demand factors when we are considering the impact that certain events will have on our ability to allocate our resources efficiently. If you think about this for a moment it is logical – supply factors are those things that affect the ability and willingness of producers to supply a good or service at a given price. When the US economy experiences an increase in AG, we should see an increase in output without any pressure on productive capacity that may result in inflation. This is a sign that resources are being allocated more efficiently. As a result, we can conclude that any factor that will lead to an increase in aggregate supply will also lead to a more efficient allocation of resources. For example during the 1990s the Australian economy saw the introduction of technology on a larger scale. This improvement in capital assets, combined with the necessary support in the form of training for the workforce, resulted in significant improvements in productivity, showing that resources were allocated more efficiently. Climatic conditions – Drought and below average rainfall (2002-03 – 06-07), floods, cyclones (coastal Northern QLD 2006) impacted efficiency in resource allocation because national output is reduced far more than the volume of inputs of labor or capital resources. Drought also had an impact in the efficiency in water, gas and electricity sectors that is, the same labor inputs have been used but less output has been produced. Sporting events (Before and After) – Events like the Sydney Olympics (2000) and Melb’s Commonwealth Games (06) may have helped in slowing productivity. Studies show during these events that worker efficiency fell perhaps due to distractions and telecasts and worker fatigue from watching TV replays at night. Changing rates of investment in new technology – Investment spending on new P&E like ICT and robotics occurs in waves or cycles, that is, speeds up or slows down. After the flurry of robotics, electronics and computer and internet based technologies in the mid-late 1990s, many recent innovations have been far less significant, tending to slow efficiency. However fairly recent spending on R&D as a proportion of GDP from 1.51 to 1.78% b/w 200-1 and 2004-05 is a sign that US productivity will rise again. BIBLIOGRAPHY www.abs.gov.auMorris, Economics Down Under 2nd Edition

Prejudice Against Women By Nancy Tuana And Young, White,...

Prejudice against women, unlike prejudice against other people groups, can be benevolent or hostile, and has been propagated through the years by means of phrases, actions, and ideologies. Society has well-ingrained prejudice against women, allowing the thoughts and actions to become unnoticeable in the everyday workings of life. Unlike other forms of prejudice, prejudice against women finds support in several creation myths allowing its perpetuity. Conceptions of women s bodies and sexuality provide a basis for discrimination and men s control over women, and by examining The Less Noble Sex by Nancy Tuana and Young, White, and Miserable by Wini Breines, a conclusion about prejudice against women is attained. The perpetuity of prejudice against women, that continues today, encounters origins in several creation myths. In a Greek creation myth, woman was created by Zeus as a punishment for the misdeeds committed by Prometheus and the rest of mankind. Zeus created woman â€Å"making her external appearance desirable in order to trick man into accepting the wickedness inside her. Although woman has the appearance of a goddess, this external covering, like Prometheus’s fat, merely disguises and masks reality – her thievish nature and her lies.† In the Christian creation, woman was created by God as a helper for man. Also, whereas man was made from dust, woman was made from one of man’s ribs; this has allowed theologians to focus on woman’s metaphysical inferiority and her

Essay on How Dr. Martin Luther King Would Respond to...

Martin Luther Kings teachings stand at the core of the strong foundation of America. Today, terrorism, war and recession are seeping in, cracking that foundation and eroding civil rights and civil liberties. And while the teachings of Dr. King came many years ago, they are especially relevant to us today as we struggle with painful losses and difficult questions about the future of America. President Bush announces almost daily that the U.S.-led attacks on Afghanistan will lead to justice. Although there may be no other realistic options at this stage of this particular conflict, Dr. King ¹s teachings encouraging non-violence give us an idea of what lies ahead if our leaders aren ¹t especially careful in managing the war and its†¦show more content†¦Yes, this may sound unrealistic, even ridiculous, to the cynical or to those who have experienced the most tragic of losses at the hand of those America is attacking. But tolerance, if not love, is the only way that anyone can move beyond desperate reincarnations of violence. America is far from foreign policy nirvana, but that does not mean that our leaders should shy away from trying to attain it. Only the seemingly impossible goals are truly worth reaching. Some politicians are even using recent events as a way to make civil liberties selectively available. The application of military tribunals to cases involving foreigners suspected of terrorism caused the Spanish government to refuse to extradite a suspect in the September 11 attacks unless the United States agreed to a civilian trial. Clearly, other countries are skeptical of America ¹s new policies that Mr. Ashcroft claims are necessary to fight terrorism. This is not to say that the answer is to become more isolationist. 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