Comparison of unusual administration methods of morphine

Comparison of unusual giving medication systems of morphia morphia is a unspecificly used analgesic. Its clinical use and the richly dependency factor ( morphia and heroin have proven to be the approximately addictive opiates) brought up the need to investigate the classic mellowways of disposal ( unwritten, rectal, iv, sc) and oppose them with somewhat non so well established highroads (nebulised, intrathecal, transdermal, sublingual etc). intromissionmorphia is a strong opioid derived from the opium poppy, Papaver somniferum1. It is used for the management of mute and blunt smart. It acts directly to central nervous system exhibiting a rapid time of action. Along with incommode relief, it take a leaks the sense of well being (euphoria). It flowerpot in addition produce a series of other central and marginal resolutions such(prenominal) as sedation, cough suppression, illness, constipation and strength flummox histamine release2. It is used during surgerie s for anaesthesia and as a pain reliever aft(prenominal) the operation. It is a do do do drugsss of natural selection for terminal c are and it is really helpful for pain management in cornerstonecer endurings3. morphia is open at several formulations and different drug administration send offs. The selection of the appropriate administration route is dependent on the extent of pain control required. For instance, parenteral morphia is used for neat monstrous pain, while oral exam morphia 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 analgesicsPharmacokinetic ParametersHalf lifeVolume of Distri scarcelyionClearanceMorphine (iv)2-3 hours3-5 litre/kg15 -20ml/min/kgFentanyl (iv)3.5-3.8 hours5-6 litre/kg21-29ml/min/kgDiamorphia(iv)2-3 legal proceeding25litre/kgUse morphia determineSource Clarkes analysis of drugs and poisons4M oreover, pharmacokinetic parameters such as bioavailability, half life and clearance and other characteristics of the drug (table 1) like situation effects, ADRs and interactions must be interpreted into account before choosing the appropriate drug route. Patients preference (or fear) for a particular proposition drug route and other psychosocial factors expertness also affect the choice of the formulation and patients compliance and finally medicines hard-hittingness.DiscussionOral routeRegarding oral route, morphia comes as a solution and as immediate or controlled (systained) release tablets and capsules(fig 2).Fig 2. Oral formulations of morphiaOral SuspensionMorphine solutions come in different strengths. Oral solutions support be appointed by writing the formula Morphine HCl 5mg and Chloroform water to 5ml but the proportion layabout be altered. Morphine Sulphate solutions (Oramorph) are forthcoming at 10mg/5ml and as concentrated solutions of 100mg/5ml3.Other excipi ents include ethanol (96%- morphine is slightly soluble in ethanol), corn syrup, sucrose, methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216) and purified water. ascribable to the high content of alcohol this drug is not recommended to alcohol misusers. radiation pattern adult process is 10-20mg all(prenominal) quad hours although when prescribed in alleviatory care dosage varies higher or lower according to the bitterness of the pain and kidney function respectively3.As this formulation is not readily mantled from GI tract, in order to produce same effects as iv venereal infection a 50%-100% increase in dose must be con steadred. Overdose jeopardize is high and can cause hypotension, respiratory depression and in some cases death. Naloxone which is an opiate antagonist is the outset line treatment in case of overdosing5.Tablets and CapsulesSolid dosage forms take for 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 circumscribed release. The short-circuit 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 find 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. personal credit line only the dose can increase whereas the frequency must go forward the same i.e. every 12 hours. It can take up to 48 hours for the morphine to r distributively the required plasma levels meaning that it is important to be taken regularly otherwise they l ose their effectiveness5. If the patience attend 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 rule however problems such as the first pass metabolism, the slow onset and the pretend of o.d. have raised questions on whether other novel administration routes can be used.IntravenousThis 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 employ a Hospiral infusion device. The patient can control the morphine use of goods and services 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 transplant s 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 supervising is needed. Side effects such as hypotension and respiratory depression mogul develop while convulsions due to high dosage are believably to occur.fig3. PCA infusion device vs syringe driverSubcutaneousSubcutaneous 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 social movement and obstruction5. A prime characteristic of the sc method is the syringe driver. The driver employ s simple syringes and bears a flow rate setting option ordinarily ml/hr which enables accurate dosing over a specific accomplishment 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 endless 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 produce 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.rectalThis drug administration route is quite a popular and is used for short term management of acute pain. Also in terminal genus 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 effected routesApart from the conventional drug routes mentioned before, it is necessary to assist into other not so popular ones such as the transmucosal, transdermal, sublingual, intrathecal and nebulised routes of administration and try to compare them.Transdermal- TransmucosalTransdermal 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 capability 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 mo rphine9. Also, transdermal fentanyl causes cut down 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-ionizedand 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 evidentiary.Sublingual routeThis route utilises soluble immediate release tablets and it is recommended to patients that have swallowing difficulties. Morphine enters into blood stream 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 morphineNebulised 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/intrathecalBoth epidural and intrathecal routes are used mostly in the hospital clinical environment. The bioavailability is high so spinal anaesthesia 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 imbed 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 learn 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.ConclusionAs it was mentioned before, morphine can be administered via different routes. However, it is vital each time to guess 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.