Local Anaesthetic Agents †Anatomy Research Paper

Local Anaesthetic Agents – Anatomy Research Paper Free Online Research Papers Local anaesthetic molecules are made of an aromatic group linked to a basic side chain by an ester or amide bond. The side chain is basic because it is made of a secondary or tertiary amino derivatives. This typical structure is demonstrated by lignocaine, as shown in the adjacent diagram. These molecules are therefore weak bases, with pKa values in the range of 8-9, so they mainly exist as ions in body fluids at physiological pH. The only exception is benzocaine, where the amino group is attached directly to the aromatic side chain. Local anaestheics act by reversibly binding to the S6 transmembrane helical segment on any of the four domains of the sodium voltage-gated channel. The S6 segment possesses a binding site accesible only from the cytosol, therby physically blocking the entry of sodium ions into the axoplasm. As a result, the inward sodium current upon neuron excitation cannot exceed the outward potassium current, the membrane cannot be depolarised to threshold and an action potential cannot be initiated. This is effective only when the anaesthetic is in its ionised quartenary form. Therefore, the compound must be able to penetrate the hydrophobic lipid-rich axon membrane (and myelin sheath, if present) to act effectively; only the electrically neutral form of the anaesthetic can do so. Once in the water-rich axoplasm, the anaesthetic ionises, and subsequent binding is hence possible. Thus, it is the coexistance of the neutral and protonated forms of the anaesthetic in solution that allows for the â₠¬Å"bypassing† of the axolemma and the relatively rapid targeting of the voltage-gated sodium channels. Another beneficial feature of anaesthetics attributed to their mechanism of action is their preferential blocking of pain and autonomic neurons, while sparing those involved with coarse touch and movement. Myelinated neurons have a higher surface density of voltage-gated channels than the axolemma of unmyelinated neurons; therefore, they are less likely to be blocked when exposed to the same dosage level of anaesthetic. Axons with larger diameters are also less likely to be blocked than ones of smaller diameter because they can conduct passively over longer distances. Since nociceptive impulses are carried by A? (small myelinated) and C (unmyelinated) fibres, pain sensation is blocked more readily than other sensory modalities. Although all neurons in the region of anaesthetic introduction will be affected to a certain extent when considering the practical anaesthetic dosages used during surgery, this mode of action nevertheless ensures that the patient does not experience sensations of pain. Numerous varietes of anaesthetics show use-dependence: the more channels are open, the greater the block becomes. This is because the entry of the blocking agents is more probable with an open channel, that possesses a wider pore. Furthermore, due to the shape of the anaesthetic molecule, the equilibrium between the closed and inactivated states of the channel will be in favour of the inactivated state in the presence of the anaesthetic, thereby greatly reducing the probability of the initiation and propagation of action potentials. Since touch, pressure and pain sensory-neurons in the anaesthetised region will relay a train of action potentials during surgery, they are the most likely to be blocked as their voltage-gated channels will cycle through open and inactivated states. This mechanism contributes greatly to the overall blocking effect of the anaesthetic. Drug solubility and the presence of either an ester or amide bond are important factors when considering the required rate of onset and duration of anaesthesia. Ester-linked local anaesthetics, such as anethocaine, are rapidly hydrolysed by both plasma and liver cholinesterases, and so have a short biological-half life and blocking duration (about one hour). Amide-linked anaesthetics, such as lignocaine, can only be metabolised in the liver by N-dealkylation, and the resultant metabolites themselves are often anaethetically active. They are therfore more widely used due to their longer blocking duration (about 2 hours). Anaesthetic solubility can also be a determining factor when choosing an anaesthetic. Benzocaine is an unusual local anaesthetic of very low solubility, and so is used as a dry powder to dress painful skin ulcers: the drug is slowly released and produces long-lasting surface anaesthesia. Lignocaine, on the other hand, is often utilised in the form of its acid salt (us ually with hydrochloric acid) and so can be injected in an aqueous form during epidural and spinal anaestheisa for a rapid blocking effect. Lastly, all local anaesthetics used are stable when heated. This is necessary to ensure that sterilisation of the anaesthetic prior to introduction into the body is effective and does not alter the anaesthetic’s binding efficacy to sodium voltage-gated channels. Although local anaesthetics are administered in such a way as to minimise their spread to other parts of the body, they are ultimately absorbed into systemic circulation. Furthermore, local anaesthetics may be injected into veins or arteries by accident. The major unwanted side effect that may occur systemic toxicity, the risk of which increases when higher doses and larger areas are involved. Thus, they are capable of interfering with normal central nervous system function. At low doses, the main effect of the anaesthetic on the CNS is stimulation: this produces restlessness, tremor, and subjective effects ranging from confusion to extreme agitation. Higher doses can cause the tremors to progress to severe convulsions, and even higher doses produce CNS depression. The main threat to life at this stage comes from respiratory depression, because of the anaesthetic’s depression of the respiratory centre and/or phrenic nerve. To reduce the possibility of such effects from occurri ng, a cuff may be used to reduce anaesthetic systemic spread when introduced in the upper limb, or by introducing vasoconstrictors such as adrenalin and felypressin when dealing with the thorax. The risk of systemic toxicity is present if the cuff is released prematurely, or if the dosage of vasoconstrictor is to low. The only exception to this rule is cocaine, which produces euphoria at doses well below those that cause convulsions due to its specific blocking effect on monoamine uptake. Procaine produces especially prominent unwanted central effects, which is a reason for its replacement by lignocaine and prilocaine, whose central effects are much less pronounced. Local anaesthetics commonly affect the cardiovascular system when present in systemic circulation. They have negative chonotropic and inotropic effects on the heart: by inhibiting the inward sodium ion current, anaesthetics decrease the cytosolic concentration of sodium ions in cardiomyocytes, which in turn reduces intracellular calcium ion stores, and this reduces both the frequency and force of contraction. Vasodilatation of arterioles is due to the direct effect of local anaesthetics on vascular smooth muscle and the indirect inhibition of the sympathetic nervous system. The combined myocardial depression and vasodilatation produces a fall in blood pressure, which may be sudden and life threatening. Cocaine is an exception: it produces opposite effects, such as increased cardiac output and arterial pressure, and increased cardiac output because of its ability to inhibit noradrenalin uptake. Another common side effect restricted only to the use of local anaesthetics in spinal and epidural anaesthesia is postoperative urinary retention due to the block of pelvic autonomic outflow. Other side effects are more rare. Hypersensitivity reactions sometimes occur, usually in the form of allergic dermatitis (most frequently during surface anaesthesia in atopic patients), but rarely as an acute anaphylactic reaction. Other unwanted side effects are specific to particular drugs, such as mucosal irritation when applying cocaine, and methaemoglobinaemia when using large doses of prilocaine due to the production of toxic metabolites (the haeme iron is oxidised from the +2 to the +3 state and so cannot bind to oxygen: subsequent symptoms include fatigue, dizziness and cyanosis). This is why prilocaine is rarely used in obstetric analgesia. 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The Pros and Cons of Allowing Cell Phones in School

The Pros and Cons of Allowing Cell Phones in School One of the more controversial and most discussed issues that school administrators face on a daily basis is where they stand with students and cell phones. It seems that virtually every school takes a different stance on the issue of cell phones  in school. No matter what your school’s policy is, there is no way to completely keep all students from bringing their phones unless you do student searches every day, which is simply not feasible. Administrators must evaluate the pros and cons of allowing cell phones in schools and make a decision based on their own student population. The fact is that almost every household owns multiple cell phones.   The age of students who own a cell phone has progressively been trending downward.   It has become increasingly common for students as young as five to possess a cell phone. This generation of students are digital natives and thus experts when it comes to technology. Most of them can text with their eyes closed. They are often far more adept than most adults at using their cell phones for many purposes. Should Cell Phones Be Banned or Embraced in Schools? There are essentially three core stances most school districts have taken with their cell phone policies. One such policy basically bans their students from having their cell phones at all. If students are caught with their cell phones, then they can be confiscated or fined. In some cases, the student may be suspended. Another common cell phone policy allows students to bring their cell phones to school. Students are allowed to use them during non-instructional times such as time in between classes and lunch. If students are caught with them in class, then they are confiscated from the student. Another cell phone policy is leaning towards a shift in administrators thinking. Students are not only allowed to possess and use their cell phones, but theyre also encouraged to use them in class as learning tools.   Teachers incorporate the use of cell phones regularly into their lessons for purposes such as research. Districts that ban their students from having their cell phones or limit their usage do this for a variety of reasons. Those include not wanting it to make it easy for students to cheat, being afraid that students are sending inappropriate content, playing games, or even setting up drug deals. Teachers also feel like they are distracting and disrespectful. All of these are valid concerns and are why this is such a hot issue among school administrators. The movement towards embracing the use of cell phones by students begins with educating students on proper use of phones at school. Administrators who are shifting towards this policy often say that they are fighting an uphill battle with a policy that has a complete or partial ban on cell phone possession and use. Administrators who have transitioned to this type of policy say that their job has become much easier and that they have far fewer issues of cell phone abuse than they did under other policies. This type of policy also clears the way for teachers to embrace cell phones as an instructional tool. Teachers who have elected to use cell phones in their daily lessons say that their students are actively engaged and more attentive than they typically are. A cell phone can be a powerful educational tool. Smartphones have the ability to provide students with so much information in an instant that teachers cannot deny that they can be powerful tools that enhance learning in the classroom. Many teachers are using them for a variety of purposes such as small group projects with research races or text competitions for correct answers. The website polleverywhere.com allows teachers to pose a question to their students.   The students then text their answers to a particular number that the teacher provides them. The website collects the data and puts it into a graph, where teachers can project their answers on a smart board and discuss the answer choices with the class. The results of these activities have been very positive. Teachers, administrators, and students have all provided positive feedback. Many teachers and students would argue that it is time to move into the 21st century and begin using the resources we have available to engage our students in the learning process more readily.