Morphine is category of drugs called opioid which potentially cause alteration in temper, physical dependance, tolerance and rewarding effects which would finally do drug dependance. Oipoid drugs have consequence on both the cardinal and peripheral nervous systems. In cardinal nervous systm opioids have effects on spinal cord and other parts of CNS. In peripheral nervous system opioid have effects of nervus tissue under run alonging musculuss within gorge and submucous rete in the wall of gud which causes irregularity. Within pheriphral nervous system, opioids cut down the redness.
Opioid receptors
The chief effects of opioids are on nerve cells where they act on receptors present on neural cell membranes. The chief opioids receptors are mu, delta and kappa. These receptors are portion of big household of receptors which have 7 transmembrane-spanning spheres of aminic acids.
The of course happening ligands for opioid receptors are ; b endorphin binds with mu receptor, the enkephalins binds with delta receptor and dynorphin binds with kappa receptors. Morphine has relatively greater affinity for mu receptor. Analgesic consequence is produced when opioid binds to any of the above 3 receptors.
All three opioid receptors are coupled with G-proteins. The G-protein consists of three fractional monetary units alpha, beta and gamma. At resting province guanosine diphosphate ( GDP ) are in contact with alpha fractional monetary unit. When the opioids binds with receptor the guanosine diphosphate ( GDP ) changes to guanosine triphosphate ( GTP ) . This as a consequence causes conformational alterations which dissociate the opioid from receptor. At the same clip alpha fractional monetary unit attached with guanosine triphosphate ( GTP ) dissociate from beta and gamma fractional monetary units and binds to the effecters, which produce cellular responce. This cause dissociation of alpha fractional monetary unit from guanosine triphosphate ( GTP ) , alpha fractional monetary unit binds back with beta and gamma and organize the composite. guanosine triphosphate ( GTP ) convert back to guanosine diphosphate ( GDP ) .
There are many different type of G-proteins found but the G-protein to which the opioid receptors coupled chiefly produce repressive effects in nerve cells.
Sites of action of opioids on nerve cells
The chief action of opioids is at pre and postsynaptic nerve cells. The consequence of opioids on postsynaptic nerve cell is chiefly being inhibitory. Whereas the chief action of opioids on presynaptic nerve cell will be suppressing the release of neurotransmitter and that is the chief consequence on nervous system. However the overall consequence of opioids in encephalon is depend on both presynaptic nerve cells on both excitatory and repressive nerve cells and its station synoptic consequence. For illustration the suppression of presynoptic nuron may do excitant effects in the following nerve cell if the neurotransmitter usually produce the inhibitory effects nevertheless the suppression of station synaptic nerve cell cause these excitant consequence non to happen. Therefore the location of and denseness of opioid receptor on the mark nerve cell describe the overall consequence of opioids on the nerve cell.
There are many diffrent type of nurons with in nervous system which are diffrent in size, form, map and the chemical nature of the neurotransmitters released from their terminuss to transport information to other nerve cells. Howeven morphia by moving on mu receptors cause suppression in release of of many diffrent type of nurotransmitters such as norepinephrine, acetylcholine and the neuropeptide, substance P.
It has been shown that morphia binds to and inhibits GABA inhibitory interneurons. These interneurons usually inhibit the descending hurting suppression tract. So, without the inhibitory signals, pain transition can continue downstream.
Pain tracts
Pain is linked with stimulation in primary centripetal nerve cells caused by strong mechanical or thermic stimulations, or the relese of chemicals by damaged tissues or redness. In event of hurting the primary sesory nerve cells release substance P and glutamate in the dorsal horn of the spinal cord. The urges are so direct to encephalon by the spinothalamic piece of lands. This go uping information can trip descending tracts, from the mesencephalon periaqueductal gray country, which exert an inhibitory control over the dorsal horn.
The opioid receptor are located in diffrent parts of the hurting transmittal tract and have contron over primary afferent nerve cells, spinal cord, mesencephalon and thalamus. The analgetic effects of opioid drugs is caused by their effects on at diffrent degrees of nervous system specially suppression of neurotransmitter release from the primary sensory nerve terminuss in the spinal cord and activation of falling inhibitory controls in the mesencephalon.
The mechanism of hurting tract involve ongoing activity in nociceptive tracts will do alterations in the degrees of neurotransmitters in primary afferent nerve cells and to alterations in sensitiveness to opioid analgesia. The nuropathic hurting is chiefly caused by decrease in opioid sensitiveness, where as inflammatory hurting is caused by addition in sensitiveness of opioids.
Inhibition of neurotransmitter releasese
The nerotransmitter are released by depolarization of presynoptic nervus terminus. This is caused by Ca++ ion entery via voltage-sensitive Ca++ channels. The nurotransmitter release could be reduced by direct suppression of these electromotive force gated chennels. Another manner to suppress nerotransmitter release is to increasing the outward K + current which as a consequence cause shortening repolarisation clip and the continuance of the action potency. Opioids create both these effects as the receptors are coupled with G-protien straight to K+ channels and voltage-sensitive Ca++ channels. or by suppressing adenylate cyclase ( AC ) , the enzyme which converts adenosine triphosphate ( ATP ) to cyclic adenosine monophosphate ( camp ) .
Clinical benefits
Morphine is a narcotic hurting direction agent indicated for the alleviation of hurting in patients who require opioid anodynes for more than a few yearss.
However usage of morphia for less terrible persistent hurting is a topic of considerable argument. Until late the opoids were merely been used for acute hurting and malignant neoplastic disease hurting syndromes. The usage of opioids in less terrible persistent hurting was thought to be less effectual with excessively many hazards. The chief frights were development of tolerance to drug, medical maltreatment etc. how of all time recent surveies have shown that prescribing of opioids for long term in these group of patients is common. Open label clinical tests and different studies have shown safety and effectivity of opioids in patients with less terrible persistent hurting
Up to late many studies and controlled trail have shown utility of opioids in the intervention of less terrible persistent hurting such as back hurting, post-herpetic neuralgy, and painful peripheral neuropathy. The surveies have shown the direct analgetic actions of opioids to cut down the unpleasantness of hurting. In the intervention of chronic low back hurting, transdermic Fentanyl significantly decreased hurting and improved functional disablement.
Controlled-release unwritten opioids were more effectual than tricyclic antidepressants in diminishing the hurting of post-herpetic neuralgy. Other surveies have documented the presence of opioid receptors in the peripheral tissues activated by redness. These findings suggest a function for opioids in the intervention of chronic inflammatory diseases such as arthritic arthritis and connective tissue upsets.
The effects of opioids in intervention of non-inflammatory musculoskeletal conditions were studied. Oral controlled release morphia was performed in patients with chronic regional, soft tissue musculosketal hurting conditions that were immune to codeine, anti-inflammatory agents and anti-depressants. Although patients experienced a lessening in hurting, they did non see important psychological or functional betterment
ESSAY 5
For the undermentioned TWO drugs describe the mechanism of action and how these agents are used therapeutically.
i‚· Morphine
i‚· Aspirin
Include precise inside informations of the action of these agents, the nature of the disease and how the drug ‘s consequence leads to clinical benefits.
Aspirin
Aspirin belongs to category of drugs called Non Steroidal Anti Inflammatory Drugs ( NSAIDs ) which work by barricading to normal activity of a type of enzymes called Cyclo-Oxygenase ( COX ) enzymes. These enzymes are responsible for production of Prostaglandins and Thromboxanes which are powerful go-betweens of redness. There are two chief type of COX enzymes COX1 and COX2 which convert a substrate known as arachidonic acid in to Prostaglandins and Thromboxanes. Each Prostaglandins and Thromboxanes have different function in different portion of organic structure
Main function of Prostaglandins in hypothalamus of encephalon is temperature ordinance where as in tummy the chief function is to protection the GI piece of land. Main map of COX 1 involves production of prostaglandin which controls the release of mucous secretion from tummy liner and protect tummy wall from acerb environment of tummy. Whereas COX 2 enzymes are chiefly involve in production of redness due to action of prostaglandin by increasing sensitiveness of hurting receptor in tegument and change of organic structure temperature due to effects at hypothalamus.
The curative ends are achieved by barricading these enzymes include anti-inflammatory, analgetic and antipyretic. Each type of NSAID is different in their map both chemically and structurally. Drugs such as aspirin block activity of both COx1 and COX 2 enzyme where as the Celebrex would merely barricade activity of COX1 enzymes. The interaction with COX enzyme for each type of NSAID is besides different for illustration acetylsalicylic acid bind with the COX enzyme irreversibly where as the isobutylphenyl propionic acid bind reversibly.
Aspirin have active ingredient salicylates. The chief map of acetylsalicylic acid is to barricade the COX1 and COX2 enzymes and hence suppress the production of prostaglandin and thromboxanes. This is achieved by acetilation of a serine residue within the active site of enzymes. As action of acetylsalicylic acid on COX enzymes is reversible at that place for the continuance of action chiefly depend on the re-synthesis of COX enzymes by organic structure.
The chief map of COX 1 enzyme is to catalysis the production of prostaglandin which leads to blood coagulum. Therefore the suppressing consequence of COX1 enzymes leads to decrease in blood coagulum formation. The suppression of COX1 enzymes besides lead to cut down in protective prostaglandin, which protect tummy liner from acerb environment. This would do the GI side effects.
The good effects are chiefly achieved by suppression of COX2 enzymes which leads to cut down production of prostaglandins which are chiefly responsible for redness and swelling. The consequence besides involves decrease in mild hurting due to redness. The prostaglandin produced by COX2 enzymes besides have effects temperature regulative Centre in the hypothalamus of encephalon. Beneficial effects involve conveying the high organic structure temperature of organic structure back to normal.
Clinical benefits
Aspirin is one of the most widely used over the counter anodyne. The chief utilizations include decrease in mild hurting of skeletal, muscular and post operative hurting. It has advantages over opioid drugs which cause drug dependence.
Small doses of acetylsalicylic acid are frequently used in patients with high hazard of following conditions:
Formation of blood coagulum due to thrombus which finally cause obstruction of blood vass and may besides interrupt of and travel in blood to barricade smaller blood vass which is called intercalation.
Cardiovascular disease angina which involve decrease of blood supply to bosom musculus and which finally cause decease of that musculus of bosom. Therefore decrease in blood curdling will cut down the hazard.
Ischemic shots which will chiefly caused by intercalation. The little blood vass in encephalon will be blocked there oxygen supply to that portion of encephalon will be reduced. This will finally hold consequence on motor map.
These jobs are associated with high hazards as they involve major variety meats of organic structure bosom and encephalon. Therefore if left untreated there will be a terrible decrease in supply of foods which leads to decease tissue.
