The Effect Of Prostaglandins On The Inflammation Pathway And The Mechanism Of Action Of Nsaids

Table 2 shows some of the chemical mediators involved in Mr X’s inflammatory process, causing it to become more severe and uncontrolled, resulting in a further decline in his clinical presentation.

When patients are prescribed to a medicine for low amounts of pain, they are usually prescribed daily use of anti-inflammatory pills such as ibuprofen or tylenol. For more severe pain, patients are often prescribed these pills in higher dosages, or even prescribed opiates such as vicodin or oxycontin (Meisel & Perrone). Anti-inflammatory pills are not as powerful as drugs such as opioids, but they present the risk of cardiovascular problems

Acetaminophen is an non-opioid analgesic while ibuprofen is a non-steroidal anti-inflammatory drug (NSAIDs). Acetaminophen is an equipotent inhibitor of cyclooxygenase 1 and 2, while ibuprofen is more selective for cyclooxygenase 1 than 2.

of prostaglandin E2, which lessen the hypothalamic target point to reduce fever, and creating active the descending inhibitory serotonergic pathways to produce analgesia. Even though acetaminophen have similarities with the analgesic and antipyretic properties of other COX inhibitors like the aspirin and the non-steroidal anti-inflammatory drugs (NSAIDs), still it does not possess considerable anti-inflammatory properties. Contrary to aspirin, acetaminophens do not hinder thromboxane and, as such, aggregation of platelet does not change.

NSAIDs are group of pharmaceutical drugs used in the treatment of fever, pain and swelling in mild to intermediate acute inflammatory

Chronic pain increases stress levels and anxiety. Do you really want to have to worry about the side effects of the NSAID's you are taking as well? Well documented research states that NSAID's can cause gastro intestinal bleeding and liver problems. There have been widely reported deaths involving NSAID's, which have since been taken off the market.

Nonsteroidal anti-inflammatory drugs, both topical and oral, are another treatment consideration for OA (Alshami, 2014). More aggressive treatment includes the use of opioids or corticosteroid injections (Alshami, 2014). Acetaminophen has a maximum daily dose of 4g/day (Mazaleuskaya et al., 2015a). The mechanism of action in acetaminophen remains unclear (Mazaleuskaya et al., 2015a). However, what is known is that the primary mechanism of action is to inhibit the synthesis of prostaglandins (Mazaleuskaya et al., 2015a). Prostaglandins originate from the arachidonic acid pathway (Mazaleuskaya et al., 2015a). This pathway promotes inflammation, fever, and pain (Mazaleuskaya et al., 2015a). I would recommend the patient take the maximum dosage of 4g/day. This would allow the patient to take 1,000 mg every 6 hours. I would also recommend that the patient alternate with ibuprofen. Ibuprofen can be taken over-the-counter (OTC) with a dosage of 800-1200mg/day or as a prescription with a dosage of 1800-2400mg/day (Mazaleuskaya et al., 2015b). Prescription dosages are typically used for long term management of OA (Mazaleuskaya et al., 2015b). Adults on a prescription dosage are recommended to take 200-800 mg every six to eight hours (Mazaleuskaya et al., 2015b). Ibuprofen acts to inhibit two cyclooxygenase enzymes, COX-1 and COX-2 (Mazaleuskaya et al., 2015b). For Jonathon, I would prescribe 800 mg of ibuprofen to be taken alternatively with acetaminophen every 6 hours. In order to maximize therapy, I would suggest that if Jonathon takes acetaminophen at 9 am then at noon he should take ibuprofen. This way he is able to take medication every three hours and stay within safe dose

Injured cells and nearby circulating cells release chemicals that initiate defensive actions and sound an alarm to other defense mechanisms. These chemicals include histamine (mostly secreted by basophils, white blood cells found in connective tissue), kinins, prostaglandins (PGs), and complement proteins.

Linoleic acid is as an additional source of arachidonic acid, and therefore, this compound also serves as a key player in eicosanoid biosynthesis [11,12]. The cyclooxygenase enzymes convert arachidonic acid via the cyclic pathway of eicosanoid biosynthesis to prostaglandin H2, which is further metabolized to prostaglandins (e.g., PGE2, PGF2α, PGD2, PGI2) and thromboxane, many of them with pro-inflammatory properties [13,14]. There are three types of cyclooxygenases, sharing 60% of their primary structure: COX-1, which is generally localized in the endoplasmic reticulum; COX-2, which is found on the nuclear envelope [14,15]; and COX-3, which occurs only in the cerebral cortex [16]. In the healthy liver, COX-1 and COX-2 work together to induce the inflammation state, and when needed, to reinstate the normal hepatic function [17,18]. At hepatic level, these cyclooxygenases are abundantly expressed during liver injury, cirrhosis, and induced tumorigenesis [19], suggesting the involvement of eicosanoids in the pathogenic mechanisms of liver injury. They are expressed by the liver macrophage-like Kupfer cells, identified by the macrophage marker ED2 (CD168) and these cells are sites of intense eicosanoid production and signaling [20]. Still, in spite of all these data, little knowledge exists about the interplay between APAP treatment and cyclooxygenase-mediated signaling pathway in the liver. It is known, though, that COX-2 overexpression in the mouse liver induces chronic hepatitis by inducing a persistent inflammatory reaction involving macrophages that causes a persistent increase in the hepatocyte death, which reinforces the inflammatory reaction and thus further death of hepatocytes

In recent years, the healthcare industry has seen a significant shift with a lot of new innovations and a number of target studies done on various topics. In particular, there has been an increased focus on understanding the inflammation and its role & relationship to chronic diseases. In this post, we are going to understand the inflammation and its role in general health & chronic diseases in little more detail.

The most feared pathophysiological effect of sepsis is the disturbance of the cardiovascular system through vasodilation and fluid loss from the vascular system into the tissue induced by elevated NO• concentrations. The successive drop in blood pressure and reduced supply of tissues leads to systemic circulatory failure and death of the patient. Inhibitor studies have shown that PARP-1 is not only involved in DNA repair, but also in septic shock. Hauschildt and coworkers have shown that the induction of pro-inflammatory cytokines by LPS treatment of macrophages could be prevented by inhibiting PARP (Hauschildt et al., 1997). An anti-inflammatory effect of PARP activity suppression either induced by Parp1 gene knockout or pharmacological inhibition was also reported (Szabó et al., 1997). Also, LPS treatment of rats led to weakened endothelial functions, which could be alleviated by administration of PARP inhibitor 3-aminobenzamide (3AB) (Szabó et al., 1996).

Inflammation is a normal immune reaction in response to tissue injury or invading exogenous molecules/ pathogens and can be either localized or systemic. The aim of acute inflammation is restoring the tissue homeostatic imbalance by promoting tissue repair and eliminating the causative stimuli through a complex but highly regulated cascade of events (Medzhitov 2008). Under physiological conditions, successful acute inflammation is followed by a resolution phase during which pro-inflammatory processes are suppressed and physiological homeostasis is achieved. However, an ongoing inflammatory event or an impaired resolution phase characterized by continuous pro-inflammatory processes results in chronic inflammation (Maskrey et al. 2011; Fullerton

In vitro: Although cyclosomatostatin could fully block the effect of somatostatin, it only partially reversed the inhibitory effect of cortistatin, a new anti-inflammatory peptide. This observation was further supported by the fact that cyclosomatostatin reversed the antiinfl ammatory effect of somatostatin and octreotide in vitro completely, while only partially reversing the effect of cortistatin

Naproxen (Naprosyn) is a nonsteroidal anti-inflammatory drug (NSAIDs) used to treat joint pain. M.H. was previously prescribed Naproxen to reduce the bilateral wrist pain and associated inflammation. Naproxen is mainly used to reduce inflammation, stiffness, and pain. NSAIDs block the formation of prostaglandins. Prostaglandins are involved in the body’s normal function and inflammatory response. Proteins, Cox-1 and Cox-2, control these prostaglandins. Cox-1 controls the formation of the prostaglandins involved in the normal function of the body’s organs. Cox-2 controls the formation of the prostaglandins involved in the body’s inflammatory response. By preventing the body from producing prostaglandins, NSAIDs reduce swelling and pain.

Figure 2 from Lasky (1992) shows the three major steps of inflammation. Step I is the initial low-affinity rolling interaction that is mediated by all three selectins. Step II involved activation of leukocytes that alter concentration gradients of various chemotactic factors. Step III is the high-affinity adhesion, change in shape of leukocyte, and finally extravasation. Figure 2 left out another important factor of selectin’s role in inflammation: PSGL-1. PSGL-1 on the plasma memebranes of neutrophils or monocytes binds to P-selectin translocated to the surfaces of inflamed endothelial cells (Zimmerman 2001). The binding of PSGL-1 by P-selectin is particularly important in the initial steps of inflammation. This intereaction is responsible for the recruitment of inflammatory leukocyte (Ley 2013).