Acetaminophen Mechanism of action

Paracetamol (acetaminophen) is generally considered to be a weak inhibitor of the synthesis of prostaglandins (PGs). However, the in vivo effects of paracetamol are similar to those of the selective cyclooxygenase-2 (COX-2) inhibitors.

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Paracetamol also decreases PG concentrations in vivo, but, unlike the selective COX-2 inhibitors, paracetamol does not suppress the inflammation of rheumatoid arthritis. It does, however, decrease swelling after oral surgery in humans and suppresses inflammation in rats and mice.

Paracetamol is a weak inhibitor of PG synthesis of COX-1 and COX-2 in broken cell systems, but, by contrast, therapeutic concentrations of paracetamol inhibit PG synthesis in intact cells in vitro when the levels of the substrate arachidonic acid are low (less than about 5 mumol/L). When the levels of arachidonic acid are low, PGs are synthesized largely by COX-2 in cells that contain both COX-1 and COX-2.

Thus, the apparent selectivity of paracetamol may be due to inhibition of COX-2-dependent pathways that are proceeding at low rates. This hypothesis is consistent with the similar pharmacological effects of paracetamol and the selective COX-2 inhibitors. COX-3, a splice variant of COX-1, has been suggested to be the site of action of paracetamol, but genomic and kinetic analysis indicates that this selective interaction is unlikely to be clinically relevant.

There is considerable evidence that the analgesic effect of paracetamol is central and is due to activation of descending serotonergic pathways, but its primary site of action may still be inhibition of PG synthesis. The action of paracetamol at a molecular level is unclear but could be related to the production of reactive metabolites by the peroxidase function of COX-2, which could deplete glutathione, a cofactor of enzymes such as PGE synthase.

Acetaminophen is thought to act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin (PG) synthesis. Unlike NSAIDs, acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, thus, has no peripheral anti-inflammatory affects.

While aspirin acts as an irreversible inhibitor of COX and directly blocks the enzyme’s active site, studies have found that acetaminophen indirectly blocks COX, and that this blockade is ineffective in the presence of peroxides. This might explain why acetaminophen is effective in the central nervous system and in endothelial cells but not in platelets and immune cells which have high levels of peroxides. Studies also report data suggesting that acetaminophen selectively blocks a variant of the COX enzyme that is different from the known variants COX-1 and COX-2.

This enzyme is now referred to as COX-3. Its exact mechanism of action is still poorly understood, but future research may provide further insight into how it works. The antipyretic properties of acetaminophen are likely due to direct effects on the heat-regulating centres of the hypothalamus resulting in peripheral vasodilation, sweating and hence heat dissipation.

NSAIDs slow healing of Musculoskeletal Injuries

OTP pain medications are quite common in our day to day lives. Very few individuals think twice before they pop in a pill to get rid of strained muscle or pain due to headache. Many people are on medications while they recover from ligament tendon, severe muscle or bone injury. In such cases both NSAIDs and OTP are prescribed. These medications are accepted commonly to relieve inflammation and musculoskeletal injuries, for example naproxen, ibuprofen and aspirin.

People are now creating awareness about risk associated with prolonged use of NSAIDs, but dangers related to use for short-term still needs attention. NSAIDs though prove to be effective in reducing inflammation and relieving pain, but this action can also affect the process of healing a lot of injuries.

Inflammation and action of NSAID

Inflammation belongs to our immune system’s response to any injury. When our immune system detects a threat or an injury, it moves white blood cells and inflammatory fluids to the part to

  1. Separate the threat by obstructing the area from the rest of our body.
  2. Promotes tissue generation and healing

Obstruction of healing

When there is reduction of prostaglandins in our body it shows other effects apart from reducing the inflammation. These substances are helpful in bone reformation. This simply means that taking NSAIDs in order to relieve pain caused due to a bone fracture prominently delay the process of healing and result in failed fusion or bone setting.

NSAIDs have also affected the healing process of tendons, ligaments and soft tissues. Tendons connect muscles to our bones and ligament connects our bones together. These connective tissues get less blood supply and results in slow healing in case of ligament injuries and tendon. Fresh blood is important to deliver the required healing materials to the tissues that are injured and promote re-growth.

If you have normal muscle pain, NSAIDs can be effective in healing which lasts for say two to three days. In case of injuries that like bone injuries, or injuries related to tendons and ligaments, NSAIDs should not be taken for treating these injuries as the prolonged treatment involved can cause harm and slow healing process.

Remember you should not take NSAIDs if you have allergies as allergic reaction caused can be mild initially but it can also lead to severe conditions like hives, swollen throat, lips and tongue or asthma attacks. Also if you have a history of pre-existing condition of heart it can lead to heart problems. NSAIDs can also cause heart stroke or heart attack, high blood pressure and these effects are common in people taking these drugs for long term. If you have liver disease you shouldn’t take NSAIDs as they are processed through liver and if you’re liver functions aren’t normal you should avoid taking it.

NSAIDs can also affect the function of your kidney. The drugs prevent the kidney from flushing out the toxins out of the body. They are also not safe for pregnant women so pregnant women need to avoid taking them.

The potential risks associated with pain medicines used during pregnancy

Severe and persistent pain that is not effectively treated during pregnancy can result in depression, anxiety, and high blood pressure in the mother.  Medicines including nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and acetaminophen can help treat severe and persistent pain.   However, it is important to carefully weigh the benefits and risks of using prescription and OTC pain medicines during pregnancy.

The published studies reported on the potential risks associated with the following three types of pain medicines used during pregnancy :

  • Prescription NSAIDs and the risk of miscarriage in the first half of pregnancy. Examples of prescription NSAIDs include ibuprofen, naproxen, diclofenac, and celecoxib.
  • Opioids, which are available only by prescription, and the risk of birth defects of the brain, spine, or spinal cord in babies born to women who took these products during the first trimester of pregnancy.  Examples of opioids include oxycodone, hydrocodone, hydromorphone, morphine, and codeine.
  • Acetaminophen in both OTC and prescription products and the risk of attention deficit hyperactivity disorder (ADHD) in children born to women who took this medicine at any time during pregnancy.  Acetaminophen is a common pain reducer and fever reducer found in hundreds of medicines including those used for colds, flu, allergies, and sleep.

Pregnant women should always consult with their health care professional before taking any prescription or OTC medicine.  Women taking pain medicines who are considering becoming pregnant should also consult with their health care professionals to discuss the risks and benefits of pain medicine use.  Health care professionals should continue to follow the recommendations in the drug labels when prescribing pain medicines to pregnant patients.

Important Facts About NSAIDS and Dog Diarrhea

When your pet hound matures, it will require a more specialized and focused attention and care in the same way that we provide old people. If you have a mature hound in your family, then you will have to be prepared to handle typical medical conditions such as dog arthritis. In most cases, you will also encounter intermittent incidence of dog diarrhea. Thus, it is important that you are well aware of the basics regarding the proper care and management of these typical complications that affect mature mutts. The life expectancy of canine is 15 years if it properly cared for and the serious health issues are immediately and properly addressed.

It is important for pet owners to develop a trained eye in identifying and determining health conditions that are critical particularly those that affect mature hounds. Critical aspects that one must have to properly understand are the symptoms, predisposing conditions and causes, treatment and special requirements and options available for its management in order to prevent further complications and damage.

NSAIDs are used to manage pain and discomfort of senior canines. One of the major issues confronting pet owners is the side effects of this class of pain relievers. This is the major reason why many quarters are taking a second look at the justifications for the continued use of NSAIDs to manage the pain as there are now concerns on the side effects that seemed to outweighing the claimed benefits of these drugs.

Many pet owners acknowledge the major contribution of NSAIDs in maintaining the quality of life of senior canines. These significant benefits are even seen as one of the major reasons for the extension of the lives of many old hounds. However , there are also some pet owners who are raising some serious concerns about the side effects of NSAIDs. In fact there are claims of cases of aggravation of the medical problem as a result of the use of NSAIDs. There are also documented cases of liver failure and early mortality of canines under treatment using NSAIDs. There is now the emerging need for all pet owners to be able to ascertain serious complications and side effects of NSAIDs on their pets during their onset in order to prevent further aggravation of the serious medical reaction.

The more common side effects and complications of NSAIDS on canines include vomiting, bowel movement problems, and pronounced lethargy. There are also documented cases of altered behavior and constipation which is attributed to the toxic reaction by the senior hounds on the NSAIDs treatment.

Before you start using the NSAIDs on your furry friend, you must have to request for a complete blood analysis and test for liver enzymes. It is important for the pet owners to understand that NSAIDs is not safe for canines who have bleeding history. It is also essential for pet owners to use NSAIDs with extreme caution when it is confirmed that their pets have serious liver problems. Finally, one must not use NSAIDs as a tandem to prednisone or aspirin. Management of pain of senior canine must go beyond the use of NSAIDs and it must involve traditional as well as conventional modalities.

Reducing Inflammation Without NSAIDS and What Are NSAIDS

Ask a typical shopper if you could reduce inflammation without NSAIDS and see what response you will get. My guess is they would ask what on earth you were talking about. Mention words like aspirin or Ibuprofen and then they might ask you what they have to do with inflammation – good question.

Let’s do a quick review. Inflammation happens when our immune system gets out of whack. To be more precise, we need to have an equal amount of omega 3 and omega 6 fatty acids in the body.

Unfortunately, modern diets are radically deficient in omega 3s, which upsets the natural balance of the immune system, which in turn results in inflammation in organs all over the body.

This problem has gotten worse over the past fifty years. Too much processed foods, saturated fats and vegetable oils have taken their toll. The medical community is aware of the problem. One of their answers has been an increased reliance on NSAIDS.

NSAIDS are nonsteroidal anti-inflammatory drugs. They can be over-the-counter like aspirin or a prescription drug. The way they work is to block either of two enzymes called Cox-1 and Cox-2. It is these enzymes that eventually cause inflammation and even fever.

Great, you say. So why are consumers trying to reduce inflammation without NSAIDS? Several reasons. Whichever one is used has to be used consistently. An occasional aspirin will not help. Continual use can result in some pretty nasty side effects. The most common ones are nausea, diarrhea, constipation, skin rash, headaches and drowsiness.

The more potent prescription NSAIDS can even cause ulcers, kidney failure and even heart attacks.

Needless to say, consumers are looking for alternatives to reducing inflammation. The simplest one has been around for thousands of years. That is omega 3 fish oil.

The omega 3s in fish oil are the ones needed to balance that omega 3/6 ratio that I mentioned earlier. Other sources are either inefficient or impractical. This is the area that you need to concentrate your research – not in which NSAIDS product is the least harmful.

Before you run out and buy a few bottles of fish oil, here are a few tips.

First, if you really want to reduce inflammation without NSAIDS, then you need to take the supplement daily. Go with a high quality product. Fish have ocean contaminants in them like mercury or other heavy metals. A reputable manufacturer will remove these toxins.

Summing up, use a supplement that is highly concentrated in EPA and DHA. Check the company’s website. The good ones will provide lab reports that tell you exactly what is and is not [pollutants and chemical additives] in each soft gel capsule. Also, look for antioxidants like vitamin E. My website can be a good starting point.