Nonsteroidal anti-inflammatory drugs
Nonsteroidal anti-inflammatory drugs (NSAIDs) alleviate pain by counteracting the cyclooxygenase (COX) enzyme. On its own, COX enzyme synthesizes prostaglandins, creating inflammation. In whole, the NSAIDs prevent the prostaglandins from ever being synthesized, reducing or eliminating the pain.
Some common examples of NSAIDs are aspirin, ibuprofen, and naproxen. The newer specific COX-inhibitors are not classified together with the traditional NSAIDs even though they presumably share the same mode of action.
On the other hand, there are analgesics that are commonly associated with anti-inflammatory drugs but that have no anti-inflammatory effects. An example is paracetamol (known as acetaminophen or Tylenol in the U.S). As opposed to NSAIDs, which reduce pain and inflammation by inhibiting COX enzymes, paracetamol has - as early as 2006 - been shown to block the reuptake of endocannabinoids, which only reduces pain, likely explaining why it has minimal effect on inflammation; paracetamol is sometimes combined with an NSAID (in place of an opioid) in clinical practice to enhance the pain relief of the NSAID while still receiving the injury/disease modulating effect of NSAID-induced inflammation reduction (which is not received from opioid/paracetamol combinations).
Long-term use of NSAIDs can cause gastric erosions, which can become stomach ulcers and in extreme cases can cause severe haemorrhage, resulting in death. The risk of death as a result of GI bleeding caused by the use of NSAIDs is 1 in 12,000 for adults aged 16–45. The risk increases almost twentyfold for those over 75. Other dangers of NSAIDs are exacerbating asthma and causing kidney damage. Apart from aspirin, prescription and over-the-counter NSAIDs also increase the risk of heart attack and stroke.
Antileukotrines are anti-inflammatory agents which function as leukotriene-related enzyme inhibitors (arachidonate 5-lipoxygenase) or leukotriene receptor antagonists (cysteinyl leukotriene receptors) and consequently oppose the function of these inflammatory mediators. Although they are not used for analgesic benefits they are widely utilized in the treatment of diseases related to inflammation of the lungs such as asthma and COPD as well as sinus inflammation in allergic rhinitis. They are also being investigated for use in diseases and injuries involving inflammation of the brain (ex. Parkinsons disease).
Immune selective anti-inflammatory derivatives (ImSAIDs)
ImSAIDs are a class of peptides being developed by
IMULAN BioTherapeutics, LLC, which were discovered to have diverse biological properties, including anti-inflammatory properties. ImSAIDs work by altering the activation and migration of inflammatory cells, which are immune cells responsible for amplifying the inflammatory response. The ImSAIDs represent a new category of anti-inflammatory and are unrelated to steroid hormones or nonsteroidal anti-inflammatories.
The ImSAIDs were discovered by scientists evaluating biological properties of the submandibular gland and saliva. Early work in this area demonstrated that the submandibular gland released a host of factors that regulate systemic inflammatory responses and modulate systemic immune and inflammatory reactions. It is now well accepted that the immune, nervous, and endocrine systems communicate and interact to control and modulate inflammation and tissue repair. One of the neuroendocrine pathways, when activated, results in the release of immune-regulating peptides from the submandibular gland upon neuronal stimulation from sympathetic nerves. This pathway or communication is referred to as the cervical sympathetic trunk-submandibular gland (CST-SMG) axis, a regulatory system that plays a role in the systemic control of inflammation.
Early work in identifying factors that played a role in the CST-SMG axis lead to the discovery of a seven amino acid peptide, called the submandibular gland peptide-T. SGP-T was demonstrated to have biological activity and thermoregulatory properties related to endotoxin exposure. SGP-T, an isolate of the submandibular gland, demonstrated its immunoregulatory properties and potential role in modulating the cervical sympathetic trunk-submandibular gland (CST-SMG) axis, and subsequently was shown to play an important role in the control of inflammation.
One SGP-T derivative is a three-amino acid sequence shown to be a potent anti-inflammatory molecule with systemic effects. This three-amino acid peptide is phenylalanine-glutamine-glycine (FEG) and its D-isomeric form (feG) have become the foundation for the ImSAID category. Cellular Effects of feG: The cellular effects of the ImSAIDs are characterized in a number of publications. feG and related peptides are known to modulate leukocyte (white blood cells) activity by influencing cell surface receptors to inhibit excessive activation and tissue infiltration.
One lead ImSAID, the tripeptide FEG (Phe-Glu-Gly) and its D-isomer feG are known to alter leukocyte adhesion involving actions on αMβ2 integrin, and inhibit the binding of CD16b (FCyRIII) antibody to human neutrophils. feG has also been shown to decrease circulating neutrophil and eosinophil accumulation, decrease intracellular oxidative activity, and reduce the expression of CD49d after antigen exposure.