October 4, 2014

Endogenous Opioids and Opioid Receptors

The term opioids are not new to many, it has been heard as the media is always abreast with all information about these opioid drugs which to the public are known mostly for the wrong reasons. People have got misinformed about these drugs so much that when you tell a layman that these drugs are used in hospital then to him you will something much worse than an alien. However to the medical fraternity these opioids are essentials that are hard to survive without. That said and left, back to the topic; Endogenous Opioids is a new term to many and if your prediction is as right as mine then you are hearing it for the first time. What does it really mean? The endogenous opioids are opiate-like substance, such as an endorphin, produced by the body. If you thought that you can live without these endogenous opioids then you need to wake up from your momentary slumber. Every day of our lives we face pain of all sorts even the most insignificant pains needs the actions of these opioids to give you peace.

Today, the endogenous opioid system is one of the most studied innate pain-relieving systems. The endogenous opioid system consists of widely scattered neurons that produce three opioids: beta-endorphin, the met- and leu-enkephalins, and the dynorphins. These opioids act as neurotransmitters and neuromodulators at three major classes of receptors, termed mu, delta, and kappa, and produce analgesia. The endogenous opioids works in the same manner as the narcotic opioids in that they bind to the same receptors and they also have both good and negative effects. There might be all sorts of information out there that you can lay your hands that may speak well of the opioids but the bitter truth is we all depend on despite the negative light they have been portrayed in.We are all naturally dependent on opioids for our emotional health. Both narcotics and internally generated endogenous opioids exert their action on the body by interacting with specific membrane receptor-proteins on our nerve cells.

There are three large pro-compounds that are produced by the body and these are: proenkephalin, prodynorphin, and pro-opiomelanocortin. However, endorphins can further decompose to small fragments, oligomers, which are still active. Oligomers pass the blood-brain barrier more readily. Enzymatic degradation of small-chain endorphins is accomplished by dipeptidyl carboxypeptidase, enkephalinases, angiotensinases, and other enzymes. This limits their lifetime in the unbound state.

Presynaptically opioid receptors inhibit transmission of excitatory pathways. These pathways include acetylcholine, the catecholamines, serotonin, and substance P. Substance P is a neuropeptide active in neurons that mediate our sense of pain. Endogenous opioids are also involved in glucose regulation. Opioid receptors are functionally designated as mu, delta, kappa among others. These categories can be further sub-classified by function or structure. Decoding the human genome has allowed the genetic switching-mechanisms that control the expression of each opioid receptor to be determined at the transcriptional and post-transcriptional level.

Opioid-driven inhibition of neuronal excitability is mediated by the activation of a variety of potassium channels in the plasma membrane. The disparate subjective and behavioral effects evoked by activation of the different categories of opioid receptor are typically not the outcome of different cellular responses, but reflect the different anatomical distributions of each receptor. Unlike kappa opioid receptors, however, both mu and delta opioid receptors internalize on exposure to agonists. Activation of any type of opioid receptor inhibits adenylate cyclase, resulting in a fall in intracellular cAMP and diminished action potential firing. This causes a reduced flow of nociceptive information to the brain. Conversely, opioid addicts undergoing withdrawal suffer elevated cAMP levels and enhanced protein kinase A activity, resulting in increased neurotransmitter release.

Role of Mu receptors in addiction

The Mu opioid receptors are the gateway to addiction. This is because they mediate positive reinforcement following direct or indirect activation. In an experiment where mice without mu receptors were used, it was found that the morphine’s analgesic and addictive properties are abolished in these mice. This shows that mu receptors mediate both the therapeutic and the adverse activities of opioids. The mice that were lacking mu receptors were found to lack of morphine-induced analgesia, reward, and dependence. The mice had increased sensitivity to pain. This shows that the mu receptors play a critical role in addiction. These mu receptors function as switches upon direct or indirect reinforcement of opioid abuse. Mu-opioid receptors are a key molecular switch triggering brain reward systems and potentially initiating addictive behaviors. The lack of mu-receptors abolishes the analgesic effect of morphine, as well as place-preference activity and physical dependence. This receptor therefore mediates therapeutic analgesia and adverse activities of morphine.

Opioid withdrawal symptom

endogenous opioids When a person has been using the opioids for some time, he will become physically adapted to the drugs so much that when he stops abruptly he will experience the symptoms of withdrawal. Withdrawal is not only faced by opioid user only but also other sick people who are on other drugs as well. However to limit the withdrawal symptoms, there are some factors that come in handy. One of these factors is the pace and how you exit from using these drugs. Your doctor will be of help in helping you by developing safe exit strategies that will limit the withdrawal symptoms.

Finally, you need more information to stay away from dependence on alcohol and drugs as these have crippled societies and that is why here at AWAREmed we are dedicated to finding the best solutions to addiction and dependence on substances. Dr. Dalal Akoury (MD) is always in the mood of helping any patient to be addiction free. Do not hesitate to call on her for help in managing any sort of chronic pain or any type of addiction as well as other diseases.

Endogenous Opioids and Opioid Receptors

Opioids and Cancer

September 27, 2014

How the use of opioids disturbs the cancer balance

What are opiods?

There are several important things about opiods that you need to know at this stage. First, it is important to note that strictly speaking, the term ‘opioids’ is used to describe a group of chemical compounds that are defined by two important characteristics: having chemical action that is similar to that of morphine and being made of a distinct chemical structure. For many of the compounds that are categorized under this umbrella, their structures vary. Whereas some have distinct alkaloid structures, others occur in the form of peptides.

The second thing is about the occurrence of opioids. Naturally, opioids are found in two distinctive forms: occurring freely in the environment and within the body of human beings. Although initially the possibility of occurrence of opioids within the body of humans was strongly refuted, rigorous research has indicated that indeed the human brain contains specific endogenous opioids that play important role in different functions.

The third thing regards the interaction of opioids with complementary chemical compounds. Further studies have indicated that there are compounds whose actions contradict that of opioids. Known as antagonists, such compounds play a highly important role in their interaction with opioids in relation to influencing particular processes in the body. We shall examine this subject later.

How are opioids used?

For years, opioids have been used for a range of functions. Basically, the use of opioids has been in the form of morphine, which is a commonly occurring plant. Morphine has been used for medicinal as well as recreational purposes for long. Since the use of the plant for medicinal purposes is what matters with regard to our discussion, we shall focus on it.

At the commercial level, morphine has actually been used to relieve pain in chronically ill patients. Take cancer for example, the disease has been known to produce intense pain in patients. To relieve patients of this, morphine-based painkillers are extensively used. This is one common and formal way in which morphine (a common source of opioids) is used for commercial purposes.

The ability of opioids in general and morphine in particular to act as a strong analgesic has been a subject of research for long. Studies have indicated that the compounds have specific effects on the nervous system which translates to drastic reduction in pain. This explains the popularity of morphine-based painkillers as the standard therapy for cancer patients who have undergone an operation as part of the therapy or simply those in advanced stages of cancer.

Therefore, whether for recreation or medicinal use, opioids, have been extensively used to relieve cancer patients of pain in the course of treatment.

How opioids act

Basically, the action of opioids on the body can best be understood when you understand what opioid receptors are. Your body is made of special compounds which act as receptors for opioids. The receptors are distributed in several parts of your body, with many of them being in the central nervous system. It is this phenomenon that explains why opioids have a very strong effect on the nervous system. Others are distributed in different parts of your body such as the lungs, liver and other internal organs.

There are several types of receptors. It is the interaction between specific opioids and receptors that causes particular feelings in the body. Whereas some receptors are meant to trigger feelings of relief when they come into contact with opioids, others are designed to trigger changes in other physiological processes when opioids are introduced. The interaction between opioids and receptors is an important process when it comes to how opioids may disturb the cancer balance in the body.

How do opioids disturb cancer balance?

Simply put, cancer balance is a situation in which the process of metastasis, angiogenesis and invasion of healthy body cells by cancerous ones is completely inhibited. Research has indicated that use of opioids as painkillers can disturb this balance, thus leading to development of cancer in the body. On the other hand, other studies have indicated that morphine, in particular, may have anti-cancer properties by inhibiting the cancer development process mentioned above.

One way in which opioids used as painkillers can disturb the cancer balance is by altering the normal functioning of the immune system. Since cancer development largely depends on the state of the immune system, any compound that alters the immune system can indirectly influence the possible occurrence, development and spread of cancer. From several studies conducted, it can be concluded that particular opioids are able to alter the normal functioning of the immune system, thus exposing a patient on whom they are used to cancer development.

On the other hand, some studies have indicated that morphine is able to induce natural cell death and, as a result, control the growth of cancer cells in the body. However, this property, which highly depends on a number of different factors such as the concentration of the morphine that is used and the state of the opioid receptors in the body, remains a subject of research. What you need to know is that there has been concrete evidence to the effect that the use of opioids for relief of pain in cancer patients may actually disturb the cancer balance and trigger fresh development of cancer. This happens because of the effect that opioids have on the immune system of the patient in the form of production and inhibition of production of important hormones.

Concluding remarks

Here at AWAREmed Health and Wellness Resource Center, we use the best approaches to administer alternative and complementary treatment of cancer to patients. Dr. Dalal Akoury is a specialist in this field. One thing, though, that sets her apart is her devotion to helping cancer patients successfully fight the devastating effects of the disease. Feel free to visit us in Myrtle Beach, South Carolina for a completely personalized administration of alternative and complementary therapies for cancer.