Opioid analgesics : two types of pain reliefe

By the force opioid analgesics share a (relatively) to:

• «weak" - hydrocodone, propoxyphene, tramadol, codeine and drugs containing a combination (used to treat the pain of medium intensity);

• «strong" - morphine, fentanyl, methadone, oxycodone, hydromorphone, etc. (used to treat severe pain).

All * (except tramadol) opioid agonists evaluated as a potentially dangerous medications and drugs, as have the ability (to varying degree) to cause physical and psychological dependence, that is, have narkogenny potential.

Tramadol stands out among all members of opioids (agonists), because unlike them he has a very low narcotic potential (and does not belong to a drug) that is confirmed by extensive clinical experience of its use worldwide, and special research. Tramadol is counted among the strong agents and written on prescription form for the potent substances

Physical dependence (and tolerance) and are a natural and predictable reaction of the organism can be considered as a state of adaptation (adaptation) of the organism to long-term effect of opioid analgesics. The most serious challenge to the use of opioids is the development of addictive behavior - addiction or psychological dependence. The development of psychological dependence, unlike tolerance and physical dependence, the effect of opioids is unpredictable and manifests itself in a greater degree, as mentioned above, patients with unfavorable genetic and psychosocial background.

Opioid analgesics : The mechanism of action

Interactions with one or more subtypes of opioid receptors, in example mu-, delta-, kappa-, sigma and epsilon at supraspinal, spinal and peripheral levels, causing analgesia, and many other effects. Opioid analgesics can be full agonists of opioid receptors, namely μ (mu)-receptor partial μ-agonist and mixed agonist-antagonists have opposite effects.

Opioids act by:

• presynaptic inhibition of production of neurotransmitters C-fiber endings,
• postsynaptic suppression of evoked activity in nociceptive path or remove the remaining parts of the regulation of inhibition of nociceptive impulses.
• increased transmission of the descending inhibition of spinal nociceptive conduction.

Opioid analgesics : what is it ?

There are two types of narcotic/opioid analgesics:

the opiates and the opioids (derivatives of opiates). Opiates are the alkaloids found in opium (a white liquid extract of unripe seeds of the poppy plant).

Opioids are any medication which bind to opiod receptors in the central nervous system or gastointestinal tract. According to Wikipedia, there are four broad classes of opioids:

• Endogenous opioid peptides (produced in the body: endorphins, dynorphins, enkephalins)
• Opium alkaloids (morphine, codeine, thebaine)
• Semi-synthetic opioids (heroin, oxycodone, hydrocodone, dihydrocodeine, hydromorphone, oxymorphone, nicomorphine)
• Fully synthetic opioids (pethidine or Demerol, methadone, fentanyl, propoxyphene, pentazocine, buprenorphine, butorphanol, tramadol, and more)

Opioids are used in medicine as strong analgesics,

for relief of severe or chronic pain. Interestingly, there is no upper limit for the dosage of opioid analgesics used to achieve pain relief, but the dose must be increased gradually to allow for the development of tolerance to adverse effects (for example, respiratory depression). According to eMedicine, "Some people with intense pain get such high doses that the same dose would be fatal if taken by someone who was not suffering from pain."

There have been debates over the addictive potential of opioids vs. the benefit of their analgesic properties for treating non-malignant chronic pain, such as chronic arthritis. Some experts believe opioids can be taken safely for years with minimal risk of addiction or toxic side effects. The enhanced quality of life which opioids may provide the patient must be considered.

Opioid analgesics - what is analgesia ?

Analgesia simply means the absence of pain without loosing consciousness.

“The analgesia system is mediated by 3 major components : the periaquaductal grey matter (in the midbrain), the nucleus raphe magnus (in the medulla), and the pain inhibitory neurons within the dorsal horns of the spinal cord, which act to inhibit pain-transmitting neurons also located in the spinal dorsal horn. ”

These areas are the areas in which the chemical mechanisms of opioid analgesics will take place

Opioid analgesics: what is pain?

• Pain is a crucial aspect of the body’s defense mechanisms
• Pain “is a part of a rapid warning relay instruction the motor neurons of the centralnervous system to minimize detected physical harm ”
• Pain can be classified into two types:

Acute Pain

• Acute pain is short-term pain or pain with an easily identifiable cause
• Acute pain “is the body's warning of present damage to tissue or disease. It is often fastand sharp followed by aching pain. Acute pain is centralized in one area before becomingsomewhat spread out. This type of pain responds well to medications ”

Chronic pain

• Chronic pain is pain that last much longer than pain normally would with a particular injury.
• Chronic pain can be constant or intermittent and is generally harder to treat than acute pain.
• Pain can also be grouped by its source and related pain detecting neurons such as cutaneous pain, somatic pain, visceral pain, and neuropathic pain
• Opioid analgesics can be used to treat many types of pain

Opioid Analgesics : what causes pain?

Certainly, the physician must always strive to eliminate the root cause of the pain. However, pain itself require active therapy, especially in the acute and severe cases. In current clinical practice, prevention and treatment of pain is achieved mainly through painkillers. Among the most widely used analgesics neopiatnye presented nonsteroidal anti-inflammatory drugs. However, these drugs are effective only for mild to moderate pain intensity, with the possible exception of injectable lornoksikama, ketorolac and diclofenac, which are estimated as more active. The most effective pain relievers are opiates (opium alkaloids) and their synthetic analogs - opioid analgesics.

• Pain is caused by the stimulation of pain receptors which are free nerve endings.

“Nocireceptors are pain receptors that are located outside the spinal column in the dorsal root ganglion and are named based upon their appearance at their sensory ends. These sensory endings look like the branches of small bushes”

• There are two types of nocireceptors that mediate fast or slow pain signals

The perception of pain is when these receptors are stimulated and they transmit signal to the central nervous system via sensory neurons in the spinal cord.

Opioid analgesics : side effects

Opioid analgesics side effects / Adverse Reactions of Opioids:

Common side effects and adverse reactions:

• nausea
• vomiting
• drowsiness
• dry mouth
• miosis (contraction of the pupil)
• orthostatic hypotension (blood pressure lowers upon sudden standing)
• urinary retention
• constipation and/or fecal impaction

Less common side effects and adverse reactions:

• confusion
• hallucinations
• delirium
• hives
• itch
• hypothermia
• bradycardia (slow heart rate)
• tachycardia (rapid heart rate)
• raised intracranial pressure
• ureteric or biliary spasm
• muscle rigidity
• flushing

Most severe side effects and adverse reactions:

• respiratory depression
• fatal overdose

Opioid Analgesics : Endogenous Opioid Peptides

“Endogenous opioid peptides are the naturally occurring ligands for opioid receptors. The term endorphin is used synonymously with endogenous opioid peptides but also refers to a specific endogenous opioid, the Beta-endorphin ”. Opioid analgesics are used for treating chronic pain.

These peptides are produced by the pituitary gland and by the hypothalamus

Opioid peptides are found in the central nervous system mainly in limbic and brainstem areas associated with pain reception, and the certain areas of the spinal cord. Their distribution corresponds to “areas of the human brain where electrical stimulation can relieve pain ”

Opioid Analgesics : Locations involved in Pain Signaling and Analgesia

Opioid analgesics pain signaling scheme.

Opioid Analgesics : the opioid receptors

Opioid analgesics affect the nervous system.

Shortly after the discovery and observance of endogenous opioid peptides, multiple classes of unique opioid receptors were found

There are four main opioid receptors, the mu receptor, the delta receptor, the kappa receptor, and the ORL-1 receptor.

The sigma receptors were once thought to be opioid receptors ,however, pharmacological testing indicated that the sigma receptors were activated by drugs completely unrelated to the opioids

The receptors are found on cell membranes of cells in the nervous system (neurons) and are found in unique distributions and have different effects.

Opioid analgesics : in future

The future of Opioid Analgesics

seems to be linked to the study of the Kappa Receptor. The kappa receptor induces analgesia without the dangerous and unwanted side effects that the mu and delta receptors are associated with. However there are not any selectively strong agonists to this receptor as of now.

Another area of research important to the future of opioid analgesics is the study of the endogenous opioid peptides.

Because these peptides are endogenous, on metabolic degradation (unlike opiates) they break down to amino acids. Hence, the metabolites are nontoxic and to not cause kidney and liver damage (6).”

Also, because they are made from amino acid residues, “a large number of analogs can be synthesized from a few basic building blocks and simple modifications may be attempted to develop analogs with a desired biological effect (6).”

The further study of the endogenous opioid peptides seems to be integral to development of new safer drugs.