What are Opioids?

Opioids or opiates are any narcotic alkaloids from immature pods of the Papaver somniferum (opium poppy).  These are considered to be the world’s oldest recognized drug.  This was discovered and used even during the prehistoric eras in the Mediterranean area. The ancient Romans and Greeks believed this drug as the ultimate panacea and it appeared in their Greek pharmacopeia as early as the 5th century BC. With the expansion of Islam, opioid use was spread from Turkey to the other parts of the world. It was the Arab traders in the 8th century BC who introduced this to the Indians and Chinese. When the Chinese emperor prohibited the smoking of tobacco in 1644, the Chinese changed to opium smoking. When the Arabs traded with Vienna, they also introduced opium to the Europeans.

At present, opioids are used to treat moderate to severe pain, severe diarrhea, and anxiety with shortness of breath, cough suppression and opioid dependence (buprenorphine and methadone). Unfortunately, these drugs are one of the most commonly abused drugs worldwide. The opioids stimulate the brain to release “euphoric” chemicals that would eventually lead to dependence and abuse.

Opioid Drugs

Opioids are classified into four general classes:

  1. Endogenous opioid peptides, those that are produced naturally by the body
  2. Opium alkaloids
  3. Semi-synthetic opioids
  4. Fully synthetic opioids

These drugs are used to manage acute pain and are effective in alleviating severe, persistent disabling pain associated with degenerative conditions (rheumatoid arthritis) and cancer. Cough suppression and severe diarrhea especially those related with irritable bowel syndrome are also prescribed these drugs.

Opioids are relatively safe for use under supervision from physicians. They should not be taken together with other medications and substances that would depress the CNS like antihistamines, benzodiazepines, barbiturates, general anesthetics or alcohol since it will increase the probability of respiratory depression that is life threatening.

List of Opioids

Since opioids are narcotic drugs that can lead to abuse and dependence, drugs classified under these are regulated by the FDA.

Opioids List of Natural or Opium Alkaloids

These drugs are naturally-occurring opioids that are alkaloids from the opium poppy’s resin.

  • Morphine
  • Codeine

Opiods List of Semi-synthetics

These are opioids that are manufactured from the opium alkaloids and are lipid-soluble. They mimic the structures of the natural opiates. When drug tests for opiates are done, these medications are not detected with the exception of dimethylmorphine because it is immediately metabolized into morphine.

  • Acetylmorphone
  • Buprenorphine
  • Heroin
  • Codoxime
  • Desomorphine
  • Diacetylmorphine
  • Ethylmorphine
  • Hyrocodone (Hycodan)
  • Hyrdomorphone (Dilaudid)
  • Meperidine (Demerol)
  • Nalbuphine
  • Naloxone
  • Oxycodone (Percodan)
  • Pentamorphone
  • Thebacon

Opiods List of Synthetics

These drugs are wholly man-made and have chemical structures that are distinct from opium alkaloids. As with the semi-synthetic opioids, these drugs are not detected in drug tests for opiates.

  • Fentanyl (Sublimaze)
  • Methadone (Dolophine)
  • Propoxyphene (Darvon)
  • Pentazocine (Talwin)

Endogenous Opioids

These opioids naturally produced in the body and are used as neurotransmitters and influence body functions such as thirst, hunger, moods, pain reactions and immunity. Endogenous opioids include:

  • Endorphins
  • Enkephalins
  • Dynorphins
  • Endomorphins

Endorphins are manufactured at the hypothalamus and pituitary glands during strenuous activities, pain, orgasm and excitement. They work as intrinsic pain relievers and resemble natural opiates in their capacity to generate a sensation of well-being and analgesia. Enkephalins, on the other hand, are pentapeptides that play a role in processing noxious stimuli directed to the body.

Dynorphins are produced in several areas of the brain such as the spinal cord, hippocampus, medulla, hypothalamus, midbrain and the pons. How they act would depend where they were released. Basically, they are modulators of pain, preserve homeostasis by controlling appetite and the circadian rhythm, temperature regulation and weight control.

Endomorphins are heavily distributed in the upper brainstem and the brain particularly in the cortex, nucleus accumbens, amygdala, hypothalamus, thalamus and dorsal root ganglia. These endogenous opioids control arousal and sedative behaviors, responses that are related to stress, reward and vigilance.

Opioid Analgesics

An opioid analgesic is a powerful pain reliever that produces an effect on the central nervous system in order to relieve pain. Some of these narcotic analgesics are used before or in the course of the surgical procedure to enhance the effects of the anesthetics. This type of analgesic is the mainstay for therapy of acute severe pain and chronic pain caused by cancer because of its effectiveness in pain control.

The opioid analgesic is more effective if given at regular intervals before the pain becomes intense. If the pain is unrelieved, the dose should be increased gradually or an additional drug (e.g. NSAID) may be incorporated. When the amount of pain decreases, the dose should also be reduced accordingly. If tolerated, the narcotic analgesic should be substituted with a non-opioid type.

Frequent side effects felt by users are nausea and vomiting, drowsiness, miosis, dry mouth, urinary retention, orthostatic hypotension and constipation (sometimes fecal impaction). Less common reactions would include confusion, delirium, hallucination, hives, hypothermia, itch, bradycardia or tachycardia, increased intracranial pressure, muscle rigidity, flushing and biliary spasm. Patients taking higher doses of opioid analgesic should be monitored closely for respiratory depression and fatal overdose. In cases like this, the antidote (nalaxone) is given intravenously.

Some individuals who are on prolonged narcotic analgesic therapy tend to develop tolerance and would need higher doses for the effects to be felt. Others develop dependence and would experience withdrawal symptoms once the drug is stopped. The dose of the drug is usually reduced gradually to prevent such from happening.

Opioid analgesics are usually taken orally but if the treatment therapy is prolonged, then a skin patch is used. For acute pain, these medications can be given intravenously or intrathecally.

Opioid Receptors

Opioid receptors are G protein-coupled receptors that use opioids as signal generating molecules (ligands).  There are three major opioid receptors (mu, kappa and delta) that are found all through the CNS predominantly in areas linked to perception of pain (brain, spinal cord) and the GI tract. The mu receptor has affinity to morphine, kappa receptors are more partial to partial agonists such as pentazocine and the delta receptors have high affinity for enkephalins (endogenous).  When the narcotic analgesics or opioid drugs attach to these receptors, the perception of pain is blocked.

Pert and Snyder from John Hopkins School of Medicine located two areas of the CNS where the opioid receptors are prevalent – spinal column and the medial thalamus (brain). Pain is first detected by the spinal column and the signals are concentrated at the medial thalamus. Opioids slow down the rate the pain messages are transmitted thus the sensation is reduced and the euphoria that comes with its use.

Opioids are classified into three different types based on how they affect the receptors. Opioid agonists are those agents that unite with receptors and instigate a physiological reaction. An example of this type is morphine. The opioid antagonist, on the other hand, has an opposite effect; it inhibits the effect of the agonists. A partial agonist has both antagonist and agonist characteristics. It binds to a receptor that induces pain relief (agonist) and to an additional receptor that will not initiate a physiological effect (antagonist).

Opioid antagonist drugs compete for binding with opioid receptors. They have higher affinity to the receptors compared with the agonists. However, they do not activate the receptors thus inhibiting the body from reacting to opiates and endogenous endorphins. These drugs are used as antidote for opioid overdose. Examples of opioid antagonist drugs are naltrexone and nalaxone.

Opioid Dependence

Dependence to opioid is basically a group of behavioral, cognitive and physiological episodes with unpredictable intensity wherein the use of opioids takes a higher priority than other activities, sometimes including ADLs. The user cannot stop using the drug and has the strong desire to take it with or without medical prescription.

Most of the abused opioids are prototypes of the mu agonists. The activation of these receptors cause euphoria (“high”) and when the levels are increased rapidly, it generates an intense but brief “thrill” or “rush”. The chronic use of opioids would result to tolerance and dependence. Individuals with opiate addiction usually use more opiates to avoid the unpleasant effects of withdrawal and not the gratifying sensations felt with first use.

Dependence or opioid addiction requires a long-term care and treatment plan. This is important to lessen the social and health effects of the condition and improve the social functioning and well-being of the person involved.

Opioid Withdrawal

Opiate withdrawal includes an assortment of symptoms that come about after significantly decreasing the dose of the opiate drug or stopping it abruptly after a prolonged and heavy usage. The system requires enough time to recuperate and compensate for the loss of the drug, thus withdrawal symptoms occur. Symptoms may differ depending on the extent of the dependence.

Opioid Withdrawal Symptoms

Symptoms are felt at different stages based on the last use:

Beginning symptoms are felt less than eight hours from last use and will peak within 36 to 72 hours. The patient will feel fear of withdrawal, anxiety, diaphoresis, cravings, chills, rhinorrhea, yawning and lacrimation.

Twelve hours from last use (peak: 72 hours) patient will experience piloerection, dialted pupils, anorexia, irritability, anxiety, dysphoria, mild to moderate insomnia, restlessness, mild tachycardia, slight hypertension, tremors and abdominal cramps.

From 24 to 36 hours from last use (peak: 72 hours) patient will suffer abdominal cramps, myalgia, diarrhea, muscle spasms particularly at the lower extremities, nausea and vomiting, severe insomnia and violent yawning.

Resolution of the physical symptoms would generally be around five to ten days. Psychological symptoms such as insomnia or dysphoria, however, would take about weeks or months to resolve.

Opioid Withdrawal Treatment

Therapy would involve supportive care and the use of medications. Generally clonidine is the customary drug used to reduce autonomic hyperactivity syndrome such as agitation, anxiety, sweating, rhinorrhea, myalgia and cramps. The major disadvantage of this medication is the resulting hypotension. Medications for vomiting and nausea are also given.

It has been found out that Buprenorphine (Suptex) works better compared to other opioid antagonists in managing withdrawal symptoms. It can cut down the duration of detox.

For the first three months, behavioral therapy and counseling is done. Abstinence is critical during these days, thus, in-patient management is recommended for close monitoring. Long-term treatment is crucial in order to prevent any relapses.

Opioid Conversion

There are times when physicians need to switch from one opioid to another or from one route of administration to another in order to meet the medical needs of the patients and the response to the drug. Accurate conversion is subject to a several factors such as drug dosage, physiologic differences in the metabolism of the drug and cross-tolerance with other opioids. Conversion must allow for other factors such as the level of residual drugs, the length of time to attain a steady-state level in the blood and the response of the patient to the drug.

Opioid Abuse

Opioid abuse takes place when the obsessive use of opioids would harm the health of the user and affects the social functioning. Individuals become addicted to opioids because of the swift, forceful euphoric sensation that is followed by a calm and comfortable drowsiness.

Risk factors that would increase the chance of abusing opioid use would include gender (males more prone), age (young adults), abuse of other drugs, and positive psychological disorder.

Opioid Addiction Treatment

Opioid dependence treatment would include a rehabilitation program where the opioid abusers are placed in a controlled environment for at least six to twelve months. There might be a necessity to detoxify the patients first before undergoing behavioral therapy. In a detoxification center, the withdrawal symptoms are managed safely.

Aside from these, opioid dependence treatment would also include the use of medications that would help reduce the unpleasant withdrawal symptoms. Methadone, Buprenorphine and Buprenorphine + nalaxone are the common drugs being used.






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