Opioids Inducing Nausea And Emesis

The main physiological consequence of nausea and emesis is the removal of toxins, which is an important protective reflex mechanism being induced during food intoxication. It however, is also seen after radiation or chemotherapy, after the administration of an opioid-based anesthetic regimen or during long-term therapy for alleviation of chronic pain. About 20 of all patients experience nausea and or emesis after opioid anesthesia. The cause of such reaction is a stimulation of the...

Dependence Liability Of Opioids Pharmacological Principles Of Addiction

Dependence or addictive liability (how addictive a drug is likely to be) depends upon how quickly the drug enters leaves the brain. Also, it is directly proportional to the analgesic potency and it depends on the opioid receptor sites with which the ligand interacts. For instance, members of mixed agonist antagonists (i.e. nalbuphine, pentazocine, butorphanbol) demonstrate a predominant interaction with the K-opioid receptor, which is characterized by a low dependence liability (Figure II-51)....

Neuraxial Administration of Opioids for Pain Therapy

Aside from the intermittent or continuous local neural blockade, such as intercostal nerve blockade or infusion of a local anesthetic through an interpleural catheter, spinal epidural analgesia is an effective technique to be used in postoperative pain therapy. Neuraxial drug administration describes techniques that deliver drugs in close proximity to the spinal cord, i.e. intrathecally into the cerebrospinal fluid (CSF) or epidurally into the fatty tissues surrounding the dura, by injection or...

Reasons For Prolongation Of Opioidrelated Respiratory Depression In Patients

In general prolongation of respiratory depression after opioid administration has to be expected when the following agents are coadministered 1. All agents that inhibit the biotransformation of opioids such as contraceptives, anti-tumor agents, anti-arrhythmics, antidepressants, systemically administered antimycotics, neuroleptic drugs, and volatile anesthetics 68, 69, 70, 71, 72 . By inhibition of conjugation of glucoronide and oxidative dealkylation, the necessary metabolic pathways for...

Reasons For Difference In Potency Of Opioids

In contrast to the analgesics that have a peripheral site of action (e.g. acetylsalicylic acid ASA), opioids act at the relay station of nociceptive-propagating pathways at the synapse of nerve conduction. Within the nerve, pain impulses are transmitted as a change in electric conduction. And in order to guarantee maintenance of the nociceptive impulse, the excitatory impulse releases a neurotransmitter at the terminal nerve. Due to its chemical configuration, the transmitter fits exactly into...

Opioids And The Cardiovascular System

Contrarily to many other anesthetics, opioids in general do not depress the cardiovascular system. This is also reflected in the higher therapeutic range (LD50 ED50) being derived in the animal (Table II-11). Such data can also be conveyed to the human, since a wide therapeutic margin of safety is directly correlated with a lack in cardiovascular impairment. While carfentanil, with a potency twice that of sufentanil, is solely used in veterinary medicine for the immobilization of wild animals...

The Antitussive Action Of Opioids Blockade Of Cough Reflex

Each cough involves a complex reflex arc beginning with the stimulation of sensory nerves that function as cough receptors. There is evidence, primarily clinical, that the sensory limb of the reflex exists in and outside of the lower respiratory tract. Although myelinated, rapidly adapting pulmonary stretch receptors (RARs), also known as irritant receptors, are the most likely type of sensory nerve that stimulates the cough center in the brain, afferent C-fibers and slowly adapting pulmonary...

Oral Transmucosal Fentanyl Citrate OTFC Stick for Treatment of Breakthrough Pain

The problem of breakthrough pain, lasting for 30 min to 2 h is often observed in patients with cancer pain (Fig. IV-16), which may present a major problem in chronic pain therapy. Breakthrough pain may appear at different instances such as Figure IV-16. Schematic representation of breakthrough pain during around-the-clock medication where in spite of a stable and constant plasma blood level, peak nociceptive afferents break through the opioid barrier Figure IV-16. Schematic representation of...

Conversion of Morphine to Heroin Diacetylmorphine

The following is a step-by-step description of morphine extraction in a typical Mainland Southeast Asian laboratory. An empty 55-gallon oil drum is placed on bricks about a foot above the ground and a fire is built under the drum. Thirty gallons of water are added to the drum and brought to a boil. Ten to fifteen kilograms of raw opium are added to the boiling water. With stirring, the raw opium eventually dissolves in the boiling water, while soil, leaves, twigs, and other non-soluble...

Neurophysiological Changes Taking Effect During Evolution Of Pain

The skin is the site where approximately 90 of over 3 million nociceptors are located. The peripheral tissue damage, in order to develop into pain of chronic nature, peripheral nociceptors of the skin are irritated over a long period of time. In order to be transmitted, a certain threshold level has to be surpassed, before so called multimodal wide-dynamic-range (WDR)-receptors pick up tactile sensation like pressure, heat, distension, and pain is transmitted to the spinal cord. There, aside...

Intrathecal Use Of Opioids

The intrathecal application of an opioid presents a more direct way to administer the opioid close to its site of action, the substantia gelatinosa at the dorsal column Figure 111-79. Example of an external pump system with a subcutaneous port for continuous infusion epidural analgesia Figure 111-79. Example of an external pump system with a subcutaneous port for continuous infusion epidural analgesia of the spinal cord. Aside from the lack of diffusion through the dura mater, the usual...

The Malingering Patient With Compensatory Pain Behavior

The malingering patient is motivated by a conscious secondary gain that may be tangible or intangible. It is important to remember that a malingerer may be uninterested in financial rewards and may instead be seeking other forms of reinforcement from employers, coworkers, or family. In contrast, the compensatory patient is interested only in monetary gain. The patient may have been injured at work or may be involved in litigation related to an automobile accident. The possibility of large...

Definitions and Concepts in Physical Dependency

Most exposures to drugs that are considered to have addiction potential do not result in the disease of addiction 11 . Each person has a particular underlying genetic risk for developing addiction if exposed to a certain type of drug in a certain environment 16, 17, 18 . Environmental factors play a critical role, and exposure to the drug(s) of abuse plays an essential role. Although the choice to try a drug may be voluntary, the drug effects can be influenced profoundly by genetic factors 11,...

Pharmacologically Resistant Psychologically Conditioned Pain

Functional and feigned pain patients who seem to magnify their physical complaints may be described as exhibiting hysteria, conversion disorder, Figure I-56. Combination of voltage- and ligand-gated ion channel at the NMDA receptor hypochondriasis, somatization disorder, depression, and malingering or compensatory behavior. These terms are used in a general fashion, without the specificity that a psychiatrist or psychologist would apply. The general practitioner may call the back pain and its...

Delivery of Opioids via the Lungs The Aerosolized Liposome Encapsulated Fentanyl AeroLEF

AeroLEF is a proprietary formulation of free and liposome encapsulated fentanyl, a potent analgesic. It is intended for administration by pulmonary inhalation for the treatment of acute pain, including breakthrough cancer pain. AeroLEF is a product designed to meet the unique dosing needs of the individual, providing real-time patient directed pain relief. Using DELEX's proprietary Rapid Onset and Sustained Effect Delivery System (ROSE-DS) platform technology, AeroLEF provides rapid onset and...

Difference In The Hypnosedative And Analgesic Effect Of Potent Opioids

Opioids in general induce a dose-related hyposedative component, which is mirrored in the electroencephalogram by an increase of activity in the slow S- with concomitant decrease of power in the fast -domain. However, when giving a large bolus dose of fentanyl (7-10 pg kg body weight) alfentanil (50 pg kg body weight) morphine (3-10mg kg body weight) or sufentanil (2-3 pg kg body weight) an immediate dominance of delta-waves in the EEG becomes evident, being accompanied by sleep. For instance,...

Oxytrex Ultra Low Dose Opioid Antagonist Combined with Oxycodone with Less Tolerance Development

Oxytrex contains a combination of oxycodone, an opioid agonist, and an ultra-low dose of naltrexone, an opioid antagonist. In the brain, opioid drugs usually inhibit the transmission of signals from neuron to neuron. However, with chronic use, the brain adapts to opioids, and the signals switch from being predominantly inhibitory to predominantly excitatory. This results in tolerance, or patients needing escalating doses of opioids to mask pain. Moreover, even when the pain stops, the brain...

Supraspinal Engrams Relevant In Transition From Acute To Chronic Pain

Nociceptive afferent signals from damaged peripheral tissue are relayed to the posterior column where they transmit to second order neurons of the spinal cord where they are being modulated. Nociceptive simuli originating in the head or the face are conveyed via the trigeminal nerve to the trigeminal nerve nucleus in the brain stem. There, all afferent signals are being modulated after which they cross to the opposite side, further ascending to the thalamus. From there, fibers ascend rostrally...

Mechanism Of Action Of Tricyclic Antidepressants

The termination of action of biogenic amines norepinephrine (NE) and serotonin (5-HT) is determined by reuptake into the presynaptic terminal. Drugs that block reuptake, such as tricyclic antidepressants, increase the efficacy of those transmitters by allowing them to remain in the synaptic cleft and activate the receptors longer (Figure I-51). It should be noted that although the exact mechanism of action of TCAs as analgesics is not known, there appears to be a close relationship between the...

Intrathecal Duros Opioid Delivery Using a Precision Miniature Catheter

To deliver drug to a specific target site, DURECT company developed a proprietary miniaturized catheter technology that can be attached to the DUROS system to direct the flow of drug directly to the target organ within the spinal cord. Undergoing preclinical evaluation, this site-specific delivery enables a therapeutic concentration of a drug to be present at the desired target opioid receptor sites without exposing the entire body of the patient to a similar dose. The precision, miniature...

AERx Pulmonary Delivery System for Morphine and Fentanyl

Another aerosol pulmonary delivery system with a built-in electro-mechanical liquid aerosol generator is shown in the following figure. The physical and mechanical details of the AERx System is initated by an aerosol generated in about 1 s by means of mechanical extrusion of a piston of an aqueous formulation through an array of micron-sized laser micromachined holes. The extrusion causes the formation of aqueous jets that break up into droplets of sizes that relates to the sizes of the holes...

Remoxy with Oradur Technology Opioid with an Abuse Resistant Formulation

Abuse of controlled-release formulations of oxycodone and other prescription opioids is a large, fast-growing problem in the US. Simply crushing and dissolving these formulations can yield the full 12 h dose to produce an immediate, large spike in opiate blood levels and a powerful morphine-like high, as well as the potential for respiratory depression and death. In the US in 2002, oxycodone abuse resulted in over 22,000 Emergency Room visits (nearly 20 of ER visits due to abuse of narcotic...

Potential Epileptogenic Potency Of Opioids

Following the administration of high dosages of opioids with different potency, epileptogenic activities in the EEG with tonic-clonic seizures can be induced in the animal. Pethidine (meperidine), morphine, alfentanil, fentanyl and sufentanil when administered in doses above 20, 180, 5, 4 and 4 mg kg body weight respectively, induced epileptogenic discharges 103 . Because such massive dosages are never used in anesthesia or for analgesia in acute or chronic pain, epileptogenic effects, although...

Overview Of The Different Opioid Receptors And Their Subtypes

Opioid receptors are distributed widely in brain and found in spinal cord and peripheral sensory and autonomic nerves. There are the three well-characterized members of the opioid receptor family, designated by the Greek symbols 8, k and The more recently discovered ORL1 receptor is placed with this family due to its high degree of structural homology. These receptors were renamed OP1, OP2, OP3 and OP4, respectively, by an International Union of Pharmacology (IUPHAR) nomenclature committee in...

Neurophysiology of Pain Type of Receptor Sites Involved in Therapy

Trauma and damage at the periphery results in inflammation and or damage of cells, resulting in the release and the formation of so-called nociceptive substances, which activate peripheral nociceptor sites (Figure I-16) 1. Formation of free oxygen radicals (ROS reactive oxygen species) like peroxides, and nitric oxide (NO), 2. release of prostanoids (prostaglandin D, E, F, I, leukotrienes), thromboxane, 3. formation of purines (adenosine, ATP), 4. release of tachykinins (substance P, neurokinin...

Sequence of Resulting in Neuropathic Pain

Therefore prevention of such transition from acute to chronic pain with opioids is the major goal in pain therapy. Also, intracellular gene expression can be prevented most successfully, if opioids are administered before nociceptive stimuli reach the cells 65 , and before neuroplastic changes within the cells are being initiated. It is because of such intracellular changes, that acute pain can become chronic if it not sufficiently treated from the start. If however, during the process of...

The Pupillary Effect Of Opioids

The miotic action of opioids on the pupil is an easily recognizable and quantifiable effect in man. The neural pathways responsible for regulating pupil size are reasonably well defined. Yet, the mechanisms behind this and related effects of opioids on the eye in humans and laboratory animals have just begun to be explored. Opioid-induced miosis in the human, dog and rabbit is thought to be mediated through the central nervous system. This action is a specific opioid effect as demonstrated by...

Avoiding Illicit Use by Combining Opioids with Antidepressants Antiepileptics

Antidepressants and antiepileptics are both effective in treating neuropathic pain, but a combination performs best. Nearly 80 of patients who took a combination of antiepileptics and antidepressant medications had a greater than 50 Visual Analogue Scale (VAS) improvement, a statistically significant finding. Whereas clinical trials have shown clear evidence in favor of using antidepressants and antiepileptic medications alone in treating chronic pain, no studies have been designed to focus on...

Differences in Pain Quality

When diagnosing pain it can be categorized into the following qualities On the other hand pain can be divided into different categories depending on its origin 1. Transient-stimulus induced pain 3. Pain from injury of afferent neurons 4. Pain from injury of central neurons. Everything should be done in order to identify the mechanisms of chronification, which may be due to 6. Structural reorganization, and or Acute pain sensations are transmitted from the periphery to the brain. At the level of...

Inhibitory and Excitatory Effects of Nociception at the Spinal Cord Level

Excitatory Transmitter Glutamate

Within the spinal cord, either an enhancement and or an inhibition of ascending nociceptive afferences come into effect. The spinal cord is also considered as the major site where a number of analgesic agents initiate their mode of action through direct binding at selective inhibitory receptor sites (Figure I-19). Figure 1-19. Summary of the different receptor sites at the dorsal horn related to inhibition and or excitation of incoming nociceptive afferent impulses Figure 1-19. Summary of the...

Opioids And Muscular Rigidity

Opioids can induce muscular rigidity, which is due to an increased tone of the striatal muscle. Especially, the muscles of the thoracic cage and of the abdomen show this rigidity, a phenomenon, which is observed after the bolus injection of a potent opioid, such as the fentanyl series (i.e. fentanyl, sufentanil, alfentanil and remifentanil Figure II-57). Increase in muscle tone is directly correlated to the -receptor interaction, because mixed agonist antagonists and highly selective -opioid...

Common Comprehensions on Prescription Drug Abuse

Small Pupils Drugs

The street value of a prescription drug is dependent on whether it is a brand or generic. Even abusers know that they get what they pay for when buying a brandname drug. Drugs that have a quick onset - immediate-release or injectable drugs -are more sought after, as well as those that have a greater intensity. The demand for drugs with a short duration of action is consistent with the rate hypothesis of reinforcement - the faster the drug enters the system, the quicker it causes the dopamine...

DUROS Implant Technology for Chronic Pain Treatment

Just as ALZA Corporation's oral and transdermal technologies can improve therapy by controlling drug delivery over hours or days, the DUROS was designed to bring the same benefits of continuous therapy for up to 1 year. DUROS technology is the platform for an implantable drug-dispensing osmotic pump Chronogesic . The system is shaped as a small rod with titanium housing, which can be as small as a matchstick, designed to release drugs Fig. IV-37 . The water drawn into the engine compartment...

Combining Oxycodone with the Opioid Antagonist Naloxone to Deter from Drug Abuse

OxyContin is an opioid agonist and a Schedule II controlled substance with an abuse liability similar to morphine. Oxycodone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing OxyContin in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. OxyContin Tablets are a controlled-release oral formulation of oxycodone hydrochloride indicated for the...

Specificity Of Transdermal Buprenorphine

Buprenorphine is an opioid analgesic administered sublingually or by injection for the treatment of moderate to severe pain. Transdermal buprenorphine BuTrans , Napp Pharmaceuticals is formulated as a matrix patch and is licensed for the treatment of moderate to severe cancer pain and severe pain not responding Figure IV-14. Composition of the two transdermal opioid systems TDS used in chronic pain therapy, the former Ravioli type and the available matrix type, both of which are marketed as...

Rotation From Oral Morphine To Transdermal Buprenorphine

Transition from morphine to buprenorphine is easily accomplished because of the number of spare binding sites, which act as a receptor reserve see Fig. IV-7 . When wanting to switch high dose morphine to buprenorphine the following conversion scale is only used as a rough estimate at start, which is followed by a titration period up to the desired effect Fig. IV-21 . Successful conversion from high dose morphine to transdermal buprenorphine in chronic pain patients was demonstrated in 47...