Opioid+Analgesics+&+Anatagonists

Use this site to develop the concepts surrounding opioid analgesics and anatagonists and their mechanism of action.
Outline of how pain works in order to need opioids:

It is important to use the pain scale in order to help understand the pain that your patient is under and it is important to understand that some patients have a higher tolerance of pain that other patients.

§ Classification – natural [|opiates], [|alkaloids] contained in the resin of the [|opium poppy] including [|morphine] , [|codeine] and [|thebaine] , but not [|papaverine] and [|noscapine] which have a different mechanism of action; § semi-synthetic opiates, created from the natural opioids, such as [|hydromorphone], [|hydrocodone] , [|oxycodone] , [|oxymorphone] , [|desomorphine] , [|diacetylmorphine] (heroin), [|nicomorphine] , [|dipropanoylmorphine] , [|benzylmorphine] and [|ethylmorphine] ; § fully synthetic opioids, such as [|fentanyl], [|pethidine] , [|methadone] , [|tramadol] and [|propoxyphene] ; § [|endogenous] opioid [|peptides], produced naturally in the body, such as [|endorphins] , [|enkephalins] , [|dynorphins] , and [|endomorphins].


 * Opiod Agonists:**

Pain control ex. Codeine, morphine, oxycodone § Mechanism of action – Opioid analgesics have a direct action on opioid receptors (mu, kappa, and delta). These receptors are linked to a G-protein that facilitates potassium conductance while inhibiting calcium conductance. This results in a relative hyperpolarization of the neuron making it difficult to excite. In addition, because calcium is required for neurotransmitter release, its inhibition prevents the release of neurotransmitters such as substance P and glutamate which are involved in the transmission of nociceptive information across nerve synapses. __Where they meet__: In the dorsal horn of the spinal cord, peripheral pain neurons meet CNS neurons. At the synapse, the pain neuron releases substance P (a pain neurotransmitter) This agent helps transfer pain impulses to the CNS neurons that carry the impulses to the brain. __Taking up space__: In theory, the spinal interneurons respond to stimulation from the descending neurons of the CNS by releasing endogenous opiates. These opiates retard the transmission of pain impulses. __Stopping substance P__: Synthetic opiates supplement this pain blocking effect by binding with free opiate receptors to inhibit the release of substance P, Opiates also alter consciousness of pain. § Pharmacokinetics – __Transmission__- Opioid agonist can be administered by any route; however I.V. provides the most rapid and reliable pain relief. __Distribution__- widely throughout the body tissues, but has relatively low plasma protein binding capacity. __Metabolism__- In the liver __Excreted__- by the kidneys § Pharmacologic effects – Opioid agonist reduce pain by binding to opiate receptor sites in the peripheral nervous system and the CNS. When these drugs stimulate the opiate receptors they mimic the effects of endorphins (naturally occurring opiates that are part of the bodys own pain relief system) This receptor site binding produces the therapeutic effects of analgesia and cough suppression as well as adverse reactions such as respiratory depression and constipation. § Adverse reactions – § Decreased rate and depth of breathing § Flushing § Orthostatic Hypotension § Pupil Constriction § Tachycardia § Addiction – Is rated as “dependence liability.” Dose escalation caused by the development of tolerance and physical dependence or addiction associated with treatment for pain that lasts more than a few days. § Drug interactions – Taking opioid agonist with TCAs, Phenothiazine, or anticholinergic may cause severe constipation and urine retention Combination with other substances that decrease respiration such as alcohol, sedatives, hypnotics, and anesthetics, increase the risk of severe respiratory depression.

How do opioids work?

Opioids bind to specific proteins called receptors that are located in the brain, spinal cord, and GI tract. This then blocks the brain's ability to sense pain. Instead of sensing the pain opioids are able to stimulate the pleasure centers of the brain causing euphoria.



§ Classification – Management of opioid overdose § Mechanism of action – Opioid antagonists attach to opiate receptors, but __do not stimulate them__, they have a greater attraction for opiate receptors than opioid agonists do. As a result, they prevent opioid drugs from producing their effects. § Pharmacokinetics – Naloxone is administered I.M., SubQ., I.V., or orally. Once distrusted they are metabolized by the liver and excreted by the kidneys § Pharmacologic effects – In a process known as competitive inhibition, Opioid antagonists block the effects of opioid agonists by occupying the opiate receptor sites, __displacing opioids attached to opiate receptors and blocking further opioid binding at these sites.__ § Adverse reactions – § Edema § Hypertension § Palpitations § Shortness of breathe § Anxiety § depression § Addiction – Psychological addiction is more common in people taking opioids recreationally, it is rare in patients taking opioids for pain relief § Allergic reactions – Allergy is revealed by symptoms such as skin rash, facial swelling or asthma, and the diagnosis can only be confirmed by skin testing and blood analysis. True 'allergy' to opioid drugs is extremely rare. § Drug interactions – No significant interactions. But can cause withdrawal symptoms if given to a patient who’s receiving an opioid agonist or who’s an opioid addict.
 * Opioid Antagonists**


 * Chapter 47:Analgesics for use of effective pain control**

Pain Classification
 * Can be divided in to two categories: Nocieptive and neuropathic pain.

Nocieptive
 * Pain result of mechanical, thermal or chemical activation of nocieptive afferent receptors and can be classified as either somatic or visceral in origin. Somatic nocieption involves pathologic conditions of the skin, muscles, fascia, and bones and is well localized. Ex: Pain associated with cavity preparation or periodontitis . In both conditions, inflammatory mediators may sensitize or activate nociceptive receptors, resulting in transduction of the noxious stimulus into electrical and biochemical signals between neurons. The electrical signal is then conducted to the brain. Viceral nociceptive pain is poorly localized. Ex angina resulting from myocardial ischemia, which can referred to the jaw, neck and arm.

Neuropathic pain: Is though to be a result of aberrant somatosensory activity either in the peripheral nervous system or the CNS. It is characterized by paroxysmal shooting or electrical shock like pains. Ex: Is pain encountered in the or facial region include trigeminal neuralgia and post herpetic neuralgia. Acute pain is associated with anxiety and the physiologic “flight or fight” responses of increase pulse and respiratory rate. Misconceptions regarding pain and analgesics: To treat the pain effectively, the clinician must first believe the patients complaint of pain.

Misconception 1
 * Patient who are in pain always have observable signs. Behaviors signs may not always been seen in patients that are trying to cope or adapt to the pain.

Misconception 2
 * Obvious pathology, test results, and the type of surgery determines the existence and the intensity of pain.

Misconception 3
 * Patients should wait as long as possible before taking pain medication. This period of abstinence will teach them to have a better tolerance for pain. Pain that is untreated often escalates in severity and disability. Without treatment, sensory input from injured tissue reaches spinal cord neurons and causes subsequent responses to be enhanced