Opioid Analgesics and Antagonists

Chapter 19 Opioid Analgesics and Antagonists



I. Opioid Agonists (Box 19-1)

• Classified into three categories; strong, moderate, and weak

A. General features

1. Mechanism of action


a. The effects of endogenous opioid peptides (endorphins and enkephalins) and exogenous opioids result from activation of specific opioid receptors (Table 19-1).

b. Opioid analgesics activate the intrinsic analgesic system (endogenous pain control system; Fig. 19-1).

• Reviewed in Rapid Review Neuroscience

(1) Electrical stimulation of the midbrain periaqueductal gray (PAG) produces analgesia without affecting fine touch.

(2) PAG activates serotonergic neurons in medullary raphe nuclei.

(3) Raphe nuclei project to enkephalin interneurons in spinal cord posterior horn.

(4) Enkephalin interneurons inhibit presynaptic nociceptor terminals and posterior horn pain transmission neurons.

(5) Morphine suppresses input from pain fibers; this can be reversed by the opioid antagonist naloxone.

c. Major subtypes of opioid receptors have varying effects (Table 19-2).


(1) Subtypes include:

(a) Delta (δ)

(b) Kappa (κ)

(c) Mu (µ)


BOX 19-1 Opioid Agonists



Strong Opioid Agonists


Fentanyl (parenteral, transdermal, transmucosal)


Hydromorphone (parenteral, oral)


Levorphanol (parenteral, oral)


Meperidine (parenteral, oral)


Methadone (parenteral, oral)


Morphine (parenteral, oral, rectal)


Oxymorphone (parenteral, oral)



Moderate Opioid Agonists


Codeine (oral)


Hydrocodone (oral)


Oxycodone (oral)



Weak Opioid Agonists


Dextromethorphan (oral)


Diphenoxylate (oral with atropine)


Loperamide (oral)


Propoxyphene (oral)


Tramadol (oral)



Opioid Agonists as Adjuncts to Anesthesia (See Chapter 8)


Alfentanil (parenteral)


Fentanyl (parenteral)


Sufentanil (parenteral)



TABLE 19-1 Effects of Representative Opioids on Opioid Receptor Subtypes

image

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19-1 Endogenous analgesia systems. Nociceptors (Aδ and C fibers) excite pain transmission neurons (PTN). Large, myelinated mechanoreceptors (Aβ fibers) excite inhibitory (e.g., enkephalinergic) interneurons (I) that inhibit pain transmission at the first synapse. Pain transmission neurons (anterolateral system) project to thalamus with collaterals to brain stem. Limbic cortex contributes to activation of periaqueductal gray intrinsic analgesia circuitry. Periaqueductal gray (A) projects to medullary raphe, which project to posterior horn to inhibit pain transmission.


(From Weyhenmeyer JA and Gallman EA: Rapid Review Neuroscience. Philadelphia, Mosby, 2007, Figure 7-10.)


TABLE 19-2 Opioid Receptors and their Associated Effects















Receptor Effects of Activation
Mu (µ) receptor Analgesia, euphoria, respiratory depression, miosis, decreased gastrointestinal motility, and physical dependence
Kappa (κ) receptor Analgesia, miosis, respiratory depression, dysphoria, and some psychomimetic effects
Delta (δ) receptor Analgesia (spinal and supraspinal)


Opioid receptors: delta; kappa; mu.


(2) All are Gi-protein coupled.

(3) Close Ca2+ channels, reducing evoked transmitter release (presynaptic)


Opioid presynaptic receptors close Ca2+ channels; decreased transmitter release.


(4) Open K+ channels, hyperpolarizing membranes (postsynaptic)


Opioid postsynaptic receptors open K+ channels; hyperpolarizing signal leads to decreased electrical activity.


2. Pharmacologic actions of opioid agonists (Box 19-2)

3. Uses


a. Relief of severe pain

b. Sedation and relief from anxiety (e.g., preoperatively)

c. Cough suppression

d. Diarrhea suppression

e. Analgesic supplement in maintenance of balanced general anesthesia

4. Adverse effects (primarily extensions of pharmacologic actions)


a. Respiratory depression and coma

b. Sedation and central nervous system (CNS) depression


BOX 19-2 Pharmacologic Actions of Opioid Agonists



Central Nervous System Effects


Analgesia


Euphoria or dysphoria


Inhibition of cough reflex


Miosis (pinpoint pupils)


Physical dependence


Respiratory depression (inhibit respiratory center in medulla)


Sedation



Cardiovascular Effects


Decreased myocardial oxygen demand


Vasodilation and orthostatic hypotension (histamine release)

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Apr 8, 2017 | Posted by in PHARMACY | Comments Off on Opioid Analgesics and Antagonists

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