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 its antagonism by naloxone. Theories have been advanced suggesting

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Alfentanil : ♦ Over 30 s i.v.

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Figure II-59. Alfentanil-induced truncal rigidity in patients following induction of anesthesia. In comparison to the rapid bolus injection of the drug, slow injection over a period of 2min resulted in a significant lesser reduction of thoracic compliance. The increase in truncal rigidity was instantly reversed by a low dose (25 mg/70 kg body weight) of the fast acting muscle relaxant succinylcholine. Adapted from [134]

Figure II-59. Alfentanil-induced truncal rigidity in patients following induction of anesthesia. In comparison to the rapid bolus injection of the drug, slow injection over a period of 2min resulted in a significant lesser reduction of thoracic compliance. The increase in truncal rigidity was instantly reversed by a low dose (25 mg/70 kg body weight) of the fast acting muscle relaxant succinylcholine. Adapted from [134]

that morphine produces its effects by direct stimulation of the Edinger-Westphal (preganglionic parasympathetic) nucleus [181]. An alternative view has been postulated that morphine depresses cortical centers, which normally inhibit the Edinger-Westphal nucleus. Others have suggested that miosis is caused by stimulation of opioid receptors located on the iris sphincter, although this opinion seems to be in the minority.

The exact site, or sites, of action within the CNS, which are responsible for opioid-induced miosis remain obscure. It is generally accepted, however, that sympathetic innervation is not essential, the miotic effect being entirely dependent on the integrity of the parasympathetic system. For example, Lee and Wang [182] have shown that dogs with a sectioned oculomotor nerve fail to show miosis even with a 30 fold increase in the dose of morphine. In contrast, dogs show normal responses following sympathectomy. While local application of a muscarinic antagonist (scopolamine) that blocks the pupil sphincter completely abolishes the pupillary effects of morphine in the rabbit, application of a sympathetic neuronal blocker (guanethidine) or of an alpha-adrenergic antagonist (phentolamine) that block the pupil dilator had no effect in those experiments. Thus, pharmacologic dissection of the autonomic innervation of the pupil suggests that opioid-induced miosis is mediated solely through the parasympathetic system.

Other CNS structures may also be involved in opioid-induced miosis. Lee and Wang [182] have shown that removal of the cerebral hemispheres potentiates the miotic action of morphine in the dog. They interpreted this effect as being a reflection of the loss of tonic inhibition originating in the occipital lobes. The latter are known to play a regulatory role in pupillary function, particularly with respect to the near-response (accommodation, convergence and miosis) and, hence, their removal might be expected to alter the pupillary response to drugs. The same authors also observed that acute or chronic optic nerve section did not alter the miotic response to morphine in dogs.

In humans, it was shown that morphine produced a dose-related miosis under conditions of low ambient light. Taken together, these findings suggest that morphine may cause miosis through more than one mechanism. The main neural structures, which are thought to regulate pupillary size are found in the midbrain, mainly the pretectal area and the Edinger-Westphal nucleus of the oculomotor complex. Because neuronal unit activity in the Edinger-Westphal nucleus has been shown to correlate with light-induced pupillary constriction. Opioids therefore depress or abolish spontaneous and light-induced firing of pupilloconstrictor neurons in the pretectal area, while the opposite effect is observed in the Edinger-Westphal nucleus where a marked increase in spontaneous firing rate resulting in madriasis. It is because of this increase in activity that certain animal species (rat, cat, monkey) demonstrate an opioid-induced mydriasis.

In addition, the brain stem region regulating pupil size is known to have multiple inputs, including the cortex and midbrain, and several others can be assumed to exist. Depression by morphine of tonic inhibitory input trom the cortex may partially account for the miosis observed by Lee and Wang [182]. These findings suggest that opioids may act directly on the neurons subserving the parasympathetic light reflex. Also, in contrast to other workers, morphine has no local action on the iris. For example, Lee and Wang [182] could not produce miosis by injecting 20% of an effective systemic dose of morphine (1 mg) directly into the anterior chamber of the eye in dogs. Although opioid binding sites have been found in the retina of the rat, cow, toad and skate, opioids injected into the anterior chamber may stimulate retinal receptors in some species, causing miosis via reflex parasympathetic output.

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Responses

  • liberio pisano
    How morphine cause truncal rigidity?
    1 year ago
  • carol
    How does morphine cause miosis?
    12 months ago
  • vincenza
    Is morphine have miosis action?
    9 months ago
  • caramella goold
    Why pethidine causes pupil constriction?
    3 months ago
  • susanna
    How do opioids cause respiratory depression?
    2 days ago

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