Naloxone

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cockblockandrun said:
Got a couple of us stumped before the boards about nalaxone...

What side effect of opioids doesn't it reverse?
Click to expand...

Constipation.

Fentanyl-induced chest wall rigidity and laryngospasm in preterm and term infants.
Fahnenstich H, Steffan J, Kau N, Bartmann P.
Source
Department of Neonatology, University Childrens Hospital, Basel, Switzerland. [email protected]
Abstract
OBJECTIVE:
To assess the occurrence of muscle rigidity after fentanyl administration in premature and term neonates.
DESIGN:
Prospective case series, observational study.
SETTING:
A university hospital neonatal intensive care unit.
PATIENTS:
8/89 preterm and term infants (25-40 wks gestational age) who received fentanyl for perioperative analgesia and sedation or intensive care procedures.
INTERVENTIONS:
Mechanical or bag mask ventilation and antagonization with naloxone.
MEASUREMENTS AND MAIN RESULTS:
We observed chest wall rigidity in 8 patients after low dosage of fentanyl (3-5 microg/kg body weight). All patients presented with respiratory distress, hypercapnia, and hypoxemia leading to bradycardia. In two patients, laryngospasm was noted and associated with muscle rigidity, thus making intubation impossible. Naloxone (20-40 microg/kg body weight) reversed the laryngospasm and muscle rigidity immediately, allowing restitution within 1 min. In our patient population, we found fentanyl-induced chest wall rigidity in 4% of neonates after fentanyl administration.
CONCLUSION:
Even low doses of fentanyl can lead to thoracic rigidity in neonates. Additionally, we observed laryngospasm in two patients and speculate that it might be a variant of muscle rigidity.
 
Chest wall rigidity and constipation are both mu receptor mediated and naloxone is somewhat nonspecific opiod receptor antagonist. Pupillary constriction has an unknown mechanism or not linked to known opioid receptor so that would be my guess although has anyone seen from clinical experience pupillary constriction being reversed after naloxone?
 
gasorrad said:
Chest wall rigidity and constipation are both mu receptor mediated and naloxone is somewhat nonspecific opiod receptor antagonist. Pupillary constriction has an unknown mechanism or not linked to known opioid receptor so that would be my guess although has anyone seen from clinical experience pupillary constriction being reversed after naloxone?
Click to expand...


The latest hall says constipation and miosis do not develop tolerance... so I am assuming they are not responsive to the effects of nalaxone.
 
J Pain Symptom Manage. 2002 Jan;23(1):48-53.
Low-dose oral naloxone reverses opioid-induced constipation and analgesia.
Liu M, Wittbrodt E.
Source
Division of Chronic Pain Management, Department of Anesthesia, St. Joseph Medical Center, 120 Sister Pierre Drive, Suite 303, Baltimore, MD 21204, USA.
Abstract
The most common side effect of opioid therapy is constipation. It is often difficult to treat and is believed to be primarily a peripheral effect. Single large doses of oral naloxone have been shown to be efficacious in reversing opioid-induced constipation. However, they often cause the unwanted side effect of analgesia reversal. This study evaluated the effects on constipation and analgesia of low doses of oral naloxone given three times daily. Patients taking stable doses of opioids with complaints of constipation were recruited for this double-blind, randomized, placebo-controlled study. Patients were given 4 mg or 2 mg of oral naloxone, or placebo, three times daily. Stool frequency and symptoms related to constipation were recorded daily. Patients also recorded the daily amount of analgesics required to maintain pain control. Nine patients were recruited for the study. All the patients who received oral naloxone had some improvement in their bowel frequency. Three of the patients also experienced reversal of analgesia, including one who had complete reversal of analgesia. This study demonstrates that reversal of analgesia still occurred despite dividing the oral naloxone into very low doses relative to the total dose of opioid used. Patients using high doses of opioids appear to be the most vulnerable to the analgesic effect of oral naloxone.
 
so whats the mechanism behind chest wall rigidity then. I was thinking of it was mu mediated inhibition of inhibitory neurons but just read that its mechanism is not clearly understood could be dopamine,GABA or mu receptor mediated..u seem pretty sure of the answer...mind sharing. Thanks
 
gasorrad said:
so whats the mechanism behind chest wall rigidity then. I was thinking of it was mu mediated inhibition of inhibitory neurons but just read that its mechanism is not clearly understood could be dopamine,GABA or mu receptor mediated..u seem pretty sure of the answer...mind sharing. Thanks
Click to expand...

Too lazy to explain so copying from Miller: See bold.

"Muscle Rigidity Opioids can increase muscle tone and may cause muscle rigidity. The incidence of rigidity noted with opioid anesthetic techniques varies greatly because of differences in the dose and speed of opioid administration, concomitant use of N2O, presence or absence of muscle relaxants, and patient age. Opioid-induced rigidity is characterized by increased muscle tone that sometimes progresses to severe stiffness with the potential for serious problems ( Table 27-4 ). Clinically significant opioid-induced rigidity usually begins just as or after a patient loses consciousness. Mild manifestations of rigidity, such as hoarseness, can occur in conscious patients. It has been demonstrated that vocal cord closure is primarily responsible for the difficult ventilation with bag and mask that follows the administration of opioids. Delayed or postoperative rigidity is probably related to the second peaks that can occur in plasma opioid concentrations, similar to the recurrence of respiratory depression.


The precise mechanism by which opioids cause muscle rigidity is not clearly understood. Muscle rigidity is not due to direct action on muscle fibers because it can be decreased or prevented by pretreatment with muscle relaxants. Mechanisms of opioid-induced muscle rigidity involving the CNS have been postulated. Pharmacologic studies using selective agonists and antagonists have suggested that systemic opioid-induced muscle rigidity is primarily due to the activation of central µ-receptors, whereas supraspinal δ1- and κ1-receptors may attenuate this effect.[118] Some aspects of opioid-induced catatonia and rigidity (increased incidence with age, muscle movements resembling extrapyramidal side effects) are similar to Parkinson's disease and suggest similarities in neurochemical mechanisms. Parkinsonian patients, particularly if inadequately treated, may experience reactions such as dystonia after opioid administration.[119]


Pretreatment with or concomitant use of nondepolarizing muscle relaxants can decrease the incidence and severity of rigidity. Induction doses of thiopental and subanesthetic doses of diazepam and midazolam prevent, attenuate, or successfully treat rigidity. Persisting in an attempt to mask-ventilate a patient with opioid-induced rigidity will probably result in gastric insufflation and inadequate ventilation or oxygenation until a muscle relaxant is administered. To minimize the occurrence of muscle rigidity and facilitate ventilation and airway management, anesthesiologists should anticipate the need for rapid neuromuscular blockade when doses of opioids are administered that produce rigidity."
 
That goes along with what I was thinking..central mu receptors..inhibiting the inhibitory neurons to muscles kinda like upper motor neuron lesion resulting in spastic paralysis?? How about others who think otherwise?
Has anyone come to a consensus to the answer for the original question..might be too late for the people taking boards..but good luck anyway guys
 
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