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Biomedical subjects

Zvia Rudich

Publications and source records attributed to Zvia Rudich.

5 recordsLinked to original sources

Controlled-release oxycodone-induced seizures.

BACKGROUND: The use of the opioid oxycodone hydrochloride in the management of chronic pain is gaining popularity principally because of its tolerability. However, opioid-related seizure in patients with epilepsy or other conditions that may decrease seizure threshold has been described in the literature; in particular, oxycodone has been associated with seizure in a patient with acute renal failure. OBJECTIVE: The aim of this article was to report a patient with a history of seizures but normal renal and hepatic function who developed seizure on 2 occasions after oxycodone ingestion. METHODS: A 54-year-old male patient presented with a history of tonic-clonic seizures that developed immediately after intracranial surgery. Long-term treatment with carbamazepine 400 mg QD was started, and the patient was free of convulsions for approximately 7 years. The patient presented to us with severe headache that was nonresponsive to an NSAID and the opiate agonist tramadol. Treatment with controlled-release (CR) oxycodone and tramadol drops (50 mg QID if necessary) was started, and tonic-clonic seizures developed 3 days later. RESULTS: Based on laboratory analysis, the patient had normal renal and hepatic function. On discontinuation of oxycodone treatment, the seizures resolved. However, due to effective pain relief with oxycodone, the patient decided to continue treatment, and seizures recurred. Carbamazepine was then administered 4 hours before oxycodone dosing, which allowed continuation of treatment without seizure. CONCLUSIONS: A patient with a history of seizures controlled with long-term carbamazepine therapy developed seizures when he started treatment with oxycodone CR at recommended doses. Oxycodone CR should be used with extreme caution in patients with epilepsy or other conditions that may decrease seizure threshold.

Analgesics, Opioid↗

Stability of clonidine in clonidine-hydromorphone mixture from implanted intrathecal infusion pumps in chronic pain patients.

Clonidine is frequently added to opioids in implantable intrathecal pumps for the management of chronic pain. In such devices, a small non-retrievable volume is always present in the reservoir, and its effect on drug stability is unknown. Furthermore, stability of clonidine, when mixed with hydromorphone, has not been previously determined. This study examined the stability of clonidine when co-administered with hydromorphone in implanted intrathecal pumps. Samples of hydromorphone-clonidine before pump refill and from residual solution at subsequent refill were obtained from chronic pain patients. Clonidine concentration was measured using HPLC. Twenty paired samples from 3 patients were analyzed. All 3 patients had a SynchroMed pump implanted for 3-5 years. We found no loss in clonidine concentration during the time between refills (35 +/- 13 days), and no correlation between clonidine concentration and time interval between refills. In conclusion, clonidine, mixed with hydromorphone, is stable when delivered by implantable intrathecal pump for long-term use.

Analgesics↗

LF 16-0687 Ms, a new bradykinin B2 receptor antagonist, decreases ex vivo brain tissue prostaglandin E2 synthesis after closed head trauma in rats.

OBJECTIVE: Bradykinin (B) contributes to secondary brain injury. This injury is mediated in part by prostaglandin (PG). Antagonism of B(2) receptors improves neurological status after brain injury, but the effect of B(2) antagonism on brain tissue PG is unknown. This study examined the effect of LF 16-0687 Ms, a new B(2) receptor antagonist, on brain tissue PGE(2) after closed head trauma (CHT). METHODS: Rats were anesthetized and received sham+saline, sham+LF 16-0687 Ms, CHT+saline, or CHT+LF 16-0687 Ms. Brain tissue samples were obtained at 24 h for determination of PGE(2) (after 2 h of ex vivo incubation) and water content. Neurological severity score (NSS) was assessed at 1 and 24 h. RESULTS: In the group receiving CHT+LF 16-0687 Ms, brain tissue PGE(2) (77.7+/-65.9 pg/mg tissue, mean+/-SD) was less than in the group receiving CHT+saline (368.1+/-186.2 pg/mg tissue) and not different than sham+saline (78.7+/-30.7 pg/mg tissue). LF 16-0687 Ms also improved NSS and decreased brain water content by 51%. CONCLUSION: We conclude that the beneficial effect of LF 16-0687 Ms on outcome after CHT is accompanied by blockade of PGE(2) increase in injured brain tissue.

Animals↗

Treatment of chronic intractable neuropathic pain with dronabinol: case report of two adolescents.

OBJECTIVE: To evaluate the effectiveness of dronabinol for the treatment of neuropathic pain refractory to previous treatment. METHODS: We studied the response (reduction of pain intensity and functional improvement) to dronabinol (5 mg/day to 25 mg/day) in two adolescents with neuropathic pain and depression refractory to previous treatments over two and five years, respectively. RESULTS: Reduction in pain intensity (45%) was achieved in patient 2 and was unchanged in patient 1. Functional improvement was markedly increased in terms of academic performance, mood and sleep in both patients over four to five months, without major adverse effects. While these improvements dissipated over time, the patients were more reconnected with rehabilitation and focused less on the intrusiveness of their pain problem in their every day lives. CONCLUSIONS: Dronabinol appeared to be effective in improving pain affect and psychosocial functioning in the treatment of refractory neuropathic pain and may be considered as an adjuvant medication in the rehabilitation process. Well-controlled placebo studies are required for further evaluation.

Adolescent↗

LF 16-0687 Ms, a bradykinin B2 receptor antagonist, reduces brain edema and improves long-term neurological function recovery after closed head trauma in rats.

Bradykinin is an endogenous inflammatory agent that enhances vascular permeability and produces tissue edema. We investigated whether LF 16-0687 Ms, a potent nonpeptide antagonist of bradykinin type-2 (B(2)) receptor, was able to reduce brain swelling and to improve the recovery of neurological function following closed head trauma (CHT) in rats. In dose-effect studies, LF 16-0687 Ms doses of 0.75-4.5 mg/kg given 1 h after trauma significantly reduced the development of edema in the injured hemisphere by a maximum of 70%. It had no effect on the brain water content of sham-operated rats. LF 16-0687 Ms also significantly improved neurological recovery evaluated by a Neurological Severity Score (NSS) based on motor, reflex, and behavioral tests. In time-window studies LF 16-0687 Ms (2.25 mg/kg) was given 1, 2, 4, and 10 h after CHT. The extent of edema was significantly reduced when LF 16-0687 Ms was given 1 h (-45%), 2 h (-52%), and 4 h (-63%) but not 10 h (-24%) after CHT. Given at any time-point, LF 16-0687 Ms significantly improved the recovery of the NSS at 24 h. In duration of treatment studies, rats tended to recover normal neurological function over 14 days after CHT. However, time to recovery was longer in severely than in moderately injured animals, unless they were treated with LF 16-0687 Ms. This study provides further evidence that blockade of bradykinin B(2) receptors represents a potential effective approach to the treatment of focal cerebral contusions.

Animals↗