Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pruritus due to cholestatic liver disease can be particularly difficult to manage and frequently is intractable to a variety of medical therapies. The aim of our study is to evaluate the efficacy of delta-9-tetrahydrocannabinol (delta-9-THC) for intractable cholestatic related pruritus (ICRP) that has failed conventional (and unconventional) remedies. Three patients were evaluated for plasmapheresis because of ICRP. All 3 patients had previously been extensively treated with standard therapies for ICRP including: diphenhydramine, chlorpheniramine, cholestyramine, rifampicin, phenobarbital, doxepin, naltrexone, UV therapy, and topical lotions. Even multiple courses of plasmapheresis were performed without any benefit for the intractable pruritus. All patients reported significant decreases in their quality of life, including lack of sleep, depression, inability to work, and suicidal ideations. All patients were started on 5 mg of delta-9-THC (Marinol) at bedtime. All 3 patients reported a decrease in pruritus, marked improvement in sleep, and eventually were able to return to work. Resolution of depression occurred in two of three. Side effects related to the drug include one patient experiencing a disturbance in coordination. Marinol dosage was decreased to 2.5 mg in this patient with resolution of symptoms. The duration of antipruritic effect is approximately 4-6 hrs in all three patients suggesting the need for more frequent dosing. Delta-9-tetrahydrocannabinol may be an effective alternative in patients with intractable cholestatic pruritus.
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PMID:Preliminary observation with dronabinol in patients with intractable pruritus secondary to cholestatic liver disease. 1219 Jan 87

The pathogenesis of initiating the pruritus in patients with cholestasis is still not completely understood. One hypothesis is, that the cause for initiating the pruritus in patients with cholestasis is the activation of nerves in the skin. The activating substances are unknown, probably they are substances who accumulate in patients with cholestasis. Therefore one of the conventional approaches to treat pruritus is to remove pruritogenic substances from the body. Examples of this approach include the administration of anion exchange resins as cholestyramine or the administration of hepatic enzyme-inducing drugs such as rifampicin or phenobarbital. None of these drugs has been conclusively shown to be efficacious. A new hypothesis is the association of pruritus with altered central neurotransmission. Altered opioid concentrations probably play a central role in the pathogenesis of pruritus. This hypothesis is corroborate by the possibility of treating pruritus in patients with cholestasis with opiate antagonists such as naloxone or nalmefene. The treatment with ondansetron may also have effects on the pruritus of patients with cholestasis. A completely new treatment strategy is the application of dronabinol (r-9-tetrahydrocannabinol).
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PMID:[Pathogenesis and treatment of pruritus in patients with cholestasis]. 1280 49

A randomized, placebo-controlled crossover trial utilizing vaporized cannabis containing placebo and 6.7% and 2.9% delta-9-tetrahydrocannabinol (THC) was performed in 42 subjects with central neuropathic pain related to spinal cord injury and disease. Subjects received two administrations of the study medication in a 4-hour interval. Blood samples for pharmacokinetic evaluation were collected, and pain assessment tests were performed immediately after the second administration and 3 hours later. Pharmacokinetic data, although limited, were consistent with literature reports, namely dose-dependent increase in systemic exposure followed by rapid disappearance of THC. Dose-dependent improvement in pain score was evident across all pain scale elements. Using mixed model regression, an evaluation of the relationship between plasma concentrations of selected cannabinoids and percent change in items from the Neuropathic Pain Scale was conducted. Changes in the concentration of THC and its nonpsychotropic metabolite, 11-nor-9-carboxy-THC, were related to percent change from baseline of several descriptors (eg, itching, burning, and deep pain). However, given the large number of multiple comparisons, false-discovery-rate-adjusted P-values were not significant. Plans for future work are outlined to explore the relationship of plasma concentrations with the analgesic response to different cannabinoids. Such an appraisal of descriptors might contribute to the identification of distinct pathophysiologic mechanisms and, ultimately, the development of mechanism-based treatment approaches for neuropathic pain, a condition that remains difficult to treat.
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PMID:A preliminary evaluation of the relationship of cannabinoid blood concentrations with the analgesic response to vaporized cannabis. 2762 66