ABSTRACT
Preclinical Research Δ9 -Tetrahydrocannabinol (THC) is a hydrophobic compound that has a potent antinociceptive effect in animals after intrathecal (IT) or intracerebroventricular (ICV) administration. The lack of a suitable solvent precludes its IT administration in humans. 2-Hydroxypropyl-ß-cyclodextrin (HPßCD) increases the water solubility of hydrophobic drugs and is approved for IT administration in humans. To investigate whether HPßCD might be a suitable carrier for ICV administration of THC in rats, two formulations containing THC complexed with HPßCD (30 and 135 µg of THC per animal) and vehicle were administered to Wistar rats. The antinociceptive effect (using the tail flick test), locomotor activity, and body temperature were evaluated. ICV injection of 135 µg of THC/HPßCD complex increased tail flick latency, reduced locomotor activity, and had a dual effect on body temperature. The 30 µg THC/HPßCD formulation only produced a hyperthermic effect. All animals appeared healthy, with no difference between the groups. These results were similar to those obtained in other preclinical studies in which THC was administered centrally using solvents that are unsuitable for IT administration in humans because of their toxicity. Our findings suggest that HPßCD may be a useful carrier for IT administration of THC in humans. Drug Dev Res 78 : 411-419, 2017. © 2017 Wiley Periodicals, Inc.
Subject(s)
2-Hydroxypropyl-beta-cyclodextrin/chemistry , Analgesics, Non-Narcotic/administration & dosage , Body Temperature/drug effects , Dronabinol/administration & dosage , Locomotion/drug effects , 2-Hydroxypropyl-beta-cyclodextrin/pharmacology , Analgesics, Non-Narcotic/chemistry , Analgesics, Non-Narcotic/pharmacology , Animals , Dronabinol/chemistry , Dronabinol/pharmacology , Drug Carriers , Drug Compounding , Drug Evaluation, Preclinical , Injections, Spinal , Male , Rats , Rats, Wistar , SolubilityABSTRACT
Fibromyalgia is a pain disorder associated with frequent comorbid mood, anxiety, and sleep disorders. Despite the frequent use of a complex, poly-drug pharmacotherapy, treatment for fibromyalgia is of limited efficacy. Oxytocin has been reported to reduce the severity of pain, anxiety, and depression, and improve the quality of sleep, suggesting that it may be useful to treat fibromyalgia. To evaluate this hypothesis, 14 women affected by fibromyalgia and comorbid disorders, assuming a complex pharmacotherapy, were enrolled in a double-blind, crossover, randomized trial to receive oxytocin and placebo nasal spray daily for 3 weeks for each treatment. Order of treatment (placebo-oxytocin or oxytocin-placebo) was randomly assigned. Patients were visited once a week. At each visit, the following instruments were administered: an adverse drug reaction record card, Visual Analog Scale of Pain Intensity, Spielberger State Anxiety Inventory, Zung Self-rating Depression Scale, and SF-12. Women self-registered painkiller assumption, pain severity, and quality of sleep in a diary. Unlikely, oxytocin nasal spray (80 IU a day) did not induce positive therapeutic effects but resulted to be safe, devoid of toxicity, and easy to handle.
Subject(s)
Fibromyalgia/drug therapy , Musculoskeletal Pain/drug therapy , Oxytocin/administration & dosage , Administration, Intranasal , Aerosols , Anxiety/drug therapy , Anxiety/psychology , Comorbidity , Cross-Over Studies , Depression/drug therapy , Depression/psychology , Double-Blind Method , Female , Fibromyalgia/diagnosis , Fibromyalgia/physiopathology , Fibromyalgia/psychology , Humans , Middle Aged , Musculoskeletal Pain/diagnosis , Musculoskeletal Pain/physiopathology , Musculoskeletal Pain/psychology , Oxytocin/adverse effects , Pain Measurement , Psychiatric Status Rating Scales , Quality of Life , Sleep/drug effects , Surveys and Questionnaires , Time Factors , Treatment OutcomeABSTRACT
A case of severe tetanus with autonomic dysfunction is reported, describing the adequate response to continuous infusions of both propofol and midazolam, and the successful use of clonidine to control sympathetic over-activity. Tolerance was not observed during the 34 days of propofol and midazolam sedation. Continuously infused clonidine provided good control in combination with sedation and paralysis in this case, and no episodes of cardiovascular derangement were seen, possibly due to the adequate management of filling pressure. Vecuronium was a suitable and manageable muscle relaxant to control skeletal muscle spasms and to facilitate mechanical ventilation.
