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Dronabinol is synthetic tetrahydrocannabinol ('THC'), which obtained FDA approval in 1985 for the treatment of HIV/AIDs-induced anorexia and chemotherapy-induced nausea and vomiting in patients who have failed to respond to conventional antiemetics. Dronabinol has also been used off-label for the treatment of OSA. This activity will provide an overview of the pharmacology of dronabinol, its indications and usage, adverse effects, contraindications, and other pertinent information. Objectives: Describe the indications for dronabinol. Describe the mechanism of action for dronabinol. Review the potential toxicity of dronabinol. Identify potential drug interactions with dronabinol. Access free multiple choice questions on this topic.

Toxicity The estimated lethal dose of IV dronabinol is 30 mg/kg (note this is for illustrative purposes as dronabinol dosing is oral). As such, the CNS toxicity (adverse CNS effects) of dronabinol is more applicable as a measure for monitoring dose-limiting toxicity. Signs and symptoms of toxicity include: Mild Intoxication: sleepiness, feelings of joy, heightened sensory vigilance, time perception difficulties, conjunctival injection, dry oral cavity, and elevated heart rate. Moderate Intoxication: Memory difficulty, feelings of detachment, mood changes, retention of urine, and decreased bowel motility. Severe: Decreased coordination of motor function, lethargy, slurring of speech, and orthostatic hypotension. Panic attacks in those with apprehension and seizures in those with a history of seizures can also occur.[11] Management of Serious Ingestion There is no specific antidote for the treatment of dronabinol toxicity. If there is a history of recent excessive ingestion, the patient should have gut decontamination with activated charcoal (at a dosage of 30 to 100g for adults, 1 to 2 g/kg in infants). Delivery through a nasogastric tube may be necessary for an unconscious patient with a secure airway. Patients with intense psychiatric complications (such as depressive episodes, hallucinations, or psychosis) may need to be isolated in a quiet and peaceful area and frequently reassured by the provider or staff. Benzodiazepines, such as diazepam (5 to 10 mg PO), can be utilized for extreme agitation. Hypotension is manageable with Trendelenburg positioning and isotonic IV hydration.[11]

Managing anorexia associated with weight loss in patients with AIDs/HIV and nausea and vomiting that can accompany chemotherapy in patients who have not responded to traditional conventional antiemetics requires an interprofessional team of healthcare professionals that may include clinicians of various types (MDs, DOs, NPs, and PAs), palliative care specialists, oncology specialists, pharmacists, nursing staff, and other clinicians from other specialties. The interprofessional model will involve open communication and information sharing, with each interprofessional team member empowered to contribute to the patient case from their own expertise to drive optimal patient outcomes. [Level 5] Anorexia Associated with Weight Loss in Patients with AIDs/HIV Level 1: Treatment of AIDs-related anorexia and weight loss was proven effective in a randomized, double-blind, placebo-controlled study with 139 patients. A statistically significant difference between dronabinol and placebo was observable in appetite. Additional measured trends included improved body weight and mood and decreases in nausea. Recent metanalyses have also shown dronabinol to be efficacious.[12] Nausea and Vomiting Associated with Chemotherapy in Patients Who Have Not Responded to Traditional Conventional Antiemetic Level 1: Treatment of chemotherapy-induced nausea and vomiting ('CINV') with dronabinol has been extensively studied as monotherapy and combined with other more traditional antiemetics such as ondansetron. Recent metanalyses have also shown dronabinol to be efficacious.[13][14]