Nausea, cancer chemotherapy

Dronabinol is indicated for the treatment of the nausea and vomiting produced by cancer chemotherapy in patients who have failed to respond adequately to other conventional treatments. This agent may be habit forming and can be expected to produce disturbing psychomimetic reactions. It should only be used under close supervision. 

Infusion devices have been used for diabetes, cancer chemotherapy, pain control (patient-controUed analgesia, ie, PGA), infection, Alzheimer s disease, Parkinson s, nausea, thalassemia, thromboembolism, and to treat severe spasms resulting from spiaal cord iajury (140—143). 

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

So, the 20th century actually led to an almost total disappearance of C. sativa for medicinal purposes. The only source for THC, which became the focus of scientific research, was fhe rafher fedious exfracfion and purification from confiscated hashish or marihuana. In 1972 the first commercially viable total synthesis of A9-THC was established and it became the first cannabinoid available as a modern medicine in the form of soft gel capsules (the active ingredient being called dronabinol from tetrahydrocannabinol) under the trade name Marinol for the prevention of nausea and vomiting during cancer chemotherapy. 

The indication prevention of nausea and vomiting during cancer chemotherapy came from experiences of marihuana-smoking patients, not from pharmacological research [129]. 

Standardised preparations of cannabinoid agonists are available for therapeutic use in some countries [238]. Dronabinol (Marinol ), an oral preparation of A -THC (67), is used clinically as an appetite stimulant in AIDS patients and an antiemetic in cancer chemotherapy. A synthetic analogue of (67), nabilone (Cesamet ), (381), is also used to suppress nausea and vomiting in cancer chemotherapy. 

Recommend a treatment regimen for a patient with nausea and vomiting associated with cancer chemotherapy, surgery, pregnancy, or motion sickness. 

Data from DiPiro CV, Taylor AT. Nausea and vomiting. In DiPiro JT, Talbert RL, Yee GC, et a I., (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 665-676, and Hesketh PJ, Kris MG, Grunberg SM, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 1 997 1 5 1 03-1 09. 

The answer is e. (Hardmanr p 930.) All the drugs listed in the question are used as antiemetics. Chlorpromazine is a general antiemetic, used orally, rectally, or by injection for the control of nausea and vomiting that is caused by conditions that are not necessarily defined. Ondansetron is indicated in the oral or intravenous route for the prevention of nausea and vomiting caused by cancer chemotherapy Diphenhydramine and dimen-hydrinate are used orally for the active and prophylactic treatment of motion sickness. Scopolamine is a transdermal preparation used in the prevention of motion sickness. The drug is incorporated into a bandage-like... 

A review of evidence supported the use of pure THC preparations to treat nausea associated with cancer chemotherapy and to stimulate appetite (Voth and Schwartz 1997). In patients with anorexia due to advanced cancer, THC (2.5 mg PO tid) was effective in stimulating appetite and was well tolerated at low doses (Nelson et al. 1994). 

The most frequently reported serious adverse events reported with cancer chemotherapy patients included death, fever, pneumonia, dehydration, vomiting, and dyspnea. The most commonly reported adverse events were fatigue, edema, nausea, vomiting, diarrhea, fever, and dyspnea. The most frequently reported reasons for discontinuation of darbepoetin alfa were progressive disease, death, discontinuation of the chemotherapy, asthenia, dyspnea, pneumonia, Gl hemorrhage, thrombotic events, rash, dehydration. 

Prevention of nausea/vomiting associated with cancer chemotherapy -... 

Antiemetic Aprepitant, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin. 

Parenteral For prevention of nausea and vomiting associated with emetogenic cancer chemotherapy. 

For immunosuppressive effects methotrexate is most frequently used in RA but also azathioprine and cyclosporin are employed. Methotrexate doses for this indication can be lower than those used for cancer chemotherapy but significant toxicity such as nausea, cytopenias and mucosal lesions, and with longterm therapy slowly progressive hepatotoxicity may still be seen. 

Activation of 5-HT3 receptors elicits prominent pharmacological responses from the cardiovascular and respiratory systems and from the gastrointestinal tract [Fozard 1992). Several 5-FIT3 receptor antagonists have been marketed for the treatment of nausea and vomiting associated with cancer chemotherapy and radiotherapy [Bunce et al. 1991). 

Nausea that accompanies the administration of cancer chemotherapy agents was resistant to drug intervention until the introduction of the serotonin receptor antagonist odansetron (see Chapter 13). The benzimidazolone-based compound itasetron (57-6) has much the same activity as its tricylcic predecessor. Condensation of 2-nitrophenyl-isocyanate (57-1) with the bridged bycyclic diamine (57-2) leads to the addition... 

Ondansetron is the prototypical 5-HT3 antagonist. This drug and its analogs are very important in the prevention of nausea and vomiting associated with surgery and cancer chemotherapy. They are discussed in Chapter 62. 

Aprepitant (Emend) for prevention of nausea and vomiting due to cancer chemotherapy. Med Lett Drug Ther 2003 45 620. 

Ondansetron, other 5-HT3 antagonists 5-HT3 blockade in gut and CNS with shorter duration of binding than alosetron Extremely effective in preventing chemotherapy-induced and postoperative nausea and vomiting First-line agents in cancer chemotherapy also useful for postop emesis Usually given IV but orally active in prophylaxis. 4-9 h duration of action very low toxicity but may slow colonic transit... 

The Schedule I designation of marijuana has been disputed over the past 15 or more years. Some physicians would like to see it as a Schedule II drug so that it could be used therapeutically in the treatment of the nausea, vomiting and anxiety caused by cancer chemotherapy and as an antiglaucoma agent (lowers intraocular pressure). It should be noted that the neuroleptic prochlorperazine is an effective antinausea drug which can be used without producing the psychoactive effects of marijuana. 

Nausea and Vomiting Associated With Cancer Chemotherapy... 

The opium alkaloids codeine and morphine served as models for the synthesis of naloxone, an important analog used to treat and diagnose opiate addicts, and also led to the discovery of endogenous opioids (enkephalins and endorphins) (see Chapter 47). Similarly, A9-tetrahydro-cannabinol (THC), the component of Cannabis sativa responsible for the central nervous system (CNS) effect, has also been found to reduce nausea associated with cancer chemotherapy (see Chapter 18). 

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