Antiemetic preparations

Information concerning commonly available antiemetic preparations is compiled in Table 27-5. 

Common Antiemetic Preparations and Adult Dosage Regimens... 

Antiemetic preparations Antihistamines (Hj receptor antagonists) Antihypertensive medications Antineoplastic agents... 

Dimenhydrinate is an antiemetic especially usehil as an antinauseant in motion sickness, and for syndromes associated with vertigo such as Meniere s syndrome, radiation sickness, and vestibular dysfunction. It may produce mild drowsiness. It is FDA Category B for Pregnancy, and is available as an OTC preparation as well as by prescription. 

Pharmaceuticals. -Hydroxybenzaldehyde is often a convenient intermediate in the manufacture of pharmaceuticals (qv). For example, 2-(p-hydroxyphenyl)glycine can be prepared in a two-step synthesis starting with -hydroxybenzaldehyde (86). This amino acid is an important commercial intermediate in the preparation of the semisynthetic penicillin, amoxicillin (see ANTIBIOTICS, P-LACTAMs). Many cephalosporin-type antibiotics can be made by this route as well (87). The antiemetic trimethobenzamide [138-56-7] is convenientiy prepared from -hydroxybenzaldehyde (88) (see Gastrointestinal agents). 

Fig. 2. Pyrazole-derived pharmaceuticals (a) butaglyon [2603-23-8] an antidiabetic (b) dazopride [70181 -03-2] an antiemetic (c) feclobuzo [23111-34 ] an antiinflammatory (d) kebuzone [833-34-9], an antirheumatic (e) muzolimin [55294-15-0], a diuretic (f) phenazobz [20610-63-3], an antiasthmatic (g) selenofob [39102-63-1], an antibiotic (h) sulfamazo [65761-24-2], an antiseptic and (i) sulfinpyrazone [57-96-5], an antigout preparation (50).

Replacement of the terminal nitrogen of the piperazine by carbon is said to enhance the antiemetic activity of the phenothiazines at the expense of the other pharmacologic effects. The simplest compound in this series, pipamazine (88), is prepared by alkylation of nipecotamide (87) with the chloropropyl phenothiazine (58). Preparation of the analogous sulfoxide begins with acetylation of the thiomethyl compound, 89 [prepared by a route... 

It is important to note diat antivertigo dragp are essentially antiemetics because many of these preparations, whedier used for motion sickness or vertigo, also have direct or indirect antiemetic properties. They prevent the nausea and vomiting diat occur because of stimulation of die vestibular apparatus in the ear. Stimulation of diis apparatus results in vertigo, which is often followed by nausea and vomiting. 

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. 

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 subcategory of dopamine receptor antagonists has found some use as antiemetic agents administered in conjunction with antimmor chemotherapy. The preparation of one of these agents based on a benzotriazole nucleus begins with nitration of the amino salicylate ester (67-1). Catalytic hydrogenation of the product (67-2) leads to the orf/zo-diamine (67-3). Treatment of this last product with nitrous acid... 

In the course of clinical treatment with methadone, certain situations relating to adverse effects are characteristic. Nausea is a general opiate effect, but complaints most frequently relate to the methadone mixture. This preparation does have a syrupy consistency, but the problem for clinicians is that the alternatives - sugar-free mixture or methadone tablets - are both more injectable, and therefore requests or implied requirements for these are often manipulative. So are requests for the antiemetic cyclizine tablets, which are crushed and injected by drug misusers along with injected methadone. As indicated in Chapter 4, thankfully these particular claims have become less common now that guidelines are much more discouraging of any use of methadone tablets. 

The previous edition of this book contained a detailed description of abuse of the antiemetic tablet preparation cyclizine by illicit drug users, nearly always crushed and injected along with methadone tablets or ampoules. Cyclizine is a constituent of Diconal along with the opioid dipipanone, and it seems that cyclizine has an opioid-enhancing effect which partly accounts for the particularly euphoriant property of Diconal. This could therefore be reproduced by combining cyclizine with the synthetic opioid methadone, and the intention to do this led to a wave of patients in the UK attempting to have their methadone prescribed in the ampoule or tablet form. 

The combination of droperidol and fentanyl is a fixed ratio preparation called innovar. Since droperidol is a neuroleptic substance, innovar is said to produce neurolept analgesia if combined with a more potent anesthetic, innovar produces neuroleptic anesthesia. A neuroleptic has adrenergic blocking as well as sedative, antiemetic, and anticonvulsant properties. Since innovar can cause extrapyramidal muscle movements, it is contraindicated in Parkinson s patients. 

Dronabinol is a rather expensive drug for chronic, long-term disease and may cost a patient several hundred dollars a month. The use of the much less expensive d8-THC should be evaluated. This compound, which parallels A9-THC in its antiemetic effects in children (see above), is considerably less expensive to prepare and is much more stable. While A9-THC is easily oxidized to cannabinol by air, J8-THC does not undergo this reaction. 

If vomiting is present and is uncontrollable with antiemetics, nothing is taken by mouth. As bowel movements decrease, a bland diet is begun. Feeding should continue in children with acute bacterial diarrhea. Rehydration and maintenance of water and electrolytes are the primary treatment measures until the diarrheal episode ends. If vomiting and dehydration are not severe, enteral feeding is the less costly and preferred method. In the United States, many commercial oral rehydration preparations are available (Table 23-3). 

A Merck gronp, in developing a synthesis of a promising antidepressant/antiemetic, found that the rapid exchange (0°C) between 3,5-bis(triflnoromethyl)bromo-benzene and iPrMgBr is the safest preparation of the potentially explosive aryl Grignard, and snitable for multikilo scale-up. 

A number of ANALGESICS can be used to offset the pain of the attack, including aspirin, codeine and paracetamol, and these are often incorporated into compound preparations together with a variety of other drugs and drug types, e.g. caffeine, buclizine, doxylamine, isometheptene, pizotifen. Sometimes drugs with antinauseant or ANTIEMETIC properties are included, e.g. cyclizine and metoclopramide. 

Cyclimorph cyclizlne tartrate morphine tartrate, cyclizine [ban, inn) (cyclizIne hydrochloride (usan) cyclizlne tartrate BW 47-83 Valoid ) is one of the piperazine series of histamine H -receptor ANTAGONISTS, and a muscarinic CHOLINOCEPTOR antagonist with SEDATIVE actions. It can be used orally or systemically as an antiemetic in the treatment of nausea, vomiting, vertigo, motion sickness and disorders of the balance function of the inner ear. It is available in preparation together with morphine (e.g. Cyclimorph ). 

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