Astemizole
Astemizole (marketed under the brand name Hismanal, developmental code R43512) was a second-generation antihistamine drug that has a long duration of action. Astemizole was discovered by Janssen Pharmaceutica in 1977. It has been withdrawn from the market in most countries because of rare but potentially fatal side effects (QTc interval prolongation and related arrhythmias due to hERG channel blockade).
Opioid
Tolerance to nausea occurs within 7–10 days, during which antiemetics ("e.g." low dose haloperidol once at night) are very effective. Due to severe side effects such as tardive dyskinesia, haloperidol is now rarely used. A related drug, prochlorperazine is more often used, although it has similar risks. Stronger antiemetics such as ondansetron or tropisetron are sometimes used when nausea is severe or continuous and disturbing, despite their greater cost. A less expensive alternative is dopamine antagonists such as domperidone and metoclopramide. Domperidone does not cross the blood–brain barrier and produce adverse central antidopaminergic effects, but blocks opioid emetic action in the chemoreceptor trigger zone. (The drug is not available in the U.S.) Some antihistamines with anticholinergic properties ("e.g." orphenadrine or diphenhydramine) may also be effective. The first-generation antihistamine hydroxyzine is very commonly used, with the added advantages of not causing movement disorders, and also possessing analgesic-sparing properties. Δ-tetrahydrocannabinol relieves nausea and vomiting; it also produces analgesia that may allow lower doses of opioids with reduced nausea and vomiting.