University:
Michigan State University
Course:
PHM 430 | Human Pharmacology
Academic year:

2023
Views:

127

Pages:

15
Author:

slypery5hy

Emesis and antiemetic drugs • In emesis the stomach empties in a retrograde manner. The pyloric sphincter is closed while the cardia and esophagus relax to allow the gastric contents to be propelled orally by a forceful, synchronous contraction of abdominal wall muscles and diaphragm. • Closure of the glottis and elevation of the soft palate prevent entry of vomitus into the trachea and nasopharynx. • As a rule, there is prodromal salivation or yawning. Coordination between these different stages depends on the medullary center for emesis, which can be activated by diverse stimuli. • These are conveyed via the: vestibular apparatus, visual, olfactory, and gustatory inputs, as well as viscerosensory afferents from the upper alimentary tract. • Furthermore, psychic experiences may also activate the emetic center. • The mechanisms underlying motion sickness (kinetosis, sea sickness) and vomiting during pregnancy are still unclear. • Polar substances cannot reach the emetic center itself because it is protected by the blood-brain barrier. However, they can indirectly excite the center by activating chemoreceptors in the area postrema or receptors on peripheral vagal nerve endings • A. Emetic stimuli and antiemetic drugs Chemoreceptor trigger zone It is also called area postrema. It is located at the caudal end of the fourth ventricle. It is outside the blood-brain barrier, but accessible to emetogenic stimuli in the blood and cerebrospinal fluid. It is rich in dopamine D2 receptors and opioid receptors, and possibly serotonin 5-HT3 receptors and NK1 receptors. Antiemetic therapy. • Vomiting can be a useful reaction enabling the body to eliminate an orally ingested poison. • Antiemetic drugs are used to prevent: • • • • • kinetosis, pregnancy vomiting, cytotoxic drug-induced postoperative vomiting, as well as vomiting due to radiation therapy Motion sickness. • Effective prophylaxis can be achieved with the: • parasympatholytic scopolamine • H1 antihistamines of the diphenylmethane type (e.g., diphenhydramine, meclizine). • Antiemetic activity is not a property shared by all parasympatholytics or antihistamines. • The efficacy of the drugs mentioned depends on the actual situation of the individual: • • • • (gastric filling, ethanol consumption), environmental conditions (e.g., the behavior of fellow travellers), and the type of motion experienced. Motion sickness. • The drugs should be taken 30 min before the start of travel and repeated every 4 to 6 h. • Scopolamine applied transdermally through an adhesive patch can provide effective protection for up to 3 d. Pregnancy vomiting • Pregnancy vomiting is prone to occur in the first trimester; thus pharmacotherapy would coincide with the period of maximal fetal vulnerability to chemical injury. • Accordingly, antiemetics (antihistamines, or neuroleptics if required) should be used only when continuous vomiting threatens to disturb electrolyte and water balance to a degree that places the fetus at risk Drug-induced vomiting • To prevent vomiting during anticancer chemotherapy (especially with cisplatin), effective use can be made of 5-HT3-receptor antagonists (e.g., ondansetron, granisetron, and tropisetron), alone or in combination with glucocorticoids (methylprednisolone, dexamethasone). • Dexamethasone 8-20 mg iv. before chemotherapy, followed by 8 mg/d orally for 2-4 days, is commonly administered. Central Nervous System. • Serotoninergic neurons play a part in various brain functions, as evidenced by the effects of drugs likely to interfere with serotonin. • Fluoxetine is an antidepressant that, by blocking re-uptake, inhibits inactivation of released serotonin. Its activity spectrum includes : • significant psychomotor stimulation • depression of appetite, • and anxiolysis. • Buspirone also has anxiolytic properties thought to be mediated by central presynaptic 5-HT1A receptors. • Ondansetron, an antagonist at the 5-HT3 receptor, possesses striking effectiveness against cytotoxic drug-induced emesis, evident both at the start of and during cytostatic therapy. • Tropisetron and granisetron produce analogous effects. • Serotonin receptors and actions Anticipatory nausea • Anticipatory nausea and vomiting, resulting from inadequately controlled nausea and emesis in patients undergoing cytotoxic chemotherapy, can be attenuated by a benzodiazepine such as lorazepam. • Dopamine agonist-induced nausea in parkinsonian patients can be counteracted with D2-receptor antagonists that penetrate poorly into the CNS (e.g., domperidone, sulpiride). • Metoclopramide is effective in nausea and vomiting of gastrointestinal origin (5-HT4-receptor agonism) and at high dosage also in chemotherapy- and radiation- induced sickness (low potency antagonism at 5-HT3- and D2-receptors). • Phenothiazines (e.g., levomepromazine, trimeprazine, perphenazine) may suppress nausea/emesis that follows certain types of surgery or is due to opioid analgesics, gastrointestinal irritation, uremia, and diseases accompanied by elevated intracranial pressure. • The synthetic cannabinoids dronabinol and nabilone have antinauseant/ antiemetic effects that may benefit AIDS and cancer patients.

Emesis and Antiemetic Drugs

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