Lesson 20 - Vomiting (CEU, 2024/25) PDF

Lesson 20 Vomiting 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25 1. Pathophysiology of vomiting Stimulus Enter of the signal Integration Effectors Unpleasant images Sensory afferent and odors,...

Lesson 20 Vomiting 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25 1. Pathophysiology of vomiting Stimulus Enter of the signal Integration Effectors Unpleasant images Sensory afferent and odors, pathways medulla emotional factors Center of Irritative stimulus Afferent pathways in GI vomit of pharynx and tract (M receptors) stomach (chemo, (5-HT3, H1, M receptors, radiotherapy, mechanoreceptors and gastroenteritis) chemoreceptors Efferent nervous stimulus: GI tract, Motion sickness and CTZ diaphragm vertigo Labyrinth: (D2, 5-HT3 Vestibular nuclei (H1, M receptors) receptors) Toxins, drugs Nausea and Release in blood vomiting emetogens Antiemetic drugs:  1. Pathophysiology of vomiting Vomit may occurs in Motion sickness. Early pregnancy Disease states (migraine…) Bacterial and viral infections. Unwanted side effects (chemotherapy…) The main neurotransmitters involved: ACETYLCHOLINE HISTAMINE 5-HT DOPAMINE SUBSTANCE P It has been hypothesized that ENKEPHALINS are also implicated. 2. Antiemetic drugs H1 RECEPTOR ANTAGONISTS. MUSCARINIC RECEPTOR ANTAGONISTS 5-HT3 RECEPTOR ANTAGONISTS DOPAMINE ANTAGONISTS NK1 RECEPTOR ANTAGONISTS OTHER ANTIEMETIC DRUGS  2. Antiemetic drugs 1. ANTIHISTAMINES: H1 RECEPTOR ANTAGONISTS PROMETHAZINE, DIMENHYDRINATE, BETAHISTINE, DOXYLAMINE Mechanism of action: Motion sickness: receptors H1, M in vestibular nuclei Gastrointestinal tract: receptors H1, M Effective against nausea and vomiting arising from many causes, including motion sickness and the presence of irritants in the stomach ADRs: Drowsiness and sedation (1° generation of antistamines)  2. Antiemetic drugs 1. ANTIHISTAMINES: H1 RECEPTOR ANTAGONISTS NAUSEA AND VOMITING IN PREGNANCY FIRST LINE TREATMENT: PYRIDOXINE (vitamin B6) 10-25 mg every 8 hours DOXYLAMINE 12.5-25 mg every 8 hours If symptoms do not resolve (anti H1), consider 1 or both of: PROMETHAZINE 12.5-25 mg intramuscularly, orally, or rectally every 4-6 hours DIMENHYDRINATE 50-100 mg orally or rectally If symptoms do not resolve, consider (1 at a time) METOCLOPRAMIDE (D antagonist) ONDANSETRON (5-HT3 antagonist) METHYLPREDNISOLONE (antiemetic effect with unknown mechanism of action)  2. Antiemetic drugs 1. ANTIHISTAMINES: H1 RECEPTOR ANTAGONISTS MENIERE’s DISEASE The cause of Ménière's disease is unclear, but likely involves both genetic and environmental factors ( possible autinmune origin) It is a disease of the inner ear that is characterized by potentially severe and incapacitating episodes of vertigo, tinnitus, hearing loss and vomiting. No cure is known, only cure the symptoms Medications for acute attacks: PROCHLORPERAZINE (also an antipsychotic) buccal or intramuscular to treat severe nausea and vomiting Short-term COURSE OF BENZODIAZEPINES Medications to help prevent attacks BETAHISTINE: H3 receptor antagonist and a partial H1 agonist DEXAMETHASONE: Intratympanic in patients with vertigo It is an immune modulator so it may be effective in patients with Meniere's disease that has an autoimmune origin  2. Antiemetic drugs 2. MUSCARINIC RECEPTORS ANTAGONIST SCOPOLAMINE (HYOSCINE) Prophylaxis and treatment of motion sickness Oral or IM administration usually reserved for patients exposed to short periods of intense motion or those highly susceptible to motion. Transdermal administration is effective and has fewer adverse effects and increased duration compared with oral administration ADRs: antimuscarinic ADRs like mydriasis, tachycardia, urinary retention, no secretions…  2. Antiemetic drugs 3. 5-HT3 RECEPTOR ANTAGONISTS GRANISETRON, ONDANSETRON, PALONOSETRON Mechanism of action: Irritative stimulus of pharynx and stomach (chemo, radiotherapy, gastroenteritis) and drugs Gastrointestinal tract: receptors 5-HT3, H1, M CTZ: receptors D2, 5-HT3 Indications Cancer chemotherapy-induced nausea and vomiting May use orally or IV with highly emetogenic chemotherapy (e.g: cisplatin ≥50 mg/m2) Prevention of postoperative nausea and vomiting. 2. Antiemetic drugs 4. DOPAMINE ANTAGONISTS METOCLOPRAMIDE Vomiting associated to migraine (BBB) Treatment of gastro-oesophageal reflux and hepatic and biliary disorders Mechanism of action: D2 antagonist act in CNS in the CTZ and periferic action on D2. Mild antagonist action on receptor 5-HT3. Agonism on 5-HT4 in the GI tract: increasing GI motility (antiemetic+antiGERD+hepatic/biliary disorders) ADRs: Dyskinesia (extrapyramidal symptoms), fatigue, stimulates prolactin release causing galactorrhoea and disorders of menstruation. 2. Antiemetic drugs 4. DOPAMINE ANTAGONIST DOMPERIDONE Doesn’t penetrate the BBB (no central ADRs) Drug of choice for vomiting in levodopa induced vomiting (Parkinson’s disease) Treatment of vomiting induced by cytotoxic treatments ADRs: Small increased risk of serious cardiac adverse effects (particularly at higher doses and in older patients)→use is now restricted. 2. Antiemetic drugs 4.DOPAMINE ANTAGONISTS ANTIPSYCHOTICS CHLORPROMAZINE, PROCHLORPERAZINE, PERPHENAZINE Effective antiemetics commonly used for treating the more severe nausea and vomiting associated with cancer, radiation therapy, cytotoxic drugs, opioids, anaesthetic They can be administered orally, IV or rectally. ADRs: Sedation (especially chlorpromazine), Hypotension and extrapyramidal symptoms including dystonias and tardive dyskinesias HALOPERIDOL, DROPERIDOL used in Acute chemotherapy-induced emesis. LIMITED USE! 13 2. Antiemetic drugs 5. NK1 RECEPTOR ANTAGONISTS Mechanism of action: Blocks substance P (NK 1 ) receptors in the CTZ and vomiting centre. Novel class of medications that present antiemetic properties in both acute and especially in delayed phases of emesis (chemotherapy-induced) APREPITANT Orally administration; effective in controlling the late phase of emesis caused by cytotoxic drugs FOSAPREPITANT Prodrug of aprepitant, which is administered IV CASOPITANT, NETUPITANT AND ROLAPITANT Newer agents Rolapitant has a significantly long half-life of 160 hours and was approved by the US FDA in 2015. 2. Antiemetic drugs OTHER ANTIEMETIC DRUGS The synthetic cannabinol NABILONE Mechanism of action: CB1 receptor agonist, reduces vomiting caused by CTZ-stimulating agents, sometimes more effective than other antiemetics. ADRs: especially drowsiness, dizziness and dry mouth, mood changes and postural hypotension are also fairly frequent. Hallucinations and psychotic reactions. High-dose GLUCOCORTICOIDS (particularly dexamethasone) Monotherapy or adjuvant in combination with PHENOTHIAZINE, ONDANSETRON or APREPITANT