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what are the different categories of nausea and vomitting? motion sickness, post operative, radiation induced, chemotherapy induced
what types of drugs will be effective in preventing motion sickness? why? muscarinic blockers, H1 antagonists. these drugs are effective because the vestibular system in the ear has M1 and H1 receptors.
what are risk factors for postoperative nausea and vomitting? anesthesia with volatile anesthetics, nitrous oxide, opioids, female gender, younger age, history of motion sickness, absence of smoking history
what type of receptors are involved in PONV? 5HT3, M, H1, D2, NK1, steroid
what receptors are involved in chemotherapy induced nausea and vomitting? 5HT3, NK1, glucocorticoid, D2
what are some important neurotransmitter receptor sites in the vomitting reflex? H1 (histamine), M1 (muscarinic), D1 (Dopamine), 5HT3 (serotonin), NKI (substance P)
list the major classes of antiemetic drugs anticholinergic, antihistamines, dopamine receptor antagonists, serotonin receptor antagonists, Neurokinin receptor antagonists, cannabinoids
which muscarinic blocker is used for motion sickness? scapolamine
list the H1 receptor antagonist (antihistamine) drugs: dimenhydrinate, diphenhydramine, meclizine, promethazine
what is the difference between dimenhydrinate and fexofenadine? ability to cross the BBB (dimenhydrinate can cross, fexofenadine cannot), ability to block muscarinic receptors (dimenhydrinate has anticholinergic effects, fexofenadine does not block M receptors)
is Dimenhydrinate a sedating or antiemetic drug? no. it is a second generation antihistamine, so it cannot cross the BBB, threfore, it is non sedating, and is not an anti emetic.
how does dimenhydrinate have cause anti-emetic effects? it has anti cholinergic effects by blocking the M receptor (it can block the H1 receptor as well)
what are two key drugs for motion sickness? scapolamien (patch put behind the ear), dimenhydrinate
list the dopamine receptor antagonists prochlorperazine, droperidol, metochlopramide
dopamine antagonists are useful for treating nausea and vomitting associated with what? PONV, CINV, NOT motion sickness!
what is the anti-emetic mechanism of action of dopamine receptor antagonists? blocks dopamine receptors (D2) in the CTZ and NTS to prevent nausea and vomitting. blocks D2 receptors in the GI tract to prevent the inhibition of intestinal motiblity associated iwth NV.
what is the most commonly used antiemetic in the D2 antagonist class? prochlorperazine
prochlorperazine is moderately effective for what? nausea caused by various Gi disorders, CINV, used alone for low emetogenic chemotherapy. mostly used as an add-on therapy. it is an antipsychotic class
what are some adverse effects for prochlorperazine? altered cardiac conduction, extrapyrimidal reactions (tarditive dyskinesia)
droperidol is mostly used for what? it is an antipsychotic used as a tranquilizer, primarily for preanesthetic agent or procedural sedation, postoperative nausea and vomitting
what are some adverse effects for droperidol? extrapyrimidal reactions (dystonia, tarditive dyskinesia), qt prolongation.
what are some clinical indicative uses for metochlopramide? modest anti-emetic effect for central and peripheral antagonism, weak 5HT3 receptor blcokade at high doses, emesis caused by cyutotoxic drug therpay
what is metochlopramide commonly used for? mostly adjunctive therapy for emesis failing first line treatment.
what is an adverse effet of metochlopramide? risk of irreversible tarditive dyskinesia wth higher dosing.
list some general uses for dopamine receptor antagonists: NOT used for motion sickness, limited use in PONV,toxicity limits its use.
which anticancer drug has the highest ematogenic potential? cisplatin
which antiemetic drug has low emetogenic potential? vinblastine
identify the receptors that are affected by low an dhigh dose metoclopramide CINV: high dose, central and peripheral D2 antagonism: low dose, has weak 5HT3 blockade at high doses. high dose too toxic for use for PONV
list the 5HT3 receptor antagonist drugs ondansetron, granisetron, dolasetron, palonosetron
what is the most useful drug clas for CINV? 5HT3 receptor antagonists
which 5HT3 receptor antagonist has higher receptor binding affinity, longer half life, and superior efficacy over others in this class? palonesetron
what is the clinical use for 5HT3 receptor antagonists? CINV- cornerstone therapy for the control for acute emesis, prevents acute NV, little effect on delayed NV when used alone. added to NK1 receptor antagonist regimen. commonly used for PONV. NOT EFFECTIVE FOR MOTION SICKNESS
what are the three classifications of CINV? anticipatory, acute (5HT), delayed (substance P)
list some adverse effects of 5HT3 receptor antagonists headache, constipation, diarrhea, QT prolongation (small)
what is the advantage of using ondansetron vs. metoclopramide? unlike metoclopramide, ondansetron does not block D2 receptors , it only blocks the 5HT3 receptors. it thus does not cause extrapyramidal effects.
list the substance P/NK1 receptor antagonists aprepitant, fosaprepitant
list some clinical uses of aprepitant CINV, most useful for delayed CINV, works best for CINV when combined with 5HT3 receptor antagonist, glucocorticoid, PONV effect for prophylaxis, not effective for rescue
which glucocorticoid isthe most used agent for CINV? dexamethasone. low risk-used as a single agent (DOC), moderate/high risk whenused in combination. effective for preventing PONV, not effective for rescue.
list the cannabinoids dronabinol, nabilone. MOA unkonwn.
what kind of anti emetic effect do the cannabinoids have? what is their clinical use? modest. clinical use: rescue for CINV (add on for NV not adequately controlled by other drugs, benefit remains controversial
list some side effects of the cannabinoids vertigo, xerostomia, hypotension, dysphoria, hallucinations, disorientation, sedation
treatment guidelines .
CINV-low emetogenic potential dexamethasone. alternative: dopamine antagonist 9prochlorperazine or metoclopramide
CINV-moderate emetogenic potential? dexamethasone + palonosetron (can substitute for any 5HT3 antagonist. alternative: use high emetogenic potential regimen
CINV-high emetogenic potential? dexamethasone+5HT3 antagonist (any) + NK1 antagonist
CINV-high emetogenic potential with NV despite optimal recommended therapy? add dopaminergic antagonist (prochloperazine or cnnnabinoid or substitute high dose metoclopramide for 5HT3 antagonist)
PONV prophylaxis? scopolamine OR dexamethasone OR aprepitant
describe the general treatment recommendations for PONV: rescue therapy not as effective but frequently needed, when PONV develop in spite of pharmacologic prophylaxis, a different class of antiemetics is chosen for rescue therapy from the class used for proophylaxis. 5HT3 antag most common rescue therapy
Created by: aferdo01