T2 Antiemetics

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Which 2 substances are used to induce vomiting following ingestion of a toxic substance?: Ipecac & Charcoal (safer & more effective)
What are the contraindications for using ipecac syrup?: 1. following ingestion of a caustic agent (acid or alkali)
2. in pt w/dec level of consiousness or impaired gag reflex
3. cases in which toxin is expected to cause loss of consciousness or impairment of gag reflex w/in short time period
4. following ingestion of liquid hydrocarbon w/ low viscosity.
How do they think ipecac works and how long does it take to vomit?: Takes 30 min. Mechanism involves activation of vagal afferents in abdomen.
Which structures are impt for maintaining balance when stationary?: Utricle & saccule. Have hair cells covered w/ cilia & dense statoconia crystals. Head moves & weight of statoconia causes cilia to bend-->hair cells get dopolarized or hyperpolarized. Vestibular nerves synapse w/ hair cells & relay position to brain stem and cerebellum.
Which structure is impt for detecting changes in position?: Semicircular canals.
Why do you get motion sickness?: Input from vestibular apparatus regarding position or movement differs from what would be expected based on experience.
What are the inhibitory receptors in the vestibular nuclei?: GABAA, GABAB, 5-HT1A, serotonergic, and mu and delta opioid receptors.
What are the stimulatory receptors in the vestibular neuclei?: D2 dopaminergic, 5-HT2 serotonergic, muscarinic Ach, and H2 and H1 histamine receptors.
Which drugs can inhibit motion sickness but initially induce vomiting due to action on area postrema?: Opioids, ex. morphine
What are the most effective drugs for tx of motion sickness?: Muscarinic Ach receptor antagonists, ex. hyoscine.
What are the most commonly used drugs for tx of motion sickness and have a duration of 24 hrs?: H1 receptor antagonists.
Describe the emetic pathway for motion sickness.: Nucleus tractus solitarus-->nerve impulses-->antiperistalsis-->Upper GI sphincter opens and epiglottis closes-->contraction of diaphragm and ab muscles-->inc intragastric P-->LES relaxes
Which chemo drug is highly emetogenic?: Cisplatin
Which chemo drugs are moderately emetogenic?: Combo or one of doxorubicin, cyclophosphamide, epirubicin, carboplatin.
Whats the difference b/w acute and delated emesis?: Acute-->w/in 24 hrs of chemo
Delayed-->more than 24 hrs most chemo.
What is the standard anti-emetic therapy for acute emesis from moderately and highly emetogenic chemo?: 5-HT3 receptor antanogist (ondansetron, granisetron, dolsetron, tropisetron) in combo w/ corticosteroids (dexamethasone)
What is the area postrema?: Area adjacent to CSF-containing ventricles. Doesnt have a BBB to large polar molecules, so can detect toxins in blood & CSF. Delayed emesis may involve this area b/c there is a projection form area postrema to NTS.
What prevents delayed emesis after cisplatin chemo?: Antagonists of substance P receptor, neurokinin-1. (NOT 5-HT3 receptor antagonists!)
What combo is currently given to prevent delayed emesis due to highly and moderately emetogenic chemo agents?: Metoclopramide & Corticosteroid.
Once anticipatory chemo emesis occurs, what tx should be given?: Anxiolytic meds (BZD's)
What receptors are found in the vomiting center (medulla)?: Muscarinic (5-HT3) and histamine (H1)
What receptors are found at the vestibular nuclei?: Muscarinic, H1 (so can you H1 and muscarinic Ach antagonists)
What are the 5 groups of drugs that can be used as antiemetics?: 1. Serotonin 5-HT3 antagonists
2. Dopamine D2 antagonists
3. Anticholinergics
4. H1 Antihistamines
5. Cannabinoids
What are the indications for serotonin 5-HT3 antagonists? (ondansetron, granisetron, dolasetron, palonosetron, ramostron): -chemo induced nausea & vomiting--given 30 minu before chemo.
-postop & postradiation nausea and vomiting
What are the SE of Serotonin 5;HT3 antagonists?: HA & constipation, prolongation of QT interval, excellent safety profile
Which antiemetic drug has the most pronounced prolongation of the QT interval and thus greatest effect on the heart?: Dolasetron
When would you give a dose reduction w/ serotonin 5 HT-3 meds?: w/ hepatic insufficiency and NOT renal insufficiency (even though excreted by both organs)
D2 antagonists antagonize receptors where?: CTZ
Which of the D2 antagonists cannot cross the BBB?: Domperidone CAN, Metoclopramide CANNOT
Which drugs are prokinetic agents b/c of their 5-HT4 agonist activity?: D2 antagonists
Which D2 antagonist can only be given orally?: domperidone. Metoclopramide also has an IV form
Which antiemetic drug causes extrapyramidal side effects?: Metoclopramide as it crosses the BBB, so domperidone is better tolerated.
Which antiemetic drug is used for postop nausea & vomiting, causes QT prolongation, is very potent and sedative, is used for schizophrenia, and is stronger than haloperidol?: Droperidol (D2 antagonist)
Which drugs are antipsychotics w/ potent antiemetic property due to D2 antagonism?: Phenothiazines.
Which antiemetic drug is used in pregnancy and used by NASA for space motion sickness?: Promethazine (H1 antihistamine)
What are the most effective drugs for motion sickness?: H1 antihistamines.
(Meclizine, Cyclizine, Dimenhydrinate, Diphenydramine, Promethazine)
Which drug is an NK1 receptor antagonist? It can be combined w/ serotonin antagonist & corticosteroid for prevention of acute or delayed N & V. SE: Fatigue, dizziness, diarrhea.: Aprepitant
Which drug is used as a transdermal patch for motion sickness?: Scopolamine (anticholinergic)
What are 2 cannabinoids used as an antiemetic?: Dronabinol and Nabilone.
During which weeks does vomiting during pregnancy occur?: starts in 4th-7th week after LMP and resolves by 20th week of gestation
What is the best tx for morning sickness?: try to avoid pharmaceutical tx-->start w/ dietary changes including small, frequent bland meals, low fat, hi carb, salty, sour.
Which drugs have been found to be better than a placebo for pregnancy emesis?: pyridoxine (B6), phenothiazines, trimethobenzamide or ondansetron, antihistamines, anticholinergics.

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