Term
| Which 4 sites when stimulated can induce vomiting? |
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Definition
"Vomiting center" is Nucleus solitarius and RF of medulla
1) GI
2) Vestibular system
3) Chemoreceptor trigger zone (CTZ) in area postrema of the floor of the 4th ventricle
4) CNS centers |
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Term
| What are the 3 basic phases of an emetic episode? |
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Definition
1) Pre-ejection
- Gastric relaxation and retroperistalsis
2) Retching phase
- Rhythmic contraction of abdominal muscles, intercostal muscles and diaphragm against closed glottis
3) Ejection phase
- Intense contraction of abdominal musculature with relaxation of UES. |
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Term
| What patients are at highest risk for post-operative nausea and vomiting (PONV) and chemotherapy-induced nausea and vomiting (CINV)? |
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Definition
Female, smokers that don't drink alcohol
- Those with history of motion sickness or morning sickness
- History of anxiety disorders. |
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Term
| What are the possible complications of untreated nausea and vomiting? |
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Definition
1) Dehydration (hypochloremic alkalosis and hyponatremia)
2) Hypotension
3) Oliguria
4) Muscle weakness
5) Arrhythmia |
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Term
| What are the 5 major classes of anti-emetics? |
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Definition
Site of action
1) M1
2) H1
3) D2
4) 5-HT3
5) NK1- substance P
M1, D2, 5HT3 (also on vagal afferents), NK1 are in area postrema
H1 is in vestibular nucleus |
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Term
| Why give an anti-cholinergic agent as an anti-emetic and what are your options? |
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Definition
M1 receptor antagonist like Scopolamine is given to prevent emetic stimulation of area postrema.
Given transdermally as prophylaxis against motion sickness
SE include dry mouth, drowsiness and vision disturbance. |
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Term
| What anti-histamines are generally used as anti-emetics? |
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Definition
1) Diphenhydramine (Benadryl)
2) Dimenhydrinate (Dramamine)
3) Cyclizine (Marezine)
4) Meclizine (Antivert)
5) Promethazine (Phenergan) |
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Term
| What are the major classes of Dopamine Receptor antagonists used to treat nausea and vomiting and how do they work? |
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Definition
All have risks for Tardive Dyskinesia
1) Phenothiazines (Prochloperazine)
- Prevent CINV by antagonizing D2 receptors in area postrema, as well as M1 and H1 receptors.
- Watch out for extrapyramidal symptoms like irreversible TARDIVE DYSKINESIA
2) Butyrophenone (Droperidol and Haloperidol)
- long half life limits use
- similar SE to Phenothiazine
3) Benzamide (Metoclopramide)
- Anti-emetic and Pro-kientic
- Central and peripheral dopamine D2 antagonism and weak 5-HT3 blockade at high doses.
- Good for cytotoxic drug therapy
- TD also a risk. |
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Term
| What is the current protocol for anti-emesis in CINV. What are common side effects? |
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Definition
5-HT3 receptor antagonists (The "Setrons")
1) Single oral dose of Dolesetron with Dexamethasone and Aprepitant (NKI antagonist)
5-HT3-a include, Palonosetron, Granisetron, Dolasetron, Ondansetron
2) EKG interval changes are common, but usually clinically insignificant, but watch out for QTc prolongation and torsade de pointes
NO evidence of cognitive, psychomotor (unlike D2-antagonists), or affective disturbances |
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Term
1) What do Aprepitant and Fosaprepitant do
2) how should they be used?
3) What side effect/interactions should you look out for? |
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Definition
Neurokinin receptor (GPCR) antagonists that prevent emetogenic effects of substance P on brainstem nucleus tractus solitarius and area postrema.
Prevent acute and delayed (5-HT3 is only acute) prevention
2) Give with Dolasetron and Dexamethasone for CINV
3) WATCH OUT in patients receiving concurrent drugs that are metabolized through CYP3A4 given their moderate inhibitory activity for the CYP3A4 metabolic pathway. |
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Term
| How are glucocorticoids like Dexamethasone used as anti-emetic agents? |
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Definition
Good for CINV but watch out for insomnia (45%) and indigestion and agitation (27%)
1) As single agents, they are used for patients at low emetic risk.
2) For moderate risk, they are added to a 5-HT3R antaoginst like Dolasetron.
3) For high risk (Cisapride, Cyclophosphamide), you add them to Dolasetron and an NKI inhibitor like Aprepitant/Fasaprepitant |
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Term
| What are Dronabinol and Nabilone and how might they be used? |
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Definition
Cannabinoid agents used as second-line anti-emetics.
Bind and stimulate CB1 cannabinoid receptors on neurons in vomiting center.
Modest effect with unfavorable SE (vertigo, xerostomia, hypotension) limit clinical utility (2nd line) |
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Term
| Why might you use lorazepan or alprazolam to treat patients suffering from emesis and nausea? |
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Definition
Benzodiazepines are anti-anxiety drugs that reduce anxiety and akathisia associated with dexamethasone (steroid) and metoclopramide (M1 inhibitor)
Give as adjunct therapy in patients who receive numerous cycles of chemo and anti-emetic effects start to diminish. |
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Term
| How do chemotherapeutic agents induce emesis? |
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Definition
Cisplatin, Cyclophosphamide and Carmustine are the worst!
2 ways.
1) Direct toxin at CTZ in area postrema (which stimulates vomiting center)
2) Indirectly by stimulating release of 5-HT3 from enterochromaffin cells in small intestine, which binds 5-HT receptors in the vomiting center |
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Term
What is the recommended treatment for each of the following classes of emetic risk?
1) High
2) Moderate
3) Low
4) Minimal |
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Definition
1) NKI Antagonist (Aprepitant and Fosaprepitant) + 5HT3R antagonist (Dolasetron) + Steroid (Dexamethasone)
2) Dolasetron + Dexamethasone
3) Dexamethasone
4) Nothing |
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Term
| What 4 things can you do if a patient receives numerous cycles of chemotherapy, and the effects of anti-emetics of choice start to diminish? |
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Definition
1) Re-evaluate risk, diseases status, medications
2) Pick new best regimen
3) Add Benzo to regimen (anxiety)
4) Consider Olanzapine or substituting high-dose IV metoclopramide (M1-inhibitor) for 5HT3R antagonist (or just adding it to regimen). |
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Term
| What are the 2 major pro-kinetic agents that are currently used for GERD, gastroparesis and other forms of GI dysmotility? |
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Definition
1) Tetracycline- macrolide antibiotic
- Stimulates motilin receptors in GI tract to increase motility
- Available oral and IV (only for acute)
2) Metoclopramide- anti-M1
- Anti-emetic and pro-kinetic effects
- Used IV when oral Tetracycline does not work, but you worry about Tardive Dyskinesia! |
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Term
How might the following drugs be used as pro-kinetic agents?
1) Domeperidone
2) Cisapride
3) Tegserod |
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Definition
1) Not FDA approved because of arrythmia risk
2) Facilitates ACh release from myenteric neurons by stimulating 5-HT4 (diffuse action makes it only available in severe cases)
3) Partial neuronal 5-HT4 receptor agonist, stimulating the peristaltic reflex and intestinal secretion, while desensitizing visceral afferents (only used in immediately life-threatening scenarios because of cardiac events) |
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