Nausea Flashcards
What are the five NT receptor sites important in the vomiting reflex?
- M1: muscarinic
- H1: histaminic
- D2: dopamine
- 5-HT3: serotonin
- NK1 receptor: substance P (chemo lecture)
1, 2 - inner ear
3, 4 - GI tract
What is the name of the anticholinergic, M1 receptor AAG? MOA?
Scopolamine
MOA: block Ach at PNS sites in smooth muscle, secretory glands, CNS
What are two clinical indications of scopolamine? What is the clinical pearl?
- px of Motion* sickness
- off-label to dry oropharyngeal secretions*
Pearl: takes 6-8hr to work, may last 72hr
- preferred over antihistamines for motion sickness in person desiring wakefulness during travel*
List the drug interactions and ADRs of scopolamine.
Interactions: other anticholinergics, CNS depressants
ADRs: xerostomia, sedation, urinary retention, blurred vision
What are the three antihistamine, H1 receptor AAG?
- dimenhydrinate
- meclizine
- promethazine
What is the MOA of dimenhydrinate?
MOA:
- central anticholinergic action by blocking CTZ
- DEC excitability of middle ear labyrinth, blocks conduction in middle ear vestibular-cerebellar pathways
What are clinical indications and ADRs of dimenhydrinate?
Indications: motion sickness*
Drug interactions, ADRs - same as scopolamine
Meclizine has the same MOA, drug interactions and ADRs as dimenhydrinate. What is special about meclizine clinical indication?
motion sickness
vertigo management**
In addition to H1 receptor AAG, what else does promethazine act on?
D2 receptor AAG
What are the three MOA of promethazine?
- DA AAG at D2 in CTZ –> limits emetic input to medullary vomiting center
- a-adrenergic blocker, depresses release of hypothalamic hormones
- competes w/histamine for H1 receptor (sedation)
What are four clinical indications for promethazine? What is the C.I.?
- motion sickness
- antiemetic*
- adjunctive for pain mgmt* (migraines)
- tx allergic conditions
C.I. - do not use in kids < 2y (potential fatal respiratory depression)*
Promethazine is substrate of CYP2D6. What are two other bolded drug interactions to be aware of?
- avoid combo w/levodopa (may inhibit antiPD effect)
- QTc-prolongation
What are promethazine and prochlorperazine ADRs?
- EPS*
- Alter cardiac conduction - life-threatening dysrhythmias*
- NMS*
other: amenorrhea/gynecomastia, antihistaminc/cholinergic ADRs
List the three classes of dopamine AG and the drugs within that class.
- Phenothiazines
- prochlorperazine
- promethazine - Butyrophenones
- droperidol - Benzamides
- metoclopramide
- trimethobenzamide
Prochlorperazine has the same drug interactions and ADRs as promethazine. What is prochlorperazine indicated for? C.I.?
Indications:
- antiemetic*
- mild/mod, but not highly emetogenic chemotherapy
C.I.
- do not use in kids < 2y*
- avoid in pregnancy - newborn EPS, withdrawal sxs w/3rd tri exposure*
Droperidol antagonizes D1/D2 receptors in the brain and is used as a preanesthetic agent for PONV. Why do we avoid this drug?
BBW - QTc prolongation (dose dependent)
When would you use trimethobenzamide?
Parkinson’s
apomorphine administration
What are the 3 metoclopramide MOA?
- Central/peripheral D2 receptor AAG at low dose
- Blocks serotonin receptors in CTZ at high dose
- Enhance response to ACh in UGI tissue - enhanced motility w/out stimulating gastric, biliary, or pancreatic secretions
What are common clinical uses for metoclopramide?
- prevent/tx CIE w/mild-moderate emetogenic agents
- prevent/tx PONV
- DM gastroparesis**
What should you not combine with metoclopramide?
Levodopa
Drowsiness is a dose-related ADR of metoclopramide. Why should you try to use the smallest dose possible and short duration? What is the BBW?
- EPS, especially acute dystonia which may be irreversible
What is the class suffix for serotonin AAG? Which is most commonly used?
“-setrons”
Ondansetron
What is the 2nd generation serotonin AAG?
Palonosetron
What is the MOA of the serotonin AAG?
Inhibit serotonin at 5-HT3 receptor in small bowel, vagus nerve, and CTZ
DEC afferent visceral and CTZ stimulation of medullary vomiting center
** primary tx for variety of causes of nausea d/t diffuse blockade of serotonin **
What are labeled indications for serotonin AAGs?
- Prevention* of CIE (scheduled, do not use PRN)
- Nausea r/t irradiation
- Prevent/tx PONV
- repeat doses given in response to inadequate control of NV are generally inadequate**
What are two off label uses of ondansetron?
- Kids w/GE in ED to reduce need for IV fluids and hospitalization
- Kids and adults with other serious NV, help avoid dehydration
What CYP is ondansetron? What other drug interactions should you know?
3A4 substrate
Clean overall, but careful with other QTc drugs
Serotonin AAGs are fairly well tolerated. What are two ADRs?
MC: HA
All agents have issues with QTc prolongation**
Clinical situation:
Vestibular nausea / motion sickness
NT: histamine, Ach
Meclizine, scopolamine
Clinical situation:
Migraine-associated nausea
NT: DA
Metoclopramide, prochlorperazine, promethazine
Clinical Situation:
Gastroenteritis
NT: DA, serotonin
Promethazine, serotonin AAG
What is the stepwise approach for nausea management with pregnancy?
- lifestyle
- vitamin B6 (pyridoxine)
- Add H1 AAG to Vit B6
- Low dose ondansetron
- Phenothiazine (promethazine or metoclopromide)
- other: ginger
What is first line therapy for NV in pregnancy according to ACOG?
Vitamin B6 (pyridoxine)
What is the H1 AAG you can add for NV in pregnancy? What is something to be aware of?
Doxylamine
Somnolence is common
Why are you concerned about using ondansetron in a preggo?
1st trimester use linked to slight increased risk of congenital heart defects & cleft palate**
Also prolongs QT interval
What med can you use to increase GI motility if needed, for gastroparesis?
Metoclopramide
Low dose and short term to decrease risk of tardive dyskinesia
If metoclopramide is not appropriate for gastroparesis, what are some other options?
- erythromycin
- domperidone or cisapride (both tightly restricted and used only by GI specialty)
