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 **
