Nausea & Vomiting Flashcards
Nausea…
Unpleasant sensation of being about to vomit, which may occur alone or with vomiting
Vomiting…
forceful expulsion of gastric contents
Retching (aka dry heaves)…
differs from vomiting bc NO expulsion of gastric contents
GI motor function is controlled at 3 levels:
1 symp & parasymp NS
2 enteric neurons
3 smooth m cells
physiologic pathways involved with vomiting in the medulla…
1 vestibular fiber stimulation
2 afferent visceral fiber stimulation
3 Chemoreceptor trigger zone input (base of 4th ventricle)
5 main neurotransmitter receptor sites related to vomiting reflex:
M1 (muscarinic) H1 (histaminic) D2 (dopamine) 5-HT3 (seratonin) NK1 (substance P)
Which receptor sites are most important from an inner ear perspective?
M1 & H1
Which receptor sites are most important in the GI tract?
D2 & 5HT3
consequences and complications of N/V:
fluid depletion, hypokalemia, metabolic alkalosis
Anticholinergic Agents work on what receptor type?
M1
M1 receptor antagonists
Scopolamine
route of scopolamine
transdermal patch (place on mastoid process)
MOA of M1 antagonists
block ACh at parasymp sites in smooth muscle, secretory glands, and CNS
indications for scopolomine
motion sickness prophylaxis
off label= dry OP secretions –> minimize aspirations post stroke
duration of action of scopolomine
starts 6-8hrs post application of patch
can last up to 72 hrs
Why do we prefer M1 blockers over H1 blockers for prevention of motion sickness?
they do not make pts sleepy (better if pt wants to be awake during travel)
ADRs of scopolamine
xerostomia, sedation, urinary retention, blurred vision (pupil dilation)
Antihistamines work on what receptors?
H1 receptor antagonists
H1 blocker drugs
Dimenhydrinate, Meclizine
MOA of H1 blockers
central anticholinergic action (blocks CTZ) and decreases excitability of middle ear labyrinth & blocks conduction of middle ear-cerebellar pathways
clinical indications for H1 blockers
motion sickness (quick onset and doesnt last very long)
Which H1 blocker is best for treating vertigo?
meclizine
Phenothiazine derivatives work on which receptors?
H1 and D2 antagonists
Example of phenothiazine derivatives:
promethazine
MOA of promethazine?
D2 blocker in CTZ (decreases emetic input to medullary vomiting center) & a adrenergic blocker (decreases release of hypothalamic/hypophyseal hormones) & competes with histamine for H1 receptor
Clinical indications of promethazine
- motion sickness
- antiemetic
- adjunctive for pain management (and migraines)
- tx allergic conditions
why do you not give promethazine to kids <2yrs?
potentially fatal respiratory depression
Drug interactions of promethazine:
- CYP2D6 substrate
- anticholinergics & CNS depressants
- Levodopa
- QTc prolongation
ADRs of promethazine
similar to typical antipsychotics:
- EPS
- may alter cardiac conduction –> dysrhythmias
- NMS
- Amenorrhea/gynecomastia
- Antihistaminic/cholinergic ADRs (like scopolamine)
Dopamine Antagonists 3 classes:
- Phenothiazines
- Butyrophenones
- Benzamides
Phenothiazine drug
prochlorperazine
MOA of prochlorperazine
blocks D1 & D2 receptors in the brain (including CTZ)
has a strong a adrenergic blocking effect
clinical indications for prochlorperazine
antiemetic (used mostly by anesthesia and chemotherapy)
*only moderately effective
contraindications of prochlorperazine
- do not use in kids <2yrs (resp depression)
- do not use in pregnant women
drug interactions and ADRs of prochlorperazine?
same as promethazine
Butyrophenone drug
droperidol
droperidol MOA
blocks central D1 & D2 receptors in brain (including CTZ)
clinical uses of droperidol
preanesthetic agent for PONV
droperidol BBW:
QTc prolongation
Benzamide drugs
- metoclopramide
- trimethobenzamide
metoclopramide MOA
centeral & peripheral D2 blocking, blocks serotonin receptors in CTZ at high doses
*enhanced motility in UGI tissues
metoclopramide indications
DM gastroparesis!!
use for PONV if pt unresponsive to other tx
ADRs of metoclpramide
drowsiness
EPS (especially acute dystonia)
What is metoclpramide’s BBW for?
acute dystonia
Serotonin antagonists 1st generation
- ondansetron
- granisetron
- dolasetron
Serotonin antagonists 2nd generation
palonosetron
serotonin antagonists MOA
block 5HT3 receptors in small bowel, Vagus N, and CTZ
These are the 1* tx for variety of causes of nausea
setotonin antagonist clinical indications:
- prevent CIE –> ALWAYS SCHEDULE THEM
- nausea from irradiation
- prevention & tx of PONV
Ondansetron unlabeled use
peds with gastric enteritis in ED
Ondansetron CYP interactions
3A4 substrate
serotonin blockers class ARDs
HA = m/c
all have issues w QTc prolongation
do these agents (aka serotonin antagonists) “chase down nausea” very well?
NAH BRAH!!
always start preemptively or right at the start of nausea for best results
what weird method for treating nausea is “on the horizon”??
inhaled isopropyl alcohol
N/V management in pregnancy:
1 lifestyle changes 2 pyridoxine (Vit B6) 3 add H1 blocker to B6 --Doxylamine* --Dimenhydrinate --Diphenhydramine 4 low dose ondansetron 5 phenothiazine --promethazine --metoclopromide
why do we not like to use ondansetron in 1st trimester?
linked to a slight increased risk of CHD & cleft palate (also prolongs QTc interval)
Other measures to help with nausea in pregnancy?
GINGER
Management of Gastroparesis:
1 dietary management 2 optimize DM tx 3 avoid meds that can delay gastric emptying 4 use metoclopramide 5 try erythromycin 6 use doperidone or cisapride
common causes of gastroparesis
DM, abd surgery, and drugs that decrease GI motility
meds that can delay gastric emptying:
- opioids
- antichoilinergics
- DM meds
- lubiprostone
domperidone & cosapride ADRs
QTc prolongation
*use only in refractory or severe gastroparesis!
agent to try and use for refractory abd pain & nausea:
TCAs
