Pharm - Tx of Nausea and Vomiting Flashcards
what are the 6 important receptor antagonists in nausea/vomiting reflex
- Serotonin (5-HT3)
- Neurokinin (NK1)
- Histamine (H1)
- Dopamine (D2)
- Muscarinic (M1)
- Cannabinoid
- dolasetron
- granisetron
- ondansetron
- palonosetron
serotonin (5-HT3) receptor antagonists
what is the -setron drug that is only indicated for IBS (not N/V)?
alosetron
what is the MOA of 5-HT3 antagonists?
block serotonin type-3 receptors at vagal nerve terminals and block signal transmission to CTZ
what is the main therapeutic use of 5-HT3 antagonists?
CINV, RINV, post-op, NVP (N/V in pregnancy)
what is the most worrisome adverse effect of 5-HT3 antagonists?
- *dose-dependent QT prolongation** (Torsade’s)
- extreme caution when using with other QT-prolonging agents (antiarrhythmics, CCB’s like diltiazem, verapamil)
what is another adverse effect of 5-HT3 antagonists?
serotonin syndrome - worry when pt on multiple drugs that are serotonin affectors
- metabolic instability
- feel terrible
- can be life threatening
all 5-HT3 antagonists have short half-lives except which?
Palonosetron and sustained-release formulation of granisetron (subQ)
- 24+ hr half-life makes them effective for delayed CINV as a single dose
- aprepitant
- fosaprepitant
- netupitant (combo only w/palonosetron)
- fosnetupitant (conbo only w/palonosetron)
- polapitant
neurokinin (NK1) antagonists
- moderate antiemetic agents
what are the therapeutic uses for NK1 antagonists?
- most effective when used in combination with 5-HT3 and glucocorticosteroid for CINV
aprepitant is used as prophylaxis for what?
post-operative N/V
- given 3 hrs prior to anesthesia
what are the pharmacokinetics of NK1 antagonists?
- netupitant/rolapitant have moderate-major active metabolites, longer half-lives so give once a day
- mild-moderate inhibition of a few key CYP450 enxymes, but less worried about than H2 and PPI’s
- diphenhydramine
- dimenhydrinate
- hydropxyzine
- promethazine
- meclizine
- cyclizine
Histamine (H1) receptor antagonists
what is the unique initial therapy for N/V during pregnancy?
Doxylamine (H1 antag) + pyridoxine (Vit B6) = Diclegis (PO)
what is the MOA of anti-histamines?
block Histamine type 1 receptors in VC and vestibular system
- agents exhibit varying levels of central anticholinergic properties
what is the treatment for motion sickness/vertigo?
- *meclizine and cyclizine**
- only indication!
what are the adverse effects of anti-histamines?
classic anticholinergic effects!
- drowsiness (CNS depression)
- dry mouth
- constipation
- urinary retention
- blurred vision
- hypotension
- phenothiazines (chlorpromazine, perphenazine, prochlorperazine)
- metoclopramide
Dopamine (D2) antagonists
what D2 antagonist stimulates ACh actions in GI tract, enhancing GI motility and lowering LES tone?
metoclopramide
- anti-emetic used to treat gastroparesis/dysmotility (but has no impact on GI secretions)
what antagonists exhibit anticholinergic effects?
anti-histamines, dopamine antagonists, muscarinic blocker
- effects can be cumulative if taken together (similar to serotonin syndrome)
what is scopolamine?
muscarinic (M1) antagonists, patch worn for 72 hours
- weak antiemetic agent, used for motion sickness (also used for end-of-life care for excessive secretions)
- dronabinol
- nabilone
cannabinoid antagonists
what does it mean cannabinoids are FDA-scheduled/controlled?
limits on quantity/refill number, etc
which cannabinoid antagonist is C-III?
dronabinol
which cannabinoid antagonist is C-II
nabilone (higher abuse potential)
what treatment are cannabinoids reserved for?
treatment-resistant CINV (last resort d/t FDA-scheduling, but very strong entiemetics)
- appetite stimulation in select patients due to severe disease
what is the MOA os cannabinoids?
stimulate predominantly-central (CB1) and predominantly-peripheral (CB2) cannabinoid receptors in VC/CTZ
- GPCR signal transduction results in decreased excitability of neurons
- minimizes 5-HT3 release from vagal afferent terminals
what are the adverse effects of cannabinoids?
- euphoria/irritability
- vertigo (dizziness)
- sedation
- impaired cognition
- xerostoma
- appetite stimulation
which cannabinoid has a large first-pass effect and is metabolized into ONE active metabolite?
dronabinol
NOTE: both have short-time to onset and long duration of action(24-36 hrs)
which cannabinoid is metabolized into SEVERAL active metabolites?
nabilone, allows fewer doses/day
NOTE: both have short-time to onset and long duration of action(24-36 hrs)
when should cannabinoids be used with caution?
when in use with other CNS depressants, other cardiovascular agents, and sympathomimetics
what is the timeline for acute N/V?
occurs <24 hrs after chemo
what is the timeline for chronic N/V?
occurs >24 hrs after chemo
what is the timeline for anticipatory N/V?
occurs BEFORE chemo given, customarily in non-treatment-naive patients
what is the HIGH-emetogenic drug regimen for chemo patients?
3 drugs, 3 days after chemo!
- NK1 antag
- 5HT3 antag
- dexamethasone
*give tx prior to chemo (for acute N/V) and for 3 days after (for delayed N/V)
what can be added if 3-drug regimen doesn’t resolve N/V?
- may add olanzapine (D2)
- may add cannabinoid
what is the MODERATE-emetogenic regimen for chemo patients?
2 drugs, 2 days after chemo!
- 5HT3 antag (polanos/granis subQ)
- dexamethasone
*give tx prior to chemo (for acute N/V) and for 2 days after (for delayed N/V)
what can be added if 2-drug regimen doesn’t resolve N/V?
- may add NK1 antag or olanzapine
- may add cannabinoid if treatment-resistance
what is the LOW-emetogenic regimen for chemo patients?
1 drug, 1 day after chemo
- dexamethasone, OR
- 5HT3 antag, OR
- metoclopramide or prochlorperazine (less likely)
*give tx day of chemo (for acute N/V)
what is the MINIMAL-emetogenic regimen for chemo patients?
0 drug regimen!
- no routine prophylaxis recommended
- if you need to prescribe, back up to LOW-emetogenic **Segars would probably prescribe 5HT3 antag
what is the general principle of breakthrough treatment for chemo-induced N/V?
add one agent from a different drug class to the current regimen - if not on a D2 antag, give a D2 antag
what is the go-to anticipatory emesis prevention/treatment?
benzodiazepine
- also important to consider non-pharmacologic measures (relaxation exercises, yoga, acupuncture, hypnosis)
what is the standard tx for motion sickness?
scopolamine (patch), dimenhydrinate, OR meclizine
what is the standard tx for vertigo?
meclizine OR cyclizine
what is the standard tx for diabetic gastroparesis?
metoclopramide
second time: what is the step-wise tx for pregnancy induced N/V?
- *Vit B6 with anti-histamine OR 5HT3 antag**
- dopamine antag
- steroid OR different dopamine antag
