N/V tx Flashcards
receptors in area postrema
chemoreceptor trigger zone
D2
NK1
5HT3
receptors in nucleus tractus solitarius
vomiting center
H1
M1
NK1
5-HT3
receptors in stomach
chemoreceptors
mechanoreceptors
5-HT3
signals transmitted to vomiting center via IX or X
receptors in vestibular system
M1
maybe H1
5-HT3 receptor antagonists
Dolasetron granisetron ondansetron (Zofran) palonosetron alosetron (only for IBS-D) Block 5-HT3 receptor at vagal nerve
Therapeutic use of 5-HT3 antagonists
CINV
RINV
post operative N/V
Pregnancy N/V
adverse effects of 5-HT3 antagonists
QT prolongation and Torade’s
caution when used with antiarrhythmics
- dolasetron very high risk!
headache and constipation
Pharmacokinetics of 5-HT3 antagonists
Palonosetron and Granisetron have long half-lives
effective for delayed CINV as single dose
all others have short half-lives
Neurokinin (NK1) antagonists
aprepitant
fosaprepitant
netupitant (combo only with palonosetron)
rolapitant
MOA of NK1 antagonists
block NK1 receptors in CTZ and vomitting center
therapeutic use of NK1 antagonists
CINV in combo with glucocorticoids and 5-HT3 antagonists
prophylaxis of post operative N/V
- only aprepitant and fosaprepitant
adverse effects of Nk1 antagonists
GI distress
CNS effects, fatigue
pharmacokinetics of NK1 antagonists
netupitant/rolapitant have longer half lives and oral routes
inhibition of several CYP450 enzymes
H1 antagonists
diphenhydramine (benadryl) dimenhydrinate (dramamine) hydroxyzine promethazine meclizine cyclizine
H1 antagonists MOA
weak antiemetics
useful for post-operative N/V
block H1 receptors in vomiting center and vestibular system
also have central anticholinergic properties!!!
Therapeurtic uses of H1 antagonists
mild N/V PONV pregnancy N/V (doxylamine/B6) motion sickness (meclizine and cyclizine) CINV RINV
adverse effects of H1 antagonists
anticholinergic effects!!!
pharmacokinetics of H1 antagonists
hydroxyzine has long half life
interactions include other anticholinergic agents pt may be on
D2 antagonists
Phenothiazine's - chlorpromazine - perphenazine - prochlorperazine metoclopramide
D2 antagonists effects
weak to moderate antiemetic
block D2 in cortex
metoclopramide stimulates Ach actions in GI enhancing motility
Therapeutic use of D2 antagonists
idiopathic, mild N/V (infections, opiates, migraines) Metoclopramide for gastroparesis PONV NVP CINV and RINV in combo with other agents
Adverse effects of D2 antagonists
classic anticholinergic effects
arrhythmias possible with larger doses
interactions of D2 antagonists
other anticholinergic agents
antiarrhythmics (QT prolongation)
anti-hypertensives
M1 antagonists
scopolamine
weak antiemetic for motion sickness
block ach signaling from vestibular nuclei to VC
adverse effects include classic anticholinergic effects
cannabinoid agonists
dronabinol (CIII)
nabilone (CII)
strong antiemetics for treatment resistant CINV
stimulates central CB1 and peripheral CB2 receptors in VC and CTZ
reduces 5-HT3 release from vagal afferents
also increases appetite in anorexic cancer or AIDS pts
short onset time and long duration of action
adverse affects of cannabinoid agonists
irritability vertigo sedation impaired cognition xerostomia sympathomimetic
interactions of cannabinoid agonists
caution with CNS depressants, CV agents, and sympathomimetics
High emetogenic regimen for CINV
NK1 antagonist (aprepitant) 5-HT3 antagonist Dexamethasone give 1 day prior and 3 days after chemo add cannabinoid in treatment resistant
Moderate emetogenic regimen for CINV
5-HT3 antagonist (palonosetran/granisetran) dexamethasone give day before and 2 days after chemo add NK1 antagonist if necessary add cannabinoid in treatment resistant
Low emetogenic regimen for CINV
Dexamethasone or 5-HT3 antagonist or metoclopramide or prochlorperazine give day prior to chemo
Pregnancy induced N/V stepped therapy
B6 + doxylamine (H1) or 5-HT3 antagonist
D1 antagonist
Steroid or different D1 antagonist
