anti-emetics, laxatives Flashcards
Where is the vomiting/emesis center
group of cells in the medulla oblongata
How is the vomiting/emesis centers activated
several mechanisms:
-afferent fibers in the gut
-chemoreceptor trigger zone
-cerebral cortex
vestibular aparatus
What is the CTZ
area postrema response to blood-born substances
serotonin 5-HT3
dopamine D2
Muscarinic M1 receptors
what is vestibular apparatus activation
fibers into cerebellum
triggers release of Ach/histamine
what is gut activation of vomiting center
vagal afferent pathways to solitary tract nucleus to vomiting center
nerve stimulation of CTZ
D2, 5-HT3, and neurokinin 1 (NK1) receptors
what are the drug categories for nausea and vomiting
cholinergic/muscarinic antagonists
dopamine receptor antagonists
serotonin receptor antagonists
cannabinoids
histamine antagonists
what is the cholinergic antagonists for N/v
scopolamine (hyoscine)
patch/injectables
what is the MOA for scopolamine
blocks ach at parasympathetic sites (smooth muscle, secretory glands, CNS)
reduces histamine and serotonin activity
what is the PK for scopolamine
Onset: 6-8hours
Duration: 72 hours
Metabolism: hepatic
T1/2: 9.5 hours
peak: 24 hours
Excretion: less than 10% in urine
what are the SE of scopolamine
similar to atropine (Bradycardia (initially) - tachy, flushing, orthostatic hypotension)
cognitive impairement (drowiness/blurred vision)
psychosis and hallucinations
what are contraindications with scopolamine
contraindicated in narrow-angle glaucoma or with other agents containing belladonna
anticholinergic agents, other CNS depressants (hydrocodone), magnesium sulfate, nitroglycerin, potassium citrate, SSRIs, thiazide
What are the dopamine receptor antagonists medications for N/V
phenothiazines - prochlorperazine
Butyrophenones - haloperidol, droperidol
Benzamides - metoclopramide, trimethobenzamide
What is the MOA of dopamine receptor antagonist medications
acts primarily on CTZ and afferent pathway in the gut
antagonize D2 dopamine receptors in area postrema (midbrain) and peripheral sites
M1-muscarinic and H1-histamine blocking effects
metocloperamide has weake 5-HT3 blockage at higher doses
what are the SE of dopamine receptor antagonists medications
extrapyramidal reactions (dystonia), tardive dyskinesia, hypotension, EKG abnormaliteis, CNS effects, psychological effects, hyperprolactinemia
what are the major interactions with Dopamine receptor antagonists
TCAs, SSRIs, Antipsychotics, opioids, anticholinergics, anti-parkinson drugs, alcohol, potassium
what are the PK of Dopamine receptor antagonists
onset:
PO: 30-40 min
rectal: approx 60 minutes
duration: 3-4 hours for oral, 3-12 hours for rectal
what is the PK for metoclopramide
duration: 1-2 hours
T1/2: 5-6 hours in adults
excretion in urine
CYP2D6
what are the serotonin receptor antagonists
ondansetron (zofran)
granisetron
what is the MOA for ondansetron
blocks serotonin centrally (chemoreceptor trigger zone) and peripherally (vagal nerve terminals0
what is the PK for ondansetron
onset: aprox 30 min
metabolism: CYP pathways
T1/2: aprox 3-6 hours in adults
peaks: 1-2 hours
excretion in urine and feces
what are the SE of ondansetron
QT prolongation, dizzinness, confusion, SOB, constipation
what are the considerations for ondansetron
EKG monitoring, potassium and magensium elvels
watch for serotinin syndrome with serotoninergic drugs
what are the contraindications with ondansetron
amiodarone
cyp3a4 inducers
QT prolonging agents
what is the Canabinoid
Dronabinol
what is the MOA of Dronabinol
activates cannabinoid receptors
what is the PK of Dronabinol
Onset: 30-60 min
Peak 2-4 hours
duration: 4-6 hours
metabolism: hepatic
T1/2: 4-5/25-36 hours
what are the SE of Cannabinoids
euphoria, CNS changes, abdominal pain, vomiting, flushing, palpitations, hypotension, xerostonia, vertgo
what are the special considerations of cannabinoids
monitor HR and BP
psychiatric changes/CNS effects
worsening N/V/abd pain
may contain propylene glycol
subastance use hx
what are contraindicatiosn of cannabinoids
alcohol
anticholinergics
CNS depresssants
CYP3A4 inhibitors/inducers
metronidazole
disulfiram
warfarin
what are the histmaine antagonist meds for N/v
promethazine
mecizine
dimenhydrinate
what is the MOA for promethazine
blocks mesolimbic dopaminergic receptors in postsynaptic sites. blocks release of hromones from the hypothalamus. blocks histmaine 1 receptors in brainstem
what are the PK of promethazine
ONset: IV: 5 min,PO/IM: 20 min
duration: 4-6 hours
metabolism: CYP
T1/2: IM approx 10 hours, IV 9-15, supp 16-19 hours
what are the SE of promethazine
EKG changes
anticholinergic effets
CNS depressionm extrapyramidal efffects orthostatic hypotension photosensitivity
what is the MOA of meclizine
blocks H1 histamine receptor and prevents vasodilation, increased capillary permeability, bronchoconstriction, and spasmodic contraction of gastriintestinal smooth muscle.
also depress labyrinth excitability and vesticular stimulation, and may affect the medullary chemoreceptors trigger zone
what is the PK of meclizine
onset; aprox 1 hour
duration: approx 24 hours
metabolism: hepatic
T1.2”: aprox 5-6 hours
excretion: urine and feces
what are the SE of meclizine
sedation, headaches, vommiting, blurred vision
what is the MOA of dimenhydrinate
binds to H1 receptor sites in peripheral sites including GI tract, respiratory tracts and blood vessels. blocks chemoreceptor trigger zones
dpresses layrthinine function and vestibular stimulation.
central anticholinergic activity
what are the PK of dimnhydrinate
onset: up to 30 min for IM and oral
duration: 4-6 hours
metabolism: hepatic
T1/2: 5-8 hours
excretion: renal