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
what are the SE of dimenhydrinate
tachy, sedation, dizziness, xerostimia, anorexia, epigastric distress, blurred vision, thickened brochial secretion
what are the types of drugs for diarrhea and IBS-D
opioid agonists
serotinin receptor modulators
bile acid sequestriants
anti-spasmodics
antimicrobial agents
what is the MOA of opioid agnoists
activation of opioid receptors in the smooth msucle of the GI tract, alters periostalis by preventing smooth msucle contraciton and relaxation.
reduced stool volume and can prevent electroylte depletion.
what are the opioid agonist medicatiosn
loperamide (imodium)
diphenoxylate/atropine
octreotide
eluxadoline
what is the MOA of loperamide
also incresase IAS and EAS tone
what is the PK of loperamide
metabolism: hepatic
t1/2: 9-14 hours
excretion feces
what are the SE of loperamide
CONSTIPATION, dizziness, abdominal pain and cramping
what is the MOA of diphenoxylate/atropine
contains small amount of atropine to prevent abuse
what ist eh PK of diphenoxylate/atropine
onset: aprox 45 min
metab: hepatic
T1/2: 2.5 hours
Excretion: feces and urine
what are the SE of diphenoxylate/atropine
flushing, tachy, CNS effects, xeroderma, vomiting, toxic megacolon, urinary retetnion
what is the MOA of Octreotide
inhibits serotonin release. inhibits secretion of gastrin, VIP, insulin, glucagon, secretin, motilin, and pancreatic polypeptide
what is the PK of octreotide
duration: 6-12 hours
metab: hepatic
t1/2: aprox 2 hours
excretion: urine
what are the SE of octreotide
bradycardia, fatigue, HA, dizziness, pruruits, hyperglycemia, hypothyroidism, cholelithiasis, abdominal pain, diarrhea, constipation, biliary obstruction, URI, cardiac arrhythmias, depression
what is the MOA of eluxadoline
binds to mu, kappa, and delta opioid receptors in the intestinal lumen. decreases intestinal motility without causing constipation
what is the PK of eluxadoline
metab?
t1/2: 4-6 hours
peak 1.5 hours
excretion: feces and urine
what are the SE of eluxadoline
dizziness, drowsiness, constipation, nausea, abodminal pian, vomiting, elevated LFTs, URI
what are the serotonin receptor modulators
alosetron and tegaserod
what is the MOA of alosetron
selective 5-HT3 agonist. acts on receptors in the enteric neurons in addition to receptors in other location centrally and peripherally. affects visceral pain, colonic transit and alters secretions in the GI tract
what is the PK of alosetron
metab: CYP
t1/2: 1.5 hours
peak 1 hour
excretion: urine and feces
what are the SE of alosetron
constipation, fatigue, HA, abodminal pain, nausea
what is the MOA for bile acid sequestrants
bind to bile salts in the intestine. inhbiits reuptake of bile salts, increases fecal loss of bile salt bound on LDL cholesterol as well
what is the PK of bile acid sequestrants
onset: peak effect 21 days
no absorption
excreted in feces
what are the SE of bile acid sequestrants
abodminal pain, bloaitng, biliary colic, gallbladder calcifcation, melena, vomiting, dental erosion/discoloration, abnromal LFTs, tinnitus, bleeding issues
what are the antimicrobials
rifaximin
metronidazole
ciprofloxacin
amoxicillin
neomycin
what is the MOA of Rifaximin
binds to bacterial DNA dependent RNA polymerase, thus inhbiting RNA synthesis
what are the PK of Rifaximin
metabolism: CYP
T1/2: 5-6 hours
excretion in feces
what are the SE of rifaximin
peripheral edema, dizziness, fatigue, ascites, nausea, HA prurutis
what are the anti-spasmodics
hyoscyamine
dicyclomine
what is the MOA of anti-spasmodics
blocks ach at parasympathetic receptors. antagonist of histamine and serotonin
what is the PK of anti-spasmodics
onset: 2-3 minutes
duration: 4-6 hours
metab: hepatic
T1/2: 3.5 hours or 7 hours for longer acting
excretion in urine
what are the SE of anti-spasmodics
tachy, mental status changes, abdominal pain, impotence, blurred vision, urinary retnetion, increased IOP
what are different medication types of constipation
stool softeners
bulking laxative
osmotic laxatives
stimulant laxatives
selective opioid antagoonists
guanylate cyclase-c agonists
what is docusate sodium
stool softener
what is the MOA of docusate sodium
lowers the surface tension at the oil-water interface of the aeces, allowing water and lipids to penetrate the stool
this helsp to hydrate and soften the fecal materaial, facilitating natural defecation
what is the PK of docusate sodium
onset: 12-72 hours
excretion in feces
what are the SE of docustate sodium
throat irritation
what are bulking laxatives
methycellulose
psyllium husk powder
wheat dextrin
calcium polycarbophil
what is the MOA of bulking laxatives
absorb and retain water in the intestine, thus increasing the mass of stool. this promotes peristaliss through distension of intestinal lumen
what are the SE of bulking laxatives
bloating, flatulence, GI distress
what are the osmotic laxatimes
saline laxatives - magnesium oxide, sodium phosphate
lactulose
polyethylene glycol
glycerin
what is the MOA of saline laxatives
retain water in intestine, thus increaseing intraluminal pressure and promotion of peristalsis
what are the SE of saline laxatives
blaoting
abdominal pain
apthous stomatitis
hypokalemia and hypophosphatemia
what is the MOA of lactulose
disaccharide that promotes fluid retention in intestine, thus increaseing intraluminal pressure and promoting peristalsis
what is the PK of lactulose
colonic microbiota convert the sugars into lactic and aecitic acid. excreted in feces
what are the SE of lactulose
dehydration, hypernatremia, hypokalemia, bloaitng, nausea, abdominal cramping, diarrhea
what is the SE of polyethrylene glycol
diarrhea, faltulene, abdominal pain, nausea
what is the PK of glycerin suppository
onset 15-30 min. poorly absorbed
what are the SE of glycerin suppository
abodminal cramping, bloating, diarrhea, irritation, tenesmus
what are the stimulant laxatives
bisacodyl and sennosides
what is the MOA of stimulant laxatives
alter fluid excretion by acting directly on the cells of the intestinal mucosa. increase motility by acting on cells
what are the opiod antagonists
naloxegol
methylnaltrexone
what is the MOA of naloxegol
Mu opioid receptor antagonists. bound to polyethylene glycol to prevent crossing BBB. blocks the effects of opioids on GI tract, thus decreaseing constipation
what is the PK of naloxegol
absorbed reapidly
metabolized via YCP
t1/2: 6-11 hours
peaks less than 2 hours
excreted in feces and urine
what is the MOA of methylnaloxegol
same as naloxegol. derivative of naltrexone
what is the pK of methylnaloxegol
T1/2: 15 hours
peaks 30 min to 1.5 hours
excreted in urine andfeces
what are the IBS-C medications
Lubiprostone
Linaclotide
what is the MOA of Lubiprostone
activates chloride channels and increases fluid secretion by the cells int he intestinal membrane. also counteracts the antisecretory effect of opioids
what is the MOA of Linaclotide
acts on guanylate cyclase on the epithelium of the intestine, icnreasing cyclinc guanosine monophosphate. the stimuates the chloride and bicarbonate secretion and intraluminal pressure, promoting peristalsis. cGMP is thought to decrease visceral pain
