ILE I U5 D2 Flashcards
Laxatives work by generally
increasing stool amount and/or changing consistency
How do saline, hyper osmotic, and chlorine channel laxatives work?
Creating osmotic gradient resulting in water being drawn into the lumen creating pressure and stimulating peristalsis
How do lubricant (mineral oil), and emollient agent laxatives work?
Soften fecal material and prevent colonic resorption of fecal water
How do stimulant laxatives work?
Stimulate motility of small and large intestine, and rectum
Bulk forming laxatives MoA
Increased fiber intake, increases stool volume and may make stools softer
Bulk forming laxatives (products)
Methylcellulose (caplets, powder to mix in water) Calcium Polycarbophil(caplets) Pysillium husk (capsules, powdered formulations to mix in water)
Bulk forming laxatives onset? Suitable for chronic use?
12-72 hours, suitable - just adding fiber. SYSTEMIC
Bulk forming laxatives ADRs
abdominal cramping, flatulence, some have high sugar content
Hyperosmotic agents MoA
Creates an osmotic gradient resulting in water being drawn into the lumen of the intestines and rectume, creating increased intraluminal pressure and stimulating peristalsis
Hyperosmotic laxative products
PEG (polyethylene glycol), glycerin suppositories
Hyperosmotic laxative duration?
12-72 hours (PEG) NON-SYSTEMIC, 15-30 min (suppositories)
Hyperosmotic laxative ADR
bloating, cramping, discomfort, diarrhea, dehydration,
Saline laxatives MoA
Create an osmotic gradient resulting in water being drawn into the lumen of the intestines and rectum, creating increased intraluminal pressure and stimulating peristalsis
Saline laxatives products
Magnesium Hydroxide (Milk of Magnesia)
Magnesium Sulfate (Epsom salts)
Magnesium Citrate
Sodium Phosphate salts –Enemas (Fleet® Enema)
Saline laxatives onset
oral; 30 min - 6 hours
enema; 2-15 min
Saline laxative ADR
Bloating, cramping, abdominal discomfort, and flatulence.•Diarrhea, dehydration, and related complications may occur, particularly with excessive use.•Elevated magnesium levels, particularly in patients with kidney failure, infants and children, and elderly
Emollient agent MoA
Anionic surfactants that increase wetting efficiency (promote mixing of aqueous and fatty substances) so that intestinal fluid mixes with fecal material to create a softer fecal mass. These are not true laxatives, but are recommended to prevent stool straining and prevent painful defecation.
Emollient agent products
Docusate Sodium (Colace® and others) –capsules and liquid•Docusate Calcium –capsules
Emollient agents onset
12-72 hours, up to 5 days
Emollient agents ADRs
diarrhea and mild cramping
Emollient agent interactions
Don’t use with mineral oil
Lubricant product MoA
Coats the stool and prevents reabsorption of fecal water. This results in a softer stool, that is more easily eliminated.
Lubricant products available
Mineral Oil oral liquid•Mineral Oil oral liquid emulsion•Mineral Oil liquid enema
Lubricant products onset
6-8 hours oral, 5-15 min enema
Lubricant product ADRs
Lipid Pneumonia –if aspirated•Leakage of Oil through anal sphincter•Absorption into intestinal mucosa, liver and spleen –foreign body reactions
Lubricant product interactions
Reduced absorption of drugs and fat soluble vitamins (A, D, E, and K)
Stimulant laxatives MoA
Since these are old drugs, their mechanisms of action are not well understood. Act locally by irritating the mucosa or stimulating the nerve plexus of the intestinal smooth muscle. May also simulate secretion of water and electrolytes into the intestine. The idealstimulant agent would act only on the colon, and not on the small intestine.
Stimulant laxatives onset
generally, 6 to 10 hours after oral use, but may be up to 24 hours.
Bisacodyl dosafge
must be delivered to site of action in colon; suppositories and ENTERIC COATED tabs
ENTERIC COATED TABS funtion
Coat allows drug to not be released until in basic pH
Where do drugs normally dissolve?
Stomach
Why wouldn’t you want bisacodyl to dissolve in stomach?
Want it to dissolve in small intestine-colon, NOT stomach
Bisacodyl ADRs
antacids, H2 agonists or PPIs; cramping, a nominal pain, diarrhea with fluid/electrolyte loss, intestinal protein loss
Senna is a __ laxative
stimulant
Bisacodyl is a __ laxative
stimulant
Senna availability
natural, tablets/pills, chocolate pieces, liquids
Senna ADRs
similar to others; black pigmentation in colon (totally benign), discoloration of urine
Castor oil
NOT a laxative! Should not be used. Really old drug, no known MoA, but appears to stimulate small and large oil
Castor oil ADRs
severe cramping, nutrient loss, excessive fluid and electrolyte loss
“first-line” laxatives after diet changes
- Assess diet; if deficient in fiber, then recommend fiber product
- If diet is correct, bisacodyl
- If this doesn’t work, see physician
Difference between OTC and Rx laxatives
OTC is much older, Rx is better understood and targets specific receptor sites, but Rx meds are much, much more expensive
Lubiprostone (Amitiza) MoA
Chloride channel activator
Acts locally in gut to open Cl channels in LUMINAL EPITHELIUM, increased Cl and intra-luminal fluid secretion, softens stool, accelerates GI transit
Lubiprostone (Amitiza) effectiveness
Typically increases number of spontaneous bowel movements by 1-2/week
Lubiprostone (Amitiza) ADRs
nausea, headaches, diarrhea
Lumiprostone (Amitiza) dosages
8 and 24 mg tabs; 24 mg BID is normal dose
Linaclotide (linzess) MoA
Activates guanylate cyclase-C receptor on intestinal epithelium
Increases intestinal fluid secretion, increases motility
Linaclotide (Linzess) effectiveness
similar to Amitiza
Linaclotide (Linzess) dose
72, 145, 290 mcg; usual is 145 qd
Plecanatide (trulance) MoA
Guanylate cyclase-C agonist, increases intra and extra cellular concentration of cyclic guanosine monophosphate (cGMP)
Electation of cGMP does what?
stimulates secretion of chloride and bicarbonate into the intestinal lumen, resulting in increased intestinal fluid and accelerated transit.
Plecanatide (trulance) dose
3 mcg qd
“Best” Rx laxative
Plecanatide (trulance)
mu-receptor antagonists MoA
inhibit PERIPHERAL mu-receptors (opioid primary receptor)
Mu receptor agonists (peripheral and central)
- Peripheral -> slows GI motility, leads to constipation
2. Central -> pain releif
Best opioid-induced constipation relief
mu-receptor
mu[receptor drugs
- Alvimopan (Entereeg)
- Methylnaltrexone (Registro)
- Naloxegol (Movantik)
- Naldemedine (Symproic)
Alvimopan (Entereg) MoA and dose
Recovery of bowel function after small/large resection, 12 mg
Methylnaltrexone (Relistor) MoA and dose
Opioid-induced constipation in palliative care, 150 mg, 8 and 12 mg injections
Naloxegol (Movantik) MoA and dose
Opioid-induceed constipation in non-cancer pain; 12.5 - 25 mg
Naldemedine (Symproic) MoA and dose
Opioid-induced constipation in adult patients with chronic non-cancer pain, 0.2 mg tabs
Best non-cancer pain drugs
Acetaminophen and ibuprofen
Lactulose MoA
Lactulose is a sugar derivative of lactose; acts as OSMOTIC AGENT similar to PEG
Lactulose products
powders and solution lactulose
Large volume administrations of PEG products is used for preparation prior to bowel procedures. Goal is to
completely clean colon to facilitate high quality endoscopic examination - patients should continue to consume solution until they are evaluating clear liquid stool with no visible fecal matter
PEG regimens
2-4 liters of solution; major ADR of concern is excessive fluid loss and dehydration
Sodium-phosphate products (SPS)
used to be OTC, but now Rx only because of large ADRs. Available in liquid or tablets
SPS ADRs
dehydration - serious complication, leads to hypotension or renal impairment, patients using these must carefully follow directions. May exacerbate congestive heart failure de to Na content along with need to consume significant amounts of fluids to prevent dehydration and renal complications
