Pharm - Tx for Diarrhea, Abd Pain & Constipation Flashcards
what are the 4 drug families used for diarrhea?
prostaglandin inhibitors
opioid agonists
5HT3 antagonists
chloride channel inhibitors
loperamine
diphenoxylate
eluxadoline
opioid agonists
alosetron
5HT3 antagonist
crofelemer
chloride channel inhibitor
this drug interferes with peristalsis (slows transit time)
- direct action on circular and longitudinal muscles of intestinal wall, slowing motility -> allowing for fluid/electrolyte reabsorption and increasing bulk/density of feces
loperamide (anti-propulsive)
what are the side effects of loperamide?
dizziness, fatigue, drowsiness and urinary retention
this synthetic opiate agonist, has a small quantity of atropine added to discourage deliberate abuse/over-dosage
- believed to exert effect locally & centrally on GI smooth muscle cells, inhibits GI motility and slows excess GI propulsion
diphenoxylate
the drug is an AGONIST at mu & kappa opioid receptors in GI tract
- also an ANTAGONIST at delta opioid receptors in GI (decreases stomach, pancreas & biliary tract secretions)
eluxadoline
what drug is indicated for IBS-D (diarrhea-predominant subtype)
eluxadoline
what are the side effects of eluxadoline?
- GI: N/V/abd pain
- hepatic/pancreatic toxicity -> pancreatitis high-risk in patients without a gallbladder!!
- CNS: dizziness, sedation, euphoria, impaired cognition
what are the contraindications for eluxadoline?
- biliary duct obstruction
- alcoholism
- history of pancreatitis
- severe hepatic impairment
NOTE: stop therapy iF severe constipation develops and lasts >4 days
this drug selectively blocks GI-based 5HT3 receptors, but is NOT indicated for N/V
- antagonism in GI modulates the regulation of pain, colonic transit and GI secretions
alosetron
what drug is indicated for chronic, severe IBS-D in women, who are not responsive to conventional therapies
alosetron
what constitutes chronic, severe IBS-D?
diarrhea, and one or more of the following:
- frequent/severe abdominal pain
- frequent bowel urgency or fecal incontinence
- restriction of daily activities due to IBS
what are the side effects of alosetron?
- constipation, dyspepsia, GERD, N/V
* *ischemic colitis** -> black box warning!!
this drug is derived from dark red sap of Croton lechleri tree
- it inhibits chloride ion secretion by blocking cAMP-stimulated CFTR and calcium-activated chloride channels
crofelemer
what drug is ONLY indicated for HIV/AIDS patients, who are on retroviral therapy, and have chronic diarrhea that has been confirmed as non-infectious
crofelemer
what are the side effects of crofelemer?
- GI: abdominal distention, elevated AST/ALT/bilirubin
- respiratory/urinary tract infections
what drug family is used to treat abdominal pain/spasms?
antimuscarinic agents
hyoscyamine
dicyclomine
clidinium/chlordiazepoxide
antimuscarinic agents
these drugs competitively inhibit autonomic, post-ganglionic cholinergic receptors
- causes decreased GI motility and spasms
antimuscarinics
what are the side effects of antimuscarinics?
classic anticholinergic effects!
- dry mouth
- urinary retention
- constipation
- drowsiness
- mental confusion
- blurred vision
what drug families are used to treat constipation?
- peripheral opioid antagonists
- Guanylate Cyclase-c (GC-c) agonists
- selective chloride (C2) channel activators
- laxative and cathartic agents
- *this drug binds GC-c on luminal surface of intestinal epithelium and increases intracellular/extracellular concentrations of cGMP**
- stimulates secretion of chloride/bicarb into intestinal lumen via activation of CFTR ion channel (trying to bring moisture into lumen -> accelerating transit)
linaclotide
what drug is indicated in IBS-C, and chronic idiopathic constipation (CIC)?
linaclotide
what are the side effects of linaclotide?
- GI: diarrhea (dehydration, electrolyte imbalance)
- GERD, dyspepsia, N/V
the drug is a PGR-1 derivative
- it increases intestinal fliud secretion by activating GI-specific cloride channels (CIC-2) in luminal cells of intestinal epithelium
lubiprostone
what drug is indicated for women with IBS-C, chronic idiopathic constipation (CIC), and opioid-induced constipation (OIC)?
lubiprostone
This med is a great choice for cancer pts and people with chronic pain who can’t stop opioids!
what are the side effects of lubiprostone?
nausea, dyspepsia, dizziness
what drug is a peripheral mu-opioid receptor antagonist?
- no common, significant CNS penetrations/actions or induction of withdrawal/pain symptoms
methylnaltrexone (alvimopan)
what drug is used only for accelerating time to GI recovery following bowel resection surgery with primary anastomosis (prevention of post-op ileus)
alvimopan
-hospital use ONLY
what are the side effects of methylnaltrexone?
abd pain, diarrhea, nausea, vomiting
why does alvimopan have a black box warning?
it carries a risk of MI with use
-REMS program requires use only in approved institutions, for max of 15 doses!
what are the 5 classes of laxatives and cathartic agents?
- stimulants
- osmotics
- salines
- bulk forming
- stool softeners
bisacodyl castor oil glycerin senna Na picosulfate
stimulants
lactulose
Mg citrate
polyethylene glycol (PEG)
sorbitol (glycerin)
osmotics
Mg hydroxide
Na phosphate
salines
dietary fiber psyllium methylcellulose carboxymethylcellulose calcium polycarbophil
bulk forming
- efficacy seen in 2-4 days
- LOTs of drug interactions (mainly with psyllium and the celluloses)
- cause bloating/obstruction
docusate “salts”
mineral oil -> penetrates stool
stool softeners
- aka surfactant or emollient
- efficacy seen in 1-3 days
these agents soften/lubricate feces by:
- increasing fluid secretion into GI tract
- inhibit water reabsorption from GI tract
stool softeners
what drug is given for pre-colonoscopy bowel prep?
- aggressive, works very well!
- has magnesium oxide/anhydrous citric acid -> metabolically converted to magnesium citrate (osmotic)
sodium picosulfate
these agents are irritating to enterocytes, GI smooth muscle leading to inflammation
- Na/K-ATPase inhibition and/or increase in PGE synthesis via cAMP/GMP
- promote water/electrolyte accumulation in GI
stimulants (irritants)
- efficacy seen in 12-36 hours (sooner with glycerin)
what is castor oil hydrolyzed to?
ricinoleic acid
what are the adverse effects of stimulants?
- abd cramping
- urine discoloration -> yellow-brown/red-pink (senna)
- fluid electrolyte disturbances
NOTE: make sure pt has ACTIVE bowels (is not constipated/impacted) before giving stimulant! can make the obstruction worse
what are the contraindications for stimulants?
GI obstruction/ileus/impaction
Mg sulfate
Mg hydroxide
Na phosphate
saline agents
- Mg/Phos ions are poorly absorbed
- osmotically retain wter in GI tract
what is the main drug interaction of saline agents?
electrolyte balance (diuretics)
what are cautions to be aware of while using saline agents?
- renal disease (electrolytes)
- CHF/HTN (sodium)
lactulose
Mg citrate
Sorbitol
**Polyethylene glycol* -> large quantities can have sam rxn as Na picosulfate
osmotic agents
these agents work to osmotically attract and retain increased water in the colon, thereby increasin moisture, softness and volume/bulk
- provide effects in 1-2 days with laxative doses (larger doses may provide catharsis sooner
osmotic agents
what is lactulose also used to treat?
severe liver disease (hyperammonemia)
- change in pH traps ammonia in GI
what are the adverse effects of osmotic agents?
- electrolyte disturbances -> watch closely!
- GI-related
large doses of this osmotic agent are used for bowel prep prior to GI scopes, radiological procedures, or surgery (fast acting 1-3 hours!)
- smaller doses can be used for constipation (can take a few days)
polyethylene glycol
