Lecture 4: Drugs for Diarrhea, Abdominal Pain, and Constipation Flashcards
What four classes of drugs are used to treat diarrhea and what drugs are associated with each? (OA(3)/SA/CCI/PI)
Opioid Agonists - Loperamide, Diphenoxylate, Eluxadoline Serotonin Antagonists - Alosetron Chloride Channel Inhibitors - Crofelemer Prostaglandin Inhibitors - Bismuth
Loperamide
What is its MOA, what is its major side-effect, and what toxicity can it lead to?
- chemically-related opioids that does NOT exhibit opiate-like effects (no physical dependence)
MOA: interferes with peristalsis (slows transit)
- circular and longitudinal muscles
SE: classic anticholinergic effects
- can cause CARDIAC TOXICITY = Death
Diphenoxylate
What is its MOA, what other drug is it commonly given with, and what is its major side-effect?
- synthetic opiate agonist; given with small amount of ATROPINE to discourage abuse
MOA: local/central GI smooth muscle inhibition (dec. GI propulsion)
SE: classic anticholinergic effects (Atropine)
Eluxadoline
What are its TWO MOAs, what is it indicated for specifically, and how does it affect pts. without gallbladders?
MOAs:
- mu/kappa receptor agonist - slows peristalsis (local)
- delta antagonist - dec. stomach/pancreas secretion
Indication: IBS-D
SEs: hepatic/pancreatic toxicity (pancreatitis in pts. w/o gallbladder), CNS related problems
- stop drug if inc. enzymes > 5x elevation
Biliary Obstruction, Alcoholism, Pancreatitis History, and Severe Hepatic Impairment are all contraindications of what drug?
When should therapy with this drug be stopped?
ELUXADOLINE
- stop therapy if SEVERE constipation develops and lasts for 4+ days
Alosetron
What is its MOA, what is it indicated for specifically, and what is a major Black Box warning of use?
MOA: selective blocking of GI 5HT3 receptors (modulates visceral pain, colonic transit, and GI secretions)
Indication: chronic, severe IBS-D NOT RESPONSIVE to other therapies (women)
BBW: Ischemic Colitis
- enroll in program, sign benefit statement, no refills without follow-up examination
What are contraindications for Alosetron use and when should it be discontinued immediately?
- GI obstruction/perforation/adhesions/toxic megacolon; diverticulitis, CD, UC; impaired circulation
- SEVERE CONSTIPATION requires immediate discontinuation
Crofelemer
What is its MOA, what is it indicated for specifically, and what are two side effects to use?
MOA: natural substance (sap) that blocks cAMP-stimulated CTFR and calcium-activated chloride channels (regulate fluid secretion)
Indication: Non-infectious diarrhea in HIV/AIDs patients
- chronic diarrhea; only group it is used with
SEs: GI-related and urinary/respiratory infections
What are two Antimuscarinic Agents used to treat Abdominal Pain? (H/D)
Hyoscyamine and Dicyclomine
Hyoscyamine and Dicyclomine
What is their MOA, what are they indicated for, and what is their side-effect of use?
MOA: competitively inhibit autonomic, post-ganglionic cholinergic receptors at multiple sites
Indications: abdominal pain and spasms
SE: classic anticholinergic-based
What are four drug classes used to treat Constipation and what drugs are associated with them? (LCA/POA(3)/GCA/SCCA)
- Laxative and Carthartic Agents
- Peripheral Opioid Antagonists
- Methylnaltrexone, Naloxegol, Alvimopan
- Guanylate Cyclase-C Agonists
- Linaclotide
- Selective Chloride (C2) Channel Activators
- Lubiprostone
Methylnaltrexone, Naloxegol, and Alvimopan
What is their MOA, what are their two indications of use, and what is the warning for use of Alvimopan?
MOA: peripheral mu-receptor antagonists (Alvimopan used ONLY in hospital)
Indications: Opioid Induced Constipation (cancer pt that cant be taken off of them) and prevention of postoperative ileus (ALVIMOPAN - accelerates time to GI recovery)
Warning: Alvimopan carries MI risk with use; REMS requires use in approved places; max 15 doses
Linaclotide
What is its MOA and what two things is it specifically indicated for?
MOA: inc. cGMP concentrations, stimulating secretion of chloride/bicarbonate into intestinal lumen (CFTR ON)
Indications: IBS-C and Chronic Idiopathic Constipation
Lubiprostone
What is its MOA, what three things is it specifically indicated for, and who should it NOT be given to?
MOA: prostaglandin-E1 derivative that inc. intestinal fluid secretion via chloride channels (CIC-2)
Indications: IBS-C in WOMEN, Chronic Idiopathic Constipation, and Opioid-induced Constipation
do NOT give to pregnant patients
What are the 5 subclasses of Laxatives and Carthartic Agents?
- stimulants, osmotics, salines, bulk forming, and stool softeners
Bulk-Forming/Hydrophilic Colloidal Agents
What are 5 members of this family (FB/P/MC/CP), what are they used for, what is their time of efficacy, and what is their adverse effect?
M: fiber/bran, psyllium, calcium polycarbophil, methylcellulose/carboxymethylcellulose
Use: inc. bulk-volume and water content (inc. GI motility) and can also support colonic bacteria/digestion
Efficacy: seen in 2-4+ days
AE: bloating or obstruction (DRINK FLUIDS!!)
Stool Softeners (Surfactant or Emollient laxatives)
What are 2 members of this family (DS/MO), what are they used for, and what is their time to efficacy?
M: docusate salts and mineral oil
Use: anionic surfactant (soften/lubricate feces)
- inc. fluid secretion/dec. reabsorption in GI tract
- mineral oil penetrates stool to soften
Efficacy: seen in 1-3+ days (mainly softens/less lax)
Stimulants (Irritants)
What are 5 members of this family (S/B/CO/G/SP), what is their MOA, and which one is used for Pre-Colonoscopy bowel prep?
M: senna, bisacodyl, castor oil, glycerin, sodium picosulfate (SP –> pre-colonscopy prep (osmotic))
MOA: irritates GI enterocytes (inflammation) –> inc. prostaglandins –> promotes water/electrolytes in GI
Stimulants
What is Castor Oil hydrolyzed to and what are glycerins 3 functions?
- hydrolyzed to ricinoleic acid
glycerin: irritant, osmotic agent, lubricant agent
Stimulants
What is their time to efficacy, what are their 3 adverse effects (AC/UD/FD), and what is a major contraindication? (GI/I/I)
Efficacy: seen in 12-36 hours
AE: abdominal cramps, urine discoloration (SENNA), and fluid/electrolyte disturbanc (long use)
Contraindication: GI obstruction, ileus, or impaction
Saline Agents
What are two members of this family (MS/SP), what is their MOA, how do they interact with diuretics, and what are two cautions of use?
M: magnesium salts (bowel prep) and sodium phosphate
MOA: ions poorly absorbed, creating hyperosmolar solution that osmotically retains water in GI tract
- can cause electrolyte imbalance in pts. on diuretics
Caution: Renal Disease and CHF/HTN (sodium)
Osmotic Agents
What are 4 members of this family (L/MC/S/PG), what is their MOA, when is efficacy seen, and what are adverse effects of use?
M: lactulose, magnesium citrate, sorbitol, polethylene glycol
MOA: osmotically attract and retain water in colon (inc. moisture, softness, volume/bulk)
Efficacy: seen in 1-2+ days with laxative doses and larger doses can provide catharsis in HOURS
AE: electrolyte disturbances and GI-related problems
What other situation can Lactulose be used in?
- also used for pts who have severe liver disease resulting in HYPERAMMONEMIA
- causes change in pH that traps ammonia in GI tract
What are large doses of polyethylene glycol (PEG-3350) used for?
BOWEL PREP prior to GI scopes or radiological procedures/surgery
