Lecture 4: Drugs for Diarrhea, Abdominal Pain, and Constipation

Question 1

What four classes of drugs are used to treat diarrhea and what drugs are associated with each? (OA(3)/SA/CCI/PI)

Answer 1

Opioid Agonists
   - Loperamide, Diphenoxylate, Eluxadoline
Serotonin Antagonists
   - Alosetron
Chloride Channel Inhibitors
   - Crofelemer
Prostaglandin Inhibitors
   - Bismuth

Question 2

Loperamide

What is its MOA, what is its major side-effect, and what toxicity can it lead to?

Answer 2

• 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

Question 3

Diphenoxylate

What is its MOA, what other drug is it commonly given with, and what is its major side-effect?

Answer 3

• 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)

Question 4

Eluxadoline

What are its TWO MOAs, what is it indicated for specifically, and how does it affect pts. without gallbladders?

Answer 4

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

Question 5

Biliary Obstruction, Alcoholism, Pancreatitis History, and Severe Hepatic Impairment are all contraindications of what drug?

When should therapy with this drug be stopped?

Answer 5

ELUXADOLINE

• stop therapy if SEVERE constipation develops and lasts for 4+ days

Question 6

Alosetron

What is its MOA, what is it indicated for specifically, and what is a major Black Box warning of use?

Answer 6

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

Question 7

What are contraindications for Alosetron use and when should it be discontinued immediately?

Answer 7

• GI obstruction/perforation/adhesions/toxic megacolon; diverticulitis, CD, UC; impaired circulation
• SEVERE CONSTIPATION requires immediate discontinuation

Question 8

Crofelemer

What is its MOA, what is it indicated for specifically, and what are two side effects to use?

Answer 8

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

Question 9

What are two Antimuscarinic Agents used to treat Abdominal Pain? (H/D)

Answer 9

Hyoscyamine and Dicyclomine

Question 10

Hyoscyamine and Dicyclomine

What is their MOA, what are they indicated for, and what is their side-effect of use?

Answer 10

MOA: competitively inhibit autonomic, post-ganglionic cholinergic receptors at multiple sites

Indications: abdominal pain and spasms

SE: classic anticholinergic-based

Question 11

What are four drug classes used to treat Constipation and what drugs are associated with them? (LCA/POA(3)/GCA/SCCA)

Answer 11

1. Laxative and Carthartic Agents
2. Peripheral Opioid Antagonists
   
   • Methylnaltrexone, Naloxegol, Alvimopan
3. Guanylate Cyclase-C Agonists
   
   • Linaclotide
4. Selective Chloride (C2) Channel Activators
   
   • Lubiprostone

Question 12

Methylnaltrexone, Naloxegol, and Alvimopan

What is their MOA, what are their two indications of use, and what is the warning for use of Alvimopan?

Answer 12

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

Question 13

Linaclotide

What is its MOA and what two things is it specifically indicated for?

Answer 13

MOA: inc. cGMP concentrations, stimulating secretion of chloride/bicarbonate into intestinal lumen (CFTR ON)

Indications: IBS-C and Chronic Idiopathic Constipation

Question 14

Lubiprostone

What is its MOA, what three things is it specifically indicated for, and who should it NOT be given to?

Answer 14

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

Question 15

What are the 5 subclasses of Laxatives and Carthartic Agents?

Answer 15

• stimulants, osmotics, salines, bulk forming, and stool softeners

Question 16

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?

Answer 16

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!!)

Question 17

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?

Answer 17

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)

Question 18

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?

Answer 18

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

Question 19

Stimulants

What is Castor Oil hydrolyzed to and what are glycerins 3 functions?

Answer 19

• hydrolyzed to ricinoleic acid

glycerin: irritant, osmotic agent, lubricant agent

Question 20

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)

Answer 20

Efficacy: seen in 12-36 hours

AE: abdominal cramps, urine discoloration (SENNA), and fluid/electrolyte disturbanc (long use)

Contraindication: GI obstruction, ileus, or impaction

Question 21

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?

Answer 21

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)

Question 22

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?

Answer 22

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

Question 23

What other situation can Lactulose be used in?

Answer 23

• also used for pts who have severe liver disease resulting in HYPERAMMONEMIA
• causes change in pH that traps ammonia in GI tract

Question 24

What are large doses of polyethylene glycol (PEG-3350) used for?

Answer 24

BOWEL PREP prior to GI scopes or radiological procedures/surgery