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Gastrointestinal > Drugs For Constipation, Diarrhea, And IBS > Flashcards

Drugs For Constipation, Diarrhea, And IBS Flashcards

1
Q

Acute vs. Chronic Diarrhea

A

Acute = less than 4 days, generally caused by an infectious agent

Chronic = persist for 3 weeks in children or adults and 4 weeks in infants, caused by infectious organism, food intolerance, drugs, or IBS/IBD

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2
Q

Antidiarrheal Agents can be classified as either ______ or ______.

A

Antimotility; antisecretory

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3
Q

Classes of antimotility agents (1)

A

Opioid agonists

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4
Q

Classes of antisecretory agents (5)

A
  1. Bile salt-binding resins
  2. Bismuth subsalicylate
  3. Octreotide
  4. Clonidine
  5. Probiotics - limited clinical
    studies; useful in acute diarrheal
    conditions, antibiotic-associated
    diarrhea, and infectious diarrhea
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5
Q

Opioid Agonists (agents and general info)

A
  1. Loperamide: Poorly crosses the blood-brain barrier. Low addictive potential. Available OTC.
  2. Diphenoxylate: Crosses the blood-brain barrier at higher doses. Greater abuse potential than loperamide. Available by prescription only. Lomotil is a combination of diphenoxylate and atropine. Atropine acts as an antidiarrheal; increased concentrations of atropine cause dry mucous membranes, blurred vision which decreases abuse potential
  3. Difenoxin: a diphenoxylate derivative. Combined with atropine to decrease abuse potential.
  4. Anhydrous morphine: Camphorated Opium tincture that contains anhydrous morphine at 2 mg/5 mL (0.4 mg/mL). Do not confuse with deodorized tincture of opium, which is 25 times stronger, and contains morphine at 10 mg/mL.
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6
Q

Opioid Agonists (MOA, PK, pregnancy, indications)

A

MOA: Interacts with peripheral mu-opioid receptors in the enteric nerves, epithelial cells and muscles in the intestine to increase fecal water absorption by inhibiting the calcium-binding protein calmodulin, controlling chloride secretion and decreases mass colonic movements

PK: t1/2: 11 hours

Pregnancy: C

Indications: Ulcerative colitis, Crohn’s Disease, irritable bowl syndrome,
acute, chronic and travel’s diarrhea

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7
Q

Opioid Agonists (ADRs and DDIs)

A

ADRs: Common- dizziness and hyperglycemia. Note: Abuse potential with this drug class and overdosage can lead to CNS depression. Use with caution in IBD to avoid toxic megacolon.

DDIs: Concurrent use of gemfibrozil and loperamide may result in an increase in loperamide plasma concentration

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8
Q

Bile Salt-binding Resins (agents and general info)

A

Agents: Colesevelam, Cholestyramine, Colestipol

General info:
Malabsorption of bile salts may cause diarrhea
- excess bile salts draw water into colon
- results in colonic secretory diarrhea

Causes of Malabsorption

  • disease of terminal ileum (Crohn Disease)
  • surgical resection

Removal of gallbladder increases bile salts in colon

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9
Q

Bile Salt-binding Resins (MOA, PK, pregnancy, indications)

A

MOA: Insoluble and osmotically inactive bile salt-binding resins bind to excess bile salts and assist in the excretion of the excess bile salts through feces (i.e. excess bile salts are eliminated without taking excess water with them)

PK: not absorbed

Pregnancy: B

Indications: hypercholesterolemia, diarrhea (off-label)

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10
Q

Bile Salt-binding Resins (ADRs and DDIs)

A

ADRs: Common - bloating, flatulence, constipation, fecal impaction, pharyngitis. The patient should take pills with plenty
of water and be upright for 30 minutes after taking the pills to avoid esophageal obstruction (pills are LARGE). Should not be used in patients with dysphagia.

DDIs: Concurrent use of colesevelam increases seizure activity because of decreased phenytoin levels. Phenytoin should be administered 4 hours prior to colesevelam.
Reduced INR in patients receiving warfarin therapy. In warfarin-treated patients, INR should be monitored frequently during colesevelam initiation then periodically thereafter.
Elevated TSH in patients receiving thyroid hormone replacement therapy. Thyroid hormone replacement should be administered 4 hours prior to colesevelam.

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11
Q

Bismuth subsalicylate (MOA, PK, pregnancy, and indications)

A

MOA: Reduces stool frequency and liquidity by inhibiting intestinal prostaglandin and chloride secretion. Has some activity against H. pylori.

PK: Onset 4 hours. Duration 6 hours.

Pregnancy: B

Indications: Peptic Ulcer Disease with H. pylori infection, diarrhea, prevention and treatment of traveler’s diarrhea, heartburn, indigestion, nausea, upset stomach

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12
Q

Bismuth subsalicylate (ADRs and DDIs)

A

ADRs: Common- constipation. High doses: black stools and BLACK TONGUE. Reye syndrome warning because salicylate is absorbed in the stomach and small intestine.

DDIs: N/A

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13
Q

Octreotide (MOA, PK, pregnancy, indications)

A

MOA: A synthetic analogue of somatostatin. Inhibits secretion of serotonin and various GI peptides and reduces intestinal fluid secretion.

PK: t1/2: 1-2 hours

Pregnancy: B

Indications: Non- infectious diarrhea, bleeding esophageal varices. Transient nausea, bloating, or pain at sites of injection in the short term, gallstone formation and hypo- or hyperglycemia in the long term

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14
Q

Octreotide (ADRs and DDIs)

A

ADRs: Common- nausea, bloating, or injection site pain. Long term use: gallstone formation and hypo- or hyperglycemia

DDIs: Concurrent use of mesoridazine
and octreotide may increase risk of QT-interval prolongation

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15
Q

Clonidine (MOA, Pk, pregnancy, indications)

A

MOA: alpha-2 adrenergic receptor agonists that interacts with specific receptors on enteric neurons and enterocytes, thereby stimulating absorption and inhibiting secretion of fluid and electrolytes and increasing intestinal transit time

PK: t1/2: 12 to 16 hours. Renal excreted: 40% to 60% unchanged.

Pregnancy: C

Indications: chronic diarrhea in diabetic mellitus

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16
Q

Clonidine (ADRs and DDIs)

A

ADRs: Common- hypotension, depression, and fatigue

DDIs: Concurrent use of clonidine with beta-blockers such as propranolol may result in increased risk of sinus bradycardia. Concurrent use of amitriptyline and clonidine may result in decreased antihypertensive effectiveness

17
Q

Constipation causes (9)

A

Defined as infrequent passage of stools.

  1. Failure to respond to the urge to defecate
  2. Inadequate fiber in the diet
  3. Inadequate fluid intake
  4. Weakness of abdominal muscles
  5. Inactivity and bed rest
  6. Pregnancy
  7. Hemorrhoids
  8. Narcotics, anticholinergic agents, calcium channel blockers, diuretics, calcium, iron supplements, and aluminum antacids
  9. Cause by another disease condition
18
Q

Constipation treatment algorithm (1, 2A-E)

A
  1. Treat specific cause
  2. No underlying diagnosis, then choose symptomatic therapy:
    A. Increase fiber +/- fiber supplementation
    B. Add osmotic laxative (PEG)
    C. Add stimulant laxative (bisacodyl)
    D. Lubiprostone or linacoltide
    E. Opioid-receptor antagonist if opioid-induced constipation
19
Q

Classes of laxatives that soften feces in 1-3 days (4)

A
  1. Bulk-forming agents/osmotic laxatives
  2. Emollients
  3. Hyperosmolar Agents
  4. Other
20
Q

Bulk-forming agents/osmotic laxatives (agents, MOA, pregnancy, indications, ADRs)

A

Agents: Methylcellulose (Citrucel®), Polycarbophil, Psyllium (Metamucil®)

MOA: Increase the water content of stool to increase stool bulk and
weight and relieve the symptoms of constipation within 3 days of
initiating therapy

Pregnancy: B

Indications: constipation

ADRs: Common- flatulence, abdominal bloating, and distention

21
Q

Emollients/Stool softeners (agents, MOA, pregnancy, indications, ADRs)

A

Agents: Docusate sodium, Docusate calcium, Docusate potassium

MOA: Are surfactant agents that work by facilitating the movement of water into the stool and the mixing of aqueous and fatty materials within the intestinal tract. Emollients are INEFFECTIVE in TREATING constipation but are used mainly to PREVENT this condition.

Pregnancy: A

Indications: Constipation (Use in situations where straining should be
avoided such as after an MI, acute perianal disease, or after rectal or
abdominal surgery)

ADRs: Common- diarrhea, nausea, bitter taste

22
Q

Hyperosmolar Agents (agents, MOA, pregnancy, indications, ADRs)

A

Agents: Lactulose, Sorbitol

MOA: nonabsorbable disaccharide that is metabolized by colonic bacteria to low-molecular-weight acids, resulting in an osmotic effect whereby
fluid is retained in the colon. Fluid retention lowers pH in colon and increases colonic peristalsis.

Pregnancy: B

Indications: Constipation, Hepatic encephalopathy

ADRs: Common- flatulence, nausea, bloating

23
Q

Polyethylene Glycol 3350 (PEG) [MOA, pregnancy, indications, ADRs]

A

MOA: Polyethylene glycol is an osmotic agent that causes retention of water in the stool resulting in a softer stool and more frequent bowel movements. It appears to have no effect on active absorption or secretion of glucose or electrolytes.

Pregnancy: B

Indications: Constipation, Colonoscopy prep

ADRs: Common- flatulence, nausea, vomiting, abdominal cramping

24
Q

Laxatives that result in soft or semifluid stool in 6-12 hours (2)

A
  1. Oral Bisacodyl

2. Magnesium sulfate (low dose, <10 g)

25
Q

Laxatives that result in eatery evacuation in 1-6 hours - stimulant laxatives (5)

A
  1. Magnesium citrate
  2. Magnesium hydroxide
  3. Magnesium sulfate (high dose, 10 to 30 g)
  4. Senna
  5. Rectal Bisacodyl
26
Q

Magnesium salts (MOA, pregnancy, indications, ADRs)

A

MOA: Cathartic action is believed to result from osmotic water retention, which then stimulates peristalsis. Agents may cause fluid and electrolyte depletion. Magnesium or sodium accumulation may occur in patients with renal dysfunction or congestive heart failure.

Pregnancy: D

Indications: Constipation, colonoscopy prep

ADRs: Common- diarrhea, dizziness

27
Q

Stimulant laxatives (bisacodyl, senna) [MOA, pregnancy, indications, ADRs]

A

MOA: Stimulate the mucosal nerve plexus of the colon and may also affect intestinal fluid secretion by altering fluid and electrolyte transport

Pregnancy: A

Indications: Constipation, Colonoscopy prep

ADRs: well tolerated!

28
Q

Intestinal Secretagogues (2 agents, MOA, PK, ADRs, pregnancy, indications)

A

Lubiprostone (Amitiza)
MOA: Chloride channel activator, opens chloride channels in GI luminal epithelium that stimulates chloride-rich fluid secretion into intestinal lumen which softens stool and accelerates GI transit time.
PK: t1/2: 1 hour
ADRs: Common- nausea, headache, diarrhea
Pregnancy: C
Linaclotide (Linzess)
MOA: Activates guanylate cyclase C receptor on intestinal epithelium. Increases intestinal fluid secretion and quickens intestinal motility
PK: not systemically absorbed so t1/2 cannot be determined, duration is 1
week
ADRs: Common- diarrhea, flatulence, abdominal pain
Pregnancy: C
Indications for both agents: Constipation, Irritable bowel syndrome with constipation

29
Q

Opioid Receptor Antagonists (3 agents, indications, PK, MOA, pregnancy, ADRs)

A

Alvimopan (Entereg)
Indication: SHORT-TERM use in hospitalized patients
PK: t1/2: 10 - 17 hours
Methylnaltrexone (Relistor)
Indication: Opioid-induced constipation in patients in PALLIATIVE care or when laxative therapy is insufficient
PK: t1/2: 8 hours
Naloxegol (Movantik)
Indication: Opioid-induced constipation in adult patients with NONCANCER pain
PK: t1/2: 6 to 11 hours

MOA: Antagonizes opioid receptors in the periphery (GI tract)
Pregnancy: B
ADRs: Common- Abdominal pain, diarrhea, nausea

30
Q

Treatment goals of diarrhea and constipation

A

Treatment of diarrhea is focused on preventing excess water and
electrolyte loss, relieving symptoms and treating curable causes.

Treatment of constipation starts with the use of dietary fiber or bulk- forming laxatives.

31
Q

Treatment goals in diarrhea-predominant IBS and constipation predominant IBS

A

Diarrhea-predominant IBS should be managed by dietary modification and drugs such as loperamide when diet changes alone are insufficient to control symptoms.

Constipation-predominant IBS should be managed by dietary modification,
increase in fiber, increase in exercise and drugs such as Intestinal
Secretagogues when above changes alone are insufficient to control
symptoms.

Gastrointestinal (7 decks)

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