Constipation, Diarrhea 2

diarrhea

• discomfort including increased frequency and decreased consistency of fecal discharge

• usually episodes initiate abruptly and subside within 1-2 days without treatment

diarrhea: risk factors

• immunocompromised

  • HIV/AIDS, DM

• elderly patients

  • nursing home contact

  • comorbidities

  • medications

• pediatric patients

  • day care contacts

  • fluid/electrolyte losses

• foodborne illness

diarrhea: etiology

• ion transport changes → secretory diarrhea

  • H₂O/electrolyte imbalance

  • unabsorbed dietary fat, laxatives, bacterial toxins

  • common pathogens → E. coli, Salmonella, Staphylococcus, Shigella

• intestinal motility modifications

  • reduced contact time

  • premature emptying

  • bacterial overgrowth

• osmolarity

  • poorly absorbed substances (ex: lactulose, H₂O/electrolytes in lumen)

• increased tissue hydrostatic pressure

drug-induced diarrhea

• magnesium-containing antacids

• laxatives

• antineoplastics

• antibiotics

• cholinergic agents

• antihypertensives

• cardiac agents

• NSAIDs

• prokinetic agents

• PPIs/H₂RAs

• colchicine

• misoprostol

diarrhea: assessment

• dehydration

  • low blood pressure

  • skin turgor test

  • mucus membranes

• abdomen

  • bowel sounds (pain?)

• labs:

  • stool

  • CMP

  • CBC

  • colonoscopy, sigmoidoscopy, biopsy

diarrhea: non-pharmacologic therapy

• dietary modifications:

  • mild, digestible foods

  • avoid spicy, fatty, sugary foods

  • BRAT diet

• rehydration:

  • oral rehydration solution (ORS)

  • Pedialyte → alternative

  • avoid gatorade

diarrhea: drug classes

• antimotility agents

• adsorbents

• antisecretory agents

• somatostatin analog

antimotility agents

• loperamide (OTC)

• diphenoxylate/atropine

• difenoxin/atropine

• paregoric

antimotility agents: MOA

• mu-opioid receptor agonists

• slows GI transit

• loperamide → peripheral action only, no CNS effects

antimotility agents: role in therapy

used for acute and chronic diarrhea

antimotility agents: clinical pearls

• safe when used in recommended doses

• can cause constipation

• diphenoxylate, difenoxin → co-formulated with atropine to discourage abuse

  • anticholinergic effects if taken at large doses

• paregoric → not commonly prescribed due to abuse potential

• loperamide → boxed warning for Torsades de Pointes, cardiac arrest, sudden death

  • often misused/abused intentionally to self-treat opioid withdrawal symptoms

  • not recommended for use longer than 48 hours

  • MDD = 16 mg/day

anti-secretory agent

bismuth subsalicylate

anti-secretory agents: MOA

anti-secretory, anti-inflammatory, antibacterial

anti-secretory agents: role in therapy

• used for secretory diarrhea, traveler’s diarrhea

• also used for indigestion, abdominal cramping

anti-secretory agents: clinical pearls

• salicylate toxicity

  • excess doses can cause N/V, tinnitus, gout attacks, bruising, bleeding

• renal impairment → risk of confusion

• AE → black tongue, black stool

• children recovering from viral infections should not use

  • risk of Reye’s syndrome

adsorbents

• polycarbophil

• kaolin-pectin

• attapulgite

adsorbents: MOA

non-specific adsorbing of nutrients, toxins, drugs, digestive fluids

adsorbents: role in therapy

symptomatic relief

adsorbents: clinical pearls

• efficacy is unknown

• polycarbophil → can be used to treat diarrhea or constipation

• well-tolerated

• separate from other medications by 2-3 hours

octreotide: MOA

• somatostatin analog

• inhibits intestinal secretion, stimulates intestinal absorption

octreotide: role in therapy

• first-line for treatment of carcinoid syndrome

  • tumors associated with profuse watery diarrhea

• useful for chemotherapy-induced diarrhea

octreotide: clinical pearls

• injection (SC, IV)

• AE → GI-related gallbladder/biliary tract complications, injection site reaction

• steatorrhea may occur with higher doses

probiotics: MOA

• restore normal intestinal function

• suppress proliferation of pathogenic microorganisms

probiotics: role in therapy

• may prevent antibiotic-associated diarrhea

• not recommended for treatment of acute diarrhea

probiotics: clinical pearls

• dosages vary

• AE → flatulence

lactase: MOA

enzyme for lactose intolerence

lactase: role in therapy

used for diarrhea secondary to lactose intolerence

lactase: clinical pearls

use with dairy consumption

antibiotics

• if systemic illness is suspected, checking for infectious source should be performed as part of clinical work-up

• for infectious diarrhea, treat with antibiotic + symptomatic therapy

diarrhea: monitoring

• resolution should be observed in 24-72 hours

• frequency/consistency of bowel movements

• appetite

• vitals

• body weight

• labs:

  • electrolytes

  • WBC

constipation

• difficult/infrequent passage of stool

• may be associated with straining or incomplete defecation

• < 3 bowel movements/week

• chronic = symptoms > 3 months

primary constipation

• normal transit time (functional): hard stools, difficulty evacuating, bloating, abdominal discomfort

• slow transit time: infrequent defecation

• defecating disorder: dysfunction of sphincter/pelvic floor muscles

secondary constipation

• medications

• lifestyle factors

• comorbid conditions

drug-induced constipation

• opioids

• anticholinergic medications

• calcium/aluminum-containing antacids

• non-DHP CCBs

• diuretics

• sucralfate

• iron

• NSAIDs

• clonidine

• colesevelam

constipation: alarm symptoms

• rectal bleeding in absence of hemorrhoids/anal fissures

• family history of colon cancer, polyposis syndromes

• anemia

• unintentional weight loss, anorexia

• severe, persistent treatment-refractory constipation

• worsening of symptoms

constipation: assessment

• abdomen

• rectal exam

• digital exam

• labs:

  • thyroid function

  • CBC

  • imaging (ex: colonoscopy)

constipation: non-pharmacologic therapy

• dietary modifications

  • increase fiber intake (20-30 g/day)

  • high-fiber foods → fruits, vegetables, beans, whole grains, bran

• increase water intake

• physical activity

biofeedback

used for disordered defecation associated with pelvic floor dysfunction

constipation: drug classes

• bulk-forming laxatives

• emollients

• osmotic laxatives

• stimulant laxatives

• sodium/magnesium salts

• intestinal secretagogues

• opioid receptor antagonists

bulk-forming laxatives

• methylcellulose

• psyllium

• polycarbophil

bulk-forming laxatives: MOA

• increases water content of stool

• increases stool bulk/weight

bulk-forming laxatives: role in therapy

• properties are similar to those of dietary fiber

• first-line for constipation

bulk-forming laxatives: clinical pearls

• typically relieve symptoms within 3 days of therapy

• few AEs (GI-related)

• patient should increase water intake

  • decreases risk of bowel obstruction

• not recommended for opioid-induced constipation

osmotic laxatives

• lactulose

• polyethylene glycol (PEG) 3350

• sorbitol

osmotic laxatives: MOA

• non-absorbable compounds → increases osmolarity → water shifts into colon

• lactulose → lowers pH → increases peristalsis

osmotic laxatives: role in therapy

• first-line for constipation

• lactulose is slightly less effective than other agents

  • PEG preferred

osmotic laxatives: clinical pearls

• effects seen after 2-3 days of therapy

• AE → flatulence, nausea, abdominal cramping

  • lactulose → diarrhea, electrolyte imbalances

• PEG has least side effects

stimulant laxatives

• senna

• bisacodyl

stimulant laxatives: MOA

stimulate mucosal nerves in the colon and increase fluid secretion

stimulant laxatives: role in therapy

reserved for intermittent use or in patients who fail to respond adequately to first-line agents

emollients

• docusate sodium

• docusate calcium

• docusate potassium

emollients: MOA

• surfactant

• mixing aqueous and fatty materials within intestinal tract increases stool moisture (“stool softeners”)

emollients: role in therapy

• prevention of constipation

• useful when straining should be avoided (ex: recovery from MI, post-rectal surgery)

• little evidence for treatment of constipation

emollients: clinical pearls

• generally given orally

• effects seen within 1-3 days of therapy

• well-tolerated

sodium/magnesium salts

• magnesium citrate

• magnesium hydroxide

• magnesium sulfate

• sodium phosphates

sodium/magnesium salts: MOA

catharic → increases GI motility

sodium/magnesium salts: role in therapy

• commonly used as bowel preparations prior to invasive procedures

• Milk of Magnesia → used to treat constipation in adults

sodium/magnesium salts: clinical pearls

• AE:

  • dehydration

  • accumulation → magnesium/sodium overload

opioid antagonists

• naldemedine

• naloxegol

• alvimopan (inpatient only)

• methylnaltrexone bromide

opioid antagonists: MOA

• peripheral opioid receptor antagonist

• blocks GI effects of opioids without affecting pain relief

opioid antagonists: role in therapy

• not considered first line for primary constipation

• primarily used for opioid-induced constipation that is refractory to laxative therapy

• alvimopan → used for short-term use in hospitalized patients to accelerate recovery of bowel function after bowel resection surgery

opioid antagonists: clinical pearls

• discontinue maintenance laxative therapy prior to initiation

• naldemedine → CYP3A4, P-gp DDIs

• naloxegol → CYP3A4 DDIs

• AE → abdominal pain, diarrhea, flatulence, nausea

• alvimopan → CI in patients receiving opioid therapy for > 7 days prior to surgery

intestinal secretagogues

• lubiprostone

• linaclotide

intestinal secretagogues: MOA

• lubiprostone → chloride channel activator

• linaclotide → guanylate cyclase C agonist

intestinal secretagogues: clinical pearls

• lubiprostone:

  • bowel movement within 24-48 hours of therapy

  • CI → patients < 18 years

  • AE → nausea, diarrhea, headache

• linaclotide:

  • take on empty stomach (30 mins before first meal)

  • CI → patients < 2 years (risk of severe dehydration)

  • AE → diarrhea, flatulence, abdominal pain

constipation: monitoring

• important to identify cause to prevent reoccurrence

• ensure symptomatic resolution

  • return to baseline frequency/consistency

  • proper diet

  • decrease reliance on laxatives

constipation: pregnancy

• diet modifications

• adequate water intake

• first-line → bulk-forming laxatives, emollients

constipation: heart disease

caution with sodium-containing products

constipation: diabetes

caution with laxatives containing sugars

constipation: kidney disease

caution with electrolyte-containing products

constipation: swallowing difficulty

avoid bulk-forming agents