• psyllium husk (Effer-syllium, Metamucil)
• semisynthetic cellulose: carboxymethylcellulose, methylcellulose (Citrucel, Cologel)
• polycarbophils (Mitrolan)

• hydrophilic muciloid
• bulk-forming laxative
• MOA:  forms gelatinous mass when mixed w/ water
  • in intestines, attract water and swell, therefore increases water in stool
  • The bulky mass stimulates the intestinal muscles, speeding stool transit time through the colon
• side efx:  allergic rxns, flatulence, borborygmi (stomach growling), intestinal obstruction, may inhibit coumarin absorption

Semisynthetic celluloses

carboxymethylcellulose, methylcellulose (Citrucel, Cologel)

• hydrophilic
• digestible; dietary fiber laxative
• MOA:  forms colloid mass w/ water
  • in intestines, attract water and swell, therefore increase water in stool
  • The bulky mass stimulates the intestinal muscles, speeding stool transit time through the colon
• side efx:  may bind and impede drug absorption

• hydrophilic
• polyacrylic resins
• bulk-forming laxative
• absorb 60-100x their weight in water
• MOA:  absorb liquid in the intestines and swell to form a soft bulky stool. The bulky mass stimulates the intestinal muscles, speeding stool transit time through the colon
• side efx:  Ca+ polycarbophils release Ca+ that is c/i in tetracycline usage

• docusates:  dioctyl sodium (calcium, potassium, sulfosuccinate) (Doxinate, Colace, Surfak)
• poloxamers (Poloxamer 188)
• castor oil (Neolid Purge)

Docusates

dioctyl sodium (or calcium, potassium, sulfosuccinate) (Doxinate, Colace, Surfak)

• surfactant laxative
• MOA:  stool softener
  • anionic surfactant
  • reduce strain of defecation by decreasing water tension btw stool and GI tract
• NO efx on intestinal peristalsis
• side efx:  not for use during abdominal pain or N/V; can irritate intestinal mucosa and increase intestinal absorption of other drugs
• recommended for short-term use

• surfactant laxative
• MOA:  stool softener
  • non-ionic surfactant
  • reduce strain of defecation by decreasing water tension btw stool and GI tract
• NO efx on intestinal peristalsis
• side efx:  diarrhea; not for use during abdominal pain or N/V

• surfactant laxative
• MOA:  produces catharsis (complete evacuation of bowels)
  • rapid-acting and effective anionic surfactant
  • converted to active form, ricinoleic acid, in small bowel
  • stimulates myenteric plexus -> stimulates intestinal peristalsis
• side efx:  colic, dehydration, electrolyte imbalance w/ OD; can induce contraction in pregnant women

• most potent class of laxatives
• predominantly act on large intestine
• increase permeability of intestinal mucosa
• increase back diffusion of water and electrolytes
• increase propulsive contractility of colon by stimulating colonic mucosal myenteric plexus
• stimulate prostaglandin synthesis and increase intestinal secretions
• diphenylmethanes: bisacodyl (Modane, Dulcolax)
• anthraquinones (Senokot)

Diphenylmethanes

bisacodyl (Modane, Dulcolax)

• stimulant laxative
• MOA: 
  
  • increase permeability of intestinal mucosa -> back diffusion
  • stimulate myenteric plexus -> increase peristalsis
  • stimulate prostaglandin synthesis
  • increase intestinal secretions
• prodrug, converted by enteric bacteria into active form, desacetyl
• administered in enteric coated tablets
• side efx:  OD can -> excessive fluid loss, intestinal enterocyte dmg -> colonic inflammatory response

• stimulant laxative
• MOA: 
  
  • increase permeability of intestinal mucosa -> back diffusion
  • stimulate myenteric plexus -> increase peristalsis
  • stimulate prostaglandin synthesis
  • increase intestinal secretions
• natural product; more gentle than synthetic drugs (e.g. bisacodyl)
• side efx:  large doses can -> abdominal pain, nephritis, melanotic pigmentation of colonic mucosa, abnormal urine coloration (pink)

• Mg-containing: magnesium sulfate (Epsom salt), magnesium hydroxide (milk of magnesia), magnesium citrate (Citroma)
• phosphate-containing:  buffered phosphate (Fleet enema)
• nondigestible sugars and alcohols:  lactulose (Cephulac), glycerine, polyethylene glycol electrolyte solution (GOLYTELY)

Magnesium containing laxatives

magnesium sulfate (Epsom salt)

magnesium hydroxide (milk of magnesia)

magnesium citrate (Citroma)

• osmotic laxative
• MOA:
  • non-absorbable -> osmotic efx -> retains water in lumen
  • causes release of CCK -> increased intestinal motility and secretion

Phosphate containing laxatives

Buffered phosphate (Fleet enema)

• osmotic laxative
• cathartic

• osmotic laxative
• MOA: 
  
  • semisynthetic disaccharide, not absorbed -> osmotic efx
  • metabolized by enteric bacteria to organic acids, i.e. fecal acidifier -> acidification of stool traps ammonia in non-toxic ammonium form
  • Tx portal systemic encephalopathy

• osmotic laxative
• osmotic and lubricant efx
• suppository

• osmotic laxative
• dissolved into 4L of water and ingested for colonoscopy
• causes complete evacuation

• mineral oil (Haley's M.O.)
• castor oil
• lubiprostone (Amitiza)

• misc. laxative
• MOA:  mixture of hydrocarbons that penetrates and softens the stool

• misc. laxative
• MOA: 
  
  • specifically activates intestinal Cl- channels in a PKA-independent way
  • increased Cl- channel activity -> increased intestinal fluid secretion -> increases intestinal motility -> increases passage of stool
• Tx chronic idiopathic constipation

• overuse of laxatives -> thorough constipation that requires several days to accumulate bulk
• lag in defecation is interpreted as continued constipation
• therefore, pt takes more laxative; vicious cycle
• if continued, bowel becomes unresponsive

• Agents that absorb water
  • cellulose derivatives, semisynthetic polysaccharides (Metamucil)
  • pull water and swell, producing more formed stool
• Adsorbers of etiological factors in the lumen
  • bismuth subsalicylate (Pepto-Bismol, Kaopectate), charcoal
  • adsorb harmful bacteria, viruses, toxins
  • bismuth subsalicylate useful in prevention of Traveler's diarrhea and Tx of H. pylori infections
• Opiates
  • paregoric, diphenoxylate w/ atropine (Lomotil), loperamide (Imodium)
• Anti-cholinergics
  • propantheline (Pro-Banthine), dicyclomine (Bentyl), anti-cholinergic + benzodiazepine (Librax)

bismuth subsalicylate (Pepto-Bismol, Kaopectate)

• MOA:
  
  • adsorbs harmful bacteria, viruses, or toxins
  • enhance secretion of mucus and HCO3-
  • inhibits pepsin activity
  • chelates w/ proteins at base of ulcer crater -> forms protective barrier against acid and pepsin
  • inhibits H. pylori
• effective adjunct for Tx and prophylaxis of duodenal and gastric ulcers, GERD, and diarrhea
• Tx Traveler's diarrhea in Mexico
• Tx H. pylori infections

• contains 0.04% morphine in benzoic acid, camphor, anise oil tincture
• MOA:
  • decrease salivary, gastric, and intestinal secretions
  • decrease motility of stomach and intestines -> increase contact time
  • increase muscle tone -> anti-spasmodic and decrease cramps
  • increase tone of  intestinal sphincters and external anal sphincter -> reduce urgency

• anti-diarrheal
• diphenoxylate = meperidine congener that has efx similar to opiates
• atropine added to reduce dose of diphenoxylate and prevent abuse
• MOA:
  • decrease salivary, gastric, and intestinal secretions
  • decrease motility of stomach and intestines -> increase contact time
  • increase muscle tone -> anti-spasmodic and decrease cramps
  • increase tone of  intestinal sphincters and external anal sphincter -> reduce urgency

• anti-diarrheal
• MOA:
  • decrease salivary, gastric, and intestinal secretions
  • decrease motility of stomach and intestines -> increase contact time
  • increase muscle tone -> anti-spasmodic and decrease cramps
  • increase tone of  intestinal sphincters and external anal sphincter -> reduce urgency
  • binds and inhibits calmodulin

• MOA:  block cholinergic receptors and reduce vagal stimulation
• do not cross BBB -> has minimal CNS side efx
• anti-spasmodic -> alleviate cramps
• also used to Tx urinary retention

• MOA:  block cholinergic receptors and reduce vagal stimulation
• do not cross BBB -> has minimal CNS side efx
• anti-spasmodic -> alleviate cramps
• more suited to alleviate cramps than propantheline

• MOA:  block cholinergic receptors and reduce vagal stimulation and have sedative efx
• anti-spasmodic -> alleviate cramps
• sedative efx -> help relieve Sx due to anxiety such as in IBS

• MOA: anti-cholinergic; blocks activation of muscarinic receptors
• Tx: prophylaxis against motion sickness
  • transdermal patch behind ear prior to travel
• side efx:  sedation, drowsiness, dry mouth

• MOA:  H1 antagonist
• OTC prophylaxis for motion sickness

• MOA:  H1 receptor antagonist
• OTC counter for motion sickness
• take 30-60 min before trip, efx last 4-6 hrs

• MOA: 
  
  • H1 receptor antagonist
  • exerts depressant efx on hyperstimulation of labyrinthine function
• Tx vertigo and Meniere's disease (vestibular disturbances)

• MOA:  H1 receptor antagonist
• Tx N/V
• side efx:  sedation

• MOA: 
  
  • antidopaminergic
  • centrally acting anticholinergic
• Tx N/V and intractable hiccup

• MOA:  antidopaminergic
• poor antipsychotic but useful antiemetic

• anti-emetic
• MOA: 
  
  • inhibits chemoreceptor trigger zone (CTZ) and vomiting center (VC)
  • antidopaminergic

• MOA:  antidopaminergic
• clinically used postop for N/V

• MOA: 
  
  • D2 receptor blocker -> in GI, D2 block -> increased local release of Ach via 5HT4-R agonism
  • stimulates GI smooth muscle
  • increases amplitude of esophageal contractions
  • accelerates gastric emptying
  • increases LES pressure
• side efx:  tardive dyskinesia
• prescribed for short periods of time (1-2 wks)
• prophylaxis for N/V prior to cancer chemo and postop N/V

• anti-emetic
• MOA:  affects CTZ
• side efx:  extrapyramidal (restlessness, involuntary movements, uncontrollable speech)
• for short-term use

• MOA:  selective 5-HT3 receptor antagonist
  • block receptors in GI and CTZ
• prevents emesis by high dose of cytotoxic drugs such as cis-platinum and radiation
• IV or oral administration

• more potent than ondansetron
• MOA:  5-HT3 receptor blocker
• oral administration

• MOA:  5-HT3 receptor blocker
• longer half-life than other 5-HT3 receptor blockers

• MOA:  5-HT3 receptor blocker
• Tx N/V associated w/ chemo
• IV administration

• MOA:  active substance in marijuana -> acts on CB-1 cannabinoid receptor
• used as antiemetic in cancer chemo if pt has failed to respond to other antiemetics
• side efx:  psychomimetic reactions

Corticosteroids

dexamethasone

methyl prednisolone

• MOA:  prevents production of PGs associated w/ chemo or radiation therapy
• enhances overal emetic efx and reduces side efx when combined w/ other antiemetics
• has inherent antiemetic efx as well

• MOA: 
  
  • substance P/NK1 receptor antagonist
  • crosses BBB and inhibits emesis via central actions
• used as adjunct drug for preventing emesis induced by cytotoxic chemo agents such as cisplatin

Benzodiazepines

lorazepam (Ativan)

alprazolam (Xanax)

• used as adjuncts to other antiemetic regimens
• used for anticipatory vomiting b/c cause somnolence and amnesia lasting for hrs
• usually given 1 day prior to chemo

• MOA:  weak bases that neutralize HCl -> prevent pepsin activation
• used for simple dyspepsia (indigestion) or adjuncts to primary therapy w/ H2 blockers or PPI's
• side efx:  significant efx on absorption of other drugs
• must be given frequently to maintain therapeutic efx

• MOA: 
  
  • weak bases neutralize HCl -> prevent pepsin activation
  • alginic acid is a floating gel that prevents regurgitation
• used for simple dyspepsia or as adjuncts to primary therapy w/ H2 blockers or PPI's
• side efx:  significant efx on absorption of other drugs

• MOA:  weak bases neutralize acid -> prevent pepsin activation
• side efx:  gas and acid reflux

• MOA:
  
  • competitively inhibit H2 receptors -> inhibit histamine-mediated acid secretion
  • blunt response to gastrin and Ach
• given bid

• MOA:
  
  • competitively inhibit H2 receptors -> inhibit histamine-mediated acid secretion
  • blunt response to gastrin and Ach
• most potent and longest half-life of H2 blockers
• given hs (once a day)

• MOA:
  
  • competitively inhibit H2 receptors -> inhibit histamine-mediated acid secretion
  • blunt response to gastrin and Ach
• given bid
• similar potency as ranitidine

• MOA:
  
  • competitively inhibit H2 receptors -> inhibit histamine-mediated acid secretion
  • blunt response to gastrin and Ach
• least potency of H2 blockers
• shortest half-life, therefore given qid (4x /day)
• side efx:  inhibits CYP450, therefore slows metabolism of many drugs

• MOA:  covalently modify sulfhydryl groups on H-K-ATPase in parietal cells -> irreversibly inactivates H+ secretion
• long duration of action
• more powerful than H2 blockers in inhibiting acid secretion
• oral administration
• used for short-term Tx of active PUD, management of Zollinger-Ellison syndrome, and in refractory gastric, esophageal, and duodenal ulcers, management of GERD

• MOA:  covalently modify sulfhydryl groups on H-K-ATPase in parietal cells -> irreversibly inactivates H+ secretion
• long duration of action
• more powerful than H2 blockers in inhibiting acid secretion
• oral administration
• used for short-term Tx of active PUD, management of Zollinger-Ellison syndrome, and in refractory gastric, esophageal, and duodenal ulcer, management of GERD

• MOA:  covalently modify sulfhydryl groups on H-K-ATPase in parietal cells -> irreversibly inactivates H+ secretion
• long duration of action
• more powerful than H2 blockers in inhibiting acid secretion
• oral administration
• used for short-term Tx of active PUD, management of Zollinger-Ellison syndrome, and in refractory gastric, esophageal, and duodenal ulcers, management of GERD
• less effective than omeprazole in severe esophagitis

• MOA:  covalently modify sulfhydryl groups on H-K-ATPase in parietal cells -> irreversibly inactivates H+ secretion
• long duration of action
• more powerful than H2 blockers in inhibiting acid secretion
• oral administration
• used for short-term Tx of active PUD, management of Zollinger-Ellison syndrome, and in refractory gastric, esophageal, and duodenal ulcers, management of GERD
• metabolized much less than other PPI's by CYP450

• MOA:  forms sticky, viscous, gel that adheres to gastric epithelial cells -> protects them from acid and pepsin
• requires acidic pH for maximal actiivty
• in chronically bedridden pts, substituted for H2 blockers or PPI's b/c alkalinization of stomach reintroduces harmful bacteria to stomach

• slowly metabolized PGE1 analog
• MOA:  stimulates mucus and HCO3- production
• side efx:  diarrhea
• primarily used in pts taking NSAIDs

• macrolide that inhibits microbial protein synthesis
• dose:  250-500 mg tid

• second line drug
• may be used instead of amoxicillin in pts allergic to penicillin
• must stagger dose if used in conjunction w/ Bismuth
• <1% resistance

• effective against G(-) bacilli
• dose:  500 mg qid
• c/i in pts allergic to penicillin

• synthetic antibiotic for use against obligate anaerobes
• 43% resistance (i.e. resistance is a problem)
• dose:  250 mg tid

• nitrofuran antibacterial and antiprotozoal

1. GI contents must be ready to reflux
   1. eaten large qty of food
   2. high fatty foods
2. anti-reflux mechanism at LES is compromised

• MOA: 
  
  • prodrug; broken down by intestinal bacteria to sulfapyridine and 5-ASA
  • 5-ASA:  active; local anti-inflammatory agent
  • sulfapyridine causes side efx
• side efx: anemia, rash, impotence

• MOA: 
  
  • prodrug; broken down to 2 molecules of 5-ASA
  • therefore less side efx than sulfasalazine, but weaker anti-inflammatory agent than sulfasalazine

• monoclonal Ab to TNF-alpha
• given IV to Crohn's disease (IBD) pts

• fusion protein containing ligand-binding portion of TNF-alpha receptor linked to Fc portion of human IgG1
• soluble TNF-alpha receptor -> binds TNF-alpha and prevents it from interacting w/ its receptor