Antidiarrheal tx; laxatives: Bahouth

Question 1

Your pt is constipated. What is the first thing you suggest they do?

Answer 1

More dietary fiber. Need 25-38g fiber daily.

Question 2

Describe the MOA of dietary fiber and bulk forming laxatives.

Answer 2

Incr. delivery of water to colon.
Increased bulk.
Reduced pressure in sigmoid colon.
Net result: more formed stools

Question 3

What are bulk forming laxatives made up of?
Describe their negative side effects. 
Metamucil
Citrucel, Cologel
Mitrolan

Answer 3

Psyllium husk- Metamucil- Allergies, obstruction, absorption probs.
Semisynthetic celluloses- Citrucel, Cologel- May bind an impede drug absorption
Polycarbophils- Mitrolan- Contraindicated w/ tetracycline use

Question 4

What are surfactant laxatives?

Name the examples and their respective side effects.

Answer 4

Salts that soften stool and reduce water tension between stool and intestinal epithelium, allowing stool to “slide along” better.
Net effect: reduce strain of defecation.

Docusates: Colace- can irritate intestinal mucosa and incr. absorption of other drugs. Do not use for >2wks.

Poloxamers- contraind. use w/ abd. pain, n/v

Castor oil- Colic, dehydration, electrolyte imbalance w/ overdose. Can induce uterine contraction in preg. women. Induces peristalsis (good for constip., bad for preg.) A serious purgative, it has often been used as a tool of torture and humiliation.

Do not use docusates, poloxamers in the context of abd. pain, n/v.

Question 5

How do stimulant laxatives work?

Name some examples and their ADEs.

Answer 5

:: Act on large intestine to reverse electrolyte and water flow back to lumen by incr. permeability.
:: Stimulate colonic myenteric plexus to cause incr. peristalsis.
:: Stimulates prostaglandin synthesis and incr. intestinal secretions.
MOST POTENT CLASS OF LAXATIVES

Dyphenylmethanes: Modane, Dulcolax- OD can cause excessive fluid/electrolyte loss, intestinal enterocyte damage–> inflamm. response.

Anthraquinones: Senokot- May cause dark pigmentation of colonic mucosa, abnormal urine coloration. More gentle than synthetic laxatives.

Question 6

The most widely used class of laxatives are:
How do they work?
Name the formulations.

Answer 6

Saline and osmotic laxatives.
Cause colon to retain water.

Mg+ containing: cause laxation by osmotic effect and by CCK release–> ^ motility, secretion.

Phospate containing: given as enema

Non-digestible sugars and alcohols-

• Lactulose. Fecal acidifier. Traps ammonia in NH4+, non-diffusable form for txing pts w/ liver failure (portal systemic encephalopathy).
• Glycerine
• Polyethylene glycol (PEG) purge for colonoscopy

Question 7

What is the hospital preferred laxative for use after opiate use or following surgery?

Answer 7

Mg+ Hydroxide, milk of magnesia. Osmotic laxative and CCK release induces motility and secretion.

Question 8

Describe the laxatives used in IBS.

Answer 8

These drugs target the Cl- channel (Lubiprostone) or agonize guanylate cyclase (Linaclotide), causing more water to follow Cl- into lumen of intestine.

Question 9

Which agent used to tx constipation is also used to tx diarrhea?

Answer 9

Fiber! Metamucil. Causes stools to absorb more water, making them solid, but not too solid.

Question 10

How do bismuth salicylate (Pepto-Bismol, Kaopectate) and charcoal work to treat diarrhea?

Answer 10

They absorbs etiological agents of diarrhea such as bacteria, toxins, viruses.

Charcoal also used in drug ODs in ER to absorb drug so it is not taken up in intestine.

Question 11

What class of drugs that are known to cause constipation are used to treat diarrhea?
How do they work to tx diarrhea/cause constipation?
Name a few of these specifically formulated for diarrhea.

Answer 11

Opiates. Given at subclinical pain doses to tx diarrhea.

Decrease GI secretions.
Decrease motility.
Incr. muscle tone.
Antispasmodics and decr. cramps.

The net effect: increase contact time between injested substance and absorptive surface of intestine.

Paregoric- morphine containing
Diphenoxylate + atropine- similar effect to opiates.
Loperamide (Imodium)- Interacts w/ intestinal opioid receptors and inhibits calmodulin.

Question 12

Describe another class of antidiarrheals that reduce gut motility. 
List some examples.

Answer 12

Antocholinergics. Inhibts vagal stimulation of enteric plexus.
Primarily for alleviating cramps (antispasmodic)
Quaternary ammonium der. of atropine: (but do not cross BBB)
Propantheline (urinary retention) and Dicyclomine (cramps)

Can combine these agents (Librax) w/ a sedative (benzodiazepine) to manage psychological causes of IBS.