Unit 7: Constipation and Diarrhea

Describe the physiology associated with bowel transit.

1. Esophagus

2. Esophageal sphincters

3. Stomach

4. Pyloric sphincter - controls how much feed is let into the small intestines

5. Liver

6. Gallbladder

7. Sphincter of Oddi - Gallbladder enters into small intestines

8. Pancreas

9. Duodenum - Small intestines starts

9, 10, 11 - small intestines

10. Jejunum

11. Ileum

12. Ileocecal valve

13, 14, 15 - large intestines

13. Ascending colon

14. Traverse colon

15. Descending colon

16. Sigmoid colon (Pelvic colon)

17. Rectum

18. Anal sphincter

Timeline for digestion

0 hours - when you put food in your mouth

1. Esophagus: Takes 3 seconds to get from mouth to stomach

2. Stomach: food will hang out in stomach for 3-5 hours

3. Pyloric sphincter through small intestines to ileocecal valve: 4.5 hours

4. Ileocecal valve to ascending colon: another hour so 5.5 hours total now

5. Ascending colon to transverse colon: another hour so 6.5 hours total

6. Traverse colon to descending colon: another 3 hours so 9.5 hours total

7. Descending colon to sigmoid colon: could be another 2.5 to 14.5 hours for a total of 12-24 hours

How long does it take for food to get from the mouth to the small intestines?

6 hours

How long does food stay in the colon?

• 6-18 hours in the colon where stool is desiccated (water removed)

What is the purpose of the villi and where is it located?

• lines the small intestines creating more surface area

• villi are where we absorb more nutrients

What is the intrinsic innervation? (Physiology of bowel transit)

• The intrinsic innervation of the gut is primarily carried out by the enteric nervous system (ENS); known as the “little brain”

• It consists of two major networks of neurons called the myenteric (Auerbach's) plexus, located between the muscle layers and controlling gut motility, and the submucosal (Meissner's) plexus, found beneath the mucosa and involved in glandular secretion and monitoring the gut environment.

• The ENS can function independently of the central nervous system, (can function without input from CNS)

What is the extrinsic innervation?

• Extrinsic innervation of the gut refers to nerves originating outside the gastrointestinal (GI) tract that connect to and influence the gut's functions (autonomic nervous system).

• These nerves, which include both sensory and motor fibers, transmit information from the gut to the central nervous system and provide signals from the brain to the gut via the vagus nerve (parasympathetic) and splanchnic nerves (sympathetic).

• This communication helps regulate vital GI processes such as motility, secretion, and the detection of visceral pain, satiety, and nausea

What do the parasympathetic fibers do?

• increase the activity of the intestinal smooth muscle and relax sphincters

What do the sympathetic fibers do?

• decrease activity and cause sphincters to contract

What are the risk factors for constipation?

• Women, older adults, inactivity, lower socioeconomic class, lower income, non-white race, symptoms of depression, history of physical or sexual abuse

What is the pathophysiology of constipation?

• Primary (idiopathic): no identifiable cause

  • Categories:

    • normal transit or functional: most common type, Pts have normal GI motility and stool frequency, may experience signs/symptoms

    • slow transit: abnormality of the GI transit time

    • Dysfunction of the pelvic floor muscles

    • Pts may present with more than one type

• Secondary: has an identifiable cause

What is the common clinical presentation of constipation?

1. Difficult or infrequent passage of stool

   1. Straining or feeling of incomplete defecation

2. Decreased stool frequency

3. Chronic constipation: symptoms lasting for greater than or equal to 3 months

   1. Estimated to be about 14% worldwide

4. Rome IV criteria:

   1. At least 2 of the signs/symptoms apply to a minimum of 25% of BM:

      1. Infrequent BM (<3 per week)

      2. Stools that are hard, small, or dry

      3. Difficulty or pain of defecation

      4. Feeling of incomplete evacuation

         1. Feeling of anorectal obstruction or blockage

         2. Physical tactics needed for defecation

         3. Loose stools are rarely occur without laxative use

1.     Describe the role of nonpharmacologic strategies in the treatment of constipation (1d) 

• Diet

  • 25-35 grams of fiber per day

  • whole grains, oats, fruits, vegetables

  • avoidance of constripating foods

    • processed cheese, concentrated sweets

  • adequate fluid intake

    • at least eight 8 ounce glasses of water per day

• Physical Activity

  • increase exercise/activity level

• Bowel Habits

  • do not ignore the urge to defecate

  • establish a regular pattern 

  • allow adequate time

• General emotional well being and avoidance of stressful situations

Identify drug classes used in the management of constipation. (2 general) 

• laxatives (bulk forming, saline, stimulant)

• hyperosmotic agents

• lubricant products

• emollient agents (stool softeners)

Describe the mechanism of action for saline laxatives used for constipation.

• MOA: create an osmotic gradient resulting in water being drawn into the lumen of the intestines and rectum, creating increased intraluminal pressure and stimulating peristalsis

Describe the mechanism of action for bulk forming laxatives used for constipation.

• MOA: increased fiber intake, increases stool volume and may make stools softer

Describe the mechanism of action for stimulant laxatives used for constipation.

• MOA: since these are old drugs, their MOA are not well understood

• Appear to act locally by irritating the mucosa or stimulating the nerve plexus of the intestinal smooth muscle

• May also stimulate secretion of water and electrolytes into the intestines

Describe the mechanism of action for hyperosmotic agents used for constipation.

• MOA: create an osmotic gradient resulting in water being drawn into the lumen of the intestines and rectum, creating increased intraluminal pressure and stimulating peristalsis

Describe the mechanism of action for lubricant products used for constipation.

• MOA: coats the stool and prevents reabsorption of fecal water. This results in a softer stool that is more easily eliminated

• (used as enema in a hospital setting; other settings are not recommended)

Describe the mechanism of action for stool softeners used for constipation.

• MOA: anionic surfactants that increase wetting efficiency (promote mixing of aqueous and fatty substances) so that intestinal fluid mixes with fecal material to create a softer fecal mass.

What is chronic constipation?

• symptoms last at least 3 months or longer

• estimated to be about 14% worldwide

1.     Differentiate the timeframe of acute versus chronic diarrhea. (1c) 

• acute

  • last for less than 3 weeks

  • BM are fewer than 3 times per week

  • hard or dry stools

  • straining during BM

  • abdominal pain or bloating

  • caused by changes in diet, travel, dehydration, lack of exercise, certain meds

  • usually resolves within a few days or weeks

• chronic

  • last for 3 months or longer

  • underlying medical condition: IBS, thyroid disorders, certain mediations; low fiber intake, sedentary lifestyle; ignoring the urge to defecate

  • symptoms similar to acute constipation but may be more persistent and accompanied by other symptoms such as fatigue, abdominal discomfort, or rectal bleeding

Bulk Forming Laxatives: ADRs and Onset of action?

• ADRs: abdominal cramping and flatulence

• 12 to 72 hours

Hyperosmotic Agents: ADRs and Onset of Action?

• ADRs: bloating, cramping, abdominal discomfort, flatulence, anal irritation due to leakage (suppositories)

• Onset of action:

  • PEG 3350 & MiraLax 12 to 72 hours

  • Suppositories: 15 to 30 minutes

Saline Laxatives: ADRs and Onset of Action?

• ADRs: 

  • Bloating, cramping, abdominal discomfort, and flatulence

  • Diarrhea, dehydration, and related complications may occur, particularly with excessive use

    1. Due to loss of electrolytes

  • Elevated magnesium levels, particularly in pts with kidney failure, infants and children, and older adults

• Onset of Action:

  • oral - 30 minutes to 6 hours

  • enema - 2 to 15 minutes

Emollient Agents (Stool Softeners): ADRs and Onset of Action?

• ADRs: diarrhea and mild cramping

• onset of action: 12 to 72 hours but may be up to 5 days 

Lubricant Products: ADRs and Onset of Action?

• ADRs:

  • lipid pneumonia - of aspirated

  • Leakage of oil through anal sphincter

  • Absorption into intestinal mucosa, liver and spleen - foreign body reactions

• onset of action:

  • oral - 6 to 8 hours

  • enema - 5 to 15 minutes

Stimulant Laxatives: ADRs and Onset of Action?

• onset of action: generally 6 to 10 hours after oral use but may be up to 24 hours

Examples of bulk forming laxatives/efficacy

• methylcellulose (meta-mucils), calcium polycarbophil, psyllium husk

• work only in the gut (non-systemic product)

• take with plenty of liquids to promote efficacy and prevent product swelling in throat or esophagus

• separate other drugs and prevent absorption by separating by at least 2 hours

Examples of hyperosmotic agents

• Polyethylene glycol 3350 )PEG 3350, MiraLax) - good recommendation (12 to 72 hour onset)

• Glycerin Rectal Suppositories (occasional use; 15 to 30 minutes onset)

Examples of saline laxatives

• Magnesium hydroxide (Milk of Magnesia) - liquid and tablets

• Magnesium sulfate (epsom salts) - powder to be mixed in water or other liquid (do not use for laxative)

• Magnesium citrate - 10 ounce bottles of liquid

• Sodium phosphate salts - enemas (Fleet enema) - adult and pediatric products

• onset: oral - 30 minutes to 6 hours; enema - 2 to 15 minutes

Examples of emollient agents (stool softeners)

• docusate sodium (Colace); docusate calcium

• these are not true laxatives because they do not stimulate a true BM

• recommended to prevent stool straining and prevent painful defecation

• onset: 12 to 72 hours but may take up to 5 days

drug interactions with emollient agents (stool softeners)

• should not be used at the same time as mineral oil, as it can result in absorption of mineral oil from the GI tract

Examples of lubricant products

• mineral oil (liquid), mineral oil (liquid emulsion), mineral oil (enema)

• onset of action: oral 6 to 8 hours; enema 5 to 15 minutes

Drug interactions with lubricant products

• reduced absorption of drugs and fat soluble vitamins A, D, E, K

Examples of stimulant laxatives (Bisacodyl)

Bisacodyl (Dulcolax):

1. Drug must be delivered to site of action in the colon

   1. Suppositories - 10 mg, acts in 15 to 60 minutes

   2. Enteric coated tablets - 5 and 10 mg

2. Rationale for enteric coated tablets

   1. Tablet coating doesn’t dissolve in acidic environment of stomach, but does dissolve as the pH approaches neutral to alkaline in the small and large intestine

   2. This allows bisacodyl to be delivered directly to the site of action

   3. Severe ADRs may occur if administered with antacid products, H2-antagonists, or proton pump inhibitors. Elevated pH will allow enteric coating to dissolve and drug will be released in the upper portion of the GI tract.

   1. Tablets cannot be crushed prior to administration

3. ADRs

   1. Severe cramping, abdominal pain, diarrhea, fluid and electrolyte loss, intestinal protein loss

Example of stimulant laxative (Senna)

1. Available in a variety of oral products: tablets/pills, chocolate pieces, liquids

2. ADRs: melanosis coli - benign black pigment in the colon with prolonged use; may be seen in colonoscopy; discoloration of urine

example of stimulant laxative (castor oil)

(Do not recommend castor oil; there are safer and more effective options)

1. Stimulates small and large intestines

   1. Do not want to stimulate small intestines because that is where medication is being absorbed

   2. ADRs: severe cramping, nutrient loss, excessive fluid and electrolyte loss

What is an example of a combination product?

• Senna and docusate: mush and push

Why do diuretic medications cause constipation?

• decrease body water to decrease swelling

• not enough water - stool becomes dry and hard

How do anticholinergic drugs cause constipation?

• Block acetylcholine’s effect

• acetylcholine is one of the primary neurotransmitters

• acetylcholine primarily stimulates the gut

• blocking acetylcholine will SLOW DOWN the gut

How do opioid medications cause constipation?

• central stimulation of u-receptors - causes pain relief

• stimulation SLOWS GI motility