Diarrhoea

Question 1

What happens when the transit time for GI Motility gets increased?

And decreased?

Answer 1

Increase in time:

Increased water absorption, causing constipation; because the faecal matter is placed in a very dense and dry state.

Decrease in time:

When the transit time for GI motility gets decreased – decreased water and nutrient absorption, which causes diarrhoea.

Question 2

What is Diarrheoa?

Answer 2

A failure of fluid handling.

An increase in stool frequency or water content.

Question 3

What are the two forms of Diarrheoa?

Answer 3

Osmotic diarrhoea and Secretory Diarrhoea

Question 4

What is Osmotic Diarrhoea?

What are the causes?

Answer 4

It is caused by an excess of osmotically active particles in the gut lumen – particularly in the large intestine

Caused by:

• Osmotic laxatives
• Excessive solutes in the lumen
• Inflammation within the mucosa
• Motility disorders

Question 5

What is Secretory Diarrhoea?

Answer 5

Bowel mucosa secretes excess water into the lumen

Caused by:
• Cholera toxin
• Other infective causes
• Specific electrolyte transport defects (e.g. congenital chloride-losing diarrhoea)

Question 6

Causes of Osmotic Diarrhoea?

Answer 6

It is caused by excessive numbers of osmotically active particles being present due to:

• Ingestion non-absorbable solutes e.g. osmotic laxatives
• Malabsorption of specific solutes e.g. glucose-galactose malabsorption or people that are lactose intolerant
• Damage to the mucosa resulting in less absorption e.g. acute viral gastroenteritis
• Motility disorders as seen in irritable bowel syndrome resulting in increased solutes reaching the colon.

Question 7

Treatment for patients with Osmotic Diarrhoea?

Answer 7

Removing the source of osmotically active particles (e.g. by fasting) stops diarrhoea

Question 8

What causes Secretory Diarrhoea?

Answer 8

Increased fluid secretion normally due to:

• Specific biological mechanisms involving pathogen-produced factors (e.g. cholera toxins)
• Inherent abnormalities in the enterocytes

Question 9

How does infection cause Diarrhoea?

Answer 9

Damage to the mucosa, which is preventing absorption (e.g. in rotavirus)

The infective organism is producing a toxin which leads to a secretion of fluid into the large intestine.

Question 10

What does Chloera do?

Answer 10

Cholera secrets a toxin that is made up of 6 b- subunits, surrounding a single a-subunit.

Question 11

What is Cholera Toxin

Mechanism of Action?

Answer 11

The toxin B subunits bind to the membrane receptor, GM1, and the A(1) subunit is inserted through the membrane.

Leading to phagocytosis of the cholera toxin, which leads to destruction of the toxin.

b) The complex is endocytosed by the target cell.
c) Proton pumps acidify the CT-containing endocytic vesicle, causing the toxin subunits to dissociate.
d) The A1 subunit is an ADP-ribosyltransferase that cleaves NAD into adenosine diphosphoribose (ADPR) and nicotinamide and covalently bonds the former to the α subunit of the Gs adenylyl cyclase–stimulatory G protein.

The intrinsic GTPase activity of the α subunit isblocked, allowing GTP to remain bound to it; the Gsα-GTP complex activates adenylyl cyclase (AdCy).

f) Increased cAMP-production, increases CFTR Chloride pump activity, & increases secretion of water into gut lumen

Question 12

Function of A1 in the absorption of Chloera?

Answer 12

A1 acts to ADP-ribosylate the alpha subunit of G-proteins, which leads to the activation of the G-protein and the activation of adenylyl cyclase, which leads to increased production of cyclic AMP.

Question 13

What is Clostridium Difficile?

Explain how Clostidium Difficle causes infection?

Answer 13

It is the major cause of diarrhoea and colitis in patients exposed to antibiotics:

– Antibiotic alters the normal colonic flora

– Because the flora is altered, C. difficile is able to colonize the large intestine (Colonic colonization of C. difficile)

– Growth (of large intestine, I THINK) and it produces toxins

Leading to diarrhoea

– Infection can lead to formation of colitis and toxic megacolon.

Question 14

What are some treatments for Clostridium Difficile?

Answer 14

– Discontinue offending antibiotic

– Metronidazole (contraindicated in patients with liver or renal impairment)

– Vancomycin (contraindicated in patients with renal impairment)

Question 15

Why is Diarrhoea sometimes a good things?

Answer 15

It removes irritating substances for gut.

Question 16

What are the steps to treating Diarrhoea?

Answer 16

– Identify cause of diarrhoea

– Restore fluids/electrolytes (–oral re-hydration therapy)

– Elimination of infection may be necessary

– Absorbent agents eg kaolin – anti-diarrhoeal drug

Question 17

What is Antidiarrheal drugs are indicated to?

Answer 17

• Severe or prolonged diarrhoea (>2 to 3 days), – to prevent severe fluid and electrolyte loss
• Severe diarrhoea in young children and older adults. – they are less able to adapt to fluid and electrolyte losses.
• When specific causes of diarrhoea have been determined
• In chronic inflammatory diseases of the bowel (ulcerative colitis and Crohn’s disease) – to allow a more normal lifestyle
• In ileostomies (surgical excision of portions of the ileum) – to decrease fluidity and volume of stool

Question 18

Contra-indications of Anti-diarrheal drugs?

Answer 18

– Toxic materials (diarrhoea could be to get those toxins out, as quickly as it can)

– Microorganisms that penetrate intestinal mucosa (eg, pathogenic E. coli, Salmonella, Shigella),

– Antibiotic-associated colitis.

Avoid in people that take:

• Opitaes
• Difenoxin, diphenoxylate, and loperamide (under two years of age)

Question 19

What do anti-motility agents do?

Answer 19

• Reduce peristalsis by stimulating opioid receptors in the bowel

This:
• Decrease GI motility
• Increase absorption of water from the bowel

Question 20

Examples of Anti-Diarrhoea Drugs?

Answer 20

Opioids
Loperamide (Imodium)
Codeine
Morphine
Co-Phenotrope
Enkephalinase inhibitor (Racecodotril)

Question 21

Mechanism of action for Opioids?

Answer 21

1. Intestinal motility–µ receptors
2. Intestinal secretion– δ receptors
3. Intestinal absorption— µ & δ receptors – controlling regulation

Question 22

Which Opioids are preferred? Why?

Answer 22

Commonly used opioids act via peripheral µ receptors

Preferred over opioids that penetrate central
nervous system.
Because if they cross the blood brain barrier, patients are more likely to become dependent on the drugs.

Question 23

What does Loperamide do?

When is it used?

ADR?

Answer 23

Increases intestinal transit time; Increases anal sphincter tone; Anti-secretory activity against cholera toxin and some forms of E.coli toxin (decreases secretory activity against cholera and E.coli)

Effective in travellers’ diarrhoea;

Doesn’t get to the brain

ADR: Abdominal cramps; dizziness, drowsiness and urticaria

Question 24

Explain Codeine?

ADRs? CIs? Cautions?

Answer 24

Weak opiate

Action largely due to metabolism to morphine – some gets to the brain

ADRs: drowsiness; long list of opioid-related minor side effects Can cause physical dependence – due to passing the brain

• Cautions: impaired respiratory function; driving
• CIs: Acute respiratory depression; paralytic ileus

Question 25

Explain Morphine?

Answer 25

• Strong opiate

- Sedation and risk of dependence greater than for codeine, but ADRs, cautions and CIs similar to codeine

Question 26

Explain Co-Phenotrope?

Answer 26

Combination of diphenoxylate and atropine

Diphenoxylate – opiate

Atropine – has antiperistaltic effect on the gut and ADR’s reduce abuse potential

Can cross BBB → can cause euphoria, respiratory depression, drowsiness, dizziness

• Presence of subclinical doses of atropine may give rise to atropine side-effects in susceptible individuals or in over dosage

Question 27

Explain Enkephalinase inhibitor - Racecodotril? CIs?

Answer 27

Act by preventing the breakdown of endogenous opioids – increasing the endogenous opioids agonist.

• Action more anti-secretory than anti-mobility
• Contraindicated in antibiotic-associated diarrhoea

Question 28

When can you not use Absorbent?

Answer 28

In acute diarrhoea!

Question 29

How do absorbents work?

Cautions?

Answer 29

• Non-selectively absorbs intestinal fluid:
• Regulates stool texture and viscosity
• Bind bacterial toxins and bile salts

Can bind other medications, so must space out from others medications by 2 to 3 hours

Question 30

What do you want to do after you have gotten rid of diarrhoea?

Answer 30

Replace the normal microflora.

Question 31

What do probiotics do?

Answer 31

Replaces normal colonic microflora.

Restores intestinal function by suppressing the growth of pathogenic bacteria

Question 32

Why are formulations important?

Answer 32

• Help to deliver drug to the site of action
• Mask or improve taste (palatability)
• Improve adherence

Question 33

What is Colonic atony/ Atonic muscle?

Answer 33

When the muscle is not working at all, might be due to low potassium level.

Question 34

Side effects of any laxatives?

Answer 34

Wind and bloating