Keele Diarrhoea

Front 1

What is the normal intake of fluid in an adult small intestine?

Back 1

9 litre/day

1.8L from diet, 7.2L endogenous secretions

Front 2

What is the normal input of fluid into the colon?

Back 2

1.5-2.0L/day

Front 3

What is the normal output of fluid in faeces?

Back 3

100-200mL/day

Front 4

What are the two forms of diarrhoea?

Back 4

Osmotic and secretory

Front 5

What causes osmotic diarrhoea?

Back 5

Excess of osmotically active particles in the gut lumen:• Osmotic laxatives• Excessive solutes in the lumen• Inflammation within the mucosa• Motility disorders

Front 6

What causes secretory diarrhoea?

Back 6

Bowel mucosa secretes excess water into the lumen:• Cholera toxin• Other infective causes• Specific electrolyte transport defects (e.g. congenital chloride-losing diarrhoea)

Front 7

What causes excessive numbers of osmotically active particles?

Back 7

• Ingestion non-absorbable solutes e.g. osmotic laxatives• Malabsorption of specific solutes e.g. glucose-galactose malabsorption• 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.

Front 8

What causes increased fluid secretion? (Leading to secretory diarrhoea)

Back 8

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

Front 9

What infections can cause diarrhoea?

Back 9

Shigella, Salmonella, E. Coli

Front 10

What is diarrhoea defined as?

Back 10

Increase in stool frequency, or water content

Front 11

How does injection cause diarrhoea?

Back 11

-Damage to the mucosa

-Toxins produced by the infective organism itself

Front 12

Infective Agents Causing Diarrhoea

Back 12

Front 13

What is the mechanism of action of the cholera toxin?

Back 13

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

Front 14

What does CFTR stand for? What is it?

Back 14

Cystic Fibrosis Transmembrane Conductance Regulator

A protein mutated in cystic fibrosis

ATPas pumps ions downhill

Front 15

How does Clostridium Difficile cause infection?

Back 15

– Alteration of normal colonic flora– Colonic colonization of C. difficile– Growth and production of toxins– Infection can lead to formation of colitis and toxic megacolon

Front 16

What is the pharmacological treatment for C.difficile?

Back 16

-Discontinue offending antibiotic

-Metronidazole (CI in patients w/liver or renal impairment)

-Vancomycin (CI in patients with renal impairment)

Front 17

How is diarrhoea treated?

Back 17

– Identify cause of diarrhoea– restore fluids/electrolytes: oral re-hydration therapy– elimination of infection may be necessary– absorbent agents eg kaolin– anti-diarrhoeal drug

Front 18

With what are antidiarrheal drugs indicated for?

Back 18

-Severe or prolonged diarrhoea (>2 to 3 days) (preventing severe fluid and elctrolyte loss)

-Severe diarrhoea in young children and older adults. (Can't adapt to flui/electrolyte losses as well)

-When specific causes of diraahoea have been determined

-In chornic inflammatory bowel diseases (Eg: Crohn's)

-In ileostomies (to decrease fluidity and volume of stool)

Front 19

What are the contraindications of antidiarrhoeal drugs?

Back 19

Diarrhoea caused by:

-toxic materials

-microorganisms that penetrate intestinal mucosa (pathogenic E.coli, Salmonella, Shigella)

-antibiotic-associated colitis

Front 20

What drugs are contraindicated with diarrhoea?

Back 20

-Opiates contraindicated in chronic diarrhea because of possible opiate dependence

-Difenoxin, diphenoxylate and loperamide are contraindicated in children younger than 2

Front 21

What are the two different types of anti-diarrhoeal agents?

Back 21

Anti-motility agents and adsorbents/bulk-forming drugs

Front 22

What do anti-motility agents do?

Back 22

-Reduce peristalsis by stimulating opioid receptors in the bowek

-Decrease GI motility

-Increase absorption of water from the bowel

Front 23

What are adsorbents and bulk-forming useful for?

Back 23

-In some forms of low-grade chronic diarrhoea

-Kaolin isn't recommended for acute diarrhoea

Front 24

What is the mechanism of action of opioids?

Back 24

1.Intestinal motility--µ receptors2.Intestinal secretion--δ receptors3.Intestinal absorption---µ & δ receptors

Commonly used opioids act via peripheral µ receptors- preferred over opioids that penetrate CNS

Front 25

What does Loperamide do?

Back 25

-Increases intestinal transit time; increases anal sphincter tone; anti-secretory activity against cholera toxin and some forms of E.coli toxin

-Effective in travellers diarrhea; adjunctive treatment in almost all forms of chronic diarrheal diseases

Front 26

What as the dose and half-life of loperamide?

Back 26

Half life = 11 hours

Dose= 4mg by mouth initially; 2mg after each subsequent stool, up to 16mg/day

Front 27

Why is loperamide used over morphine for diarrhoea relief?

Back 27

Loperimide is 40-50 times more potent than morphine as an anti-diarrhoeal agent but it lacks significant abuse potential

Front 28

What are the adverse drug reactions of loperamide?

Back 28

Abdominal cramps, dizziness, drowsiness and urticaria (hives)

Front 29

What is the daily dose for codeine?

Back 29

30mg 3-4 times daily by mouth

Front 30

What is the duration of action of codeine? Why?

Back 30

4-6 hours. Mainly due to metabolism to morphine

Front 31

What are the adverse drug reactions of codeine?

Back 31

Drowsiness, can cause physical dependence, constipation

Front 32

What are the cautions of codeine?

Back 32

Impaired respiratory function, driving

Front 33

What are the contraindications of codeine?

Back 33

Acute respiratory depression, paralytic ileus

Front 34

What is the daily dose of kaolin and morphine?

Back 34

550-800mcg/10mL dose, once every 6 hours

Front 35

What is Co-Phenotrope a combination of?

Back 35

Diphenoxylate and Atropine

Front 36

Why is atropine added with the opiate, diphenoxylate?

Back 36

Because it's an antiperistaltic and it's ADRs reduce abuse potential

Front 37

What are the side-effects of Co-Phentotrope, and why?

Back 37

Can cause euphoria, respiratory depression, drowsiness and dizziness because it can cross the blood brain barrier

Front 38

What is racecodotril?

Back 38

An Enkephalinase inhibitor

Front 39

How does Racecodotril act?

Back 39

By preventing breakdown of endogenous opioids> antisecretory action

Front 40

What does Racecodotril get metabolised to?

Back 40

It's a prodrug, which is metabolised to thiorphan which is much more active

Front 41

What is Racecodotril contraindicated in?

Back 41

Antibiotic-associated diarrhoea (it's better tolerate than loperamide)

Front 42

What do adsorbents do?

Back 42

-Non-selectively absorbs intestinal fluid

-Regulates stool texture and viscosity

-Bind bacterial toxins and bile salts

Front 43

How much kaolin suspension should you take after each loose stool?

Back 43

-20-120mL 20% suspension

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

Front 44

What are Probiotics?

Back 44

-Replaces normal colonic microflora and restore intestinal function and suppresses the growth of pathogenic bacteria

Front 45

What is the daily dose of Lactobacillus Acidophilus?

Back 45

2 tabs or 1 packet of granules 3-4 times daily

Front 46

How much lactose is there in a probiotic dairy product?

Back 46

200-400g