Physiology and pharmacology of the large bowel Flashcards
Out of the 10L of material which enters the small intestine per day, how much can be reabsorbed back into the body?
8.5
Which is leakier, the small or large intestine?
Small
What happens when the small intestine has a defect in the amount of water it absorbs?
The large intestine has to compensate but it cannot compensate enough for the large increase in water, so the amount of faecal material produced by the body increases instead!
If the large intestine displays dysfunction in water absorption, what is the consequence of this?
There is a rise in faecal material, but the rise is not as large as when the small intestine is dysfunctional, as the small intestine is responsible for the largest amount of absorption in the digestive tract
The ileum connects to the colon by what?
Ileocecal valve
What is the main difference between the histology of the small intestine vs large intestine? Why?
Small intestine = brush border
Large intestine = smooth border
Brush border is designed to increase the SA for absorption from the intestinal tract
What are the main roles of the large intestine?
- Absorption — associated with the ascending arm
2. Storage of faecal material — associated with the descending arm
What are the distinct muscle movements used by the intestinal tract?
- Peristalsis
2. Segmentation
What is peristalsis?
When the muscles squeeze fluid along the intestinal tract
What is segmentation?
This is when the muscles break up the material in the intestines
What are the 2 key processes occurring in the large intestine?
- Secretion of mucus — to protect the large intestine, this is under control of the PNS
- Absorption of H2O from faecal material
How does the large intestine manage to absorb water from faecal material?
Salt channels in the intestinal wall allow Na+ ion movement from faecal material into cells, which causes H2O to follow across the intestinal wall with it
What is the pathology associated with too much H2O absorption in the large intestine?
Constipation
What is the pathology associated with too little H2O absorption in the large intestine?
Diarrhoea
What are the different mechanisms of the rectum which prevent unwanted release of faecal material?
- The anal rectal angle — this is the angle at which the rectum is held at, it prevents the process of defaecation
- The anal sphincter — this is a band of muscle which is closed and should only open during the defaecation process
Explain the process of defaecation
- Holding position
- Puborectalis muscle and external anal sphincter are contracted
- Faecal material is therefore held in the rectum (anorectal angle) - First stage of defaecation
- Puborectalis muscle and external anal sphincter relax
- Levator ani, diaphragm and rectus muscles contract
- Anorectal angle is corrected - Second stage of defaecation
- Internal anal sphincter relaxes
- Rectal contraction
- Defaecation is completed
What is the effect of the sympathetic nervous system on the GIT? (fight or flight)
- Inhibits peristalsis
- Inhibits contraction of the bladder and rectum
What is the effect of the parasympathetic nervous system on the GIT? (rest and digest)
Increased peristalsis of the GIT
Which nerves are involved in the process of defaecation?
— Initial mass movements
— Larger mass movements
— Final stage of defaecation
- Initial mass movements
- Myenteric plexus in the colon and rectum - Larger mass movements
- Parasympathetic nerves in the sacral spinal cord (PELVIC NERVES - Final stage of defaecation
- SOMATIC nervous system activation of the anal branch of the pudendal nerve — voluntary relaxation of the anal sphincter leads to defaecation
What is the difference, in brief, between the somatic and autonomic nervous system?
Somatic = sensory and motor pathways — controls movement and muscles
Autonomic = motor pathways only — controls internal organs and glands
How much of faecal material is water vs solid?
75% water and 25% solid
Treatment of IBS
- Antispasmodics
- Dicycloverine
- Propantheline
Side effects of sulphalazine
- Nausea
- Rashes
- Blood disorders
N.B MoA is unknown but it is used for UC and rheumatoid
What is the trade name for loperamide?
Immodium = ANTI-MOTILITY DRUG
MoA of loperamide
Acts on mu-opioid receptors on the neural plexus of intestines to decrease peristalsis and increase transit time. This causes increased water absorption and stool firmness
Main side effect of loperamide
Drowsiness — warn about driving and machinery
Contraindications of loperamide
- For those with acute ulcerative colitis, it may increase the chance of megacolon and perforation
- Patients with bacterial diarrhoea (C.diff, dysentry, E.Coli)
MoA of codeine phosphate
- ANTI MOTILITY DRUG
Acts on mu-opioid receptors on neural plexus of intestines to DECREASE peristalsis and INCREASE transit time for the intestinal tract, this will increase water absorption and stool firmness to alleviate diarrhoea
Side effects of codeine?
Constipation
Potential for dependence and opioid toxicity
MoA of co-phenotrope
- ANTI MOTILITY DRUG
- Congener of pethidine with little/no analgesic activity
- It DECREASES peristalsis and INCREASES contact of contents with the mucosa
Side effects of co-phenotrope
Can cause dependency as it can cross the BBB
Contraindication of co-phenotrope
In children as they are susceptible to overdose
MoA of Kaolin
- ANTI MOTILITY DRUG
- Hydrated aluminium silicate
- Adsorbs toxic molecules and acts as a binding agent which hardens the faecal material, alleviating the diarrhoea
Which drug can be used alongside kaolin?
Morphine
- If used below the painkilling effect, it can DECREASE peristalsis, INCREASE transit time and therefore help alleviate diarrhoea by increasing water absorption and stool firmness
How does calcium carbonate act as an anti-motility drug?
It is an antacid which induces a constipating effect
What is the first line treatment for diarrhoea?
Loperamide
Cophenotrope
Codeine
- Kaolin and morphine are less widely used
What is ispahgula husk and methylcellulose?
An undigestable BULK FORMING LAXATIVE drug which is given when the fibre content in the diet cannot be increased, this treats CONSTIPATION
What is the MoA of ispahgula husk and methylcellulose?
Increases the bulk of stools which more effectively stimulates the stretch receptors in the mucosa of the rectum and therefore help to initiate defaecation
- Full effect takes days
What type of drug is lactulose?
Osmotic laxative = treats CONSTIPATION
MoA of lactulose
It is a synthetic disaccharide broken down by gut bacteria to release osmotically active sugars/alcohols. This increases the level of water retention in the stools
Side effect of lactulose
Acidifies stool reducing ammonia producing bacteria present in the gut
- This can be helpful in patients with liver failure due to the role of ammonia in hepatic encephalopathy
Contraindication of lactulose
Patients with heart failure and electrolyte disturbances
What type of drugs are senna and sennosoids?
Stimulant laxatives - TREAT CONSTIPATION
MoA of senna and sennosoids
Stimulates nerve endings in the small bowel and activates the myenteric plexus
- This increases bowel movements and secretion of water & electrolytes from the colonic mucosa
- At the same time, this decreases the time for water absorption and hence softens the faece
Side effects of senna and sennosoids
Abdominal cramps
What type of drug is sodium picosulphate/bisacodyl?
Stimulant laxative
MoA of sodium picosulphate/bisacodyl
An irritant which acts to decrease water absorption and hence soften the faeces
How is sodium picosulphate administered?
Tablet - effective in 6-12 hours
Suppository - effective in 1 hour
Which drugs can be affected by sodium picosulphate/bisacodyl?
Preparations that reduce stomach acidity such as antacids, proton pump inhibitors, diuretics and corticosteroids
What are the main drug types for constipation treatment?
- Bulk forming laxatives: Ispahgula husk and methylcellulose
- Osmotic laxatives: lactulose
- Stimulant laxatives: senna and sennosoids & sodium picosulphate/bisacodyl
Main side effect of anti-constipation drugs
Abdominal cramps
What does excessive use of laxatives lead to?
- Melanosis coli
2. Tolerance
What is melanosis coli?
Condition associated with pigmentation of the large intestine
- Pigmentation associated with presence of lipofuscin = looks like a tiger skin
- Condition can be reversed if laxative is removed and is considered harmless