Constipation Flashcards
What is peristalsis?
Peristalsis is a involuntary reflex action causing radially symmetrical constriction and relaxation of the intestinal muscle which propagates like a wave propelling contents within the digestive tract along.
What is the main function of the large intestine?
Location of reabsorption of salt and water leading to the drying of faeces.
When does constipation occur?
When there is excess drying of a stool (increased water reabsorption) increasing the difficulty of defecation.
Excess drying of the stool is associated with the period of time the faeces is stored within the large intestine before defecation.
What does are the main purposes of colonic bacterium?
- Bacteria found in the colon (large intestine) is responsible for the production of some essential vitamins.
Examples include Vitamin K and Biotin. Once secreted by the bacterium, these vitamins and then absorbed into the bloodstream. - Colonic bacterium also produces some gases from undigested polysaccharides.
- Fermentation of indigestible polysaccharides
- Leads to the development of the caecum and lymphatic system
How can constipation be defined?
Defined as the passage of hard stools less frequent than that of the patient’s normal pattern.
Therefore frequency of defecation in constipation is in to the patient’s normal pattern rather than a specific frequency.
How would you approximately quantify the frequency of constipation?
Going less than 3 times a week
How else would you classify a patient that is experiencing constipation in terms of their toilet habits?
Straining on more than 25% of occasions
Hard stools more than 25% of occasions
When would you classify a patient experiencing chronic constipation?
If in the previous six months, if a patient has experienced any of the 3 symptoms:
- Going to the toilet less than three times a week
- Straining or hard stools on more than 25% of occasions
More than 50% of the time, this is chronic constipation
How many prescriptions for laxatives each year in the UK?
10 million
What fraction of the elderly, adults and young children experience constipation?
1/7 adults
1/5 elderly
1/3 young children
Therefore the young and elderly are more at risk.
Does constipation affect women or men more?
Women and it is often seen in late pregnancy
What dietary factors contribute constipation?
Low fibre diet
Diets that are high in animal fat (these tend to be lower in fibre also)
Inadequate fluid intake
Caffeine and alcohol (both are diuretics promoting water loss and hence drying of the stool)
What is imaginary constipation?
When elderly patients are worried they are constipated but they naturally go less to toilet anyway as they get older (often eat less as well)
Aside from dietary factors what else causes constipation?
Age
Ignoring the urge to defecate
What are the medications that cause constipation as a side effect of their use?
The Seven As:
Antacids - Aluminium and calcium salts
Antispasmodics
Antidepressants - Tricyclic, SSRIs
Antiepileptics - Carbamazepine, Oxcarbazepine
ACE inhibitors
Anticholinergics
Antipsychotics - Haloperidol
Plus:
Beta blockers
Bisphosphonate - Alendronic acid
Calcium channel blockers
Diuretics
Iron
NSAID- Meloxicam
Opioid painkillers
PPIs
Statins - Atorvastatin, Rosuvastatin
How do antispasmodics cause constipation?
Contain anticholinergic ingredients which reduces bowel motility
Antidepressants because of the mechanism of the drug, can also have an anticholinergic effect
How do opioid cause constipation?
Abuse of what medications can also cause constipation?
Laxatives
If a patient experiences constipation alongside diarrhoea, what condition may they have?
Irritable bowel syndrome
State examples of obstruction within the bowel which may contribute to constipation.
Scarring - IBD
Adhesion
Intestinal
Abdominal hernias
Gallstones wedged in the intestine
Volvulus
Foreign bodies
Intussusception
Haemorrhoids
Fissures
What is volvulus?
When a loop of the intestine twists around itself and the mesentery of the bowel supports it causing bowel obstruction.
What are some of the symptoms of volvulus?
Abdominal distension
Vomiting
Pain
Constipation
Bloody stools
What is intussusception?
It is the inversion of one portion of the intestine with another (one bit joins up with another).
What are some diseases that can causes constipation?
Diabetic neuropathy (contribute to inefficient bowel movements)
Spinal cord injuries
Tumours
Cerebrovascular accident
Multiple sclerosis
Parkinson’s
Connective tissue disorders
Hirschsprung disease
Hypothyroidism
Aside from the factors we have already considered, what other factors can contribute to constipation?
Mechanical problems of the anus and rectum
Lead poisoning
Pregnancy
Travel
Immobility (bed bound patients)
What four areas would you ask about in order to make a diagnosis?
Medical history
History of symptoms
Medications
Change in diet and lifestyle
Which questions would you ask surrounding the history of symptoms to evaluate a constipation diagnosis?
Describe the symptoms you are experiencing (frequency, consistency)?
What is your normal pattern of defaecation?
How long have the symptoms been present?
How intense are the symptoms?
Are you experiencing any other symptoms?
What is the impact of this on your daily life?
Are you experiencing faecal impaction or defaecation?
Are you experiencing any other symptoms?
What changes in diet and lifestyle would you consider asking about?
Changes in jobs
Stress
Holidays
Changes in diet
Alcohol and caffeine intake
What is the prevalence of constipation in children?
5-30%
Cause of constipation in children?
Unknown
Often change in diet (from breast milk, which is a laxative to semi solid foods)
What are some of the symptoms of constipation in children?
Infrequent bowel habits
Foul swelling wind and stools
Excessive flatulence
Irregular stool texture
Abdominal pain, distension, discomfort
Soiling/overflow
What are some of the causes of constipation in the elderly?
Age related decline in GI motility
Decreased mobility (bed bound, sedentary lifestyle)
Poor diet - low solid and liquid intake
Wasting of pelvic floor muscles
Side effects of medications
Can result in faecal impaction
What are the goals of constipation management?
Resume a normal bowel habit/ bowel frequency
Ensure comfortable defaecation
Prevent laxative dependence
Relieve discomfort
State the four types of laxatives?
Bulking agents
Stimulant laxatives
Faecal softeners
Osmotic laxatives
What are some examples of bulking agents?
Ispaghula husk
Methylcellulose
What are some examples of stimulant laxatives?
Senna
Bisacodyl (oral or rectal)
Dantron
Sodium picosulfate
What are some examples of faecal softeners?
Docusate (oral or rectal)
Glycerol (suppository)
Archis oil (enema)
What are some examples of osmotic laxatives?
Macrogols
Lactulose
Magnesium hydroxide / sulphate
Phosphate (suppository and enema)
Sodium citrate (microenema)
How do you differentiate acute and chronic constipation?
Acute less than 4 weeks, Chronic less than four 4 weeks
What is the first line treatment for both acute and chronic treatment?
Providing lifestyle advice
Diet, adequate fluid, exercise
Treating any underlying causes
This could be control of disease (IBS for examples), alternative medication
What is the first line drug treatment for acute and chronic constipation and what should you do if there is limited response?
Bulking forming laxative (Ispaghula husk)
No response after 1-3 days:
STOP the bulk forming laxative and initiate an osmotic laxative such as macrogol or lactulose
Some but insufficient response after 1-3 days: add in a osmotic laxative
What should you do if a patient has failed to respond to both a bulking forming and osmotic laxative?
After 1-3 days the osmotic laxative has not worked, then introduce a stimulant laxative (Senna).
If Senna has produced a response, when would you reduce the dose/ stop the drug?
Gradually reduce the dose and stop after a soft stools have been produced at least 3 times a week without straining.
How should you reduce the dose if senna is used in conjunction with an osmotic laxative such as Macrogol?
The Senna should be reduced and stopped first and then the Macrogol over a couple of months. May need to up-titrate Macrogol dose first of offset dependence on stimulant laxative in production of soft stools.
What would you use if stimulant laxatives are inefficient in chronic constipation?
Prucalopride
What type of drug is Prucalopride?
A selective serotonin 5HT-4 receptor agonist, with pro-kinetic properties meaning that it stimulates GI motility
For how long is Prucalopride used?
If it yields a response normally six months, use should be reviewed after 4 weeks and stopped if there is no response after that time
What does of Prucalopride is usually used?
2mg once daily but for the elderly this may be reduced to 1mg once daily
Dose increases do not impact the efficiency
When is Prucalopride contra-indicated?
Crohn’s disease
Ulcerative Colitis
Intestinal obstruction
Intestinal perforation
Toxic megacolon
What are some of the side effects of Prucalopride?
Headache and GI disturbances which links to its serotonin activity
How long does Prucalopride take to work?
1-2 weeks
Which other 5HT-4 agonist is licensed for constipation?
Linaclotide
What is the difference between faecal loading and faecal impaction?
Faecal loading - when there is a build up of faecal material within the colon, normally produces soft stools
Faecal impaction - when there is dry, hard material that can’t be evacuated from the body, normally produces hard stools
What is the first and second line guidance for the treatment of faecal impaction (hard dry stools)?
First line:
High dose oral macrogol - Osmotic laxative (Movicol or Laxido) - aim for response within 48 hours
Second line:
Add in a stimulant laxative (Senna or Bisacodyl) - aim for response within 12 hours
Why are macrogols used as the first line in faecal impaction?
In faecal impaction there are hard, dry stools and therefore use of macrogols which are an osmotic laxative, water can be drawn into the stool softening it and hopefully making it easier to pass.
If the response is slow or inadequate in faecal impaction to osmotic and stimulant laxatives what are the next options?
Glycerol or Glycerol plus Bisacodyl suppositories
This should yield a response within 30 minutes
If the response is still inadequate:
Sodium phosphate enema should be used (an osmotic laxative, very potent) plus Archis oil retention enema
What is a main counselling point for Archis oil?
Contains peanuts, should not be used for anybody with a peanut allergy
What is the first step in the guidelines for the treatment of faecal loading and why?
Stimulant laxative such as Senna or Bisacodyl
Stool is already soft so very limited effect is osmotic laxative is used.
If faecal loading is inadequately / slow response to stimulant laxatives what is the next step in the guidelines?
Use of docusate (stool softener and stimulant effect) or a sodium citrate mini enema (mini laxative)
Which laxative type should not be used in opioid induced constipation and why?
Bulk forming laxatives
This is because bulk forming laxatives work to increase the faecal mass and this causes the colon to become distended and stimulate peristalsis.
However when a patient is taking opioids, these reduce contractility of the colon and reduce peristalsis. So opioids have an antagonistic effect on bulk forming laxatives and therefore use should be avoided.
What is the first line treatment for opioid induced constipation and why?
Osmotic & stimulant laxative
Stimulants work directly on the bowel to stimulate peristalsis, they overcome the opioid effect
What is the second line treatment for opioid induced constipation?
If stimulant laxative treatment is unsuccessful use:
Peripherally acting mu-opioid receptor antagonists such as:
Naroxegol
Methylnatrexone
Naldemedine
What is some of the lifestyle advice provided to patients with constipation?
Increase fibre in the diet (aim for 30 grams a day, most adults only get 18 grams)
Increase physical activity
Adequate fluid - at least 2L daily
What laxatives can be considered for use in pregnancy and breastfeeding?
First line: Bulk forming laxative
Second line: depending on response can add in or solely use Osmotic laxatives.
Stimulant laxatives can be used (but not close to term as can trigger contractions)
Can also use glycerol suppositories
What laxatives should be considered for use in children?
First line: Bulk forming laxative plus non-punitive behavioural interventions
Paediatric macrogol / Cosmo Col
Second line: Add a stimulant laxative
If bulk forming is not tolerated switch to stimulant laxative
Third line: Add lactulose (or softening laxative) if macrogol is not tolerated
Laxatives may needed be used for several months
For which patients is macrogol paediatric not licensed for?
Under 2s
Can suppositories and enemas be used in children?
Not recommended for routine use
What are some key counselling points regarding the bulk forming laxative Ispaghula husk?
Ensure to maintain an adequate fluid intake (preferably water) as these laxatives will dehydrate by drawing water into the stools
Sachets should be poured into a full glass of water and taken straight away
Take 30 minutes to half an hour before other medication
Take after meals but definitely not before bed (triggers peristalsis which is less at night so not effective)
What is the recommended dose for Ispaghula husk?
12 years and over: 1 sachet twice a day
What is the recommended dose for Methylcellulose?
Three to six 500mg tablets to be taken twice a day with at least 300mL of water
What are some of the counselling points for Methylcellulose?
Do not take just before bed
Adequate fluid intake throughout treatment
How long does it take for bulk forming laxatives to have an effect?
2-3 days
How long does it take for Macrogols to have an effect?
1-3 days
What are some of the key counselling points of Macrogols?
Dissolve sachets in 125mL of water
Do not take other medicines 1 hour before or after other medicines
There are different flavours available and can be mixed with squash
What is the doses for macrogols (chronic constipation)?
1-3 sachets daily in divided doses usually for up to 2 weeks; maintenance 1-2 sachets daily
What is the doses for macrogols (faecal impaction)?
8 sachets within a six hour period for 3 days; if the patient has a heart condition do not take more than 2 sachets (in 250mL of water) within a one hour period.
When is use of Macrogols contra-indicated /cautioned?
Crohn’s disease, Ulcerative Colitis, Toxic Megacolon
Intestinal obstruction
Intestinal perforation
Heart disease (due to sodium content of the medicine)
Impaired swallowing reflex
How long should Macrogol be used for?
2 weeks in the treatment of chronic constipation (unless you have a disease that causes constipation)
3 days in the treatment of faecal impaction
What does Macrogol cause contain which is beneficial?
Macrogol also contains essential electrolytes including potassium and sodium to help mitigate the potential for electrolyte imbalance and dehydration as less water is reabsorbed and retained in the bowel.
What is the dose of Lactulose to be used in treatment of constipation in adults?
Initially 15mL twice daily but then this can be adjusted according to the response
How long does it take for Lactulose to work?
Up to 2 days
Is it safe for Diabetic patients to use Lactulose?
Yes, despite its name Lactulose does not affect circulating blood sugar levels as it is not absorbed through the gut wall
What are some of the side effects of Lactulose?
Abdominal pain
Nausea
Vomiting
Flatulence (self limiting)
Diarrhoea
How long does Magnesium hydroxide (Milk of Magnesia) take to work?
Usually 3-6 hours
This means it can be abused quite easily
What is the dose of Magnesium hydroxide in adults with constipation?
30-45mL as required, dose to be mixed with water at bed time
What is the maximum recommended duration use of Magnesium hydroxide when it is sold OTC?
Maximum 3 days use
When is use of Magnesium hydroxide C/I or cautioned?
C/I: Acute GI conditions
Cautioned: elderly, debilitated
What class of laxative is Docusate?
It is a faecal softener but also has a stimulant effect
What is the dose of Docusate for use in adults with chronic constipation?
100mg to be taken three times a day, can be increased to maximum 500mg daily in divided doses
How long does Docusate take to work?
12-72 hours for tablets
Only 15 minutes for suppositories
Is Docusate safe to be taken whilst breast feeding?
Its oral use is cautioned in breastfeeding as traces have been found in breast milk
Why are stimulant laxatives only recommended for short term use?
Can cause electrolyte disturbances but most importantly can cause a lazy bowel and stop the bowel working properly as its function relies on the senna stimulating peristalsis.
What is the initial dose of Senna in the treatment of constipation in adults?
7.5-15mg once daily, usually taken at bed time, higher doses up to 30mg once daily prescribed under medical supervision.
This is the same dose for liquid (syrup) and tablets.
How long does Senna take to work?
8-12 hours
From what age group is Senna licensed for?
12 years and over.
Aged 12-17 can only be sold under the supervision of a Pharmacist.
What are some of the new OTC recommendations for Senna that helps to support its safe use?
Advise patients that lifestyle interventions are the first line in the management of constipation and that stimulant laxatives such as Senna should only be used following osmotic and bulk forming failure.
Only smaller pack sizes are available for OTC use, for 1 or 2 short treatment courses.
What are some of the contra-indications for Senna use?
Atony
Intestinal obstruction
Undiagnosed abdominal pain
What are some of the side effects of Senna?
Albuminuria
Diarrhoea
Electrolyte and fluid imbalance
GI discomfort
Haematuria
Skin reactions
Urine discolouration
What electrolyte disturbance is associated with long-term Senna use?
Hypokalaemia
What are examples of Dantron laxatives?
Co-danthramer (PEG) or Co-danthrusate (Docusate)
When is Dantron used?
Only used in terminally ill patients (constipation in palliative care) due to its potential carcinogenic effect
What is the dose of Co-Danthramer for treating constipation in palliative care in adults?
1-2 capsules once daily, dose should be taken at night or
5-10mL (5mL of strong solution) once daily at night
What are some of the C/I of Dantron?
Acute abdominal conditions
Acute inflammatory bowel disease
Intestinal obstruction
Severe dehydration
What are some of the side effects of Dantron?
Abdominal cramps
Asthenia
GI disorders
Hypermagnesemia
Skin reactions
Urine discolouration turns red
What is the dose of sodium picosulfate used for treating constipation in adults?
5-10mg once daily, dose to be taken at bedtime
How long does sodium picosulfate take to work?
6-12 hours, PowerPoint says 8-14 hours
When is sodium picosulfate contraindicated?
Intestinal obstruction
Undiagnosed abdominal pain
What are some of the most common side effects associated with sodium picosulfate?
Diarrhoea
GI discomfort
What is a brand name for Bisacodyl?
Dulcolax
What is the dose of Dulcolax recommended?
5-10mg once daily, dose to be taken at night; increased if necessary up to 20mg once daily at night
Can Bisacodyl be used in children?
Can be used in children under 10 but higher doses are not licensed in this age group
What are the common side effects associated with Bisacodyl?
GI discomfort, nausea
What are some of the contra-indications of Bisacodyl?
Acute abdominal conditions
Acute inflammatory bowel conditions
Intestinal obstruction
Severe dehydration
How long does Bisacodyl take to work?
10-12 hours for the tablets, suppositories work in 20-60 minutes
What are the benefits of using suppositories/enemas?
Much quicker onset of action
Briefly outline the mechanism of bulk forming laxatives.
Bulk forming laxatives contain indigestible polysaccharides which when they enter the intestine. They increase the osmolality when broken down causing the retention of water in the GI tract, leading to the softening of the stool and expansion.
These bulkier stools then distend the colon and then promote peristalsis as presence of the expanded stool stimulates the colonic mucosal receptors.
This stimulates the parasympathetic nervous system causing the release of acetylcholine.
Acetylcholine activates M2/M3 muscarinic receptors in the GI tract causing peristalsis and passing of the stool.
What is the secondary effect of bulk forming laxatives?
Creates a mucus layer and facilitates defaecation
Briefly outline the mechanism of stimulant laxatives.
Stimulant laxatives work on the intestinal mucosa and stimulate local nerve plexus of the myenteric nerve plexus this increases secretion of fluid and electrolytes. This stimulation of the parasympathetic nerves within the colon leads to the stimulation of contraction of longitudinal smooth muscle but not circular smooth muscle which causes peristalsis and the evacuation of stools through the intestine.
Also decreases transit time
What is a secondary effect of stimulant laxatives?
Increases the secretion of water and electrolytes into the bowel, leading to stool softening
Briefly outline the mechanism of osmotic laxatives.
Osmotic laxatives are poorly absorbed so they act as osmotic agents and increase the water retention in the gut lumen. They themselves are absorbed into the stool as they are hyperosmolar and they soften the stool by promoting retention of water and electrolytes within the stools making them easier to pass.
What electrolyte is present within osmotic laxatives and what secondary effect does this have on the mechanism of action?
Osmotic laxatives also contain magnesium. Magnesium stimulates the release of cholecystokinin from the small intestine. This results in:
Inhibition of gastric emptying
Increases intestinal gastric secretions
Induces colonic motility
Decreases the transit time through the gut, meaning that there is a reduced amount of time for the reabsorption of fluids and electrolytes
Describe the how the structure of senna has been designed to optimise its activity within the intestines.
Senna is an anthraquinone that has been combined with sugars to form glycosides (this just means that the sugar element of the Senna is attached to the rest of the structure via a glycosidic bond). The colonic bacterium present in the large intestine cleaves the glycosidic bond causing the release of the active drug molecule which is known as Sennoside A and B.
What effect does the anthracene glycoside derivates, Sennoside A and B have on the GI tract?
Result in stimulation of the myenteric nerve plexus causing an increase in intestinal smooth muscle activity, and hence peristalsis.
Lead to an increase in prostaglandin E2 secretion
Reduces colonic water absorption
What is the effect of the metabolite of Sennoside A/B on COX-2?
(Information from Drug Bank)
Sennoside A/B is metabolised by the colonic gut bacterium to the active metabolite Rheinanthrone. This increases the expression of COX-2 on macrophages leading to an increase in Prostaglandin E2 expression. The increase in Prostaglandin E2 results in a decrease of aquaporin 3 expression in the mucosal epithelial cells of the large intestine. A reduction in aquaporin 3 expression means that less water is reabsorbed and therefore more is retained within the faeces making it easier to pass.
What is the effect of Rhein an additional metabolite of Sennoside A, B?
Rhein excites submucosal acetylcholinergic neurons resulting in an increase in chloride and prostaglandin secretion. The movement of chloride ions into the large intestine helps to draw water into the lumen (due to increase osmotic pressure).
How do stool softeners work?
Also known as an emollient laxative, they reduce the surface tension of the stool, enabling fats and water to be able to penetrate the stool making them easier to pass, by essentially lubricating the stool.
How does Paraffin and Archis oil work?
Create a barrier between the stool and the intestinal wall.
How does Prucalopride work?
Prucalopride acts as a selective stimulator (agonist) of the 5-HT4 receptors. 5-HT4 receptors are found throughout the GI tract primarily in smooth muscle cells, enterochromaffin cells and myenteric nerve plexus. Activation of these receptors results in release of acetylcholine which acts on M2/M3 muscarinic receptors as part of the parasympathetic drive causing an increase in peristalsis/propulsion of faeces.
What are PAMORAS and how do they work?
They are competitive antagonists at intestinal mu-opioid receptors and therefore prevent activation of the intestinal mu-opioid receptors and opioid induced effects such as hypertonicity, reduced GI motility and increased fluid absorption.
This resumes normal peristalsis and propulsion.
Can laxatives for children available for sale OTC?
No, they must be referred to the GP for an examination. The first line of Paediatric Macrogol is POM.
What are some of the red flags for constipation?
Pain on defaecation
Patients over the age of 40 with a sudden change in bowel habit
Over 14 days duration
Associated fatigue
Presence of blood in stools
Repeated failure of laxatives
Suspected laxative abuse
