Wk 3 - Pharmacology: Diarrhoea and Constipation Flashcards
What are the three main causes of diarrhoea?
- Infection: bacteria, virus, parasite
- Medications - 7% of adverse reactions
- Chronic bowel disorders
List some of the main infective diarrhoeal diseases?
- Bacteria: E.coli, Salmonella enteriditis/typhi, Vibrio cholera, Campylobacter jejuni, C.difficile, Shigella
- Virus: Norwalk virus, Rotavirus, Adenovirus
- Parasites: Cryptosporidium parvum, Entamoeba histolytica
What is the most common infective diarrhoeal disease in under 2s?
Rotavirus and Bacteria
What is the most common infective diarrhoeal disease in adults?
- Viral
- Bacteria
- Camyplobacter
Describe what happens in infective diarrhoeal disease.
- There is malabsorption of water and nutrients, which leads to dehydration and malnutrition.
- Changes to gut wall - affect absorption.
List some medications that cause diarrhoea.
- Cholinergics - increase ACh
- Cytotoxic agents - loss of gut epithelia
- Broad-spectrum antibiotics - change in gut flora
What are some chronic bowel disorders that affect diarrhoea and also constipation?
- IBD - ulcerative colitis and Crohns
- Endocrine disease - diabetes and thyroid disease
- IBS
- Diverticular disease
- Malabsorption syndromes eg coeliac disease, pancreatic insufficiency, cystic fibrosis
- Psychological eg stress
- Self-induced laxative abuse
- Antibiotic-associated colitis
- Chemotherapy GI irradiation
What are the physiological outcomes of diarrhoea?
- Dehydration – H2O, Na loss + cannot reuptake Na
- Metabolic acidosis – HCO3 loss
- Potassium depletion – K (hypokalaemia)
- Hypovolaemia
- Cardiovascular collapse
- Death
List the signs of dehydration (95% vs 90% dehydration).
95% dehydration:
- Thirst
- Skin turgor (worse as we age tho)
- Tachycardia
- Dry mucous membranes
- Sunken eyes
- LAck of tears
- Sunken anterior fontanelle (hole at the top of the head)
- Oliguria (good indicator esp in infants and children)
90% dehydration – life-threatening:
- Anuria
- Hypotension
- Feeble and very rapid radial pulse
- Cool and moist extermities
- Diminished conciousness
- Signs of hypovolaemic shock – leading to death
How is acute diarrhoea treated?
- Oral rehydration therapy – prevention or reversal of dehydration
- Antimotility drugs – relieve symptoms (not recommended in children + sometimes issue when the cause is infective as want to get rid of infective agent)
- Antisposmadics – reduce cramping and pain
- Antibacterials – usually no requires in simple episodes
What is oral rehydration therapy composed of?
- Na
- Glucose
- K
- Citrate
- Cl
- clean water
Usually isotonic then maybe hypotonic when rehydrated
What is the priority in acute diarrhoea?
Prevention or reversal of dehydration particularly in elderly and children
Why/how does oral rehydration therapy work?
- ORS works because of the Sodium-Glucose Co-Transport System (SGLT1)
- The co-transport of Na into epithelial cells via SGLT1 requires glucose
- Two Na ions and one glucose are transported together across the membrane via the SGLT1 protein
- Then Na/K ATPase transports Na back into blood and K into epithelial cells
- Wherever Na goes, H2O follows
What are antimotility drugs?
Antimotility agents are drugs used to alleviate the symptoms of diarrhoea. They increase muscle tone but diminish propulsive activity + reduced awareness of urge.
What is the mechanism of action of antimotility drugs?
They bind to the μ opioid receptor in the submucosal plexus of the intestinal wall
List some antimotility drugs.
All opiates
- Codeine
- Morphine
- Loperamide - relatively selective in GI tract, reduced BBB and central activity (so no euphoria)
- Cophenotrope
What are some S/Es of antimotility drugs?
Nausea, vomiting, cramps, paralytic ileus (problem esp in Crohns)
What are antispasmodics?
Muscarinic antagonists that inhibit gastric emptying
List some examples of antispasmodics.
- Atropine (not really used for diarrhoea relief)
- Propantheline
- Dicycloverine
In which condition are antispasmodics mostly used?
In IBS to reduce GI motility and spasms
How do antispasmodics work ie mechanism of action?
Blocking parasympathetic action of the myenteric and submucosal neural plexus
When would you normally prescribe antibiotics for a diarrhoeal episode?
Travellers diarrhoea give co-trimoxazole as prophylaxis
What do you prescribe for pseudomembranous colitis or c.difficile?
Metronidazole or vancomycin
What organism causes the majority of diarrhoeal disease?
Viruses
What is the most important aspect of the treatment of diarrhoea?
Prevent dehydration using ORT
What is the mechanism of action of antimotility drugs?
Diminish propulsive activity via mu opioid receptor
List some reasons causing constipation.
- Disease
- Dehydration
- Ignoring the urge
- Laxative abuse
- Travel
- IBS
- Milk
- Medications
- Reduced physical activity (elderly)
- Chronic idiopathic constipation
- Colon or rectal problems
Constipation is most common among…
- Women (due to hormone changes)
- Over 65s (due to reduced physical activity)
- During and after pregnancy
List some diseases associated with constipation.
- Neurological: MS, PD, Stroke, Spinal cord injury, Chronic idiopathic injury
- Metabolic/endocrine: Diabetes, Poor glycaemic control, Uraemia, Hyperkalaemia, Hypothyroidism
- Systemic disease: Amyloidosis, Lupus, Scleroderma
All generally lead to slower movement of stool through the colon
List some medications that cause consipation.
- Pain meds (narcotics)
- Diuretics
- Antisposmadics
- Aluminium antacids
- Antidepressants
- Iron supplements
- Antiepileptics
List the types of agents used to treat constipation (4).
- Bulk formers
- Stimulants
- Osmotics
- Foecal softners
What are bulk-forming laxatives?
- Unprocessed wheat bran OR
- Ispaghula husk
- Methylcellulose (also softener)
- Sterculia polysacchride polymers
How do bulk-forming laxatives relieve constipation?
- Increasing foecal mass: bacterial proliferation and hydrophilic action
- Stimulates peristalsis (reaction to mechanical stretch)
List some stimulants used to relieve constipation.
- Bisacodyl
- Dantron
- Senna
Decreasing order of stimulation
How do stimulants work?
They increase intestinal motility. Anthraquinone group (dantron and senna) also stimulate smooth muscle activity.
Stimulate myenteric nerve plexus, increase gut motility, water and electrolyte transfer
How long does it take for stimulants to take effect?
Usually 6-12hrs (Bisacodyl - 15 to 30 mins rectal admin)
List some foecal softeners.
- Liquid paraffin (not used anymore)
- More used Arachis oil
Traditionally liquid paraffin was used as a foecal softener but not anymore because of…
- Anal seepage and anal irritation
- Granulomatous reaction
- Lipoid pneumonia
- Reduced lipid-soluble vitamin uptake
How do osmotic laxatives work?
- Withdraw fluid from the bowel or retain the fluid they are administered with
- Accelerate transfer through small intestine, large volume in colon
List most commonly used osmotic laxatives.
Usually sugar or saline preparations
- Lactulose - metabolised by gut bacteria - lactic and acetic acid have osmotic action (24hr)
- Macrogols - ethylene glycol sequesters fluid - causes dehydration (so need extra fluid)
Also magnesium salts - rapid, need adequate fluid intake, often abused + can cause central effects in overdose
What are bowel cleansers and when are they used?
- Sodium acid phosphate, Sodium picosulfate.
- Used before colonic surgery, colonoscopy, radiology.
What are three potential side effects of stimulant laxatives?
Cramps, diarrhoea on long-term use, tolerance
Who can be constipated?
Anyone but more in older, sedentary, pregnant, post-surgery, women, medication
