Clinical Pharmacology of Antispasmodics, Antidiarrhoeals And Laxatives Flashcards
Describe some disorders of inappropriate GI motility.
- DIARRHOEA - ranges from inconveniences to cause of death and malnutrition. DRUGS - preserve fluid/electrolyte balance especially in infants AND ELDERLY
- CONSTIPATION - DRUGS = reduce viscosity of contents in lower colon/improves colonic lubrication - facilitate passage
- IBS
Describe antimotility drugs in diarrhoea treatment.
- OPIOIDS e.g loperamide
- Oral/liquid administration
- Act on μ- opioid receptors in myenteric plexus to inhibit ACh release and reduce motility
- Poor penetration of CNS therefore no analgesic or addictive properties
Describe adsorbents in diarrhoea treatment.
- EXAMPLE - methylcellulose
- Absorb water and increase stool bulk
- Adsorb intestinal microorganisms
- Coat/protect the intestinal mucosa
- Much less effective than antimotility drugs
Describe fluid transport modifiers in diarrhoea treatment.
- EXAMPLE - Bismuth Subsalicylate (PEPTO-BISMOL)
- Stimulates absorption of fluids and electrolytes by the intestinal wall (anti-secretory action)
- Reduces hypermotility of the stomach
What is the aim of laxatives in constipation treatment?
Accelerate movement of food through the GI tract
Describe bulk-forming drugs in constipation treatment.
- EXAMPLE - ispaghula husk
- Absorb water and increase stool bulk
- Increase intestinal distension, thereby increasing peristaltic activity
- Colonic bacteria use the hydrated material as a metabolic substrate.
- Increase in the bacterial cell mass with a consequential softening of the faeces
- Full effect takes 1-3 days
Describe osmotic laxatives in constipation treatment.
- EXAMPLE - Lactulose
- Non absorbable compounds that hold water in the intestines by osmosis.
- Distends the bowel, increasing intestinal activity
- Lactulose may take up to 24 hours to act
Describe faecal softeners in constipation treatment.
- EXAMPLE - Liquid paraffin
- Agents become emulsified with the stool and soften/lubricate it for easy passage
Describe stimulant laxatives e.g senna in constipation treatment.
- Administered in an innocuous form
- Converted to their active forms by bacteria in the colon - irritate the mucosa, inducing low grade inflammation
- Stimulates peristalsis
- Promotes accumulation of water and electrolytes
- Excessive use can cause diarrhoea
Constipation is a known side effect of atropine. How does it do this?
- Nonspecific antimuscarinic antagonist that binds to all muscarinic receptors including M3.
- Blocks secretion and smooth muscle contraction
Describe the sympathetic and parasympathetic fibres in the ENS.
- PARASYMPATHETIC - Excitatory (stimulate SMC and peristalsis)
- SYMPATHETIC - Inhibitory
- Neurons in ENS can function independently - influenced by PNS and SNS
Describe the role and innervation by the myenteric plexus.
- Responsible for peristalsis within bowels
- Acts independently from CNS - innervated by ANS - connects central and enteric nervous systems
Describe the derivation and location of the myenteric plexus.
- Between circular and longitudinal muscle layers in lower esophagus, stomach and intestines
- Receives messages from vagus nerve and responds by transmitting messages to muscle cells
Describe antispasmodics in IBS treatment.
- Anti-muscarinics e.g. hyoscine butylbromide (competitively antagonise action of ACh in enteric plexus)
- Adverse side effects including dry mouth, blurred vision and cardiac arrhythmia
- Drugs that act directly on smooth muscle to relax it e.g. peppermint oil and mebeverine
- Helps prevent cramping in IBS
Describe IBD with examples.
- Autoimmune inflammatory disorders of large and small intestines
- EXAMPLES: Crohn’s and Ulcerative colitis
Name some forms of treatment for IBD.
- Anti-inflammatory drugs
- Immunosuppressive drugs
- Changes in nutrition
- Surgery
Describe aminosalicylates in IBD treatment.
- Anti-inflammatory drugs e.g. mesalazine
- Used to treat mild to moderate UC and maintain remission
- Administered orally or as an enema
- Oral tablets have a pH sensitive coating which prevents absorption in the stomach and small intestine →absorbed in large intestine
- Thought to inhibit inflammatory mediators including prostaglandins and cytokines in the gut
Describe corticosteroids in IBD treatment.
- EXAMPLE - Prednisolone
- Anti-inflammatory and immunosuppressive drugs
- Inhibits synthesis of inflammatory mediators
- Treats moderate to severe attacks of UC and Crohn’s
Describe antibodies to TNF-α in IBD treatment.
- TNF-α causes activation of immune cells and release of inflammatory mediators
- Inhibitors of TNF-α e.g infliximab induce remission in 1/3 of Crohn’s patients resistant to conventional therapy
- No good evidence that anti-TNF-α antibodies effective for UC
