Pharmacological Basis For Treatment Of GI Disorders Flashcards
Name some H2 receptor antagonists?
Ranitidine, cimetidine, (famotidine, nizartidine)
What are H2 receptor antagonists used to treat?
Peptic ulcer reflux oesophagitis
What is the mechanism of action for H2 receptor antagonists?
Inhibits histamine, ACh and gastrin secretion on parietal cells.
Reduces gastric acid secretion and therefore reduces pepsin secretion
How much can H2 receptor antagonists decrease basal and food-stimulated acid secretion by?
90%
What do H2 receptor antagonists promote?
Healing of duodenal ulcers
Give some side effects of H2 antagonists
Diarrhoea, muscle cramps, transient rashes, hypergastrinaemia
What is hypergastrinaemia?
Hyper secretion of gastrin
What can cimetidine cause?
Gynaecomastin in men
What is gynaecomastin?
Enlarged chest tissue
What does cimetidine inhibit?
P450 enzymes
Which is more potent- Ranitidine or cimetidine?
Ranitidine
Give some proton pump inhibitors
Omeprazole, lanzoprazole, pantoprazole
What are the clinical uses of proton pump inhibitors?
Peptic ulcers, reflux oesophagitis, part of treatment for H. Pylori and Zollinger-Ellison syndrome
What is the mechanism of action of proton pump inhibitors?
irreversibly inhibits the hydrogen/potassium ATPase pump, which decreases basal and food-stimulated gastric acid secretion
What are the side effects of proton pump inhibitors?
Headache, diarrhoea, mental confusion, rashes, somnolence, impotence, gynaecomastia, dizziness
What is somnolence?
Needing lots more sleep than usual
What drugs protect the gastric mucosa?
Prostaglandins (PGE2 and PG12)
Misoprostol
What do prostaglandins inhibit?
Gastric acid secretion and the activity of parietal cells
What do prostaglandins increase?
Mucosal blood flow that can augment the secretion of HCO3 - and mucus
What might prostaglandins induce?
Labour/ abortion
What are the effects of inhibition of dopamine at D2 receptors?
Increased release of ACh and improve antroduodenal coordination
What does increased ACh release mean in the gut?
Increased peristalsis in all of small intestine, increased intragastric pressure (increased LOS tone and increased tone of gastric contractions)
What are the effects of metaclopramide on gastric motility and emptying?
Inhibits D2, 5-HT3 receptors
Stimulates 5-HT4 receptor
prokinetic effects
What is the effect of inhibiting D2 and 5-HT3 receptors?
Inhibits vomiting
What are the prokinetic effects metaclopramide has?
Stimulates presynaptic excitatory 5-HT receptors and inhibits nitrenergic neurones -> coordinated gastric motility
What does metaclopramide do?
Treats GI reflux, stimulates gastric motility and accelerates gastric emptying
What is the clinical utility of metaclopramide?
Symptoms of gastroparesis, promotes gastric emptying and anti-emetic effects via central pathways
Give examples of antispasmodic agents
Propantheline, dicloxerine, mebeverine
How do antispasmodic agents work?
Decrease bowel spasm by relaxing the smooth muscle in GIT
What is propantheline?
Antimuscarinic agent
What do muscarinic receptor antagonists inhibit?
Parasympathetic activity- reduces bowel spasm
What are the goals of pharmacological interventions for gastric ulcers?
Reduce acid secretion with H2 receptor antagonists, neutralise secreted acid with antacids and attempt to eradicate H. pylori
How does inhibition of acid secretion help heal gastric ulcers?
Removes the constant irritation to give it some time to heal
When can drugs be used to inhibit or neutralise gastric acid secretion?
Peptic ulcer reflux oesophagitis and Zollinger-Ellison syndrome
What is the general mechanism of antacid action?
neutralise gastric acid, increase pH of gastric acid
How does an alginate raft barrier help in the stomach?
Immediate local protection as it forms over the stomach contents which keeps the acid in the oesophagus
What does pepto bismol do?
Protects gastric mucosa, toxic against H. pylori
How does pepto bismol protect the gastric mucosa?
- forms a base over the crater
- adsorbs pepsin
- increases HCO3 - and prostaglandin secretion
What does H. Pylori have that helps it to go through the thick mucosal lining?
Corkscrew mechanism and mucinase activity
How do you treat H. Pylori?
Combination therapy using an antibiotic and a drug that inhibits acid production
What happens if metronizadole is taken with alcohol?
Patient will feel severely ill and may stop taking the drug - buildup of acetaldehyde which leads to an unpleasant flushing and nausea
What happens if you take metronizadole in the first trimester of pregnancy?
Birth defects
Do toxic substances accumulate upon prolonged constipation?
No
What are the symptoms of constipation?
Headache, appetite loss, nausea, abdominal distension and stomach pain
What happens if you hold faeces in?
Increased water loss and dryer faeces (so more painful and harder to defecate)
What are the causes of constipation?
Decreased motility of large intestine
What can cause decreased motility of the large intestine?
Damage to the enteric nervous system of the colon (affects the initiation of the vagovagal reflex)
What factors can increase colonic motility?
- Increased fibre, cellulose and complex polysaccharides
- bran, foods with high fibre
- laxatives
- Mineral oil
- castor oil
What does excessive use of laxatives lead to?
Decreased responsiveness
How does mineral oil help constipation?
Lubricates faeces
What are the causes of constipation in the elderly?
Diet, inactivity and drugs (or the interaction of them)
What are the alarm signs in constipation?
- Acute onset in elderly
- weight loss
- blood in stool
- anaemia
- family history of colon cancer or IBD
How can constipation be managed?
- Diet, fluid intake and exercise
- increased fibre intake
What are the two types of laxatives?
Bulk laxatives, plant gums
How do bulk form in and osmotic laxatives work?
Retain water in the gut lumen which leads to the promotion of peristalsis
Give an example of a bulk laxative
Methylcellulose
Give some examples of plant gums
Agar, linseed, bran, polysaccharide polymers
What are some other effects of laxatives?
Bloating and flatulence
How do osmotic laxatives work?
Increases and maintains volume of fluid in the lumen of bowel by osmosis, which increases the transfer of gut contents into the intestine
What can some side effects of osmotic laxatives if given in high doses?
Flatulence, cramps, diarrhoea, vomiting and tolerance
Give an example of an osmotic laxative
Lactulose
Give the mode of action of lactulose in constipation
Colonic bacteria breaks it down into short chain fatty acids -> osmotic pressure increases and/or biomass increases -> softening of the faeces -> stimulation of peristalsis -> shorter colonic transit time
What do pergatives do?
Increase passage of food through the intestine
What do anti-diarrhoea drugs lead to?
Decreased movement
What do antispasmodic drugs lead to?
Decreased movement as it relaxes smooth muscle in GIT
What are the therapeutic strategies to diarrhoea treatment?
- maintain fluid and electrolyte balance
- use of anti-infectives (not if viral)
- use of non-microbial anti-diarrhoeal agents
- anti-motility drugs
How does loperamide work?
Decreases passage of faeces and duration of illness
How do codeine and loperamide work?
Anti-secretory action-> intestinal motility
How does bismuth subsalicylate work?
Decreases fluid secretion in the bowel
What is the mechanism of action of loperamide?
Opioid receptor agonist-> binds to the u-opioid receptor of the myenteric plexus of the large intestine
What does stimulation of the u-opioid receptor by loperamide inhibit?
Gastric emptying, increases sphincter tone, induces stationary motor patterns and blocks peristalsis
How does loperamide reduce force and speed of colonic movement?
Increases haustral mixing of the proximal colon and inhibits propulsive mass movement of the distal colon
