Pharmacological basis of GI treatment Flashcards
What are 4 examples of H2 receptor antagonists?
→ranitidine
→cimetidine,
→ famotidine
→nizartidine
What are clinical uses of H2 receptor antagonists?
→ Peptic ulcer reflex oesophagitis
What do H2 receptor antagonists inhibit and promote ?
→Inhibits histamine, ACh and gastrin stimulated acid secretion on parietal cells
→Promotes healing of duodenal ulcers
What does stopping treatment of H2 receptor antagonists do?
→Stopping treatment means relapse
How is the H+/K+ pump activated by action of gastrin?
→Gastrin can activate ECL cells to release histamine
→ it binds to H2 receptors on parietal cells
→activates the H+/K+ ATPase pump
What do H2 receptor antagonists reduce?
→Reduces gastric acid secretion and as a consequence reduces pepsin secretion
What can H2 receptor antagonists decrease?
→Can decrease basal and food stimulated acid secretion by 90%
What can 4 side effects of H2 receptor antagonists be?
→diarrhoea
→muscle cramps
→transient rashes
→hypergastrinaemia
What is a side effect of cimetidine?
→ Gynecomastia
What does cimetidine inhibit?
→ P450 enzymes
What does a low IC50 mean?
→ Drug is more powerful
What does IC50 mean?
→ Inhibitory concentration
What are 4 examples of proton pump inhibitors?
→ omeprazole
→ lanzoprazole
→ pantoprazole
→ rabeprazole
What are clinical uses of proton pump inhibitors?
→Peptic ulcer → reflux oesophagitis →therapy for H. Pylori → treatment for Zollinger-Ellison →Drugs of choice if hyper-secretion occurs
What is the mechanism of action of proton pump inhibitors?
→ Weak bases - inactive at neutral pH and irreversibly inhibit the H+/K+ ATPase pump
→ Decrease basal and food stimulated gastric acid secretion
What are side effects of proton pump inhibitors?
→Headache →diarrhoea → mental confusion →rashes →somnolence → impotence → gynecomastia → dizziness
What protects the gastric mucosa?
→ PGE1
→ PGE2
What drugs protect the gastric mucosa?
→ misoprostol - stable analogue of PGE1
What does misoprostol inhibit?
→Inhibits basal and food stimulates gastric acid secretion
→Inhibits histamine and caffeine induced gastric secretion
→Inhibits the activity of parietal cells
What does misoprostol increase and induce?
→Increases mucosal blood flow and can augment the secretion of HCO3- and mucus
→Induces labour/abortion
What does metoclopramide do?
→inhibits pre and postsynaptic dopamine (inhibits ACh) receptors as well as 5HT3
What do 5HT3 receptors do?
→receptors which inhibits vomiting
What does dopamine inhibit?
→ ACh release
How does dopamine inhibit ACh?
→inhibits the release of ACh from intrinsic myenteric cholinergic neurons by activating prejunctional D2 receptors
What kind of effects does dopamine have on the gut and where?
→relaxant effects on the gut by activating D2 receptors in the lower oesophageal sphincter and stomach
What does dopamine do in the distal and proximal areas of the gut?
→can induce contraction in the proximal
→relaxation in the distal
What does increased ACh mean?
→Increased ACh means increased intragastric pressure →due to increased LOS tone
→ increased tone of gastric contractions
What does an increase of ACh do to contraction and emptying?
→These improve antral duodenal contraction which →accelerates gastric emptying
→relaxes the pyloric sphincter
What two properties does metoclopramide have?
→ antiemetic properties via central effects
→relieves headache via central effects
What is metoclopramide useful for?
→GI reflux
What does metoclopramide stimulate and accelerate?
→ S: gastric motility
→ A: gastric emptying
What neurons does metoclopramide stimulate?
→inhibitory nitregic neurons
→mediate NO release
What are the 6 effects of metoclopramide?
→Inhibits presynaptic and postsynaptic D2 receptors
→Stimulates the release of ACh / SP from enteric neurons
→Elicits mixed 5-HT agonist and antagonist effects, e.g., stimulates excitatory 5-HT4 receptors (ENS), but inhibits 5-HT3 receptors (CNS);
→Stimulates inhibitory nitregic neurons – mediate NO release
→Increases intragastric pressure -↑ LOS and gastric tones
→Motility stimulant - improves antro-duodenal coordination and accelerated gastric emptying
What are 3 examples of antispasmodic agents?
→Propantheline
→ dicloxerine
→ mebeverine
What do antispasmodic agents do?
→Decrease spasm in bowel, they have relaxant action on GIT (smooth muscle in GIT)
What is propantheline?
→antimuscarinic agent
What do muscarinic receptor antagonists do?
→inhibit parasympathetic activity which reduces spasm in the bowel
What is the goal in pharmacological intervention in gastric ulcer?
→Reduce acid secretion with H2 receptor antagonists
→Neutralise secreted acid with antacids
→Attempt to eradicate H. pylori
What kind of bacteria is H.Pylori?
→H.Pylori is a gram negative bacillus
What is the mechanism of action of antacids?
→Neutralize gastric acid
→increase the pH of gastric acid
What does bismuth chelate do?
→Protects gastric mucosa →Forms a base over crater of ulcer →Adsorbs pepsin →Increased HCO3- and PG secretion →Toxic against H. Pylori - used as part of a triple therapy to eradicate it →Blackens stool and tongue
What can bismuth chelate cause?
→Can cause encephalopathy
How do prostaglandins protect the mucosal layer?
→Stimulating bicarbonate secretion
→Reducing H+ secretion
→Promotes vasodilation
Why do NSAIDS (e.g. aspirin) cause gastric bleeding?
→ Inhibit PG synthesis
What reduces bleeding from NSAIDs?
→Celecoxib
→ rofecoxib
What is H.Pylori a risk factor for?
→ gastric cancer
What is a 3 combination therapy for H.Pylori?
Omeprazole, amoxicillin and metronidazole
What cytoprotective effects does bismuth chelate have?
→Provide a physical barrier (coat) over the surface/base of the ulcer
→Enhances local synthesis of PGs
→Promote bicarbonate secretion
What reaction happens if metronidazole is taken with alcohol?
→Disulfiram like reaction
What does disulfiram do to alcohol?
→ Inhibits acetaldehyde dehydrogenase so acetaldehyde builds up
What are consequences of constipation?
→Headache →Loss of appetite →Nausea →Abdominal distension and stomach pain →Holding of fecal matter → Water loss and drier feces → painful and harder to defecate
What are 3 causes of constipation?
→Decreased motility of large intestine
→Old age
→Damage to enteric nervous system of colon
What are factors that can increase colonic motility?
→Increased fibre, cellulose and complex polysaccharides
→Bran, fruits, vegetables with high fibre
→Laxatives but excessive use - decrease in responsiveness
→Mineral oil - lubricates feces
→Castor oil - stimulates motility of colon
What are alarm signs for people with chronic constipation?
→Acute onset in older individuals →Weight loss →Blood →Anaemia →Family history of colon cancer or inflammatory bowel disease
What can purgatives do?
→modulate/hasten food transit in the intestine
What are bulk laxatives?
→Bulk laxatives - methylcellulose
→Plant gums (sterculia, agar, linseed, bran)
What do bulk laxatives do?
→They retain water in the gut lumen → promote peristalsis but take a few days to work
→Increase the stools solid content /Bloating and flatulence
What do osmotic laxatives do?
→Increases and maintains the volume of fluid in the lumen of the bowel by osmosis
What do high doses of osmotic laxatives cause?
→flatulence → cramps →diarrhoea → vomiting →tolerance
What do anti-diarrheal agents do?
→Maintain body fluids and electrolytes
What are 4 causes of diarrhoea?
→Infectious agents
→Toxins
→Anxiety
→Drugs
What does oral rehydration therapy do?
→maintain fluid and electrolyte balance
What does loperamide do?
→Selective on GIT
→Decreases passage of feces
→Decreases duration of illness
What does bismuth subsalicylate do?
→Decreases fluid secretion in bowel
→Safe for young children
→Tinnitus and blackening of stool
What type of drug is loperamide?
→Opioid receptor agonist
Where does loperamide exert its effects?
→Exerts effects on mu opioid receptor of the myenteric plexus of the large intestine
What does loperamide do to the GIT?
→reduces smooth muscle activity in the GIT
→reduces passage of feces
What does loperamide increase?
→Increases haustral mixing of proximal colon
What does loperamide inhibit?
→Inhibits propulsive mass movement of the distal colon
Why does loperamide not have CNS effects?
→ Does not cross the blood brain barrier
What does loperamide reduce?
→ Force and speed of colonic movements
