Pharmacology -- Antacids, motility and anti-motiliy agents Flashcards
3 treatments for ulcers
- Proton pump inhibitors
- H2 receptor blockers
- Antacids
5 treatable GIT conditions
- Reflux esophagitis
- Peptic ulcers
- Delayed gastric emptying
- Inadequate propulsion of chyme
- Infections and inflammations
How are peptic ulcers formed?
Imbalance favoring the acid pepsin aggression vs. mucosal defense
Describe how helicobacter pylori infection contributes to the formation of peptic ulcers
- Gastrin is a hormone that promotes acid secretion in the stomach
- Ordinarily, increase HCl inhibits the production of gastrin
- H. pylori blocks the inhibition of gastrin and instead allows gastrin to keep increasing stomach pH
5 drug targets in ulcer therapy
- Neutralizing acids with antacids
- H2 receptor blockers (cimetidine, ranitidine)
- M1 M3 blockers (propantheline)
- Adenylyl cyclase inhibitors
- H+/K+ ATPase pump blockers
2 H2 (histamine) receptor blockers
- Cimetidine
- Ranitidine
3 disadvantages of cimetidine
- Short duration of action
- Interaction with p450 enzymes
- Anti-androgenic effects
Alternative to cimetidine
Ranitidine (also an H2 receptor blocker)
3 advantages to using ranitidine as an alternative to cimetidine
- Longer duration of action
- No p450 interactions
- Weaker anti-adrogenic effects
What is emoprazole
An irreversible inactivtor of the H+/K+ pump
Why is it that omeprazole only blocks the H+/K+ pump in the stomach and not anywhere else in the body that needs it?
- Target dependent
- Can only be activated by low pH
- i.e. it is a prodrug activated by low pH
Why is it that many NSAIDs are accompanied by omeprazole?
NSAIDs are known to cause bleeding and ulcers, so omeprazole is used as an adjunct to prevent damage to the stomach due to its long duration of action
Side effect of omeprazole
Gastric mucosal hyperplasia
Possible mechanism for the side effect of omeprazole
Excessive gastrin secretion
Mechanisms of action of antacids
- Neutralization of intragastric HCl
- Increase in intragastric pH
leads to
- Reduction of pepsin activity
Systemic antacid
Sodium bicarbonate
Adverse effect of systemic antacids
Increase in blood pH
3 nonsystemic antacids
- Calcium
- Magnesion
- Aluminum
Problem with nonsystemic antacids
Poorly absorbed
Therapeutic effects of antacids
Effective management of peptic ulcers
Disadvatanges of antacids
- Frequent dosing required
- Disagreeable taste
2 properties of sodium and potassium antacids
- Rapid onset
- Short duration of action
3 properties of calcium antacids
- Rapid onset
- Long duration of action
- Limited effect on pH
3 properties of magnesium antacids
- Rapid onset
- Large effect on pH
- Laxative
2 properties of aluminum antacids
- Slow onset
- Constipative
What is sucralfate?
A mucosa protecting drug
Explain the mechanism of sucralfate
- Complexes with protein at ulcer site to form a protective layer
- Binds to pepsin
Describe the effects of reflux esophagitis (i.e. the series of events)
- Inappropriate relaxation of the lower esophageal sphincter
- Flow og gastric content into esophagus
- Irritation and inflammation of mucosa
2 ways to intervene in reflux esophagitis
Intervene at the following events:
- Inappropriate relaxation of LES (by increasing its tone)
- Flow of gastric content into esophagus (by countering acidity with antacids)
Describe the series of events in gastroparesis
- Damage to gastric nerve or smooth muscle (diabetes)
- Delay in gastric emptying
How to intervene in the event of gastroparesis
Prokinetic drugs to counteract effects of damage to nerves or smooth muscle
3 adverse effects of cholinergic drugs
- Stimulation of salivary, gastric, pancreatic and intestinal secretions
- No coordination of gastroduodenal contraction
- Cardiac and asthma conditions could be exacerbated
5 effects of D2 receptor antagonists
- Block inhibitory presynaptic D2 receptor
- Increase lower sphincter tone
- Increase force of gastric contraction
- Increase coordination of gastroduodenal coordination
- Increase gastric emptying
2 side effects of D2 antagonists
- Parkinson-like side effects
- Increase in prolactin levels and breast tenderness (gynecomastia, galactorhea)
3 effects of 5HT4 agonists
- Increase lower sphincter tone
- Increase gastroduodenal coordination
- Increase gastric contractions
2 types of activity that ondansteron has
- 5HT3 antagonistic activity
- Antiemetic acitivity
3 causes of constipation
- Functinoal disorders
- Drug treatments
- Low residue diets
2 causes of diarrhea
- Bacterial or viral infection
- Chronic inflammatory disease
Drug type to treat constipation
Laxatives
Drug type to treat diarrhea
Anti-diarrheal
4 laxative mechnisms of action
- Secretory or stimulant
- Saline
- Emollient
- Bulk forming
What is castor oil
Secretory laxative
Mechanisms of castor oil (secretory laxative) action
- Increased prostaglandins and adenylate cyclase
- Increased Cl channels
- Increased fluid accumulation
- Increased fluid flow and peristalsis
NOTE: Other mechanism = inhibition of water reabsorption in lower intestine
2 bulk-forming agents
Bran
Psyllium husk
Mechanism of action of bulk forming agents
- Formation of large hydrophilic mass
- Increased bulk and water content
- Decreased intestinal transit time
- Decreased viscosity of luminal content
- Increased flow through bowel
3 saline laxatives
- Magnesium hydroxide
- Sodium phosphate
- Sodium sulfate
Mechanism of saline laxatives
Drawing water into intestine by osmotic process
4 disadvantages of laxatives
- Lead to habituation
- Damage to myenteric plexus
- Colonic atony
- Excessive loss of Ca++
Therapeutic priorities in the treatment of constipation
- Increase fiber in diets and increase fluids
- Bulk agents
- Osmotic laxatives
- Stimulants
3 antidiarrheal drugs
- Opioids
- Morphine
- Codeine
3 mechanisms of antidiarrheal drugs
- Act on interstinal neurons –> increased absorption and reduced fluid secretion
- Act on CNS
- Alter pattern of motility to increase resistance to flow
What are the motility alterations made by anti-diarrheal drugs?
- Increased segmental contraction
- Decreased propulsive contractions
Mechanism of anti-diarrheal morphine and codeine
- Motility alterations
- Increased segmental contractions
- Decreased propulsive contractions
- Cross the blood brain barrier –> exhibit both CNS and local action
2 advantages of using loperamide and diphenoxylate as anti-diarheal agents as opposed to morphine and codeine
- No CNS effects
- Low abuse potential
When should opioids not be used in the treatment of diarrhea?
When the diarrhea is induced by enteric infections
3 types of prokinetic drugs
- Cholinergic drugs
- D2 receptor antagonists
- 5HT4 agonists
