GI diseases Flashcards
(37 cards)
1
Q
- Parietal cells secrete?
- Chief cells secrete?
- D cells secrete?
- G cells secrete?
A
- Hydrochloric acid
- Pepsinogen
- Somatostatin
- Gastrin
2
Q
Why the main side effect of NSAIDS is GI problems?
A
because it decreases the production of prostaglandins necessary for the protective action against gastric acid on mucosa
3
Q
Prostaglandins
-function on the GI tract (4)
A
- increase bicarbonate production from mucous cells
- dilate blood vessels –> increase blood supply to mucous cells
- maintain normal function of the mucous
- form a protective layer
4
Q
Why does ICU patients have a higher risk of ulcer formation?
A
Because gastric acid production is increased in stress situations
5
Q
Antacids
- names
- mechanism
A
-Aluminium hydroxide, Calcium carbonate, Magnesium hydroxide
- Reduce intragastric acidity - main mechanism
- weak bases that react with gastric hydrochloric acid to forma salt and water
- rapid effect
- given 1h after meal –> neutralized gastric acid for up to 2h
- increase intragastric pH + decrease pepsin activity
6
Q
Why is calcium carbonate not used as an antacids anymore?
A
- because it produces CO2 which could cause antrum distension
- CO2 activates G cells –> increase gastrin secretion –> further increase the production of gastric acid
- if high doses are used –> high amounts of calcium would be absorbed –> systemic effects
7
Q
Antacids
-may affect the absorption of other medications by:
A
- binding the drug (reducing it’s absorption)
- increase intragastric pH –> alter the drug’s dissolution or solubility
8
Q
Antacids - absorption and effect on stool consistency:
- Magnesium hydroxide
- Calcium carbonate
- Aluminium hydroxide
A
- strong laxative effect, not absorbed from gut
- absorbed from gut
- not absorbed from gut, constipating action
9
Q
H2-receptor antagonists
- names
- mechanism of action
A
-Cimetidine, Ranitidine
- decrease hydrocholoric acid secretion
- block histamine H2 receptors on parietal cells
- decrease nocturnal acid but less effect than PPIs against stimulated secretion
- decrease pepsin secretion
- not very effective to reduce stimulated gastric acid secretion
10
Q
H2-receptor antagonists
- pharmacokinetics
- unwanted effects
A
- selective
- very safe
- only therapeutic effect –> reduction of gastric acid secretion - 60-70%
-headache, dizziness, diarrhea, constipation
Cimetidine
- weak anti-androgenic agent (Gynecomastia)
- potent P450 enzyme inhibitor
- may increase the concentration of many drugs
11
Q
Proton pump inhibitors (PPIs)
- names
- mechanism of action
A
-Esomeprazole, Omeprazole
- decrease hydrochloric acid secretion
- IRREVERSIBLY block H+/K+ ATPase in active gastric parietal cells
- most potent of all
12
Q
Proton pump inhibitors (PPIs)
- pharmacokinetics
- indications
A
- given orally (coated to prevent inactivation in the stomach) or parenterally
- metabolized in the liver
- 1/2 life of 1-2h
- may require 3-4d. to achieve their full effectiveness
- GERD, peptic ulcer, GI bleeding, part of H.pylori eradication therapy, non-ulcer dyspepsia, prevention of stress
- preventing ulcers caused by NSAIDs
- Zollinger-Ellison syndrome
13
Q
Proton pump inhibitors (PPIs)
-steps of how it acts
A
-lipophilic weak bases
- Absorbed in the intestines
- Reach systemic circulation
- Reach parietal cell
- Diffuse into the parietal cell canaliculi
- With the acidic environment of the lumen they become protonated (active)
- Converted to compounds that irreversibly inactivate the parietal cell H+/K+ ATPase
14
Q
Proton pump inhibitors (PPIs)
- why are repeated doses necessary?
- is tolerance possible?
A
Because it doesn’t block ALL the pumps at once. A few days are necessary to see an effect and also if u discontinue the drug.
No, because the cells are not able to adapt due to the fact that almost all of the pumps are inhibited
15
Q
Mucosal protective agents
-names
A
-Misoprostol, Sucralfate
16
Q
Mucosal protective agents
-names
A
-Misoprostol, Sucralfate
17
Q
Sucralfate
- mechanism of action
- other info
A
- polymerized in the acid environment - poorly soluble
- polymer binds to injured tissue and forms a protective coating over ulcer beds
- an aluminum sucrose sulfate
- accelerates the healing of peptic ulcers and decrease the recurrence rate
- toxicitiy is very low - no systemic effects
18
Q
Antibiotics
-H. pylori infection
A
- chronic infection with H.pylori is present in most patients with recurrent non-NSAID induced peptic ulcers
- eradication of H.pylori decreases the rate of recurrence of ulcer in these patients
- Antibiotics + PPIs –> usually at least 2 antibiotics
Omeprazole + Clarithromycin + Amoxicillin
Omeprazole + Clarithromycin + Metronidazole
Omeprazole + Tetracycline + Metronidazole + Bismuth
19
Q
Antibiotics
- H. pylori infection
- combination of drugs
A
- chronic infection with H.pylori is present in most patients with recurrent non-NSAID induced peptic ulcers
- eradication of H.pylori decreases the rate of recurrence of ulcer in these patients
- Antibiotics + PPIs –> usually at least 2 antibiotics
Omeprazole + Clarithromycin + Amoxicillin
Omeprazole + Clarithromycin + Metronidazole
Omeprazole + Tetracycline + Metronidazole + Bismuth
20
Q
Sources of input to the vomiting center
A
- “Chemoreceptor trigger zone” - activated by different drugs and toxins or by the vesicular nuclei. Dopamine, serotonin, opioid, NK1 receptors
- Vestibular system - Muscarinic and histamine receptors
- Vagal and spinal afferent nerves from the GI tract
- CNS
21
Q
Drugs with antiemetic actions - names
- Selective 5-HT3 receptor antagonists
- D2 dopamine antagonists
- H1 antagonists
- Muscarinic receptor antagonists
A
- Ondansetron
- Metoclopramide, Domperidone
- Meclizine
- Scopolamine
22
Q
Prokinetic agents
- names
- function
- indication
A
- Neostigmine, Metoclopramide, Domperidone, Erythromycin
- increase GI motility
- GERD, gastroparesis/ post-surgical gastric emptying delay or decreased intestines motility
23
Q
Neostigmine
A
- acetylcholinesterase inhibitor
- increase acetylcholine in synapsis –> increase peristalsis
24
Q
Metoclopramide, Domperidone
A
- D2 receptor antagonist
- decrease sympathetic activity, indirectly increase parasympathetic activity
- promote GI motility
- Metoclopramide - can cross blood-brain barrier –> when used chronically can cause symptoms of parkinsonism, hyperprolactinemia, etc.
- Domperidone - cannot cross blood-brain barrier –> low risk of CNS toxicity
25
Erythromycin
- motilin receptors on GI smooth muscle stimulator
| - macrolide antibiotic
26
Laxatives
- names
- function
- Docusate, Magnesium hydroxide, Lactulose, Senna, Bisacodyl
- increase bowel movement
27
Laxatives
- indications
- contraindication
- before examination, before/after surgery, before birth (obstipation during pregnancy)
- drug induced obstipation, intoxication, hemorrhoids
-obstruction of the bowel
28
Laxatives "Vicious Circle)
TOLERANCE
1. Constipation
2. Drug is given
3. Defecation + electrolytes loss
4. Kidneys try to compensate for the electrolyte loss
5. Reabsorption of sodium and water
6. increase absorption of sodium = potassium loss
7. Can lead to hypokalemia (muscle weakness)
8. Lower motility of bowels
9/ Could exacerbate constipation
29
Laxatives
| -Types
1. Bulk-forming laxatives - 12-72h to work
- fiber in the food: ass bulk and water
2. Stool surfactant agents (Softeners) - 12-72h work
- anionic surfactants: add water and fats
- Docusate
3. Osmotic laxatives - 12-72h (oral)/ 30min-1h (rectal) to work
- create osmotic effect and increase water holding = water secretion
- Magnesium hydroxide, Lactulose
4. Stimulant laxatives (Cathartics) - 6-10h to work (fast)
- act on intestinal mucosa/ enteric nervous system and increase water/electrolyte secretion
- Senna, Bisacodyl
30
Anti-diarrheal agents
| -name
-Loperamide, Somatostatin, Ocreotide
31
Loperamide
- mechanism of action
- unwanted effects
- opioid agonist --> no unwanted effect but drug effect is only local --> minimal CNS effect
- activates u opioid receptors in enteric nervous system and slows motility with negligible CNS effect
-mild cramping but little or no CNS toxicity
32
Somatostatin
- action on the anterior pituitary
- action on the GI system
- paracrine function in nervous system
- decrease release of growth hormone, TSH, prolactin
- decrease release of gastrin, cholecystokinin, secretin, motilin, vasoactive intestinal peptide, gastric inhibitory polypeptide, 5-HT
- decrease intestinal fluid secretion, motility, gallbladder contraction, portal and splanchnic blood flow
- decrease pancreatic function: release of glucagon, insulin, exocrine secretory function
33
Ocreotide
- indications
- unwanted effects
- acute hemorrhage from esophageal varices in liver cirrhosis (decrease portal venous pressure)
- diarrheas with: carcinoid syndrome (increase secretion of 5-HT and kallikrein)
- GI fistulae
-GI --> cramps, nausea, vomiting, diarrhea, constipation, hyperbilirubinemia, gallstones, hyperglycemia or hypoglycemia, hypothyroidism, bradycardia, dizziness, dyspnoae
34
Anti-spasmodics
- name
- mechanism of action
- indications
- Drotaverine
- causes imbalance of calcium --> decrease activity of the muscle
- irritable bowel syndrome, abdominal pain and cramps, diarrhea alternating with constipation, flatulence
35
Inflammatory bowel disease
- treatment for the mild stage of the disease - name
- mechanism of action
- Sulfasalazine (5-ASA + sulfapyridine)
- decrease activity of immune cells = decrease synthesis of prostaglandins, leukotrienes, cytokines
- systemic absorption of the sulfapyridine moiety --> nausea, GI upset, headache, myalgias, bone marrow suppresion
36
Inflammatory bowel disease
| -treatment for the moderate stage of the disease - name
- Methotrexate
| - immunomodulator
37
Inflammatory bowel disease
| -treatment for the severe stage of the disease - name
- Adalimumab, Infliximab
| - anti-TNF antibodies
