Gastrointestinal System Flashcards
Define peptic ulcer
Defined as breach or break in the mucosa of stomach or duodenum
Imbalance between:
Aggressive factors:
gastric acid, pepsin,h.pylori
Defensive factors :
HCO3, mucus, prostaglandin
What are the major receptors of the stomach ?
3 main secretagogues:
H2 receptor : secrete Histamine
M3 receptor: secrete Ach
CCK receptor: Gastrin
1 defensive: PG receptor-secrete PG via EP3
How is acid released into the stomach ?
Food in the stomach activates gastrin and Ach from ganglion cells that act on CCK+M2 receptors on ECL. Release histamine from ECL.
Act on H2 receptors of parietal cells—> generation of CAMP—>activates H+K+ATPase—->acid release into lumen.
Cytoprotective roles of PG (5)
- Inhibit gastric acid secretion
- Stimulate gastric mucosa secretion
- Inhibit gastrin release
- Promote mucus and HCO3 secretion
- Ability to reinforce the mucus layer covering gastric and duodenal mucosa which is buffered by HCO3 secreted into this layer.
How does H pylori break defence mechanism of stomach?
Inhibits somatostatin which removes the inhibitory action on gastrin —> stimulating acid release.
4 approaches to treat peptic ulcer
- Drugs inhibiting / decreasing acid secretion in stomach
- Neutralize acids
- Ulcer protectives
- Anti H pylori drugs
What are the gastric acid secreting inhibitors ?
- Acting on H2 receptors
- PPI
- Anticholinergics
- Prostaglandin analogue-misoprostol
MOA of H2 blockers
Competitive blockers of H2 receptors on parietal cells.
Uses of H2 blockers (5)
- PUD
- Stress and gastric ulcers
- ZES
- GERD
- Prophylaxis of aspiration pneumonia
Long term s/e of cimetidine
Inhibit binding of DHT to androgen receptors—> loss of libido, gynecomastia, galactorrhoea, impotence .
Problem with bolus of iv injection of H2 blockers
Rapid release of histamine —> arrhythmias and cardiac arrest
H2 blockers cause transient elevation of ….
CNS effects of H2 blockers (7)
Plasma aminotransferases
1. Confusion-delirium
2. Headache
3. Dizziness
4. Hallucinations
5. Restlessness
6. Coma
7. Convulsions
What are the egs of Enzyme inhibitors?
Vit K cannot cause enzyme inhibition
Valproate
Ketoconazole
Cimetidine
Carbamazepine
Erythromycin
INH
Least potent and most potent H2 blocker
Least: cimetidine
Most: famotidine
All H2 blockers are competitive blockers except ….
Famotidine : competitive-non competitive
Loxatidine : competitive
Famotidine has …….action on receptors
Inverse agonist
Nizatidine importance
- Has anticholinergic activity —>cause bradycardia and increase gastric emptying
- 100% bioavailability
All H2 blockers except famotidine …..
Absorption of ……not affected by food.
Inhibit gastric first pass metabolism of ethanol
Cimetidine
Omeprazole is inactive at …..ph
MOA of omeprazole
Neutral ph
Omeprazole is enteric coated tablet, goes into the intestine , diffuses into the blood, gets into the parietal cell- at ph <5; it breaks into sulfonamide compound , which inhibit H+/K+ ATPase irreversibily and decrease acid secretion.
All PPI are enteric coated .why?
PPI that can be given iv (3)
To protect them from acidic gastric juice.
Thus they should not be crushed or broken before swallowing.
Esomeprazole
Lansoprazole
Pantoprazole
All PPIs are prodrugs, they get converted to active moeity ……in intestine
t1/2 of PPI…..
Duration of action of PPI….
Sulfenamide
1.5 hours
24 to 48 hours
PPI must be taken half an hour before food. Why?
On prolonged Rx, PPI cause ……
Coz food decreases bioavailability.
Atrophic gastritis
Most potent PPI and longest acting PPI
Most potent : lansoprazole
Longest acting: rabiprazole
Safest PPI in pregnancy
…… and …… are enzyme inhibitors that decrease metabolism of ……
Lansoprazole
Omeprazole and esomeprazole
Diazepam
Lansoprazole enhances metabolism of ……..
……..have only oral formulation
Theophylline
Omeprazole
Anticholinergic drugs egs (4)
Pirenzepine
Telenzepine
Propantheline
Oxyphenonium
MOA of anticholinergics
Inhibit M3 receptors on gastric mucosa—> decrease gastric secretion.
Anticholinergics are not preferred. Why? (4)
- They exhibit weak antisecretory effect compared to H2 blockers
- They decrease basal acid secretion by 40-45%
- Also in doses needed to decrease gastric secretion, there is dryness of mouth, urinary retention, tachycardia, glaucoma.
- Decrease volume of gastric juice without raising its PH.
What are PGE1 and PGE2 analogues of prostaglandin ?
PGE1: misoprostol
PGE2: enprostil, rioprostil
What are the types of antacids?
Systemic antacids: sodium compounds
Non systemic antacids: calcium, Mg, Al,mix
Magaldrate: Mg-Al mix
S/e of antacids
- Cause hypokalemia
- Do not decrease gastric acid, just raise the gastric Ph, —>more gastrin release—»thus leading to acid rebound.
Pharmacokinetics of antacids
Antacids taken on empty stomach acts only for 30-60 mins as it takes soo much time for gastric acid to pass into duodenum.
But if given with meals, they act for about 2-3 hours.
Which are the weak and strong antacids?
Weak: aluminum compound
Strong: mg compound.
S/e of aluminum compound (2)
- Inhibit motility, delays emptying causes constipation
- Inhibit PO4 reabsorption
Increase calcium reabsorption from bones
—>hypercalcemia,hypercalciuria, osteomalacia
S/e of Mg compounds
C/I of mg compounds
Strong, longer duration of action.
Increase GI motility, cause diarrhoea
Renal insufficiency
5-10% get reabsorbed, rest eliminated into kidney.
Advantages of Magaldrate (3)
- Fast (Mg) and slow (aluminium)
- Mg salts-laxative, Al salts- constipation
- Gastric emptying least affected as
Aluminium salts tend to delay it
And Mg salts hasten it.
Uses of antacids (2)
- Self prescribed by patients
- Relieve intermittent pain relief and acidity.
Eg of MagAldrate
Which anti ulcer drug act neither by secretion nor reducing secretion of gastric acid ?
gelusil
Sucralfate - at Ph<4; it’s gastroprotective
DOC for prevention of NSAID induced peptic ulcers
Most specific drug for NSAID induced PUD
PPI
Misoprostol
Which PPI cause least CYP2C 19 inhibition?
What is CYP2C19 do?
Which PPI causes max CYP2C19 inhibition?
Pantoprazole > Rabeprazole
Responsible for activation of clopidogrel
Omeprazole
Esomeprazole
Ranitidine + sucralfate is bad idea. Why?
Sucralfate at ph<4, it polymerises and stick to the base of the ulcer, ranitidine can’t act.
( Ranitidine increases gastric Ph )
Long term side effect of PPI (3)
- Decrease absorption
a). Fe- fe deficiency anemia
b). Ca- osteoporosis-increase fracture
c). B12- megaloblastic anemia
d). Mg- hypomagnesemia - Increase infection
C. Difficile pneumonia - Dementia, CKD
Adverse effects of cimetidine (3)
- Antiandrogen effect
- Increase prolactin - galactorrhoea
- Increase lipid soluble- cross BBB
Confusion, headache, dry mouth
Anti H pylori drugs
Triple therapy:
C-clarithromycin
A-amoxicillin / M-Metronidazole
P- PPI
Quadruple therapy:
T- Tetracycline
O-omeprazole
M-Metronidazole
B-Bismuth
Ulcer healing drug taken away from market .why?
Carbenoxolone
Due to its mineralocorticoid action-HTN, hypokalemia
Pathology of vomiting
Due to vomiting center in medulla oblongata.
Near the vomiting center are centres for respiratory,salivation, vascular control.