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.
Vomiting center impulses are from :..(4)
CTZ: receptors: M, CB1, NK1,5HT3,D2
NTS receptors: M,H1,NK1,5HT3,D2
Cerebellum : M , H1
Cortex: smell, sight, pain, psychological
Impulse of vomiting from GIT
Cytotoxic drugs,radiation, other Git irritants
Release 5HT from enterochromaffin cells
Act on 5HT receptors on extrinsic pathway of enteric NS
Send impulse that acts on 5HT3 receptors of CTZ,NTS -to vomiting centre-vomit.
Impulse of vomiting from blood.
Huge release of 5HT / release of 5HT from platelets ; spill into circulation, reach CTZ via blood vessels, act on 5HT3 receptors on CTZ —> signals to VC—>vomiting.
Impulse of vomiting from vestibular appendix
If body is rotated/equilibrium lost/ Ototoxic drug given —> vestibular apparatus in inner ear is activated —> send impulse to cerebellum, act on H1 and M1 receptors —> impulse to VC—>vomiting.
Egs of anticholinergic antiemetics . Use
Hyosine
Dicyclomine
Use for motion sickness
Disadvantages of hyosine (4)
- Brief duration
- Produces sedation
- Dry mouth
- Poor efficacy for vomiting of other etiologies
Use of dicyclomine (2)
Motion sickness
Morning sickness
Egs of H 1 antihistamines (6)
- Diphenhydramine
- Dimenhydrinate
- Doxylamine
- Meclizine
- Promethazine
- Cinnarazine
MOA of H1 antihistamines (2)
Block H1 receptors in CTZ and NTS
Minor M blocking action
Use of H1 antihistamines (2)
- Motion sickness for 4-6 hours
- Chemotherapy induced NV (CINV)
Drawbacks of antihistaminics (2)
Dry mouth, sedation
H1 antihistaminic with prominent anticholinergic action
Importance of meclizine . Use
Doxylamine
Meclizine:
Less sedating, long acting
Use: sea sickness for 24 hours
Egs of neuroleptics (4)
- Chlorpromazine
- Triflupromazine
- Prochlorperazine
- Haloperidol
MOA of antiemetics with neuroleptics (3)
- Block D2 in CTZ,NTS
- Block M and H1 receptors
5 uses of antiemetics (5)
- Post op N&V
- Disease induced vomiting: gastroenteritis,uremia, liver disease, vomiting etc.
- Malignancy associated and chemotherapy induced vomiting
- Radiation sickness
- Morning sickness- only for hyperemesis gravidarum
Egs of NK1 receptor antagonist (2)
MOA
Aprepitant
Fosaprepitant
Highly selective NK1 receptor antagonist for NK1 receptors of CTZ,NTS
Uses of Aprepitant (2)
- Cisplatin induced vomiting
Multiple cycles of chemo - Post operative nausea and vomiting
MOA of ondansetron
- Block 5HT3 receptor in gut and CTZ,NTS
ie, block both central and peripheral relay
Rx for cisplatin induced vomiting (2)
Acute vomiting : ondansetron
Delayed vomiting :
ondansetron+ Aprepitant
Iv injection of ondansetron can cause what s/e (4)
Hypotension
Bradycardia
Chest pain
Allergic reaction
Importance of ganisetron (2)
10-15 times more potent than ondansetron.
More effective in repeat cycle of chemotherapy
Max affinity for 5HT3 receptor
5HT3 antagonist removed from market. Why?
Palonasetron
Alosetron- constipation, ischemic colitis
Newer 5HT3 antagonists (3)
Dolasetron
Palonasetron
Tropisetron
Longest acting and most potent 5HT3 blocker
Shortest acting 5HT3 blocker
S/e of dolanosetron
Palonasetron
Ondansetron
QT prolongation
Egs of prokinetics (5)
Metoclopramide
Domperidone
Cisapride
Mosapride
Ito pride
MOA of prokinetics
Neurotransmitters that act on GIT
1. Excitatory: 5HT4 agonist
Ach release - prokinesis
2. Inhibitory: DA,5HT3 receptors
NO release- relaxation
Therefore:
Prokinetics act by increasing 5HT4 agonist , and D2,5HT3 blockers
Site of action of different prokinetics (4)
Metoclopramide: 5HT4+, 5HT3-,D2-
Cross BBB- cause EPS
Domperidone : D2 - does not cross BBB,no EPS
Cisapride: 5HT4 agonist , 5HT3 antagonist
Tegaserod: 5HT4 agonist
Newer congeners of cisapride (3) . Importance
Mosapride
Renzapride
Zacopride
They don’t cause QT prolongation like cisapride
Metoclopramide has prokinesis of Gastric but not ….
Antiemetic given for levodopa induced vomiting
Colonic
Domperidone- as it doesn’t cross BBB
Use of metoclopramide beyond ……weeks causes tardive dyskinesia
12 weeks
C/I for <20 yr old
Most potent antiemetic in preoperative period is …..
Ondansetron > palonasetron
Which antiemetic rx for diarrhoea dominant IBS and not for N/V?
Antiemetic that can also decrease acid secretion by acting on H1 receptors
Alosetron
Promethazine
MOA of stool softeners
Decrease stool surface tension by increasing water penetration into stool
What are the 2 kinds of stool softeners and s/e
- Liquid paraffin:
S/e:
a. unpleasant- swallowing wax
b. Decrease fat soluble absorption
c. Granulomas in intestinal wall
d. leakage of paraffin wax from anus is embarrassing - Docussate -better, as they don’t interfere with fat reabsorption
Eg of stimulant purgatives . MOA
C/I
Prune juice
Senna
Bisacodyl
They act on colon -to stimulate/irritate the mucosa -to increase secretion and motility.
Subacute intestinal obstruction
Pregnancy- can contract the uterus.
Which drug causes melanosis coli? (2)
Define melanosis coli
S/I of bisacodyl
Senna , Carcara
Lipofusin deposit in the colonic wall -harmless
Increase NO release
Rx for IBS types
Constipation predominant:
Rx:
1. Dietary fiber
2. Antidepressant:SSRI
3. Increase Cl- into colon:
Lubiprostone-PG activate CFTR
Linaclotide- guanyl cyclase activator
- Tegaserod-increase colon secretion by 5HT4 agonist .
Diarrhea:
Rx: 1. antimotility-loperamide
2. TCA
S/e of tegaserod
Newer 5HT4 agonist . Importance.
MI/Stroke -drug banned
Prucalopride- not cause MI/stroke can be used to rx constipation
Egs of osmotic laxatives (2)
MOA
Lactulose
Magnesium
They attract and retain water in GIT.
Egs of suppositories (2)
Bisacodyl
Sodium phosphate enema
Chronic laxative use can cause …..
Hypokalemia
Drugs for rx opioid induced constipation (5)
PAMORA
Peripherally acting M opioid Receptor Antagonist
1. Methylnaltrexone
2. Naldemedine
3. Naloxegol
4. Alvimopan
5. Lubiprostone
Loxiglumide is ……..
CCK receptor antagonist -gastric prokinetic agents
MOA of plecanatide
Use
Guanylate cyclase stimulator which acts by increasing CGMP- which stimulates CFTR-increasing Cl-ion into gut.
Use for idiopathic constipation
Abusing with anthranoid laxatives/senna causes…..
Ammonium urate kidney stones
Laxative that decreases blood ammonia in hepatic encephalopathy
Lactulose
Drugs to decrease ammonia in hepatic encephalopathy?
- Neomycin-
Kill Gi bacteria- decreases NH3
S/e: intestinal villi atrophy - Lactulose-preferred.
Nh3–>NH4
Nh4 is not reabsorbed-excreted.
Non diarrhoeal uses of ORS (4)
- Burns
- Heat stroke
- Post trauma
- TPN—> enteral nutrition
MOA of racecadotril
Inhibit enkephalinase
Enkephalin—> broken down by enkephalinase. Racecadotril inhibits that.
It’s an oral drug
DOC for secretary diarrhoea (3)
Octreotide
Atropine
Racecadotril
Anti diarrheal drug chemically related to opioid analgesic-meperidine
What are the peripherally acting opioid M agonist ?
Loperamide
Act on GIT—> decrease motility
Diphenoxylate: cross BBB- euphoria,abuse
Prevent this by adding atropine.
Loperamide- does not cross BBB.
Preferred drug for acute exacerbation of UC
Drug for worsening of UC/long term control.
Prednisolone / budesonide(oral)
5ASA - mesalamine
Which biological rx used in IBD is associated with risk of PML?
Natalizumab.
Name 2 alpha integrin therapy. Importance
Natalizumab - cause PML
Vedolizumab - don’t cause PML.
Opioid agonist act on GIT for diarrhoea by …..(2)
- Decrease intestinal motility- stimulate m receptors
- Decrease secretions- delta receptors
-on small and large intestines
Anticholinergics used for diarrhoea. Moa
Dicyclomine
Hyoscyamine
Decrease intestinal motility and cramps
MOA of clonidine in diarrhoea (3)
- Facilitates absorption
- Increase intestinal transit time
- Inhibits secretion of fluid and electrolytes.
Use of clonidine (2)
Diabetic diarrhoea
Diarrhoea caused by opiate withdrawal
Synthetic somatostatin agonist for anti diarrhoea
Moa (3)
Octreotide
- Decrease GI motility
- Decrease intestinal secretion
- Inhibit 5HT,gastrin,CCK,motilin,pancreatic polypeptide
Use of Octreotide (2)
S/e
- Rx secretary diarrhoea due to carcinoid Tumor
- VIPoma
Increased risk of gall stones due to CCK inhibition.
Indication of antiobesity drugs
Long term rx
BMI >30kg/sqm or
BMI >27kg/sqm with significant comorbidity
MOA of orlistat
S/e (5)
Gastric and pancreatic lipase inhibitor
S/e:
1. Steatorrhoea
2. Oily spotting
3. Fecal urgency
4. Abdominal pain
5. Headache
Risk of ……with orlistat (4)
Cholilithiasis
Oxalate Nephrolithiasis
Add Vit ADEK
Increases warfarin effect
Lorcaserin is ……
S/e (4)
5HT2C agonist
1. Dry eyes
2. Dry mouth
3. Constipation
4. Hyperprolactinemia
Risk of ……with lorcaserin (5)
Serotonin syndrome
NMS
Cardiac valve defects
Mood disorder
Priapism
MOA of liraglutide
S/e (3)
GLP-1 agonist
S/e:
1. GI upset
2. Pancreatitis
3. Acute cholelithiasis/ cholecystitis
Risk of …….with liraglutide
Thyroid cell hyperplasia
Injectable drug -use sc OD
Worsening of depression is seen with ….antiobesity drug
Phentermine+ topiramate ER
Ne+ GABA agonist
S/e of phentermine+topiramate (6)
Headache
Dry mouth
Cognitive impairment
Acute myopia
Glaucoma
Tachycardia
Worsening of migraines seen with …..
MOA
Naltrexone + bupropion ER
Opiate antagonist + DA/NE reuptake inhibitor
S/e of naltrexone+ bupropion (3)
Tachycardia
Suicidal thoughts
HTN
