Final exam lecture 3 Flashcards by Matti Daniel

anatomy of stomach

Fundus is the top
two valves.
(pyloric valve and esophageal valve.)

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Name the 4 kind of drugs affecting gastric secretion.

Antacids
H2 histamine receptor antaginists
PPIs
Protectants

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drugs that increase GI motility

Laxatives
prokinetic drugs

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Drugs that reduce GI motility

Antidiarrheal
Anti emetic

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Explain the physiological control of GI secretions

We eat food
It activates G cells to make gastrin
gastrin acts on ECL to produce histamine
Histamine, AcH and gastrin act on parietal cells to activate proton pumps

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Effect of parietal cells being acted upon by histamine, gastrin or Ach

Histamine, Ach and gastrin acidify the lumen of the stomach by activating parietal cells

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how is the acid secretion is stomach halted

acid acts on D cells to produce somatostatin. Somatostatin feedsback and shuts down G cells.

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What do D cells do?

Deaccelerate to shut down acid secretion via somatostatin.

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mucus is produced by cells in stomach through

prostaglandins

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How does aspirin cause ulcers of stomach

decrease prostaglandin production, decreasing mucus

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Name 4 of the antacids

NaHCO3
CaCO3
AL(OH)3
MG(OH)2

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What is the neutralizing capacity of the antacids

NaHCO3- High
CaCO3- moderate
AL(OH)3- High
MG(OH)2- High

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Adverse effects of the antacids

NaHCO3- systemic alkilosis, fluid retention
CaCO3- hypercalcemia, nephrolithiasis, milk-alkali syndrome
AL(OH)3- constipation, hypophosphatemia
MG(OH)2- diarrhea

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difference in side effects between AL(OH)3 and MG(OH)2

Al causes constipation
Mg causes diarrhea

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Which cells produce histamine that acts on parietal cells

ECL cells

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how do histamine receptor antagonists work? (H2RA)

They competitively inhibit H2 histamine receptors

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H2RA drugs names

End with -tidine
(cimetidine, ranitidine, Nizatidine, Famotidine)

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Mechanism of PPI inhibition of acid secretion

Directly binds and blocks ability of protein pump to exchange a proton for K+. Leading to profound inhibition of gastric acidification.

Leads to irreversible inhibition through disulfide bond.

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PPI drug names

End with -prazole
(esomeprazole Purified S enantiomer), omeprazole S and R enantiomer)

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Structure of PPI

Hexene next to 5 membered ring with two nitrogens

How are PPIs activated

By acidic PH in the parietal cells

What may occur during withdrawal of PPIs

Hypergastrinemia occurs and may result in rebound hypersecretion of gastric acid.

compare H2 blockade and PPI

H2 blockade damps down peaks in acid production.
PPI completely prevents acid producton

People who take PPIs chronically have

hypergastrinemia

Why does hypergastrinemia happen on PPIs

Reduced gastric acid removes somatostatin inhibition of gastrin secretion.

side effects of PPI

Increased risk of infection Vit B12 deficiency Decreased Ca 2+ absorption/ increased bone fractures (increased bone resorption)

What are the two mechanisms of PPI therapy causing fractures

1) decreased calcium absorption causes a decline in Ca. causes secondary hyperparathyroidism, increasing bone resorption 2) Hypergastrinemia causes Parathyroid hyperplasia

______ are prodrugs that must be protonated to become active and form ______ bonds

PPIs, covalent disulfide bonds

MOA of sucralfate

It is an AlOH complex of sucrose. It polymerizes and forms a protective barrier at ulcer site. Acidic PH activates complex.

Name two mucosal protective agents

Misoprostol Sucralfate

Misoprostol MOA

Semisynthetic PGE derivative. Instead of mimicking mucus, it stimulates gastric cells to produce their own

H. pylori combo treatment (with example)

BSS Antibiotic (metronidazole, clarithromycin, tetracycline, amoxicillin) H2 blocker or PPI example- Metronidazole+ omeprazole+clarithromycin X 2 weeks

Example of bulk and osmotic laxatives

Psyllium (metamucil) PEG 3350 (MiraLAX ) Methylcellulose (citrucel) Lactulose (duphalac)

example of stimulant laxatives

Castor oil, bisacodyl (dulcolax), senna

What situations would prokinetic drugs be used

Gastroparesis parkinsons opioid induced constipation

What is Metoclopramide? What is it use for?

Metoclopramide is a dopamine receptor antagonist. It is used for promotion of gastric emptying for post OP, diabetic, gastroparesis patients

name opioid receptor antagonists that cant cross BBB

Naloxegol (movantik) Alvimopan (entereg) naldemedine (SYMPROIC)

Opioid induced constipation can be avoided by ________

Biased agonists like olicerdine (instead of morphine)

How do Prucalopride (motegrity) and tegaserod (zelnorm) work

5HT4 agonists, leading to increased cAMP, PKA activation and release of ACH

What is prucalopride (motegrity) indicated for

Chronic idiopathic constipation in adults

WHat is tegaserod (zelnorm)indicated for

Indicated for treatment of IBS with constipation in women UNDER 65

Age range of zelnorm (tegaserod)

Under 65 and no prior heart conditions

How do chloride channel activators work?

Increases amount of Cl in gut, leads to increased Na+ and increased H20

Example of chloride channel activators

Lubiprostone (amatiza) Linaclotide (linzess) Plecanatide (Trulance)

What are chloride channel activators used for

IBS+constipation

how does Tenapanor work?

Inhibits Na/H exchanger in gut. This leaves more Na+ in lumen and h20 follows. Leads to increased movement in intestine

How do anti-diarrheals work

Slow peristalisis to increase water and electrolyte absorption

Name anti diarrheals

Diphenoxylate Active in CNS loperamide (imodium) both opiates, but loperamide poorly traverses BBB