Gluconeogenesis

Substrate  for  gluconeogenesis  :
pyruvate
Lactate
Glycerol
Propionate
Glucogenic  aminoacids


Tissue  location :
Mainly  in  the  liver
Lesser  extent  in  renal  cortex

Intracellular  location :
  - partly  mitochondrial
  -  partly  cytsolic

Significance  of  gluconeogenesis :

  - maintains  blood  glucose  level

 -  Clears  up  the metabolites  like  lactate, glycerol etc.

Gluconeogenesis  from glucogenic aminoacids

The Cori Cycle  (Lactic acid cycle)

Treatment of peptic ulcer

Gastric/duodenal

• Mucosal defensive factors- mucus, mucosal blood blow, formation of HCO- 3 and PGE  2   & PGI2
• Aggressive factors- acid, pepsin, NSAIDs, H. pylori
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• Physiology of HCl secretion
• Gastric parietal cells have receptors for gastrin (from antral G cells), histamine (from ECL cells), acetylcholine ( from vagal efferents) and prostaglandin (PGE2 & PGI2- from gastric mucosa)
• Enterochomaffin-like cells histamine
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• Stimulation of H2 receptors by histamine activation of adenyl cyclase  increase in cAMP activation of protein kinases stimulates H+ secretion from H+  /K+ ATPase (proton pump- final step) into the canalicular surface, H+ combines with Cl to form HCl  gastric lumen
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• Activation of M3 by Ach and gastrin receptors activation of phoshpolipase C IP3-DAG increase in cytosolic Ca++  activation of protein Kinases stimulation of  H+ secretion from H+  /K+ ATPase (proton pump) 
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• Stimulation of PG receptor by PGE2  inhibits cAMP in parietal cells and Gastrin release from antral cells decrease in HCl secretion
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• PGE2 also increases mucosal blood flow and mucus and HCO3 secretion cytoprotective effect
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• So, H2 antagonists, proton pump inhibitors, anticholinergics, HCl neutralizing agents and H Pylori inhibiting agents are the anti-ulcer drugs
• Also, ulcer protective and ulcer healing agents

Classification

I. Drugs which reduce gastric acid secretion

A. H2 receptor antagonists (H2antihistaminics) -cimetidine, ranitidine, famotidine, roxatadine, loxatadine

B. Proton pump inhibitors- omeprazole, lansoprazole, pantoprazole, rabeprazole

C. Anticholinergics- propanthelin, pirenzepine, telezepine

D. Prostaglandin analogs- misoprostol (PGE1), enprostil (PGE2), rioprostil (PGE1)

II. drugs which neutralize gastric acid (antacids)

A. systemic- sodium carbonate

B. non-systemic aluminium hydroxide, aluminium phosphate, magnesium trisilicate, megaldrate, magnesium hydroxide, calcium carbonate

III. Ulcer protective- sucralfate, colloidal bismuth subcitrate

IV. Ulcer healing drugs- carbenexolone sodium

V. Anti H pylori drugs (used in combination)

 amoxicillin, clarithromycin, metronidazole, tinidazole, tetracycline 

I. Drugs which reduce gastric acid secretion

A. H2 antagonists

MOA-  block H2 histaminic receptors  in gastric parietal cells ↓ HCl secretion

Cimetidine

ADR- 

Headache, GI upset

Antiandrogenic effect (displaces dihydrotestosterone from the receptor), ↑prolactin gynecomastia, loss of libido, impotence, decrease in sperm count

•Inhibits cytochrome P450– inhibits the metabolism of theophylline, sulfonul ureas, warfarin, mexiletineà toxicity

•Bolus IV injection à histamine releaseà bradycardia, arrhythmias and cardiac arrest

•CNS effects- hallucinations, delirium, convulsion and coma

Uses-

Duodenal ulcer – 400mg bid, or 800 mg hs for 8 weeks

Gastric ulcer

Stress ulcer and gastritis

Zollinger –Ellison syndrome (gastric hypersecretory state)

Dietary & mucosal proteins are also adsorbed to this coat which form another layer & provides further resistance to the  ulcer base so that aggressive factors (acid, pepsin) don’t come in contact with the ulcer base

Also increases mucosal PGE2 synthesis and HCO3 formation
Stimulates epithelial & fibroblast growth factor promotes healing