GI Pharmacology

Lecture 1 After Midterm Exam

Objective:
This sheet is going to describe drugs used to treat common medical condition involving the Gastrointestinal tract which is Peptic Ulcer.

You Know:
Stomach is lined with non-ciliated columnar epithelial cells, modified contain glands to function as secretory epithelium. HCL which is secreted by the partial cells is very irritant to the lining epithelium of the stomach, so how we will protect it?? By the mucous secretion that is going to coat the epithelial lining and isolate it(epithelial ) from the irritant(HCL).

Q A N

What will happen if this mucus coat is disrupted? HCL can reach the epithelial and cause irritation to it and that is called peptic ulcer.

I am not going to re-type the slides, just extra note and explanation, feel free to hate me. Slide No.: 2

Page No.: 1

Upper GI drugs deal with stomach and duodenum only; there are also Lower GI drugs

Page No.: 2 Causes of Peptic Ulcer

Slide No.: 1

NSAIDs bind to Cyclo-oxygenase 1, 2 non-selectively so it inhabits the synthesis of Prostglandin (PG), and PG is important in the synthesis of the mucous. Zollinger Ellison Syndrome: tumor in the pancreas, in the non-beta cells produce large amount of gastrin and Gastrin will promote acid secretion.

Page No.: 2 Treatment:

Slide No.: 2

There are several methods that are used to treat people suffering from peptic ulcer which

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Slide No.: 1

The pic on the left represent Gastric Gland the Gland which is found in the stomach has many types of cells, the Dr mentioned the cells and what they secrete ECL: Entro-chromatic like cells Pepsin: responsible of breaking down proteins in the stomach Canaliculi inside the parital cells is the place where the acids is first secreted then it will be secreted in the lumen of the stomach.

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Slide No.: 1

This figure talks about the three pathways control parital cell acid secretion First pathway called Parasympathetic pathway through the Vagal N. Sight, smell, taste of food cause stimulation of Vagal nerve to release Ach. Then the Ach. will bind to M3-R (Muscarinic Receptor) that is found on the surface of parital cells and stimulate acid secretion.

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Continued

Also Vagal has receptors in ECL cell M3R these are Histamine secreting cells, then Histamine will Bind on its receptors on the surface of parital cells and induce acid secretion. Another pathway for the Vagal nerve , it has receptors on the G cells and induce

GI Pharmacology
Lecture 1 After Midterm Exam

The doctor read Slide No.: 2 Please note that the Vagus nerve pathway control both the Gastrin receptor pathway and Histamine pathway. The Gastrin pathway control Histamine pathway and they all work through H+/K+ ATPase Pump. Also notice that there is active and resting pumps keep this in mind as it will show up later.

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Slide No.: 2

Proton pump inhabitor are specific go directly inside the canaliculus to become near the enzyme that is going to inhabit and bind to it irreversibly and this pump will not function anymore! But as we know that our enzymes are in continuous regeneration , so the drug will bind to one enzyme for example and inhabit it then this enzyme will be degraded and new will be formed the new ones are not inhabited so we don't have tolerance for the PPI.

Page No.: 7 work again since the inhibition was irreversible.

Slide No.: 1

Last point 4-5 days to synthesis new pumps / not that the new pumps are going to

Page No.: 7 the absorbed, that will interfere with bone remodeling.

Slide No.:2

PPI reduce the acidity in the stomach and when the acidity is reduced the amount of

Page No.: 8

Slide No.: 1

Competitively inhabit the Histamine from binding on its receptor on the parital cells, reversible binding, it is selective for H1 so we don't see that much side effects This drug doesn't cross the blood brain barrier even in high concentrations. H1 has something to do with inflammation and asthma. Page No.: 8 Slide No.: 2

You need to know the names of the drug but don't worry about the structure, but this is to compare who they are similar to the structure of histamine the material that they antagonizing GERD: Gastro Esophygeal Reflux Disease Page No.: 9 nowadays, Increase secretion of prolactin so interfere with lactation Page No.: 10 Anti-acids drugs in Jordan called mallops? Mg(OH)2 can also be used to treat constipation. CHF: Congestive Heart Failure Page No.: 12 Cytoprotective: protect the cell from the acids Slide No.: 1 Slide No.: 1 Slide No.: 2

Cimetidine was the first synthetic drug in the 7ti the most ptent and the most used

Page No.: 12 PG analogue since PG induce mucous secretion Note how Misoprotol structure is similar to PGE1 structure

Slide No.: 2

GI Pharmacology
Lecture 1 After Midterm Exam

Page No.: 13 one to think about. Page No.:

Slide No.: 1

PG analogue doesn't considered as the first line therapy for H.Pylori , anti-biotic is the first

Slide No.: 1

14 H.Pylori cause erosion of the membrane also it stimulate acids secretion.

This figure above can help you remember the four methods of treatment.

You should NEVER forget the golden role: "Peptic ulcer disease is always peptic ulcer disease"