MedChem GI

Peptic Ulcer symptoms

burning in stomach especially when empty

• Can cause bleeding in GI

Peptic Ulcer common causes

Alcohol, Caffeine, Pregnancy, H. Pylori, NSAIDs, Corticosteroids, Iron

Peptic Ulcer treatment

Lifestyle and PPI/H2RA/Antacids/PCAB

H. Pylori association and effects

Associated with most ulcers

• causes epithelium thinning

• increase acid secretion

GERD cause

Chronic acid reflux, due to a weak esophageal sphincter

GERD lifestyle treatments

Stress, lifestyle

GERD drug treatments

H2RA, Antacids, PCABs, PPIs

What do mucous neck cells secrete and what do they do

The secrete bicarb and mucous to protect the gastric mucosa

What do parietal cells secrete and what do they do

Gastric acid - Acid

Intrinsic Factor - Pepsinogen to pepsin

What stimulates parietal cells

Gastrin, Histamine, Ach

What do ECL cells secrete

They secrete histmamine

What stimulates ECL cells

Ach

What do cheif cells secrete andw hat do they do

They secrete Pepsinogen and Lipase

Pepsin precursor

pepsinogen

What stimulates Chief cell

Ach

What stimulates G cells

Peptides, proteins

What do G cells produce and effect

Make gastrin which activate parietal cells

What stimulates D cells

Gastric acid

What do D cells do and effect

Make somatostatin which lowers parietal cells gastric acid output

H2RA MOA

Binds to and antagonizes Histamine receptors on Parietal cells

H2RA onset and duration

Onset 30-60 minutes, 12-24 hours duration

H2RA adverse effects

Fatigue, confusion

Long term - Deficiency in iron and B12

What is Tachyphylaxis

Rapid lack of response when taking drug

What kind of heartburn are H2RAs taken for

Acute

PPI MOA

Irreversibly inhibits active H/K ATPases

PPI Adverse effects

Headache, Nausea, increased risk of bone fracture, increased risk of H. Pylori

how are PPIs activated

Acid must acitvate them

How are PPIs metabolized

MEtabolized by CYP2C19 priamrily and CYP3A4

PPI DDIs

Warfarin, cyclosporine, diazepam

Omeprazole CYP effects

Inhibits CYP2C19 and induces 1A2

How long are PPIs used for before seeing provider

14 days

PCAB MOA

Irreversibly blocks proton pumps at K binding site

Why PCAB over than PPI

Can bind inactive or active pump, rapid and contiued effect

Antacid MOA

Neutralizes acid

Antacid uses

Symptomatic relief

What antacid is best in pregnancy

Calcium Carbonate

What emdications interact with Antacids

Fluoroquinolones, Tetracyclines, Azithromycin, Levothyroxine

Side effects of AlOH and MgOH

AlOH - Constipation

MgOH - Diarrhea

Triple therapy versus quadruple therapy

Triple therapy

• Clarithromycin

• Amoxicillin/Metronidazole

• PPI/H2RA/PCAB

Quadruple therapy

• Adds a Bismuth Salt

Scuralfate MOA and use

Used to protect lining of stomach

Sucralfate contraindications and issues

Avoid if renal failure, Avoid if Aluminum toxicity, can inhibit absorption of other drugs

Misoprostal Use and class

Used in chronic NSAID ulcers, protects mucosa

When to avoid Misoprostol

Pregnant

Misoporstol Adverse effects

Cramping, diarrhea

What kinds of receptors and pump are found on parietal cells

H/K ATPase

M3 receptor, H2 receptor, Gastrin receptor, EP3 prostaglandin receptors

How does an electron donating sidechain on a histamine analogue impact it

Donating - more basic imidazole, more ionization, harder to be absorbed, more N^π

How does an electron withdrawing sidechain on a histamine analogue impact it

Withdrawing - more acidic imidazole - less ionization - easier absorption and more N^J

What is the impact of a 4’ methyl on the imidazole

More N^J

What is the impact of adding a Sulfur into the spacer

Lowers imidazole PKA - more absoprtion

What is the purpose of the Polar tail on an H2RA

Needed for antagonism and H2 Receptor

How does cimetidine inhibit CYP enzymes

The 4’ methyl imidazole is believed to bind to the heme

What enzyme catalyzes gastric acid production

Carbonic Anhydrase

CO2 + H2O → CO3H2 → H+ + HCO3-

What GI meds are BEERs critieria

PPI and H2RA

Why might esomeprazole be better than omeprazole

Esomeprazole is metabolized less by CYP2C19, this mean it is more bioavailable and may be better if someone is a poor CYP2C19 metabolizer

How do PPIs irreversibly inhibit

Disulfide bond

What are the 3 SAR parts to a PPI

Sulfinyl, Benzimidazole, 2-pyridyl methyl

Do PCABs or PPIs need enteric coating

PPI needs enteric coating to be absorbed in Duodenum. If acidified, the N on the 2-pyridyl methyl will be protonated and unable to do nucleophilic attack

PCAB does not need enteric coating due to being ionized in stomach and working in stomach