Pharm Sci III - Drugs used in the treatment of GI diseases

what are examples of GI disorders

- acid peptic diseases

- GERD

- IBD

what is IBD

inflammatory bowel disease

what are 2 types of IBD

- Crohn's disease

- ulcerative colitis

what diseases are acid peptic diseases

- gastroesophageal reflux

- gastric ulcers (ulceration of stomach)

- duodenal ulcers (ulceration of small intestine)

- stress induced mucosal injury

what causes acid peptic diseases

acid, pepsin or bile overwhelming the defensive factors of the GI mucosa

what are most peptic ulcers caused by

- Helicobacter pylori (bacterium)

- NSAIDs overuse

- hyperacidity

- hyperchlorhydria ( high gastric stomach acids)

what are symptoms of peptic ulcers

- periodic pain

-n/v

- loss of appetite -

- heartburn

what is the goal for the treatment of peptic ulcers

- reduce acidity

- promote mucosal defense

what drugs reduce acidity in peptic ulcers

- antacids

- H2 receptor antagonists

- PPI

- mucosal protective agents

antacids

- neutralize acids in the stomach by reacting with HCl (weak bases)

- mostly OTC

- S/E: gas and bloating

what drugs are antacids

- sodium bicarbonate

- calcium carbonate

- magnesium hydroxide

- aluminum hydroxide

- simethicone

- maalox

which antacids do NOT cause bloating

- magnesium hydroxide

- aluminum hydroxide

- maalox

what is the brand name for sodium bicarbonate

- baking soda

- alka seltzer

sodium bicarbonate

- highly soluble

- buffers HCl

- may cause metabolic alkalosis

- may exacerbate HF, HTN, edema

what is the brand name for calcium carbonate

tums

calcium carbonate

- constipation

- kidney stones

- long duration of action >>> hyperactivity rebound

what is the brand name for magnesium hydroxide

milk of magnesia

magnesium hydroxide

- diarrhea

- dangerous when used with renal failure

= kidneys can't filter extra magnesium

what is the brand name for aluminum hydroxide

mylanta

aluminum hydroxide

- constipation

- used with magnesium to counteract constipation

what is the brand name for simethicone

gas x

activated charcoal

- alters elasticity of mucus coated bubbles causing to break down

H2 receptor antagonist

- block histamine at histamine H2 receptors in parietal cells in the stomach and reduce H production >>> reduce HCl production

- Tx: dyspepsia, peptic ulcers, and GERD

- reversible (no bond formed)

which H2 blocker is no longer recommended for treating active ulcers

cimetidine

may induce impotence and gynecomastia

H1 receptors

allergies

H2 receptors

GI

H2 receptor antagonist drugs resemble what

histamine but they just block the receptor; inactive (no histamine affects)

what drugs are H2 receptor antagonist

- cimetidine

- ranitidine

- nizatidine

- famotidine

H2 antagonist indications

- GERD

- PUD

- erosive esophagitis

- adjunct for GI bleeding

- zollinger-ellison syndrome

H2 antagonist S/E

- h/a

- lethargy

- confusion

- diarrhea

- flushing

what is the brand name for cimetidine

pepti-max

what is the brand name for ranitidine

wal-zan

what is the brand name for nizatidine

zinga

what is the brand name for famotidine

pepcid

pepcid (famotidine)

- binds with CYP450 inhibitory

- may inhibit absorption of other drugs that require acidic environment

what decreases the effectiveness of H2 blockers and increases gastric acid production

smoking

what kind of ring does H2 receptor antagonist have

imidazole ring

what H2 receptor antagonist are available in IV and IM

- cimetidine

- ranitidine

- famotidine

the imidazole ring of histamine is not required for ____ antagonism of histamine at H2

competitive

separation of ring and nitrogen group with the equivalent of ___ carbon chain is necessary for optimum antagonist activity

4

the terminal Nitrogen group should be ____, ___ ___ for maximal activity

- polar

- non basic (resisdence)

what is GERD

long term condition where acid from the stomach comes into the esophagus

what is the main symptom of GERD

heart burn

what is the main cause of GERD

inappropriate constriction of LES

more severe GERD is and how is the damage seen

erosive esophagitis

endoscopically

what drug class are more effective than H2 receptor antagonist in achieving GERD therapy goals of resolution of symptoms and healing of esophagus

PPI

PPI (Proton Pump Inhibitors)

irreversibly bind to H+/K+ ATPase enzyme >>>> achlorhydria (ALL gastric acid secretion blocked)

what cells release H+ during HCl production

parietal

process called proton pump

t/f: H2 blockers and antihistamines do not stop the action of PPI

true

what is the final step in acid secretion in parietal cells

extrusion of pumping protons into lumen of stomach by membrane H+/K+- ATPase pump (active energy)

what is the pH of the stomach

~ 2

what is the chemical drug class of PPI

benzimidazole

what are PPI converted by and into what

converted by sulfenamide via covalent interactions with sulfhydryl groups with cysteine to form disulfide bridges

what activates the release of HCl in the stomach

- Histamine

- Acetylcholine

- Gastrin

what drugs are PPI

- prilosec (omeprazole)

- prevacid (lansoprazole)

- protonix (pantoprazole)

- nexium (esomeprazole magnesium)

- strontium (esomeprazole)

- aciphex (rabeprazole)

- dexilant (dexlansoprazole)

prilosec (omeprazole)

- prodrug

- Delayed release

- tx: heartburn. GERD, ulcer, erosive esophagitis

prevacid (lansoprazole)

- prodrug

- delayed release

- tx: heartburn. GERD, ulcer, erosive esophagitis

dexilant (dexlansoprazole)

- PPI

- heals erosive esophagitis, non erosive GERD, and heartburn relief

PPI interactions

- drugs dependent on pH (acidic) to absorb

- with diuretics and digoxin >>> increased risk of hypomagnesaemia

- reduced bioavailability with antacids and sucralfate

- increase concentration of cilostzaol and methotrexate

PPI S/E

- diarrhea

- abdominal pain

- n/v

- Upper respiratory tract infection

- flatulence

- pernicious vit 12 deficiency (3 yrs longer taking)

- osteoporosis

mucosal protective agents

protect mucosal lining

= prostaglandins

- prevention and treatment of acid peptic disorders

what drugs are mucosal protective agents

- Carafate (sucralfate)

- misoprostol

- pepto-bismol (bismuth subsalicylate)

- antacids

Carafate (sucralfate)

- mucosal protective agent " artificial barrier"

- poorly absorbed in GI tract

- 8 sulfate esters + aluminum hydroxide

- MOA: attract and bind to base of ulcers and erosions >> protective barrier over areas (from pepsin)

- DO NOT ADMINSTER WITH OTHER DRUGS

Carafate (sucralfate) S/E

- constipation

- dry mouth

- nausea

t/f: Carafate (sucralfate) may impair absorption of other drugs like tetracycline

true

t/f: Carafate (sucralfate) bind with phosphate and used in chronic renal failure to reduce phosphate levels

true

prostaglandin analogs

- mucosal protective agents by enhancing production of mucus or bicarbonate

- inhibit: PGE + PGI

- stimulate: PGF

- limited therapeutic uses due to lack of specificity

misoprostol

- prostaglandin analogs semisynthetic PGE1 (20 C)

- OFF LABEL- ABORTIONS

- cytoprotective by stimulating GI mucus and bicarbonate secretion, increase mucosal blood flow and cell regeneration

-tx: NSAID induced ulcers

antacids

- promote gastric mucosal defense

= mucus: HCl barrier

= bicarbonate: buffer HCl

= prostaglandins: prevent proton pump activation

t/f: antacids prevent the over production of acid

false; do NOT

t/f: antacids neutralize acid once in stomach

true

Antacids: raising pH 1.3-1.6

neutralizes gastric acid 50%

antacids: raising pH 1.3-2.3

neutralizes gastric acid 90%

Antacids drug interactions

- reduce ability of other drug's absorption

- chelation

= chemical binding

= inactivation

= insoluble complexes

antacid S/E

aluminum and calcium: constipation

magnesium: diarrhea

calcium carbonate: gas and belching

anitflatulents

to relieve painful symptoms associated with gas

= bind or alter intestinal gas

Pepto-Bismol (bismuth subsalicylate)

- Mucosal Protective Agent

- bismuth compounds

- OTC

- tx: dyspepsia and acute diarrhea

- excellent safety profile

- used with other drugs for H. pylori infection

what is Zollinger-Ellison syndrome

-rare disorder that occurs when 1 or more tumors form in pancreas and duodenum

- tumors release large amounts of gastrin that causes stomach to produce large amounts of acid

what drugs help treat Zollinger-Ellison syndrom and how

PPI by stopping the mechanism that pumps acid into stomach and helps relieve peptic ulcer pain and promote healing

IBD

- inflammatory bowel disease

- spectrum of remitting and relapsing chronic inflammatory intestinal conditions

what are GI symptoms of IBD

- diarrhea

- abdominal pain

- bleeding

- anemia

- weight loss

IBD are divided into what 2 subgroups

- ulcerative colitis

- Crohn's disease

ulcerative colitis

mucosal inflammation of the colon starting at anal verge and extending proximally to the

Crohn's disease

transmucosal inflammation of any part of GI tract but most commonly in adjacent ileocecal valve

what drugs treat ulcerative colitis

- 5- aminosalicyclic acid (5-ASA)

what drugs are 5-ASA

- mesalamine

- sulfasalzine

mesalamine

- 5-ASA

- 1st line therapy for mild - moderate

- used in combo with glucocorticoid for severe

- PO or suppositories

- activity limited to lining (local effect)

sulfasalazine

- 5-ASA linked to sulfapyradine by azo bond

- azo PRODRUG

- delivers 5-ASA to distal GI tract

- azo links prevent absorption in stomach and sm intestine

what drugs treat Crohn's disease

- steroids

- immunosuppressants

t/f: surgery may be required in Crohn's disease if drug therapy aren't effective; removing section of colon

true

t/f: patients with Crohn's disease should have regular screenings for colorectal cancer due to increased risk

true

Crohn's disease: glucocorticoids drugs

moderate - severe

- cortisone

- dexamethasone

- prednisolone

- triamcinolone

steroid structure

17 carbons arranged in 4 rings with 28 hydrogen bonds

cortisone (cortisol)

- pregnane (21 C) hormone synthetic

- non-selective

- rescue therapy (flares)

decadon (dexamethasone)

- 16 a methyl group increases stability, anti inflammatory activity, lipophilicity and receptor affinity

- used in COVID-19 therapy

orapred (prednisolone)

- pregane (21 C) synthetic

- most commonly used

for steroids, the double bond between carbon 1 and carbon 2

increase anti inflammatory activity

kenalog (triamcinolone)

- 9a-fluoro group increases the anti-inflammatory potency

for steroids, the fluorine and 9a postion

increases anti inflammatory potency

IBD with thiopurine derivatives

used off label to treat severe IBD or steroid resistant/ dependent

how do thiopurine derivative work in IBD

impair purine synthesis and inhibit cell proliferation

- increased dose: RA and GI inflammation

- decreased dose: cancer