Pharm GERD and Liver Disease

drug classes to treat GERD and PUD

•Antacids

•Histamine-2 receptors antagonists

•Proton pump inhibitors

•Antibiotics (PUD)

•Misoprostol

•Sucralfate

•Bismuth subsalicylate

Antacids examples

Calcium carbonate (e.g., Tums)

Magnesium salts

Aluminum salts

Antacids mechanism of action

•Antacids partially neutralize the HCl in the stomach. By increasing the pH level, the activation of pepsin is also inhibited.

•Symptomatic treatment only – Use PRN, after meals, at bedtime

antacids adverse events

•Chalky taste, cramps, constipation (aluminum-containing products), or diarrhea (magnesium-containing products)

•Calcium carbonate: may cause hypercalcemia

•Magnesium-containing products: may cause hypermagnesemia (hypotension, nausea, vomiting, and electrocardiographic changes)

may reduce rate and extent of drug absorption (iron, tetracycline, quinolones)

Histamine-2 receptor antagonists (H2RAS) examples and use

Cimetidine (Tagamet)

Famotidine (Pepcid)

Nizatidine

used for mild GERD, ulcer healing, and H. pylori eradication in combination with other agents

H2RA mechanism of action

reversibly inhibit H2 receptors and dec acid secretion

H2RA contraindications

reduce dose with older adults or low CrCl

start with low doses in older adults to avoid CNS effects

H2RA adverse events

headache, drowsiness, fatigue, dizziness, confusion

prolonged use can result in tolerance

cimetidine can cause gynecomastia and ED

H2RA interactions

cimetidine increases effects of warfarin (risk for bleeding) and phenytoin

reduces absorption of drugs that require an acidic environment

Proton pump inhibitors (PPI) examples and use

Dexlansoprazole (Dexilant)

Esomeprazole (Nexium)

Lansoprazole (Prevacid)

Omeprazole (Prilosec)

Omeprazole-sodium bicarbonate (Zegerid)

Pantoprazole (Protonix)

Rabeprazole (AcipHex)

Moderate-to-severe GERD; prevention of NSAID-induced PUD; ulcer healing; most potent acid suppression agents available)

Most effective when taken in morning, 30 - 60 minutes before the first meal

PPI mechanism of action

irreversibly bind to gastric proton pumps, inhibiting acid secretion and producing long lasting suppression of acid secretion

PPIs contraindications

avoid sodium bicarb products during pregnancy (risk of metabolic alkalosis and fluid overload)

PPIs adverse effects

headache, diarrhea, constipation, abd pain

long term effects:

-elevated gastrin

-osteoporosis

-infections

-B12 deficiency (acid is needed to absorb B12 from food)

-hypomagnesemia (reducing acidity makes it difficult for magnesium to be absorbed)

omeprazole may reduce metabolism of clopidogrel (inc bleeding risk)

Potassium-Competitive Acid Blocker (PCAB) examples and use

Vonoprazan (Voquezna)

Vonoprazan plus amoxicillin and clarithromycin (Voquenza Triple Pak)

Vonoprazan plus amoxicillin (Voquenza Double Pak)

Used for treatment of GERD, eosinophilic esophagitis, H. pylori infection, and PUD

PCAB mechanism of action

reversible and competitive inhibitor of potassium-binding site on parietal cell proton pumps

PCAB contraindications

do not take with rilpivirine, atazanavir, nelfinavir (lowers medication effectiveness, so HIV may become resistant to tx)

PCAB adverse effects

C-diff assoc diarrhea

osteoporosis

severe skin rxns

B12 deficiency

hypomagnesemia

hypersensitivity reaction that triggers an inflammatory response in the kidney's tubules (tubulointerstitial nephritis)

Misoprostol (Cytotec) and Misoprostol/diclofenac (Arthrotec) use

prophylaxis against NSAID induced ulcers

misoprostol mechanism of action

inhibits acid secretion and increases mucosal defenses

misoprostol contraindications

pregnancy

hypersensitivity to prostaglandins

misprostol adverse effects

diarrhea (inc with magnesium use), abd pain, flatulence, nausea (take with food to reduce risk)

sucralfate mechanism of action and use

forms viscous, adhesive substance that attaches to and protects ulcers against noxious gastric content

used to prevent stress ulcers and maintain duodenal ulcers

sucralfate contraindications

caution in renal dysfunction and older adults d/t risk of aluminum accumulation

separate this med by 2 hours before or 6 hours after other meds (food/drugs can interfere with mechanism of action)

sucralfate adverse effects

constipation (most common)

aluminum toxicity

1st line tx for H. pylori

optimized bismuth quadruple

-PPI

-bismuth subcitrate

-tetracycline

-metronidazole

or PCAB in combo with antibiotic

A pt has a risk for bleeding/ulcer but they need to take an NSAID, how can we reduce risk?

• Taking with food/milk can help reduce irritation 

• Take NSAID with PPI or misoprostol

non-selective BB used for prevention of variceal hemorrhage

propanolol- more CNS effects

nadolol - may be preferred d/t once daily dose

carvedilol

BB for portal HTN mechanism of action

• Volume of blood to portal circulation is reduced 

• Vasoconstriction and reduced blood flow to the portal vein 

octreotide mechanism of action

causes vasoconstriction and reduced portal blood flow, which reduces portal pressure

helps to reduce variceal hemorrhage and mortality related to it

octreotide adverse effects

hyperglycemia

prolonged QT interval

diuretics used for acites

spironolactone (gold standard)

combo of spironolactone and furosemide (5:2 ratio, given to prevent e- abnormalities)

amiloride (2nd line)

drugs to treat hepatic encephalopathy

lactulose (1st line, osmotic laxative)

rifaximin (2nd line, antibiotic)

polyethylene glycol (3rd line, osmotic laxative)

how does lactulose aid in hepatic encephalopathy?

helps to get rid of ammonia in the blood through acidification of the GI tract

how does rifaximin aid in hepatic encephalopathy?

it inhibits the growth of organisms in the bowel that produce ammonia

how does polyethylene glycol aid in hepatic encephalopathy?

causes large volume diarrhea to allow enhanced removal of ammonia through the gastrointestinal tract

antimicrobials used to treat spontaneous bacterial peritonitis

cefotaxime (1st line)

levofloxacin (2nd line)

sulfamethoxazole-trimethoprim (3rd line)