Pharm II - GERD, Constipation, & Diarrhea

antacid compounds (4)

•aluminum compounds

•magnesium compounds

•calcium compounds

•sodium compounds

MOA of antacids

•bind with gastric acid to produce neutral/low acidity salts

•reduce pepsin activity if pH >5

•stimulates release of prostaglandins

does it matter which antacid someone uses?

no except for sodium compounds have special considerations

2 examples of magnesium containing antacids

magnesium hydroxide (milk of magnesia)

magnesium carbonate (gaviscon)

AE of magnesium containing antacids

•diarrhea

•cardiac arrhythmias (bradycardia, prolonged PR interval, widened QRS, prolonged QT interval, peaked T waves)

•respiratory depression

•hypotension

•N/V

•muscle paralysis

example of aluminum containing antacids

aluminum hydroxide (Mylanta)

AE of aluminum containing antacids

•constipation

•bone demineralization

•intestinal obstruction (inhibits peristalsis)

example of calcium containing antacids

calcium carbonate (TUMS, Rolaids)

AE of calcium containing antacids

•constipation

•milk-alkali syndrome

•hypercalcemia - stones, groans, bones, psychic overtones

example of sodium containing antacids

sodium bicarbonate (Alka-Seltzer)

AE of sodium containing antacids

•sodium overload

who should avoid sodium containing antacids?

•CKD

•CHF

•HTN

•cirrhosis

•edema

•sodium restricted diets

drug interactions of antacids

Cimetidine, Ranitinde (H2 blockers) - dissolution and/or absorption affected; recommend 1 hour gap between administration

Alkalinize urine - promotes excretion of acidic drugs; delays excretion of alkaline drugs

examples of H2 receptor antagonists (H2RA) (4)

cimetidine

famotidine

ranitidine

nizatidine

what do all H2RAs end in?

-tidine

MOA of H2RAs

competitive inhibition of histamine at H2 receptors of gastric parietal cells → inhibits gastric acid secretion/volume and increases pH

pharmacokinetics with H2RAs

hepatic metabolism w/ glomerular filtration and renal tubular secretion

who should receive reduced doses of H2RAs?

•severe renal or hepatic insufficiency

•elderly pts

indications of H2RAs

•GERD

•duodenal ulcers

•gastric ulcers

•Zollinger Ellison Syndrome (high doses only)

•heartburn, "acid indigestion", "sour stomach"

AE of H2RAs

•HA

•gynecomastia, reduced libido, impotence

•somnolence

•fatigue

•dizziness

•confusion, hallucinations (anticholinergic properties) (cimetidine worst offender)

•constipation/diarrhea

•pneumonia

drug interactions of H2RAs

•theophylline - increased effects

•warfarin - lower dose to protect against elevated PT/INR

•phenytoin - increased levels

•nidedipine - increased levels

•propranolol - increased levels

•antacids - prevent absorption of H2 blockers due to increase in pH

•inhibitor of CYP1A2, CYP2C19, CYP3A4

examples of proton pump inhibitors (PPIs)

omeprazole

esomeprazole

lansoprazole

dexlansoprazole

pantoprazole

rabeprazole

omeprazole-sodium bicarbonate

what do all PPIs end in?

-prazole

MOA of PPIs

irreversible inhibition of H+, K+-ATPase (proton pump) to precent production of gastric acid

how are PPIs metabolized?

liver metabolism via cytochrome P45-CYP2C19 and CYP3A4

how long is the half life of PPI and why does it last longer?

half life of 1 hour but last due to irreversibly binding to proton pumps

metabolism phenotypes especially with PPIs (5)

•ultrarapid

•rapid

•normal

•intermediate

•poor

what would be a key indication that someone is a rapid or ultrarapid metabolizer of PPIs?

what should you do then?

that the initial dose game them no relief but they get great results from an H2RA (ex: famotidine)

up the dose of the PPI

indications for PPIs (7)

•GERD

•duodenal ulcers

•gastric ulcers

•Zollinger Ellison Syndrome (long-term)

•healing of peptic ulcers

•heartburn, "acid indigestion", "sour stomach"

•stress ulcer prophylaxis**

how long and how frequent is treatment with PPIs?

4-8 weeks and can be dosed daily to BID

when should PPIs be taken?

take 30-60 mins before meals

what should you consider when stopping PPI? why?

consider long term treatment, step down dosing, or switching to H2 blockers

high risk of recurrence

AE of PPIs

•pneumonia - affects WBC function, highest risk in first 4-5 days

•fractures - reduced absorption of calcium

•rebound acid hypersecretion

•hypomagnesemia - cramps, tremors, palpitations

•diarrhea

•decreased absorption of Vit B12 and calcium

drug-drug interaction of PPIs

clopidogrel - decreases effectiveness of anti-platelet effects

***if at risk for GI bleed - use PPI

***if not at risk, do not use PPI

•may decrease oral bioavailable of B12 and certain drugs that require acidity for GI absorption (ex: digoxin, antifungals, HIV meds)

non pharm treatment for GERD

•for everyone: elevate head of bed 6-8" while sleeping, weight reduction in overweight/obese pts

•individualized: avoid high risk food, protein rich diet, small meals, avoid eating before bed, avoid smoking/alcohol/caffeine, avoid tight fitting clothing, take drugs that cause irritation with plenty of water

first line tx with persistent reflux

lifestyle modifications

first line pharmacologic tx for persistent reflux

PPI

what is mild, intermittent heartburn?

<2x weekly and NOT troublesome

OTC tx for mild, intermittent heartburn

patient-directed therapy x2 wks

antacids and/or H2RA BID (OTC) or PPI once daily (OTC)

treatment for moderate-severe sxs (subjective)/esophageal injury (complications)

•PPI daily or BID x 8-16wks

OR

•H2RA QID (except famotidine BID) x 8-12 wks

•interventional therapy: laparoscopic nissen fundoplication, Roux-en-Y bypass

•***esophageal injury will likely need long-term therapy

What should you do for refractory GERD?

further assessment:

•ensure compliance

•further dx testing (EGD, pH monitoring, manometry(

•test H pylori status

Treatment options for refractory GERD (5)

•treat other etiologies appropriately

•increase dose

•switch to another PPI

•add H2RA at bedtime

•antireflux surgery

What kind of symptoms will you see with patients older than 60?

chest pain

asthma

poor dentition

jaw pain

What kind of treatment for patients older than 60 with GERD?

PPI once daily

What should you do with a patient who has chest pain and reflux?

If sxs persist?

cardiac work up & PPI BID x 4 weeks

consider diagnostic testing

54 y/o pt presents with complaints of intermittent heartburn over the last 2 months. The pt notes sxs twice a week after eating spicy meals or large meals close to bedtime. No alarm sxs have been noted. What do you recommend for the patient?

A) Omeprazole BID x 4 weeks

B) Famotidine BID x 2 weeks

C) Cimetidine once daily x 4 weeks

D) Pantoprazole 4x/daily x 8 weeks

E) Ranitidine as needed x 4 weeks

B) Famotidine BID x 2 weeks

•omeprazole is technically once daily

•he's only having sxs a couple times a week

What electrolyte is most responsible for bone changes in patients who have been on long term PPIs?

A) Calcium

B) Potassium

C) Chloride

D) Sodium

E) Magnesium

A) Calcium

AND

E) Magnesium

Signs and sxs of PUD (6)

•epigastric pain

•N/V (coffee ground emesis)

•appetite changes

•weight loss

•bloating

•melena

antiulcer medications (6)

•H2 blockers

•PPI

•Sucralfate

•Misoprostol

•Antacids

•Antibiotics (H. pylori)

MOA of Sucralfate

undergoes polymerization and cross-linking which forms viscous/sticky gel that adheres to ulcer crater that can last up to 6 hours

uses of Sucralfate (3)

•acute and maintenance therapy of duodenal ulcers

•some indications it can help heal gastric ulcers

•long term use of NSAIDs

AE of Sucralfate

constipation

DDI with Sucralfate

blocks absorption of theophylline, digoxin, warfarin, fluoroquinolones

Sucralfate CI in who?

renal insufficiency/failure

MOA of Misoprostol

analog of prostaglandin E1 and serves as replacement to endogenous prostaglandins to promote cytoprotective mucous, suppress gastric secretion, and maintain mucosal blood flow

AE of misoprostol

•dose related diarrhea and abdominal pain

•dysmennorhea and spotting

indications of Misoprostol

•NSAID induced PUD

•cervical ripening

Misoprostol CI in who? why?

pregnancy

may induce uterine contractions

Where do ulcers more commonly form with H. pylori?

duodenum

Benefits of tx of H. pylori

•reduced risk of recurrence of ulcers

•aids in healing of ulcers

•produces tumor regression in 60-90% of MALT lymphoma

•decreased risk of gastric carcinoma by 40% after 15 years

How do you diagnose H. pylori?

•direct biopsy during EGD

•stool testing

•Urea breath test

2 treatment options for H. Pylori

Triple Therapy

Quadruple Therapy (Bismuth)

What it Triple Therapy composed of and how long is it used for?

PPI + Clarithromycin + Amoxicillin OR Metronidazole

10-14 days

What is Quadruple Therapy composed of and how long is it used for?

PPI (BID) + Metronidazole + Tetracycline + Bismuth subsalicylate

10-14 days

What do you have to do after treating H. pylori?

test for eradication at least 4 weeks after completing treatment

Indications for laxatives (11)

•reduce pain with defecation

•reduce amount of strain in pts with hx of aneurysm, MI, CVD, cerebrovascular dz

•compensate for loss of tone in abdominal/perianal musculature in older pts

•allow for fresh stool sample

•empty bowel before treatment

•facilitate transports of dead parasites

•bowel prep prior to surgery/colonoscopy

•modify effluent after ileostomy/colostomy

•prevent fecal impaction in bedridden pts

•remove ingested poisons

•correct pregnancy/drug induced constipation

Precautions with laxatives (2)

•pregnancy - may induce labor due to GI stimulation

•lactation - can be excreted in breast milk

CI for laxatives (6)

•appendicits

•regional enteritis

•diverticulitis

•ulcerative colitis (increased risk of inflammation, toxic megacolon, bowel perforation)

•acute surgical abdomen (increased risk of perforation)

•bowel obstruction (increased pressure can cause distention and ischemia)

What are the different classifications of laxatives by MOA? (4)

•bulk-forming

•surfactant laxatives

•stimulant laxatives

•osmotic laxatives

MOA of bulk-forming laxatives

•non-absorbable, nondigestible and swell in water to form a gel

•softens stool and increases bulk

•encourages growth of colonic bacteria

•stretches bowel wall to stimulate peristalsis

MOA of surfactant laxatives

•decrease surface tension to allow penetration of water into stool

•inhibits fluid absorption from the intestines

•increases fluid electrolyte excretion into intestinal lumen

MOA of stimulant laxatives

•stimulate peristalsis

•soften stool by increased secretion of water and electrolytes into intestine, decrease water and electrolyte absorption

MOA of osmotic laxatives

water retention increases stool bulk and stimulates peristalsis

What are the different classifications of laxatives based on clinical/therapeutic effect? (3)

•group I

•group II

•group III

Group I laxatives

•rapid onset and create stool with watery consistency

•good for preparation of diagnostic procedures and/or surgery

Group II laxatives

•intermediate latency (6-12 hours) with semifluid stool

•most frequently abused laxatives

Group III laxatives

•slow acting (1-3 days) results in soft, formed stool

•good for chronic constipation and reduces straining

examples of bulk-forming laxatives (3)

methylcellulose

psyllium

polycarbophil

indications for bulk-forming laxatives (4)

•constipation

•diverticulosis

•IBS

•diarrhea

AE of bulk-forming laxatives

intestinal obstruction/impaction typically caused with lack of fluid intake

example of surfactant laxative

docusate sodium (Colace)

what group category are surfactant laxatives? how long do they take to work?

group III

take a few days

Surfactant laxatives CI with what? why?

mineral oil

increased risk of pneumonia and nutrient malabsorption

examples of stimulant laxatives (3)

•bisacodyl (Dulcolax, Fleet laxative)

•Senna (Senokot, Ex-lax)

•Castor oil

route of administration of bisacodyl (2)

what should you know about each route?

which class of laxative?

•oral - give at night for morning effect, do not give with milk, swallow only (no crushing/chewing)

•suppository - works within 15-60 mins, risk of proctitis, side effect of burning sensation

•class II

CI for Bisacodyl (4)

•acute abdomen

•acute hepatitis

•impaction

•ulcerated hemorrhoids

What are Senna laxatives? How long do they take to work? Which class of laxatives?

plant-derived - anthraquinones

6-12 hours

class II

Side effect of Senna

yellow/brown or pink urine

CI of Senna (6)

•pregnancy/lactation

•children <12

•obstruction

•CHF

•UC

•GI bleed

Why is Castor oil different from other stimulant laxatives?

class I agent instead of class II

What does Castor oil act on? When is it commonly used?

acts on small intestine

used in preparation for radiologic procedures

examples of osmotic laxatives (4)

•magnesium salts

•sodium salts

•polyethylene glycol

•lactulose

MOA of magnesium and sodium salts

•draws water into intestinal lumen

•low doses produce soft or semifluid stool in 6-12 hours

•high dose used prior to surgical/radiographic procedures

AE of magnesium and sodium salts (4)

•dehydration

•hypermagnesemia - do not use in CKD, dialysis pts

•fluid retention (sodium only) - exacerbates HTN, CHF, edema

•acute renal failure esp if concurrent use of ACE/ARBs, diuretics

MOA and use of Polyethylene Glycol

•increases intestinal water retention

•used in chronic constipation

AE of polyethylene glycol (3)

•abdominal bloating

•cramping

•flatulence

how long can it take before polyethylene glycol laxatives work?

2-4 days

what is lactulose?

semisynthetic disaccharide composed of galactose and fructose

MOA of lactulose

•lactulose metabolized by bacteria into lactic acid, formic acid, and acetic acid

•creates a mild osmotic action

•increased excretion of ammonia

what should you be concerned about with lactulose?

portal HTN and hepatic encephalopathy