Weekly Recaps: Modules 1-4, Exam 1 Flashcards by Mr. Bobbits

The COGENT trial found that addition of ____________ to ______________ reduced gastrointestinal events without increasing cardiovascular events.

Omeprazole (Nexium) and clopidogrel (Plavix)

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Patients with known ______________ can remain on PPI therapy.

Osteoporosis

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Concern for hip fractures and osteoporosis should not affect the decision to use _______ long-term except in patients with other risk factors to hip fracture.

PPIs

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With the exception of non-C.diff enteric infections, after a median of three years of use, ______ (GI drug class) did not increase the risk of chronic kidney disease, dementia, bone fracture, myocardial infarction, pneumonia, micronutrient deficiencies, and gastrointestinal cancer.

PPIs

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PPI therapy is safe up to ______ years and that limiting prescription of PPI therapy because of concerns of long-term harm is not warranted.

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Hallmark symptom of heartburn

Retrosternal chest pain in association with certain foods or in the first hour or two after eating, or constantly.

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Treatment goals of PPIs

Relieve associated symptoms, promote esophageal healing, avoid complications, prevent recurrence.

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Step 1: Lifestyle modification/non-pharmacological interventions for GERD

Dietary modification, avoid contributing medication, smoking cessation, avoidance of ETOH, weight loss, etc.

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The foods that can trigger GERD

chocolate, caffeine, alcohol, acidic food, spicy food.

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Drug class of multivalent cations with many precautions, drug interactions and adverse effects.

Antacids

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______________ (GI med)

Caution in renal disease
Diarrhea

Milk of Magnesia

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Belching
Constipation
Caution in renal disease
Milk Alkali Syndrome

Tums
Maalox regular chewable

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Caution in renal disease
Constipation

AlternaGel

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Gastric distention/belching
Caution in renal disease
Alkalosis
Fluid retention

Alka-Seltzer

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Class of gastric acid-suppressing agents frequently used in various gastric conditions.

H2 Receptor Antagonists (H2RAs)

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Cimetidine
Famotidine
Nizatidine
Ranitidine

What drug class?

H2RAs (H2 receptor antagonists)

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Esomeprazole
Lansoprazole
Omeprazole
Omeprazole/sodium bicarbonate

What drug class?

PPIs (Proton Pump Inhibitors)

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Step 1 Treatment of GERD:

Lifestyle Modifications
Antacids
Patient Directed Therapy
- OTC H2RAs (up to BID)
- OTC PPIs (up to QD)

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Step 2 Treatment of GERD:

Lifestyle Modifications

Standard Dose Acid Suppressing Therapy

H2RAs (BID)
- 6-12 weeks
PPIs (QD)
- 4-8 weeks
- Increase to BID with inadequate symptom response

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Step 3 Treatment of GERD:

Lifestyle Modifications

PPIs (QD - BID)
4-16 weeks

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Step 4 Treatment of GERD:

Endoscopic procedures
- RF applied LES
- Formation of plication
- Injection of bulking agent or prosthesis
- Nissen procedure

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Typical Clinical Presentation of GERD

“Heartburn” – hallmark symptom
i.e. Retrosternal chest pain in association with certain foods or in the first hour or two after eating, or constantly.

Worsening when recumbent or bending over

Regurgitation
Hypersalivation
Belching

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Atypical Clinical Presentation of GERD

Chronic cough
Asthmatic symptoms
Hoarseness
Pharyngitis
Chest pain
Dental erosions

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Complicated Clinical Presentation of GERD

Dysphagia
Bleeding
Weight loss
Choking
Chest pain

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Non-Pharmacological Treatment of GERD

Individualized lifestyle modifications* Elevate head of bed 6-8 inches Dietary changes Late meals / specific foods Weight reduction Avoid contributing medications ASA, NSAIDs, bisphosphonates Smoking cessation Avoid of alcohol Avoid tight–fitting clothing Remain upright 30’ p eating

Mechanism of action Weak bases (increases pH) Neutralize gastric acid and pepsin Place in therapy Used as needed for mild GERD Immediate relief Short term, NOT indicated for chronic use Clinically significant DIs Binding Absorption (20 ↑ gastric pH) Weakly acidic drugs ↓ Renal elimination / reabsorption(20 ↑ urinary pH) Weakly basic drugs  elimination  renal tubular reabsorption Weakly acidic drugs  elimination  renal tubular reabsorption Sodium content HTN, CHF

Antacids

Mechanism of actions Competitively inhibits histamine on the histamine2 receptor decreasing acid secretion in a dose dependant fashion Histamine stimulates gastric acid secretion Place in therapy Mild1 to moderate2 GERD Delayed onset of symptom relief Higher doses may provide greater symptomatic relief and healing of erosive espohagitis3 (50% of patients with GERD) May be more costly than QD PPIs Greatest benefit in decreasing acid in fasting state (i.e.. nocturnal acid secretion) vs fed state where acid section is also driven by gastrin and ACh Adverse effects Generally well tolerated Headache, fatigue, dizziness, diarrhea, constipation Drug Interactions Cimetidine – cytochrome P450 (3A4, 2D6, 1A2, 2C9)

H2RAs (H2 Receptor Antagonists)

Mechanism of action Covalently binds to H+/K+ ATPase proton pump of parietal cells Produces a dose dependent inhibition of gastric acid secretion PPI’s are prodrugs that need to be exposed to an acidic environment to exert effect Traditional PPIs should be administered 30-60’ before a meal for max pH control. Newer PPIs have greater flexibility in dosing w/regard to meals Place in therapy Superior to H2RAs in moderate to severe disease1 Empirically in patients (up to BID) with troublesome symptoms Non-response at BID dosing = treatment failure PPIs are safe in pregnant patients if clinically indicated Category C

PPIs (Proton Pump Inhibitors)

Antacids < H2RAs < PPIs

Onset of Action: < 5 minutes Duration of Action: 20-30 minutes Symptomatic Relief: Excellent

Antacids

Onset of Action: 30-45 minutes Duration of Action: 4-10 hours Symptomatic Relief: Excellent

H2RAs

Onset of Action: 2-3 hours Duration of Action: 12-24 hours Symptomatic Relief: Superior

PPIs

In acid environment it turns into a viscous, sticky polymer that binds selectively to ulcers and erosions creating a protective layer.

Sucralfate

 Efficacy comparable to H2RAs

Sucralfate

Foods that may worsen GERD (Decreased LES Pressure)

Fatty/fried foods Carminatives Chocolate Coffee/caffeinated drinks Garlic Onions Chili peppers

Medications that may worsen GERD (Decreased LES Pressure)

Anticholinergics Barbituates Benzodiazepines Caffeine Dopamine Estrogen Ethanol Isoproterenol Nicotine Nitrates Opioids Phentolamine Progesterone Theophylline Dihydropyridine Calcium Channel Blockers

Foods that may worsen GERD (Direct Irritants to the Esophageal Mucosa)

Carbonated Beverages Citrus Fruits Coffee Orange Juice Spicy Foods Tomatoes

Medications that may worsen GERD (Direct Irritants to the Esophageal Mucosa)

Aspirin Biphosphonates Dabigatran Doxycycline Iron NSAIDs Quinidine Potassium Chloride

This med, ______________: - Combination product. - Forms a viscous solution that floats on surface of gastric contents.

Gaviscon

Patient-directed therapy with antacids (>12 years old):

Maalox - Magnesium hydroxide/aluminum hydroxide with simethicone Gaviscon - Antacid/alginic acid Tums - Calcium Carbonate

Patient-directed therapy with nonprescription H2RAs up to twice daily (>12 years old):

Tagamet - cimetidine Pepcid AC - famotidine Axid AR - nizatidine Zantac - ranitidine

Patient-directed therapy (> 18 years old) with nonprescription PPIs (taken once daily):

Nexium 24HR - esomeprazole Prevacid 24HR - lansoprazole Prilosec OTC - omeprazole Zegerid OTC - omeprazole/sodium bicarbonate

There is no significant difference in efficacy among the _____ or _____ when given at equipotent doses.

PPIs, H2RAs.

- Cimetidine is associated with numerous clinically significant DIs - Dose reduction in renal and hepatic insufficiency and in the elderly - Duration of suppression ranges from 6-10 hours and varies with dose Which drug class?

H2RAs

- Food may affect absorption. Given 30-60' before a meal. More flexibility in term of dosing with newer agents (eg. dexlansoprazole) - Delayed onset: 3-4 days for full inhibition - Duration of action up to 24 hours due to covalent, irreversible inhibition of proton pump

PPIs

One thing we always should push BEFORE prescribing medications.

Individualized lifestyle modifications

Lifestyle modification with standard dose (Prescriber directed) acid suppression therapy H2RAs (BID) x 6-12 weeks or PPIs (QD) x 4-8 weeks (↑ to BID with inadequate symptom response ) Which step?

Step 2

PPIs (QD-BID) x 4-16 weeks Which step?

Step 3

Life style modification / non-pharmacological interventions such as dietary modification, avoid contributing medication, smoking cessation, avoidance of EtOH, weight loss, etc. Which step?

Step 1

For step ___, PPI therapy should be initiated at once a day dosing, before the first meal of the day. (PPIs (QD-BID) x4-16 weeks

Step 3 (PPIs (QD-BID) x4-16 weeks

For patients with ________ response to once daily therapy, tailored therapy with adjustment of dose timing and / or twice daily dosing should be considered in patients with night-time symptoms, variable schedules, and / or sleep disturbance.

partial

In patients with partial response to PPI therapy, ____________ the dose to twice daily therapy _________________ may provide additional symptom relief

increasing, or switching to a different PPI

Onset of Action Antacids: H2RAs: PPIs: 2-3 hours. <5 minutes, 30-45 minutes

Antacids: <5 minutes H2RAs: 30-45 minutes PPIs: 2-3 hours

Duration of Action Antacids: H2RAs: PPIs: 4-10 hours, 12-24 hours, 20-30 minutes

Antacids: 20-30 minutes H2RAs: 4-10 hours PPIs: 12-24 hours

Symptomatic relief Antacids: H2RAs: PPIs: superior, excellent

Antacids: Excellent H2RAs: Excellent PPIs: Superior

Surgical intervention. Which step?

Step 4

Maintenance PPI therapy should be administered for GERD patients who continue to have symptoms after PPI is discontinued and in patients with complications. Which step?

For patients with partial response to once daily therapy with a ________ (GI drug class), tailored therapy with adjustment of dose timing and/or twice daily dosing should be considered in patients with night-time symptoms, variable schedules, and/or sleep.

PPI

In patients with partial response to ____ therapy, increasing the dose to twice daily therapy or switching to a different _____ may provide additional symptom relief.

PPI

Maintenance _____ (drug class) therapy should be administered for GERD patients who continue to have symptoms after the PPI is discontinued, and in patients with complications including erosive esophagitis and Barrett's esophagus

PPI

H_____ (GI drug class) therapy can be used as a maintenance option in patients without erosive disease if patients experience heartburn relief.

Histamine-receptor antagonists (H2RA)

Bedtime H2RA therapy can be added to ____________________ in selected patients with objective evidence of night-time reflux if needed, but may be associated with the development of tachyphylaxis after several weeks of usage

daytime PPI therapy

___________ (gastric and duodenal) are defects in the GI mucosa that extend through the muscularis mucosa

Peptic ulcers

Causal relationships of PUD associate with ___________ infection, NSAIDs and SRMD.

H. Pylori

Therapy for _______ includes non-pharmacological interventions (similar to GERD) and pharmacological with acid suppression (antacids, H2RAs, PPIs) and/or mucosal protection (sucralfate, colloidal bismuth, misoprostol), and if present, H Pylori eradication

PUD

Three treatment options for PUD:

- Acid suppression - Mucosal protection - H Pylori eradication

________________ - In acid environment it turns into a viscous, sticky polymer that binds selectively to ulcers and erosions creating a protective layer - Efficacy comparable to H2RAs - Chemically, contains Al(OH)3, thus behaves as Aluminum as far as ADRs (eg constipation), DIs (eg chelation)

Sucralfate

___________ - MOA unclear - coats ulcers and erosions, creating a protective layer against acid and pepsin - It may stimulate PG and mucus secretion - It binds bacterial endotoxins and has direct antimicrobial activity against pylori

Bismuth

mis_________ - it stimulates mucus and bicarbonate secretion, replaces PG stores and enhances mucosal blood flow - Approved for prevention of NSAID-induced ulcers in high-risk patients

Misoprostol

Because of the critical role of __________ in the pathogenesis of peptic ulcer, eradication of this infection is a standard care in patients with gastric or duodenal ulcers

H. pylori

All PUD regimens include ____________ & ______________ therapy (PPI or H2RA)

2 antibiotics & acid suppression

The PUD regimens (which include 2 ABTs and acid suppression therapy, may include __________________

Bismuth preparation

H2RAs not recommended for prophylaxis in treatment of ______________

NSAID induced ulcers

For NSAID induced ulcers:

H2RAs are not recommended for prophylaxis.

NSAID induced ulcers:

Prevention: Misoprostol or PPI. H2RAs not recommended for prophylaxis.

Treatment of NSAID induced ulcers:

- Discontinue NSAID If possible - Eradicate H Pylori if (+) - H2RAs or PPIs

- _________ heal NSAID-related ulcers more effectively as compared with H2RAs and are therefore the antisecretory drug of choice for treating NSAID-related ulcers, especially when NSAIDs are continued

PPIs

- Patients with NSAID-associated ulcers should be treated with a PPI for a minimum of ___ weeks

____________ is an option for healing only if NSAID will be stopped

Sucralfate

For stress ulcer prophylaxis there's no recommendation for PPIs over H2RAs.

The American Society of Health-System Pharmacists recommends _______________________________________ in the following scenarios: - coagulopathy(defined as a platelet count <50,000 cells/mm3, an INR >1.5, or a PT >2 times control) - mechanical ventilation for longer than 48 hours - history of GI ulceration/bleed within 1 year before admission - head/spinal cord injury - burns on more than 35% of body surface area - ICU patients with multiple trauma - transplant patients perioperatively - and patients with at least two of the following risk factors—sepsis, ICU stay longer than 1 week, occult bleeding for at least 6 days, and use of high-dose corticosteroids (>250 mg daily of hydrocortisone or its equivalent).

stress ulcer prophylaxis

In rare cases where PPIs or H2 blockers cannot be administered for stress ulcer prophylaxis, ______________ is a suitable oral alternative.

sucralfate

Approach to treatment of constipation should begin with determination of cause, including these options:

- Opiates - Anticholinergics (eg. tricyclic antidepressant (amitryptiline), diphenhydramine, benztropine, etc.) - NDHP-CCB (eg verapamil) - Oral iron preparations - Calcium or aluminum antacids - NSAIDs - Clonidine - Diuretics

Non-pharmacological interventions for constipation: _____, _____, _____ - Probiotics: limited data

(diet (fiber), exercise, fluids)

Three medications for constipation that are safe in pregnancy:

- Bulk formin agents (methylcellulose - Citrucel) - Emolients [softeners] (docusate - Colace) - Hyperosmotics (polyethylene glycol - Miralax)

- Administer 240 mL of water with each dose to prevent esophageal / GI obstruction and worsening symptom - Physical binding of other substances including medications - Safe in pregnancy

Bulk-forming agents

- Facilitate mixing of aqueous and fatty materials in the intestinal tract - Used for prevention, NOT treatment. Commonly prescribed with medications that may cause constipation (chronic opiate use, iron supplementation) - Safe in pregnancy

Emolients

- Osmotic effects to retain fluid in GI tract - Safe in pregnancy

Hyperosmotics

DO NOT use this constipation med in pregnancy

Lubricant laxative - (mineral oil, castor oil)

Goals of treatment for diarrhea:

- Identify and treat primary cause - Manage secondary causes - Prevent electrolyte & acid/base disturbances & dehydration - Provide symptomatic relief

Note the __________ goal is NOT ALWAYS to stop diarrhea!

primary

Secondary causes of diarrhea can include __________________. An evaluation of ______________ and possible substitution of offending ________________ should be considered (if possible).

medications

Medications that can cause diarrhea:

- Magnesium containing antacids - Metformin (1/3 of patients) - Antibiotics (25% incidence) - Anti-inflammatory / anti-gout agents (eg. colchicine)

We do not routinely use _________ antibiotics in patients with acute diarrhea.

empiric

This classic diarrhea is due to enterotoxigenic Escherichia coli (ETEC), and generally produces malaise, anorexia, and abdominal cramps followed by the sudden onset of watery diarrhea. The illness is generally self-limited with symptoms lasting for approximately one to five days.

Traveler's diarrhea

Antibiotics are warranted to treat diarrhea in those who develop ______ diarrhea, characterized by more than ______ unformed stools daily, fever, or blood, pus, or mucus in the stool. In addition, some travelers desire antibiotic treatment for milder disease if the illness is a large burden on a business trip or vacation.

severe four

For mild to moderate diarrhea, ____________ drugs (eg. loperamide) may be used as monotherapy.

anti-motility

For severe diarrhea, anti-motility drugs [eg. _____________ (med)] may be used cautiously as adjunctive therapy.

loperamide

Severe diarrhea is characterized by:

more than four unformed stools daily, fever, or blood, pus, or mucus in the stool.

The initial step in the treatment of Clostridium difficile infection (CDI) caused by an ABT is ______________ of the inciting antibiotic as soon as possible

cessation

Therapy for ___________ difficile infection (CDI) consists of oral metronidazole >> oral vancomycin

non-severe

“general purpose antiemetic"

Promethazine

Promethazine is an example of a:

“general purpose antiemetic"

P_________________ (med) is not very effective in treatment of severe N/V.

Promethazine

Lorazepam is a:

Benzodiazepine

________________ are sedatives, not antiemetic agents.

benzodiazepines

B_____________________ (psych drug class) bind to GABA-A receptors. GABA is the major inhibitory NT in the CNS

Benzodiazepines

Sedative and anti-anxiety effects → reduce anticipatory N/V associated with chemotherapy b___________ (psych drug class)

Benzodiazepine

ADRs - CNS - sedation, hallucinations, euphoria; CV - hypotension b______________ (psych drug class)

Benzodiazepines

Why is self-directed therapy (OTC) limited to 2 weeks?

- prevent serious conditions from going undiagnosed - re-evaluate for efficacy - prevent adverse effects of PPIs.

3 most common causes of peptic ulcer disease:

H. pylori, NSAIDs, and stress-related mucosal damage.

Regarding NSAID-induced ulcer therapy, if on an NSAID...

...get off of it.

Bloody stools are usually, not always, in __________________.

infectious diarrhea

For treating C. Diff, take m______________ for mild to moderate diarrhea, and v_________________ for severe diarrhea.

Metronidazole, vancomycin.

NSAID ulcer prevention:

Reduce NSAID dose, or use prophylactically with misoprostol or a PPI.

Traveler's diarrhea subsides in ______ days.

2-3

Mineral oil can cause an increased risk of _________________

aspiration pneumonia.

________________ the diarrhea is NOT a goal of treating diarrhea.

Stopping

What are the underlying causes of GERD (physiologically) and what are some things that can worsen GERD symptoms?

Anything that puts pressure on the stomach/gastric area. This includes hiatal hernias, gastric band, gastric sleeve, pregnancy, tight pants/belt.

What non-pharmacological interventions should be instituted for all GI conditions discussed?

- Losing weight - Elevate HOB with foam wedge 4-8" - Dietary guidance - Avoid tight clothes and waist bending - Smaller meals - No eating within 3' of sleep - No ETOH or smoking - Evaluate current meds

All PPIs and H2RAs are equally effective at standard doses,

If the pt doesn't like a PPI, take them off it.

Try one PPI, it's hit or miss, and if it doesn't work try a different one.

AE of PPIs:

- increased dementia risk - if osteopenic then increased issues - osteoporosis and fractures

GERD can be a symptom of quite a few things.

For drug treatment of PUD you'd want to do tx in this order of recommendation:

1) Clarithromycin triple therapy 2) Bismuth quadruple therapy 3) Sequential therapy 4) Hybrid therapy

If PUD is caused by an NSAID, get the pt off the NSAID.

In the case of CINV, what is the rationale behind the combination of various agents?

To prevent acute CINV for moderately or highly emetogenic chemotherapy.

Insoluble fiber is best for constipation.

Anticholinergics mnemonic:

Can't see, pee, spit, or shit.

Non-pharm interventions for constipation?

- Elevate feet with stool while pooping - Increase insoluble fiber - Adequate fluid intake over age 19 - Increase exercise - Biofeedback aided pelvic floor training - Probiotics

Lactulose and magnesium products are pregnancy category B.

Magnesium antacids are low risk in pregnancy.

Long-term mag citrate should be avoided in preganancy despite being category B.

Laxatives may provide relief for constipation occuring during the post-partum period when mother is not breastfeeding.

For pregnancy always avoid categories C, D and X.

Stopping the diarrhea is never a treatment goal of diarrhea.

Sometimes a cause of constipation is the suppression of defecation, and this may include the misuse of certain medications.

90% of acute diarrhea is caused by viruses, bacteria, and protozoa.

10% of diarrhea is caused by meds, toxic ingestion, ischemia, food intake (dairy, nonabsorbable food, fat substitutes, sugar free diabetic candy), laxative abuse, food intolerance, IBS, IBD, lactase deficiency, DM, B12 deficiency anemia, malabsorption, fecal impaction, diverticulosis, and celiac sprue (gluten intolerance).

TD subsides in 2-3 days (viral or bacteria).

C. Diff diarrhea requires meds: metronidazole and/or vancomycin.

IV Vancomycin does not treat C. Diff. It has to be PO.

Mineral oil leads to an increased risk of aspiration pneumonia.

Chronic diarrhea: caused by functional or inflammatory bowel disorders, endocrine disorders, malabsorption syndromes, and drugs (laxative abuse, etc).

Chronic diarrhea may be intermittent or continual.

Universal Tx goals of diarrhea are relieving symptoms, maintaining hydration, treating the underlying cause, and maintaining nutrition.

Universal Treatment Goals of Diarrhea (x4):

- relieving symptoms - maintaining hydration - treating underlying cause - maintaining nutrition

Treatment goals for DM1 and DM2 are the same.

Treatment goals of DM1 and DM2: reduce, control, and manage long-term micro/macro-vascular and neuropathic complications, preserving beta cell function, preventing acute complications from high BG levels, minimizing hypoglycemic episodes, and maintaining the patient's overall QOL.

Treatment goals of DM1 and DM2:

- reduce, control, and manage long-term micro/macro-vascular and neuropathic complications. - preserving beta cell function - preventing acute complications from high BG levels - minimizing hypoglycemic episodes - maintaining the patient's overall QOL.

Metformin causes diarrhea due to increased sugar added into the intestines.

Hypoglycemia is NOT a common side effect of metformin.

Metformin significantly reduced all-cause mortality and risk of stroke in overweight patients with T2DM compared with intensive therapy with sulfonylurea or insulin in the UK-PDS. Metformin also reduced diabetes-related death and MI compared with a conventional therapy arm.

Metformin is considered foundational therapy along with lifestyle modifications for T2DM and is often used in combination with other antihyperglycemics for synergistic effects.

TZDs are associated with increased CV events and edema.

Incretin mimetics are associated with weight loss. They may be desirable in obese patients.

What are specific contraindications to metformin? - T1DM - eGFR <30mL/min - radiographic procedures with nephrotoxic dyes - hypersensitivity - hypoxemia - sepsis - dehydration - liver disease

What are specific contraindications to metformin?

- T1DM - eGFR <30mL/min - radiographic procedures with nephrotoxic dyes - hypersensitivity - hypoxemia - sepsis - dehydration - liver disease

Regarding metformin and radiographic procedures with nephrotoxic dyes, you need to hold the metformin 3-5 days before and after the procedure.

When should insulin be considered in DM2?

AIC of 9 or higher, or BG >300.

Examples to decrease likelihood of hypoglycemia: - D/C oral secretagogues like SU (sulfonlyureas) and GLN (glinides) - start with long-acting insulins if a basal-bolus regimen if not used - start a period of more relaxed glycemic targets - Adjust dose every 3-to-4 days until SMBG at goal - Inject rapid and regular acting insulins before a meal, not after the meal - Make sure patient is willing to check their BG.

Examples to decrease likelihood of hypoglycemia:

- D/C oral secretagogues like SU (sulfonlyureas) and GLN (glinides) - start with long-acting insulins if a basal-bolus regimen if not used - start a period of more relaxed glycemic targets - Adjust dose every 3-to-4 days until SMBG at goal - Inject rapid and regular acting insulins before a meal, not after the meal - Make sure patient is willing to check their BG.

Go low and slow when prescribing antihyperglycemics.

Unless contraindicated, all patients should have concomitant disease states tightly controlled and be on medications that have shown to improve long term outcomes. What are these medications? - ACE inibitors (ACEIs) - Statins - Aspirin (ASA)

- ACE inibitors (ACEIs) - Statins - Aspirin (ASA)

No test question on PPIs with clopidogrel (as of 1/28/23...)

(Just keep in mind.)

Triple therapy with x2 ABT and a PPI is the preferred FIRST treatment for PUD, per the book.

All patients with a history of CV disease should receive aspirin daily as secondary prevention strategy.

Plavix is an option if the patient is allergic to ASA.

The ADA recommends ASA for DM when there's no history of CVD when patient is 50 YOA or older, and has at least one additional risk factor.

Why should sliding scale insulin be avoided for routine use?

SS is basically playing catch-up, and the goal of therapy is to be prophylactic.

ADR of insulin: hypoglycemia, lipodystrophy, weight gain, peripheral edema, injection site reaction

If taking SN and/or GLN, check your blood sugar once a day.

How should DM therapy be monitored? - SMBG - HGAIC - Outcomes - BP - cholesterol - Symptom resolution and history of episodes

Estrogen can worsen GERD. (Including birth control)

Pressure on gut causes reflux.

TSH is a highly sensitive bioassay of the thyroid axis. A two-fold change in free T4 levels will result in a 100-fold change in TSH levels. This biologic magnification by TSH allow it to be used in early diagnosis as well as in closely titrating therapy.

Lay on left side to help reduce GERD/reflux (also helpful in pregnancy).

Pregnancy requires higher doses of levothyroxine (Synthroid).

Synthroid (levothyroxine) is used for hypothyoidism.

PTU and methimazole is used for hyperthyroidism.

Use lowest dose of PTU in pregnancy for hyperthyroidism. If untreated hyperthyroidism, there's a risk of spontaneous abortions, premature delivery, low birth rate, and full-blown eclampsia.

Hypothyroidism in pregnancy if untreated or inadequately treated: high risk of stillbirth, HTN, preeclampsia, anemia, cardiac abnormalities in mother and baby, low birth rate.

Regarding thyroid replacement therapy there's no evidence one product is better than another, however these products do have differences in bioavailability. Patients should be monitored on the same product.

NSAID-Induced Ulcer Therapy

- if on NSAID, stop the NSAID -

Regarding NSAID-Induced Ulcer therapy, if symptoms persist even after stopping NSAID:

Start on H2RA or PPI, and if those symptoms keep going then do an endoscopy.

NSAID Ulcer Prevention:

- reduce NSAID dose to the lowest dose that's helpful - OR prophylax with misoprostal or a PPI in combination WITH that NSAID

COX 2 selective NSAID (Celebrex, celecoxib) is an option, but studies have shown celecoxib is no better than an NSAID and a PPI.

- Maybe consider celecoxib if someone wants it once a day? Maybe if pt not a good candidate for adherence?

Thyroid medications can exacerbate cardiac morbidities. Being aware of the pt's cardiac risk factors is very important.

Synthroid should be taken first thing in the morning with water.

Avoid tube feeding, grapefruit, etc when taking Synthroid.

What adjunct medications are used in hyperthyroid disease until biochemical euthyroidism can be achieved? What is the rationale?

Beta Blockers: only Nadolol and Propranolol. These two relieve palpatations, tremors, anxiety, and heat intolerance.

Sucralfate (carafate) will reduce the absorption of any medication within 2 hours of taking it. Should probably wait 4 hours if you need the med to be fully absorbed.

Triple therapy (x2 ABT and a PPI) is #1 tx for treating PUD.

Chronic alcohol ingestion is not a common cause of PUD.

Preferred first-line option for treating a newly-diagnosed patient with H. pylori infection and a penicillin allergy:

A quadruple drug regimen: - bismuth subsalicylate - metronidazole - tetracycline - PPI

A quadruple drug regimen for H. pylori in pt allergic to penicillin: - bismuth subsalicylate - metronidazole - tetracycline - PPI

Standard dose PPI, clarithromycin 500 mg, and amoxicillin 1000 mg (all BID): Consider in non-penicillin-allergic patients who have not previously received a macrolide.

Standard triple therapy for PUD.

Standard dose PPI, clarithromycin 500 mg, metronidazole 500 mg (all BID): *for penicillin allergy

Consider in penicillin-allergic patients who have not previously received a macrolide or are unable to tolerate bismuth quadruple therapy.

Bismuth 525 mg, metronidazole 250 mg, tetracycline 500 mg (all QID) + ranitidine 150 mg (BID) OR standard dose PPI (QD-BID)

Consider in penicillin allergic patients

Bismuth 525 mg, metronidazole 250 mg (both QID) + amoxicillin 100 mg (BID) + PPI (BID)

Consider in patients where macrolide or tetracycline is an issue.

Misoprostol or PPI recommended in prevention of NSAID induced ulcers (not H2RAs).

10-14 days of triple therapy is recommended.

Meclizine is usually the preference in treating N/V. Less drowsy.

Meds that can treat N/V: - scopolamine - antihistamines - meclazine (preferred; less drowsy) - phenothiazines (chlorperazine, proclorperazine, promethazine). Can cause hyperprolactinemia and extrapyrimidal symptoms (like lip smacking, etc). Maybe don't use in patient's at risk for these extrapyrimidal symptoms. - Butyrophenones (droperidol, haloperidol) (mostly for CINV) Like a chemical restraint; don't use in people that don't have CINV, and don't require restraining. - Benzamides (domperidone, metoclopramide [common], trimethobenzamide[rare]) - corticosteroids (for CINV) - Cannabinoids (dronabinol [more in nausea than in appetite]) - benzodiazepines (usually CINV) - Serotonin Antagonists (dolasetron, granisetron, ondansetron, palonosetron[for CINV, IV while in chemo]) - Neurokinin-1 antagonists. (aprepitant, rolapitant, netupitant) - Others: Olanzipine (gained traction in CINV), doxylamine/pyridoxine (can buy OTC and combine, good for pregnancy induced N/V).

Look at AEs. Dosing: what it can be used for. Don't worry about IV/IM. Look at CINV prophylaxis. Post-operative N/V? Put in sidenote for table.

Recommended Drug Regimen for Prevention of CINV Based on Emetogenic Risk. [1/4] Risk: Minimal Acute CINV (Day 1): None Delayed CINV (Days 2-4): None

Recommended Drug Regimen for Prevention of CINV Based on Emetogenic Risk. [2/4] Risk: Low Acute CINV (Day 1): Dexamethasone OR 5-HT antagonist Delayed CINV (Days 2-4): None

Recommended Drug Regimen for Prevention of CINV Based on Emetogenic Risk. [3/4] Risk: Moderate Acute CINV (Day 1): 5-HT antagonist + dexamethasone Delayed CINV (Days 2-4): Dexamethasone (days 2 and 3) for agents with known risk for delayed nausea and vomiting.

Recommended Drug Regimen for Prevention of CINV Based on Emetogenic Risk. [4/4] Risk: High (includes AC regimens) Acute CINV (Day 1): NK receptor antagonist + 5-HT antagonist + dexamethasone + olanzapine Delayed CINV (Days 2-4): If aprepitant is used, continue days 2 and 3. Continue dexamethasone days 2-4 for non-AC highly emetogenic regimens. Olanzapine (days 2-4)

Common meds that cause constipation: - analgesics: opioids - anticholinergics - antidiarrheals - antihistamines - anti-psychotics and anti-depressants (the ones that are anticholinergic) - aluminum-containing products (Mag runs, Al blocks the road) - Calcium channel blockers (can cause edema) - Calcium-containing products (cause constipation in pregnant women dealing with GERD) - Clonidine - Diuretics (dry you out) - iron-containing supplements (pull moisture out, stool more compact/hard) - Ondansetron - Phenothiazine (anti-cholinergic) - volume depletion meds - laxative abuse (rebound effect)

Common causes of constipation: - cholinergics (huge cause) (can't see, pee, spit, shit) (Benadryl, muscle relaxers like Flexeril, promethazine, - normal transit constipation (may not be getting enough water, eating "right" foods, getting dry in colon) - slow transit constipation (malnourished - gastro-colonic disorders, like ulcerative colitis, IBS, etc. Gastroparesis? - deliberate suppression of defecation (kids, not wanting to use public restrooms). Adults can refuse too, get psychological distress - perceptions about bowel frequency (ethnic considerations?)

Magnesium: PPIs may decrease magnesium level, which can lead to muscle spasms, arrhythmias, seizures, and fatigue. This typically occurs after long-term administration of PPIs, usually longer than a year. Treatment may require magnesium replacement and PPI discontinuation.

Elderly patients taking a PPI are at greater risk of bone fractures, so the patient pushed to maintain a good diet and exercise routine and get enough calcium and vitamin D supplements to lower this risk. This is because PPIs lower gastrointestinal pH, absorbing less calcium from food. Supplements containing calcium and vitamin D can enhance bone health and reduce the risk of fractures. For patients using PPIs, calcium citrate, a kind of calcium supplement that can be absorbed in high stomach pH, maybe a better choice.

It's critical to identify the source of diarrhea in H. pylori patients who are receiving treatment. A thorough history of the patient's current medications must be taken first. Investigating whether the diarrhea is brought on by the side effect of drugs, particularly the antibiotics being taken to treat the infection, is crucial. If a drug side effect is responsible for diarrhea, changing to a different antibiotic/reducing the dosage, or administering probiotics may be an option.

There are some potential adverse effects of long-term acid suppressive therapy to consider. Although hypomagnesemia is a rare side effect, periodic measurement of serum magnesium levels may be necessary for early detection and early intervention for subclinical hypomagnesemia (Kinoshita et al., 2018).

Bismuth-containing quadruple therapy is considered the second-line treatment for eradicating Helicobacter pylori. This method is considered the first line of treatment for strains that have developed antibiotic resistance. Bismuth, a PPI, and the antibiotic combination of metronidazole and tetracycline are used for 14 days (Goderska et al., 2018).

17-6. [GERD] Which one of the following medications may worsen the symptoms of GERD by decreasing lower esophageal sphincter pressure? A. Nifedipine B. Alendronate C. Naproxen D. Quinidine E. Ferrous sulfate

17-7. [GERD] What is the best treatment regimen for a 55-year-old patient who complains of difficulty swallowing for the last 3 months? A. Patient-directed therapy with OTC PPI for 2 months. If no improvement, then refer to physician for further evaluation B. An 8-week course of metoclopramide 10 mg three times daily. If no improvement, then refer to physician for further evaluation C. An 8-week course of standard dose PPI (once daily) plus further diagnostic evaluation by physician for complicated symptoms D. An 8-week course of standard dose PPI (once daily) plus standard dose H2- receptor antagonist for breakthrough symptoms E. Lifestyle modifications only

17-8. [GERD] The goals of treatment of GERD are to: A. Alleviate symptoms B. Promote healing of mucosal injury C. Prevent complications D. Decrease esophageal pH to less than 2 E. A, B, and C are all correct

17-10. [GERD] Which recommendation would be most appropriate regarding calcium supplementation for prevention of bone fractures in a healthy 24-year-old woman taking omeprazole 20 mg once daily for GERD? A. Elemental calcium 2000 mg daily in divided doses B. No calcium is needed because she does not have risk factors for osteoporosis or fractures C. Elemental calcium 2000 mg daily plus vitamin D 800 units daily D. Calcium citrate 500 mg four times daily E. Calcium gluconate 1 gram IV every month

17-11. [GERD] What is the best treatment option for a patient with GERD symptoms that are refractory to the initial PPI regimen? A. Change to a different PPI B. Increase the frequency of the current PPI to twice daily C. Change to a high-dose H2-receptor antagonist regimen (eg, rantidine 150 mg four times daily) D. A and B only E. A, B, and C

17-12. [GERD] PPIs decrease stomach acid by which of the following mechanisms? A. Inhibiting gastric H+ /K+ -adenosine triphosphatase in gastric parietal cells B. Inhibiting histamine2 receptors in gastric parietal cells C. Forming a viscous solution that floats on the surface of the gastric contents D. Forming a protective coating over the damaged mucosa E. Increasing GI motility

17-13. [GERD] Maintenance therapy is indicated for patients with: A. Continued symptoms after PPI discontinued B. Barrett esophagus C. Erosive esophagitis D. Extraesophageal syndromes associated with GERD E. All of the above

17-14. [GERD] Which of the following is not considered a potential risk associated with the use of PPIs? A. Clostridium difficile infections B. Community-acquired pneumonia C. Hyperkalemia D. Bone fractures E. Hypomagnesemia

18-1. [PUD] Which of the following is not a common cause of peptic ulcer disease (PUD)? A. Chronic alcohol ingestion B. Nonsteroidal antiinflammatory drugs (NSAIDs) C. Stress-related mucosal damage D. Helicobacter pylori infection E. All of the above are common causes of PUD

18-3. Which of the following is an indication for stress ulcer prophylaxis (SUP) in critically ill patients according to the 1999 American Society of Health-System Pharmacists (ASHP) published guidelines? A. Mechanical ventilation for longer than 48 hours B. Patients admitted to telemetry for heart failure C. Platelet count greater than 50,000/mm3 (50 × 109 /L) but less than 150,000/mm3 (150 × 109 /L) D. Thermal injuries to more than 15% of body surface area E. Admission to ICU on enteral feedings

18-5. [PUD] A 65-year-old woman presents with new onset epigastric pain, recent 10-pound (4.5kg) weight loss, and anemia. What diagnostic test should this patient undergo? A. Urea breath test B. Stool antigen testing for H. pylori C. Esophagogastroduodenoscopy (EGD) D. H. pylori serology testing E. Manometry

18-6. [PUD] A prophylactic medication regimen to prevent NSAID-induced ulcers would not be recommended in: A. A 65-year-old patient on long-term NSAID therapy for osteoarthritis B. A 60-year-old patient on aspirin therapy for cardioprotection C. A 72-year-old patient with history of GI bleeding on NSAID therapy for osteoarthritis D. A 30-year-old patient who takes NSAID for occasional tension headaches E. An 80-year-old patient on high-dose corticosteroids for lupus and history of GI bleeding

18-7. [PUD] A preferred first-line option for treating a newly diagnosed patient with H. pylori infection and a penicillin allergy is: A. A triple-drug regimen consisting of a proton pump inhibitor (PPI), clarithromycin and tetracycline B. A triple-drug regimen consisting of a PPI, levofloxacin, and tetracycline C. A quadruple-drug regimen with bismuth subsalicylate, metronidazole, tetracycline, and a PPI D. Dual therapy consisting of a PPI and metronidazole E. None of the above

18-8. [PUD] Which one of the following should be considered when evaluating a patient who has failed H. pylori eradication therapy? A. Patient adherence B. Preexisting antimicrobial resistance C. Potential reinfection D. All of the above E. None of the above

18-9. [PUD] Which of the following tests can be used to confirm eradication of H. pylori? A. Urea breath test B. Stool antigen assay C. EGD with biopsies D. Serologic testing E. Both A and D

18-10. [PUD] Which of the following statements is true regarding misoprostol? A. Misoprostol is a synthetic prostacyclin analog that exogenously replaces prostacyclin stores B. Misoprostol is safe to use in pregnancy C. Misoprostol is indicated for reducing the risk of H. pylori-induced gastric ulcer D. Misoprostol is limited by a high frequency of GI side effects E. Misoprostol is the drug of choice for stress ulcer prophylaxis ****** This question is suspicious. Google search says Cytotec can induce contractions/cause abortions.

18-11. [PUD] Which of the following is an independent risk factor for the development of NSAID-induced peptic ulcers? A. Concomitant use of corticosteroids B. Alcohol consumption C. Concomitant use of selective serotonin receptor inhibitors (SSRIs) D. Smoking E. All of the above

18-14. [PUD] Which of the following is not a goal of PUD therapy? A. Resolve symptoms B. Increase acid secretion C. Promote epithelial healing D. Prevent ulcer-related complications E. Prevent ulcer recurrence

18-15. [PUD] Refractory peptic ulcers will most likely require which of the following interventions? A. An increase in the H2RA dose B. An evaluation of serum pepsin to exclude Zollinger-Ellison syndrome C. H. pylori testing if not done previously D. Combination therapy with an H2RA and PPI E. All of the above

20-1. [N/V] A 52-year-old man presents with chronic lower back pain that he has managed with ibuprofen 400 mg PO three times daily. He reinjured his back moving boxes and 2 days ago was started on hydrocodone 5 mg/acetaminophen 325 mg every 4 hours as needed for pain. He also has a history of hypertension and asthma for which he takes lisinopril 20 mg daily, hydrochlorothiazide 25 mg daily, fluticasone 250 mcg/salmeterol 50 mcg twice daily, and albuterol MDI two puffs as needed for shortness of breath. Today he complains of nausea with one episode of vomiting this morning. What is most likely to be causing his nausea and vomiting? A. Lisinopril B. Hydrochlorothiazide C. Hydrocodone D. Acetaminophen E. Fluticasone

20-2. [N/V] All of the following are true regarding nausea except: A. It is an objective finding B. It is accompanied by tachycardia C. It increases salivation D. It is accompanied by diaphoresis

20-3. [N/V] The adverse effects of doxylamine (antihistamine, anticholinergic) include: A. Salivation, diarrhea, insomnia B. Dry mouth, constipation, drowsiness C. Salivation, constipation, insomnia D. Dry mouth, diarrhea, drowsiness

20-4. [N/V] Benzodiazepines are associated with all of the following adverse effects except: A. Respiratory depression B. Sedation C. Dyskinesia D. Amnesia

20-5. [N/V] A 57-year-old obese woman is scheduled to undergo lengthy abdominal surgery. She smokes one pack of cigarettes per day, does not drink alcohol, and has a history of motion sickness. Which set of risk factors predisposes this patient to postoperative nausea and vomiting (PONV)? A. Female sex, smoking history, and alcohol history B. Body habitus, history of motion sickness, and alcohol history C. Female gender, history of motion sickness, and duration of surgery D. Body habitus, smoking history, and alcohol history E. Female gender, history of motion sickness, and smoking history

20-6. [N/V] Nonpharmacologic treatment options for motion sickness include: A. Increasing exposure to movement to acclimate to it more quickly B. Reading in a moving vehicle to distract from the motion C. Restricting ventilation to prevent olfactory stimulation of motion sickness D. Placing the head between the knees to reduce visual stimulation E. Sitting in the center of a boat to reduce the magnitude of the movement

20-7. [N/V] Which of the following statements about aprepitant is true? A. It is a 5-HT3 antagonist B. It is ineffective for prevention of PONV C. It is renally eliminated D. It prevents acute and delayed CINV when used with standard antiemetics

20-8. [N/V] A 58-year-old man is undergoing surgical toe amputation. He does not have patient-specific risk factors for PONV, and his surgery will be short with minimal risks for PONV. He was not given PONV prophylaxis prior to the procedure but experiences nausea and vomiting in the postanesthesia care unit. The nurse asks you for a treatment recommendation. Which of the following options is the best recommendation? A. Diphenhydramine 25 mg orally B. Ondansetron 8 mg orally C. Scopolamine transdermal patch D. Granisetron 0.1 mg IV E. Dexamethasone 5 mg IV

20-9. [N/V] A 62-year-old woman with acute myeloid leukemia is in clinic to receive her first day of cytarabine 100 mg/m2 IV and daunorubicin 45 mg/m2 IV, which is a moderately emetogenic, non-anthracycline/cyclophosphamide regimen. Which of the following prophylactic antiemetic regimens would be preferred for prevention of acute nausea and vomiting in this patient? A. Palonosetron plus dexamethasone B. Dolasetron plus lorazepam C. Metoclopramide plus dexamethasone D. Granisetron plus aprepitant E. Prochlorperazine plus dexamethasone

20-10. [N/V] A 65-year-old woman is being treated for refractory chronic myelogenous leukemia (CML) with hydroxyurea. Which one of the following antiemetic regimens would be the most appropriate to administer prior to the hydroxyurea dose for preventing CINV? A. Granisetron plus dexamethasone plus aprepitant B. Palonosetron plus dexamethasone C. Dexamethasone D. Metoclopramide E. No prophylaxis is required

20-11. [N/V] A 69-year-old woman with non–small-cell lung cancer is scheduled to receive her first cycle of cisplatin 100 mg/m2 plus gemcitabine 1000 mg/m2 . Which of the following oral regimens would be most appropriate for preventing acute and delayed nausea and vomiting? A. Ondansetron, dexamethasone, and aprepitant on days 1–4 B. Ondansetron, dexamethasone, and aprepitant on day 1 C. Ondansetron and dexamethasone on day 1, and aprepitant on days 1–4 D. Ondansetron day 1, dexamethasone days 1–4, and aprepitant day 1 E. Ondansetron day 1, dexamethasone days 1–4, and aprepitant days 1–3

20-13. [N/V] A 30-year-old woman is going deep-sea fishing this weekend. The last time she went on a similar excursion, she got seasick about an hour after leaving port and shortly after drinking three margaritas and eating several tacos. She asks you to recommend something to help prevent seasickness. What is the best recommendation? A. Apply a transdermal scopolamine patch 1 hour before the trip B. Take granisetron one mg orally 4 hours before the trip C. Take aprepitant 40 mg orally 3 hours before the trip D. Take meclizine 50 mg orally if nausea or vomiting occurs E. Take methylprednisolone 8 mg orally if nausea or vomiting occurs

20-14. [N/V] A 26-year-old woman in her first trimester of pregnancy (week 9) is experiencing severe nausea and vomiting that is interfering with her ability to maintain an acceptable level of nutrition. Which one of the following antiemetic regimens would be the most appropriate? A. Methylprednisolone 12 mg orally twice daily as needed B. Droperidol 0.625 mg orally every 12 hours as needed C. Doxylamine 10 mg/pyridoxine 10mg, two tablets at bedtime D. Dolasetron 100 mg orally every 8 hours as needed E. Dronabinol 5–15 mg/m2 every 2–4 hours as needed

________________ may be performed in patients not responding to an adequate trial of a twice-daily proton pump inhibitor.

Endoscopy

The goals of GERD treatment are to alleviate symptoms, decrease the frequency of recurrent disease, promote healing of mucosal injury, and prevent complications.

Pharmacologic options can be stratified by effectiveness: antacids are inferior to histamine-2 receptor antagonists (H2 RAs), and H2 RAs decrease acid secretion less than PPIs.

Aluminum or magnesium-containing antacids may result in electrolyte abnormalities, particularly in patients with renal impairment. Antacids are usually well tolerated, and potential side effects include constipation or diarrhea depending on the formulation being used. Antacids may also chelate with medications such as fluoroquinolones, tetracyclines, iron products, and thyroid hormones; therefore, doses should be separated by several hours to avoid decreased efficacy.

Most H2RAs are renally eliminated and may require dose adjustment in renal dysfunction.

Cimetidine has unique adverse effects such as gynecomastia and vitamin B12 deficiency, which limit patient tolerance during chronic therapy.

PPIs (eg, omeprazole, lansoprazole) block gastric acid secretion by inhibiting gastric H+/K+-adenosine triphosphatase in gastric parietal cells, producing a profound, long-lasting antisecretory effect capable of maintaining the gastric pH above 4, even during postprandial acid surges.

PPIs provide significant reduction in gastric acid and the greatest relief of symptoms, especially in patients with moderate-to-severe GERD, with high rates of healing erosive disease.

Most patients should be instructed to take their PPI in the morning, 30 to 60 minutes before breakfast to maximize efficacy. Due to their slow onset of action, PPIs are most effective when taken on a scheduled basis.

All PPIs can decrease the absorption of medications that require an acidic environment to be absorbed (eg, dabigatran, encapsulated itraconazole, dipyridamole) and are metabolized by the cytochrome P-450 system to some extent.

PPIs are generally well tolerated; the most common side effects are headache and GI effects such as diarrhea and nausea.

In patients with documented hypocalcemia, it is reasonable to replete calcium with the citrate rather than the carbonate salt due to improved absorption in a less acidic environment.

Infectious complications attributed to chronic PPI use include spontaneous bacterial peritonitis, small intestinal bacterial overgrowth, Clostridium difficile infection, and pneumonia.

Metoclopramide, a central dopamine antagonist, accelerates gastric emptying and can increase LES pressure. Metoclopramide has been studied for GERD symptom relief in conjunction with a PPI; however, potential side effects can be significant and include extrapyramidal effects and tardive dyskinesia.

Many patients who have heartburn symptoms two or more times per week may successfully self-treat with a short-term (maximum 2-week) course of nonprescription PPI therapy. Although this strategy is neither sensitive nor specific for diagnostic purposes, it is a reasonable initial option to achieve symptom control. Patients experiencing symptoms beyond the 2-week course should be evaluated by a provider.

On presentation to a health-care provider, patients may have already attempted a nonprescription trial of self-directed therapy with all three of the major pharmacologic classes. After confirmation of a GERD diagnosis, a trial of a scheduled PPI for 8 weeks is typically recommended, monitoring for symptomatic improvement.

Most patients with nonerosive GERD respond positively to a PPI trial and therefore should be evaluated for an appropriate long-term maintenance therapy. Adherence and appropriate administration should be monitored throughout therapy.

For patients with refractory nocturnal symptoms or symptoms not controlled with daily therapy, a trial of twice-daily PPIs may provide benefit.

Patients who wish to stop long-term PPI therapy should be slowly titrated off using a stepwise or prolonged taper due to the potential for rebound gastric acid hypersecretion with sudden withdrawal.

GERD is common during pregnancy, and 30% to 50% of pregnant women report heartburn symptoms. Lifestyle modifications such as eating smaller meals can reduce heartburn and regurgitation. Mild-to-moderate GERD symptoms can be treated with antacids that have limited systemic absorption, such as calcium, magnesium, and aluminum. Also, compounds containing sodium bicarbonate should be avoided due to risk of metabolic alkalosis in both the mother and the fetus, as well as precipitating fluid overload.39

Pregnant patients with severe, frequent heartburn can be started on a PPI.

Peptic ulcer disease (PUD) refers to a defect in the gastric or duodenal mucosal wall that extends through the muscularis mucosa into the deeper layers of the submucosa. PUD is a significant cause of morbidity and associated with substantial health care costs.

Although there are many etiologies of PUD, the three most common are (a) Helicobactor pylori (H. pylori) infection, (b) use of nonsteroidal anti-inflammatory drugs (NSAIDs), and (c) stress-related mucosal damage (SRMD).

Complications of PUD include gastrointestinal (GI) bleeding, perforation, and obstruction.

Complications of untreated or undiagnosed H. pylori infection include gastric cancer and PUD.

Risk Factors for Ulcers and GI Complications Related to NSAID Use:

* Age older than 65 years * Concomitant anticoagulant use * Preexisting coagulopathy (elevated INR or thrombocytopenia) * Concomitant corticosteroid therapy * Previous PUD or PUD complications (bleeding/perforation) * Cardiovascular disease and other comorbid conditions * Multiple NSAID use (eg, low-dose aspirin plus another NSAID) * Longer duration of NSAID use * High-dose NSAID use

Risk Factors for Ulcers and GI Complications Related to NSAID Use: * Age older than 65 years * Concomitant anticoagulant use * Preexisting coagulopathy (elevated INR or thrombocytopenia) * Concomitant corticosteroid therapy * Previous PUD or PUD complications (bleeding/perforation) * Cardiovascular disease and other comorbid conditions * Multiple NSAID use (eg, low-dose aspirin plus another NSAID) * Longer duration of NSAID use * High-dose NSAID use

SRMD occurs most frequently in critically ill patients due to mucosal defects caused by gastric mucosal ischemia and intraluminal acid. The ulcers are usually superficial, but SRMD may also penetrate into the submucosa and cause significant GI bleeding.

Physiologically stressful situations that lead to SRMD include sepsis, organ failure, prolonged mechanical ventilation, thermal injury, and surgery. Critical care patients with these specific characteristics are at highest risk.

Damage to the mucosal defense system is the primary method by which H. pylori and NSAIDs cause peptic ulcers.

Systemic inhibition of prostaglandin (PG) synthesis is the primary means by which NSAIDs cause PUD.

Radiologic and/or endoscopic procedures are usually required to document the presence of ulcers. Because endoscopic testing is invasive and expensive, it is only indicated in patients 60 years of age or older with new-onset dyspepsia.

Patients with dyspepsia who are younger than 60 years may forego endoscopy but should be tested for H. pylori using noninvasive methods and treated if positive.

Those who test negative for H. pylori should be offered a trial (4–8 weeks) of acid suppression therapy or proceed to endoscopy.

Testing for H. pylori infection is indicated in patients with active PUD, history of documented PUD, low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma, or history of endoscopic resection of early gastric cancer.

The urea breath test can also be used to confirm eradication of H. pylori infection.

Stool antigen assays can be useful for initial diagnosis or to confirm H. pylori eradication. They have high sensitivity and specificity and are affected less by concomitant medication use.

Patients with PUD should avoid exposure to factors known to worsen the disease, exacerbate symptoms, or lead to ulcer recurrence.

The goals of PUD therapy are to resolve symptoms, reduce acid secretion, promote epithelial healing, prevent ulcerrelated complications, and prevent ulcer recurrence. For H. pylori–related PUD, eradication of H. pylori is an additional outcome.

Regarding PUD non-pharm therapy, patients should be advised to reduce psychological stress and avoid cigarette smoking, alcohol consumption, and NSAID or aspirin use, if possible. Patients who require chronic NSAID therapy (eg, for rheumatoid arthritis) may be given prophylaxis with misoprostol or a PPI.

The duration of therapy for H. pylori eradication is controversial; US guidelines recommend either 10 or 14 days.16 A treatment duration of 14 days should be considered because of higher eradication rates than with a 10-day course; however, the data supporting this recommendation are based on a relatively small number of participants in clinical trials.

Confirmation of H. pylori infection eradication is recommended in all treated patients. Testing should occur at least 4 weeks after completion of the eradication regimen and 1 to 2 weeks after discontinuation of PPI. Eradication may be confirmed by either the urea breath test or stool antigen testing. Eradication may also be confirmed by endoscopy, but this should only be done when endoscopy is required because it is more expensive and invasive.

In patients at risk for NSAID-induced ulcers, PPIs at standard doses reduce the risk of both GUs and DUs as effectively as misoprostol and more effectively than H2 RAs.

Misoprostal is a synthetic prostaglandin E1 (PGE1 ) analog that exogenously replaces PG stores, misoprostol is indicated for reducing the risk of NSAID-induced GUs in patients at high risk of complications from ulcers (eg, the elderly and patients with concomitant debilitating disease), as well as patients at high risk of developing gastric ulceration, such as patients with a history of ulcers. Misoprostol 200 mcg four times a day reduces ulcer complications by inhibiting acid secretion and promoting mucosal defense. It is superior to H2 RAs for prevention of NSAID-induced ulcers. Misoprostol use is limited by a high frequency of bothersome GI effects such as abdominal pain, flatulence, and diarrhea, and it is contraindicated in pregnancy due to potential abortifacient effects.

Selective COX-2 inhibitors are no more effective than the combination of a PPI and a nonselective NSAID in reducing the incidence of ulcers.

NSAIDs with COX-2 selectivity were developed in an attempt to reduce the incidence of PUD and its complications.

COX-2 Selective Inhibitors (celecoxib)

This drug is a negatively charged, nonabsorbable agent that forms a complex by binding with positively charged proteins in exudates, forming a viscous, paste-like adhesive substance that protects the ulcerated area of the gastric mucosa against gastric acid, pepsin, and bile salts. Limitations of ___________________ include the need for multiple doses per day, large tablet size, and interaction with a number of other medications (eg, digoxin, fluoroquinolones).

Sucralfate (Carafate)

Adverse effects of ___________ (GI med) include constipation, nausea, metallic taste, and the possibility for aluminum toxicity in patients with renal failure. ______________ is effective for treatment of NSAID-related ulcers when the NSAID will be stopped, but it is not recommended for NSAID-related ulcer prophylaxis.

Sucralfate

Appropriate Indications for Stress Ulcer Prophylaxis in Intensive Care Unit Patients * Mechanical ventilation for longer than 48 hours * Coagulopathy or hepatic failure (platelet count < 50 × 103 /mm3 [50 × 109 /L], INR > 1.5, or aPTT > two times control) * History of GI ulceration or bleeding within 1 year of admission * Head trauma or Glasgow Coma Score of 10 or less (or inability to obey simple commands) * Thermal injuries to more than 35% of body surface area * Multiple traumas (injury severity score of 16 or greater) * Partial hepatectomy * Transplant patients in the ICU perioperatively * Spinal cord injuries * Two of the following risk factors: sepsis, ICU stay for more than 1 week, occult bleeding lasting 6 or more days, and use of high-dose corticosteroids (> 250 mg/day of hydrocortisone or equivalent)

Low-dose maintenance therapy with a PPI or H2 RA is only indicated in patients with severe complications secondary to PUD, such as gastric outlet obstruction or patients who need to be on long-term NSAIDs or high-dose corticosteroids and are at high risk for bleeding.

The primary goals of treatment are to relieve the symptoms of nausea and vomiting, increase quality of life, and prevent complications such as dehydration or malnutrition. Drug therapy for nausea and vomiting should be safe, effective, and economical.

To treat nausea and vomiting most effectively, it is important to first identify and treat the underlying cause.

Stimulation of D2 receptors in the CTZ leads to nausea and vomiting (Figure 21–1). There are three main groups of dopamine antagonists: phenothiazines, butyrophenones, and prokinetic agents. Phenothiazine antiemetics act primarily via a central antidopaminergic mechanism in the CTZ. Phenothiazines used to treat nausea and vomiting include promethazine, prochlorperazine, and chlorpromazine. Availability in multiple dosage forms (ie, oral, parenteral, rectal) permits use in a variety of settings including severe motion sickness or vertigo, gastritis or gastroenteritis, NVP, PONV, and chemotherapy-induced nausea and vomiting (CINV).

Phenothiazines may cause sedation, orthostatic hypotension, and extrapyramidal symptoms (EPS) such as dystonia (involuntary muscle contractions), tardive dyskinesia (irreversible and permanent involuntary movements), and akathisia (motor restlessness or anxiety). Chronic phenothiazine use has been associated with EPS, but single doses have also caused these effects.21