Gastrointestinal Drugs and Exogenous Hormone Therapies (Ch. 64, 65, 68, 82-84)

Peptic Ulcer Disease (PUD)

imbalance between mucosal defense factors such as mucus, bicarbonate, blood flow, and prostaglandins and aggressive factors such as H. pylori, NSAIDs, pepsin, and gastric acid

Mucosal Defensive Factors (4)

-mucus

-bicarbonate

-blood flow

-prostaglandins

Aggressive Factors (4)

-H. pylori

-NSAID use

-gastric acid

-pepsin

PUD Etiology (3)

1. H. Pylori

2. NSAIDS

3. Zollinger Ellison syndrome

PUD Risk Factors (4)

-smoking

-reduced bicarbonate production

-increased acid production

-stress/anxiety

*********diet and alcohol are NOT associated

Gastroesophageal Reflux Disease (GERD)

erosive esophagitis or nonerosive reflux disease characterized by heart burn and regurgitation

GERD Etiology

relaxation of lower esophageal spincter

-H. pylori NOT associated

GERD Treatment

DOC = proton pump inhibitors (PPIs)

-histamine 2 receptor antagonists (H2RA's)

-lifestyle changes: smoking cessation, weight loss, avoid alcohol and late meals, sleep with HOB elevated, avoid certain foods

Anti-Ulcer Regimen

1. antibiotics

-eradicate H. pylori

-at least two, preferably three

2. anti-secretory agents: PPIs and H2RAs

-blocks H2 receptors

-suppresses acid secretion

-10-14 day course

3. mucosal protectant = sucralfate

-barrier over ulcer

4. anti-secretory enhancing mucosal defenses = misoprostol

-stimulates secretion of mucus and HCO3

-increases blood flow

-suppresses gastric acid

5. antacids

-neutralizes gastric acid

Anti-Ulcer Antibiotics (6 - ABCMTT)

at least 2, preferably 3 should be prescribed

REMEMBER ABC MTT

-amoxicillin

-bismuth

-clarithromycin

-metronidazole

-tetracycline

-tinidazole

Histamine 2 Receptor Antagonists (H2RA's)

1. prototype(s): cimetidine, famotidine, nizatidine

2. action

-blocks H2 receptors

-reduces volume and acidity of gastric secretions

3. indications

-promotes healing of peptic & duodenal ulcers

-GERD and heartburn

-zollinger ellison syndrome

-acid indigestion and sour stomach

4. adverse effects

-cimetidine has many different SE compared to others, see other drug cards

-pneumonia is risk for all prototypes

***all drugs in this class are less effective than PPIs

H2RA Prototype Drugs

cimetidine, famotidine, nizatidine

H2RA Actions

-blocks H2 receptors

-reduces volume and acidity of gastric secretions

H2RA Indications

-promotes healing of gastric and duodenal ulcers

-GERD and heartburn

-zollinger ellison syndrome

-acid indigestion and sour stomach

What makes Cimetidine different from the other H2RAs?

-taking with food may extend effect of this drug

-AE = confusion, hallucinations, CNS excitation

-IV bolus can cause hypotension/dysrhythmias

-ANTI-ANDROGENIC EFFECT

-may cause levels of warfarin, phenytoin, theophylline, and lidocaine to rise

-antacids may decrease effect of this drug

Why would H2RAs cause an increased risk for pneumonia?

reduced stomach acidity can cause imbalance in microbiome, which then puts patient at risk for pneumonia

Proton Pump Inhibitors (PPIs)

1. prototype(s): omeprazole, pantoprazole

2. action: acts more efficiently (2 hours) & longer (days/weeks) compared to H2RAs

3. indications

-duodenal and gastric ulcers

-esophagitis, GERD

-hypersecretory conditions

-stress ulcers

4. adverse effects (rare)

-headache, NVD (possible C. diff, report diarrhea)

-pneumonia, fractures, hypomagnesemia

-rebound acid hypersecretion (MUST TAPER)

5. drug interactions

-HIV antivirals

-reduced absorption of ketoconazole and itraconazole

-decreases efficacy of clopidogrel but less risk for GI bleed

6. nursing

-notify HCP for s/sx of respiratory infection, hypomagnesemia, and severe diarrhea

-should not exceed timeframe of 6-12 weeks unless absolutely necessary for patient

PPI Prototypes

omeprazole, pantoprazole

PPI MOA

acts longer (days/weeks) and has a more potent suppression (2 hours) of gastric acid secretion than H2RAs, resulting in greater reduction of acidity and volume of gastric secretions

PPI Indications (4)

-duodenal and gastric ulcers

-esophagitis, GERD

-hypersecretory conditions

-stress ulcers

PPI Potential AEs

-headache

-NVD (possible C. diff, report diarrhea)

-pneumonia

-fractures

-hypomagnesemia

-rebound acid hypersecretion (MUST TAPER)

PPI Drug Interactions

-HIV antivirals

-reduced absorption of ketoconazole and itraconazole

-decreases efficacy of clopidogrel but less risk for GI bleed

PPI Nursing Considerations

notify HCP for s/sx of respiratory infection, hypomagnesemia, and severe diarrhea

Pantoprazole

commonly given IV in ICU for stress ulcers or for those staying for long periods of time

-convert to PO form ASAP

Sucralfate (Carafate)

1. action

-forms protective barrier over ulcers against acid and pepsin

-does not prevent nor cure, only promotes healing

-attachment lasts 6 hrs, not absorbed, eliminated through feces

-does NOT have acid neutralizing or minimizing capability

2. indication: duodenal ulcers

3. SE = constipation; give plenty of fluids; not systemically absorbed so minimal side effects

4. interactions

-antacids that contain aluminum (give 30 min apart)

-impedes absorption of phenytoin, theophylline, digoxin, warfarin, and fluoroquinolones (give 2 hrs apart)

5. nursing

-don't give other PO meds within 30 min, this drug will impede absorption

-you can break, dissolve, or give suspension (large tablets)

Sucralfate MOA

-forms protective barrier over ulcers against acid and pepsin

-does not prevent nor cure, only promotes healing

-attachment lasts 6 hrs, not absorbed, eliminated through feces

-does NOT have acid neutralizing or minimizing capability

Sucralfate Indication

active or maintenance therapy of duodenal ulcers

Sucralfate SE

constipation; give plenty of fluids; not systemically absorbed so minimal side effects

Sucralfate Drug Interactions

-antacids that contain aluminum (give 30 min apart)

-impedes absorption of phenytoin, theophylline, digoxin, warfarin, and fluoroquinolones (give 2 hrs apart)

Sucralfate Nursing Considerations

-don't give other PO meds within 30 min, this drug will impede absorption

-you can break, dissolve, or give suspension (large tablets)

Misoprostol

1. class: prostaglandin E1 analog

2. action

-suppresses secretion of gastric acid

-promotes secretion of HCO3 and mucous

3. indication: prevention of ulcers caused by NSAIDs; considered category X drug that is used to induce abortion

4. AE = diarrhea, abdominal pain, spotting/dysmenorrhea;

5. nursing: childbearing age women = pregnancy test before staring this drug

Antacids

alkaline compounds (magnesium, aluminum, calcium, sodium)

1. action

-neutralizes stomach acid and decreases pepsin activity

-decreases the destruction of gut wall

-stimulates prostaglandins & improves mucosal defenses

2. indications: peptic ulcer disease & GERD

3. adverse effects

-constipation (aluminum) or diarrhea (magnesium hydroxide); combination therapy is best = maalox, mylanta

-sodium loading/hypernatremia; caution in hypertension or HF patients

-flatulence (calcium & sodium)

4. drug interactions: cimetidine (give 30-60 min apart) and sucralfate (give 1 hr apart)

5. nursing

-needs regular schedule (ex. 1 and 3 hrs after meal and bedtime); DO NOT TAKE PRN; dose varies depending on type

-caution in impaired renal function

-caution in hypertension or HF patients

Antacid MOA

-neutralizes stomach acid and decreases pepsin activity

-decreases the destruction of gut wall

-stimulates prostaglandins & improves mucosal defenses

Antacid Indications

1. peptic ulcer disease

2. GERD

Antacid AE

-constipation (aluminum) or diarrhea (magnesium hydroxide); combination therapy is best = maalox, mylanta

-sodium loading/hypernatremia; caution in hypertension or HF patients

-flatulence (calcium & sodium)

Antacid Drug Interactions

-cimetidine (give 30-60 min apart)

-sucralfate (give 1 hr apart)

Antacid Nursing Considerations

-needs regular schedule (ex. 1 and 3 hrs after meal and bedtime)

-DO NOT TAKE PRN

-dose varies depending on type of ulcer

-caution in impaired renal function

-caution in hypertension or HF patients (sodium loading risk)

Laxative Types (5)

1. bulk forming

2. surfactants

ex. docusate (colace)

3. stimulants

ex. bisacodyl (dulcolax)

4. osmotic

ex. lactulose, magnesium compounds

5. chloride channel activator

ex. lubiprostone

Laxative Groups (3)

1. rapid = watery

2. intermediate = semifluid

3. slow = soft

Rapid-Acting Laxatives

-works in 2-6 hours

-results in watery stool

-seen in surgical prep

Intermediate-Acting Laxatives

-works in 6-12 hours

-results in semifluid stools

-is often abused by public

Slow-Acting Laxatives

-works in 1-3 days

-soft by formed stool

Laxatives

1. action: depends on type (5 types in 3 categories)

2. indication

-stool softening

-adjunct to anti-helminthic, removing digested toxins

-surgical/diagnostic prep

-modifying effluent from ileostomy or colostomy

-prevention of impaction, correcting constipation

3. nursing

-contraindicated in abdominal pain/cramping, nausea, appendicitis, enteritis, diverticulitis, ulcerative colitis, impaction or bowel obstruction

-healthy gut is key; make sure you hear normoactive bowel

-caution in pregnancy/lactation

-lots of fluids for bulk forming/surfactants

-osmotic laxatives need caution in renal dysfunction

-can be abused, esp. in elderly

Etiology of Laxative Abuse

-false belief of daily BM

-aggressive marketing of OTC meds

-disordered eating

Problems with Laxative Abuse

chronic use diminishes defecatory reflexes, leading to further dependence

-colitis

-fluid and electrolyte imbalance

Treatment of Laxative Abuse

-patient education

-cessation of laxatives

-increased FAF: fiber, activity, fluid

-bowel training that is consistent and revolves around the quality of stools (NOT frequency)

***laxatives should be used briefly if necessary

Serotonin Receptor Antagonists

1. drugs: ondansetron, granisetron, dolasetron, palonosetron

2. action: blocks type 3 serotonin receptors (5-HT3)

3. indications: prevents and relieves nausea RT radiation, chemotherapy agents, anesthesia, viral gastritis, and pregnancy; DOC for CINV

4. adverse effects

-headache, dizziness, diarrhea

-a prolonged QT interval (RF torsades de pointes; caution in HF, electrolyte abnormalities, and bradycardia)

5. nursing

-PO, IV, IM

-may be combined with dexamethasone for inc. effect

-give med BEFORE nausea/vomiting as preventative

-caution in HF, electrolyte abnormalities, and bradycardia

SRA Prototypes

ondansetron, granisetron, dolasetron, palonosetron

SRA Action

blocks type 3 serotonin receptors (5-HT3)

SRA Indications

***DOC for CINV (chemo induced n/v)

-prevents and relieves nausea RT radiation, chemotherapy agents, anesthesia, viral gastritis, and pregnancy

SRA AE

-headache, dizziness, diarrhea

-a prolonged QT interval (RF torsades de pointes; caution in HF, electrolyte abnormalities, and bradycardia)

SRA Nursing Considerations

-PO, IV, IM

-may be combined with dexamethasone for inc. effect

-give med BEFORE nausea/vomiting as preventative

-caution in HF, electrolyte abnormalities, and bradycardia

Ondansetron may be combined with _______ for increased effect.

dexamethasone

Benzodiazepines as Anti-emetics

1. drug: lorazepam

2. action

-sedation

-suppression of anticipatory emesis

-anteretrograde amnesia

-may help control extrapyramidal symptoms

3. indication: combined with other drugs to reduce CINV

Dopamine Antagonists

1. drugs: phenothiazine (phenergan), butyrophenone (haldol), metoclopromide (reglan), promethazine

2. action: suppresses emesis by blocking dopamine 2 receptors in trigger zone of chemoreceptors

3. indications: emesis associated with surgery, chemo, other toxins

4. adverse effects: extrapyramidal reactions (dystonia and/or parkinsonian gait), anti-cholinergic effects, hypotension, sedation

5. nursing: promethazine should be used with caution as there are RF respiratory depression and local tissue injury

Drugs for Motion Sickness

1. scopolamine

2. antihistamines

Scopalamine

1. class: muscarinic antagonist, anticholinergic

2. action: suppresses nerve traffic in neuronal pathway that connects vestibular apparatus of inner ear to vomiting center

3. SE = dry mouth, blurred vision, drowsiness, urinary retention, constipation, disorientation (anticholinergic SE)

4. routes: PO, transdermal behind ear, subcutaneous

Antihistamines for Motion Sickness

1. drugs: dimenhydrinate, meclizine, cyclizine

2. action: block histaminergic and muscarinic cholinergic receptors

3. SE = sedation, dry mouth, blurred vision, urinary retention (similar anticholinergic effects)

Antidiarrheal Drugs

loperamide and diphenoxylate

-these drugs only provide symptom relief and NOT underlying cause

Loperamide

structural analog of meperidine; opioid & antidiarrheal

-suppresses bowel activity and fluid secretion

-low potential for abuse; does not cross BBB

Diphenoxylate

activates opioid receptors in GI tract, decreasing intestinal motility and slowing transit time; allows more time for absorption of fluid and electrolytes

-fluid, volume, and frequency of defecation is reduced

-severe overdosage = NALOXONE

-high doses can cause morphine-like effects; atropine is added to formulations to prevent abuse

-schedule V drug

-IBD pts may develop toxic megacolon (contraindication)

Metoclopromide (Reglan)

1. class: prokinetic, antiemetic, dopamine receptor antagonist

2. action: suppresses emesis and inc. upper GI motility

3. indications

-GERD

-diabetic gastroparesis

-post-op N/V, chemo, intubation of GI tract

-safe to use for pregnancy N/V

4. AE = EPS in elderly; sedation & diarrhea in high doses

5. contraindications

-GI hemorrhage, perforation, obstruction

-long-term use (time should be as short as possible)

Drugs for IBS

1. alosetron (IBS-D)

2. lubiprostone (IBS-C)

3. linaclotide (IBS-C)

4. 5-aminosalicylates

5. glucocorticoids

6. immunosuppressants

7. immunomodulators

8. antibiotics

Alosetron

1. action

-blocks 5-HT3 receptors in viscera, causing increase in colonic transit time, reduced intestinal secretions

-more normal bowel pattern with less pain

2. indication: women with severe IBS-D over 6 months

3. adverse effects

-constipation can cause RF impaction, obstruction, perforation, fatal GI toxicity

-can cause ischemic colitis

4. interactions

-CYP450 (carbamazepine, phenobarbital, cimetidine, ketoconazole, quinolone)

-contraindicated in pts with hx of other bowel disorders

5. nursing: patients must be enrolled in a risk management program and sign physician/patient agreement

Sulfasalazine

1. class: 5-aminosalicylates

2. action: metabolizes in gut to form 5-ASA and sulfapyridine, which reduces inflammation

3. indication: acute, mild to moderate UC and crohn's; rheumatoid arthritis

4. adverse effects

-nausea, fever, rash, and althralgias common

-anemia & agranulocytosis

5. nursing

-report s/sx of fever or sore throat

-CBCs regularly

-safe in pregnancy/lactation

Inflixamab

1. class: immunomodulators, monoclonal antibody

2. action: inhibits tumor necrosis factor alpha

3. indications

-1st line for inducing remission of severe disease or perianal Crohn's disease

-rheumatoid arthritis

4. dose/route: IV induction regimen at 0, 2, and 6 weeks followed by infusions every 8 weeks

5 adverse effects

-infusion reactions (fever, chills, pruritus, cardiopulmonary)

-increased RF lymphoma

-immunosuppressant effects puts patients at risk for sepsis, HBV and TB, invasive fungal infections

Palifermin (Kepivance)

1st drug to be approved for oral mucositis

-synthetic form of KGF (keratinocyte growth factor)

-mucositis caused by chemo or hematological malignancies

-increases epithelial cell levels

-AE include rash, erythema, increased amylase and lipase, visual changes, taste distortion

-binds with heparin, do not give together (IV)

-give 24 hrs before or after chemo

Biosynthesis of Endogenous Estrogen

1. males

-testosterone is converted to estradiol and estrone in small quantities

2. females

-in ovaries, follicular phase, and by placenta

-after childbearing, estriol and estrone are more dominant

Actions of Endogenous Estrogen

-binds to receptors on cell nucleus, less on cell membrane

-estrogen receptor (ER) alpha on vagina, ovaries, mammary glands, vascular epithelium, hypothalamus

-ER beta on ovary, prostate, lungs, brain, bones, blood vessels

Physiologic Effects of Endogenous Estrogen

support development and maintenance of female reproductive tract and secondary sex characteristics

How is estrogen important in the reproductive process?

-stimulates uterine blood flow

-stimulates growth of uterine musculature

-secretion of thickened mucous from endo-cervical glands and acidifies vagina

-breast ductal proliferation

-milk production

Estrogen Metabolic Actions Throughout Lifespan

-positive effect on bone

-reduces risk for cardiovascular disease

-blood coagulation

-neuroprotective effect on CNS

-maintain glucose homeostasis

Exogenous Estrogen - Non-Contraceptive Indications

1. menopausal hormone therapy

-smallest amount for shortest time possible

-can be given transdermal for hot flashes/night sweats (vasomotor symptoms)

2. female hypogonadism

3. acne

4. cancer palliative care (breast & prostate)

5. transgender transition

Adverse Effects of Exogenous Estrogen

1. endometrial hyperplasia and cancer

-MUST give progestin alongside estrogen to decrease risk for those with uterus

-can give alone to pts who have had hysterectomies

2. breast cancer

3. thromboembolic events

4. gallbladder disease and accentuation of liver disease

5. headache, nausea*** (take w/ food), fluid retention

6. categorized as hazardous for HC personnel to handle

Contraindications of Exogenous Estrogens

-history of DVT, PE, MI, stroke

-liver disease

-estrogen dependent tumors or breast cancer

-pregnancy

-undiagnosed vaginal bleeding (indicates possible cancer)

Exogenous Estrogen - Interactions

-CYP substrates

-antidiabetic drugs

-thyroid preparations

-anticoagulants

Exogenous Estrogen - Routes

1. oral

2. transdermal

-local effects, best if main complaint = vaginal dryness

3. intravaginal

PO Estrogen Types

1. conjugated (premarin)

2. esterified (menest, estrace)

Transdermal Estrogen

local effects, best if main complaint = vaginal dryness

1. emulsion (estrasorb)

2. spray (evamist)

3. gels (estrogel)

4. patches (estraderm, climara, estradot, menostar)

Intravaginal Estrogen

1. tablets (vagifem)

2. cream (estrace vaginal, premarin vaginal)

3. vaginal rings (estring, femring)

Biosynthesis of Endogenous Progestin

by corpus luteum in ovary (luteal phase) and the placenta

Action of Endogenous Progestin

binds with progesterone receptors on cell nucleus -> progesterone regulatory element on target gene -> desired response

Physiologic Effects of Endogenous Progestin

-promotes proliferation of endometrium during cycle

-causes endocervical secretions to be scant and thick

-breast development

-raises body temperature

-can cause CNS effects = sleepiness and depression

How is progestin important to the reproductive process?

-essential for normal pregnancy progression

-suppresses uterine smooth muscle prior to end of preg.

-decreases GI motility

-growth and proliferation of breast tissue

-elevation of maternal serum pH

-suppresses maternal immune response

Exogenous Progestin - Non-contraceptive Indications

1. menopausal hormone therapy

-used in conjunction with estrogen for women w/ uterus to decrease RF endometrial hyperplasia and cancer

-in women with a uterus, you can give progestin alone

-when DC a combo drug, stop estrogen first

2. dysmenorrhea

3. amenorrhea

4. infertility

5. prematurity prevention

6. endometrial hyperplasia and cancer

Exogenous Progestin - Adverse Effects

-breast tenderness

-headache

-abdominal pain

-depression

-decreased cervical mucus/endometrial layer

-spotting/irregular bleeding

-inc. risk for breast cancer with estrogens

-considered hazardous drug for employees

Considerations of estrogen/progestin hormone therapy

-in women with a uterus you can give progestin alone, but not estrogen on its own; it must be used together.

-when DCing a combo drug, stop estrogen first

Exogenous Progestin - Routes

1. oral

2. intramuscular

3. subcutaneous

4. intravaginal

5. transdermal patch with estrogens

Oral Progestins

-medroxyprogesterone acetate (provera)

-norethindrone (micronor)

-levonorgestrel (plan b)

-norgestimate

-in combination with estrogens PO

SQ and IM Progestin

medroxyprogesterone acetate (depo provera)

Intravaginal Progestin

micronized progesterone

Menopausal Hormone Therapy Considerations

-careful screening of risks and patient education

-in women who will benefit, use lowest dose for shortest time

-try non-pharm strategies for symptom relief

-women with uterus = estrogen + progestin

-women without uterus = estrogen only

-discontinue estrogen FIRST, then progesterone

Women WITH a uterus should receive what kind of hormonal therapy?

-estrogen/progestin combination

-progestin alone

Women WITHOUT a uterus should receive what kind of hormonal therapy?

only estrogen, should NOT receive progestin

3 Approved Indications - Menopausal Hormone Therapy

1. vasomotor symptoms

-hot flashes and night sweats

2. vulvar/vaginal atrophy

-topical recommended

3. prevention of osteoporosis

What conditions would it NOT be appropriate to take hormone replacement therapy?

-prevention of cardiovascular disease

-dementia

Combined Oral Contraceptives (COC)

lowest dose of ethinyl estradiol + progestin

1. drugs: ethinyl estradiol/norethindrone

2. actions

-inhibits follicular maturation & ovulation as a result

-thickens cervical mucous (barrier)

-creates an inhospitable uterine lining

3. indications: contraception

4. adverse effects

-PE, MI, strokes

-breast cancer, benign hepatic adenoma

-HTN, abnormal bleeding, SE related to hormone imbalance

5. ABSOLUTE contraindications

-thrombophlebitis, thromboembolic disorder, CV disease

-liver dysfunction/abnormality

-breast cancer

-undiagnosed vaginal bleeding

-pregnancy

-smokers over age 35 DT risk for developing clots

-other: HTN, HD, DM, gallbladder issues, uterine leiomyoma (fibroids), migraine, epilepsy; avoid in breastfeeding

6. nursing

-patient education regarding signs of thromboembolic issue and hypertension risk

-educate taking pills as prescribed: first day/Sunday start; backup method; same time everyday and what to do if they miss a pill

7. drug interactions

-CYP450 drugs reduce COC efficacy (st. john's wort)

-increased dosing of warfarin and hypoglycemics may be needed

-may cause theophylline, tricyclic antidepressants, diazepam, and chlordiazepoxide to reach toxic high levels

Why are COCs contraindicated in breast cancer but not endometrial?

taking estrogen and progestin together decreases the risk for developing endometrial cancer but NOT breast cancer

-promotes growth of breast cancer

Absolute contraindications of using COC

-thrombophlebitis, thromboembolic disorder, CV disease

-liver dysfunction/abnormality

-breast cancer

-undiagnosed vaginal bleeding

-pregnancy

-smokers over age 35 DT risk for developing clots

***basically anything that increases your risk for clots

SE caused by estrogen excess

-nausea

-breast tenderness

-edema, bloating

-HTN

-migraine

-cervical mucorrhea

-polyposis (polyps in GI tract)