Pharm - GI & Hormones

peptic ulcer disease

patho: imbalance between mucosal defensive factors (mucus, bicarb, blood glow, prostaglandin, aggressive factors such as h. pylori, NSAIDS, gastric acid, pepsin)

PUD etiology

H. pylori and NSAIDs

PUD risk factors

-smoking

-reduced bicarb production

-increased acid production

-hiatal hernia

GERD

gastroesophageal reflux disease

due to lower tone of esophageal sphincter

GERD aggravating factors

chocolate

coffee

smoking

spicy foods

DOC for PUD caused by h. pylori

antibiotics such as:

-amoxicillin (#1 choice)

-clarithomycin

-metronidazole

-tetracycline

-tinidazole

combine 2 or more for several weeks

Omeprazole (Prilosec): MOA

a proton pump inhibitor

MOA: suppresses acid secretion by inhibiting HK-Atpase (the enzyme that makes gastric acid)

reduces acid secretion by 90%

Omeprazole (Prilosec): indications

for PUD caused by NSAIDS, GERD, esophagitis, stress ulcers

act more efficiently and longer on H2 receptor antagonists

use for no longer than 6-12 weeks (some ppl can be on it for decades)

Omeprazole (Prilosec): A/E

Rare

• HA

• Diarrhea

• N/V

• Pneumonia ⭐️

• Fractures (when used for a long time)

• Rebound acid hypersecretion⭐️ (occurs bc med is taken off abruptly)

• Hypomagnesemia

• Increased risk of C. diff (Report diarrhea immediately)⭐️

Omeprazole (Prilosec): D/I

Reduced effect of some HIV antivirals; reduce absorption of ketanozole & itraconazole. These drugs should not be combined w/ PPIs

if clopidogrel is combined with a PPI, the risk for GI bleeding (Major A/E) will be reduced, but antiplatelet effects may be reduced as well

Pantoprazole (Protonix): uses

given IV in the ICU to prevent stress ulcers via drip or push

stress ulcers cause 60-80% risk of death, most ICU pts are on this med

Proton Pump Inhibitors (PPIs)

-prazole

Pantoprazole (Protonix): routes + dose

PO, mostly IV

powder, 40 mg/vial reconstituted for IV use, give over 15 min, filter is needed to remove precipitates

Pantoprazole (Protonix): adverse effects

-diarrhea

-HA

-nausea

-dyspepsia

-dizziness

-hypomagnesemia

-osteoporosis/ fractures

Cimetidine (Tagamet): MOA

Blocks H2 receptors, thereby reducing the volume & gastric acidity of gastric secretions

Cimetidine (Tagamet): indication

Class: H2RAs

H2 receptors are located on parietal cells in stomach which promotes secretion of gastric acid

if they are stopped, then there is less stomach acid

purpose: promote healing of gastric + duodenal ulcers, relieves GERD Sx’s, Zollinger Ellison syndrome, heartburn.

Histamine 2 Receptor Antagonist drugs

-Cimetidine⭐️

-Ranitidone⭐️

-Famotidine

-Nizatidinine

side effects are rare but possible

Cimetidine (Tagamet): adverse effects

• confusion

• hallucinations

• CNS depression or excitation

• pneumonia⭐️

• IV bolus can cause hypotension + dysrhythmias

• Anti-androfemic effect (opposes male hormones, causing gynecomastia)⭐️

Cimetidine (Tagamet): D/I

Mat cause levels of warfarin, phenytoin, theophylline & lidocaine to rise

Antacids may decrease effect of cimetidine

Increase risk for candidiasis infx d/t change in acid base balance causes in the microbiome.

Ranitidine (Zantac)

has rare side effects:

may incr. risk of pneumonia d/t elevation of gastric pH

accumulation of

Histamine 2 Receptor Antagonists end in

-dine

Antacids prototype

Maalox / Mylanta

Antacids MOA

neutralize stomach acid;

indicated for PUD (but other meds such as prilosec & zantac work better)

fast acting but short duration

prilosec and omeprazole duration

24hrs, taken once a day

***antacids start working faster but have shorter duration

Maalox (magnesium)

promotes diarrhea

Mylanta (aluminum)

promotes constipation

Antacid administration

-tablets to be thoroughly chewed and followed by glass of water of milk (preferred)

-take about 7x/day after meals and HS

-thoroughly shake liquid form

Metoclopramide (Reglan)

dopamine antagonist, promotes gastric emptying

Metoclopramide (Reglan): purpose

-suppresses emesis by blocking receptors for dopamine and serotonin

-promotes gastric emptying by increasing tone + motility of the GI tract by enhancing acetylcholine

Metoclopramide (Reglan): indications

orally for:

-diabetic gastroparesis

-suppression of gastroesophageal reflux

IV for:

-chemo induced N/V

-off label for vomiting in early pregnancy

Metoclopramide (Reglan): adverse effects

-sedation

-diarrhea

-tardive dyskinesia (repetitive involun. movements esp in elderly)

Metoclopramide (Reglan): contraindications

-GI obstruction

-perforation

-hemorrhage

Sucralfate (Carafate)

effective antiulcer drug

given w other meds

minimal side effects

Sucralfate (Carafate): MOA

Undergoes polymerization and cross linking reactions resulting in a viscid, sticky gel that adheres to the crater surface and prevents acid from reaching the area for about 6 hours

Does not have acid neutralizing capacity and does not decrease acid secretion

Is not systematically absorbed

Sucralfate (Carafate): route

oral

4x/day

large, chalky tablets

difficult to swallow, dissolving in water or giving suspension is best

Sucralfate (Carafate): considerations

-do not give other oral meds within 30 mins of this drug or absorption being impeded

-antacids interfere w drug effect by raising pH >4

-admin 4X a day

⭐️Common S/E: constipation

No A/E

Sucralfate (Carafate): rx interactions

-Anti-acids that contain aluminum (give 30 mins apart)

-impeded absorption: phenytoin, theophylline, digoxin, warfarin, fluoroquinolone abxs (give 2 hr apart)

laxatives

indicated for constipation + GI procedures requiring clean colon

drugs that promote constipation

opioids

anticholinergics

antacids

laxative indications

-hemorrhoids

-after episiotomy

-CV disease

-loss of pelvic/abd. tone

-prevent impaction in bedrest

-spinal cord pts

-before surgery/colonoscopy

-ingesting poison

5 laxative categories

-bulk-forming

-surfactant

-stimulant

-osmotic

-misc.

what kind of laxative is docusate sodium (colase)?

surfactant

what kind of laxative is dulcolax?

stimulant

what kind of laxative is used for procedures such as colonoscopy?

magnesium citrate

lactulose

osmotic laxative used in hepatic disease when pts have high ammonia levels

will cause bad diarrhea

laxative abuse

can be d/t false beliefs that a daily bowel movement is necessary

+ aggressive marketing of these drugs

chronic exposure to laxative diminishes natural ability to poop

laxative abuse tx

-abrupt cessation

-increase activity, increase fiber

-increase fluid

-bowel retraining

Diphenoxylate (Lomotil)

antidiarrheal agent

opioid agent - prescription only

has no effect on CNS except in very high doses (MS like effects)

formulated w atrophine to discourage abuse

what class is Diphenoxylate (Lomotil)?

schedule V drug

Diphenoxylate (Lomotil): MOA

activates opioid receptors in GI tract

decreases intestinal motility, slows intestinal transit time

allows for absorption of fluid and electrolytes

fluid, volume, frequency is reduced

Diphenoxylate (Lomotil): antidote

naloxone

Loperamide (Imodium)

antidiarrheal

little to no potential for abuse, not regulated

analog of meperidine (demerol) - an opioid

Loperamide (Imodium): MOA

suppresses bowel motility

used to reduce volume of discharge from ileostomies

Infectious Diarrhea

-may or may not need tx

-usually self-limiting but antibiotics may be needed

-infxn requiring antibiotics: shigella, salmonella, campylobacter, clostridium

Zofran (ondansetron)

5-HT3 antagonist antiemetic

prevents N/V associated w chemo

Zofran (ondansetron): adverse effects

-dizziness, light-headedness

-diarrhea/constipation

-headache requiring analgesia

-rare tachycardia, angina

Zofran (ondansetron): route + dose

PO or IV

IV infusion; usually diluted in 50mL of D5W or NS

Promethazine (Phenergan) class

dopamine antagonist

Promethazine (Phenergan): indications

reduce emesis associated w surgery, cancer, or chemo

DO NOT GIVE IV unless given w large amt of fluid

Promethazine (Phenergan): MOA

suppress emesis by blocking dopamine 2 receptors in CMZ

Promethazine (Phenergan): adverse effects

-extrapyramidal rxns (tremors)

-anticholinergic effects (dry mouth)

-hypotension

-sedation

Scopolamine (Transderm Scop)

muscarinic antagonist (anti-cholinergic)

Scopolamine (Transderm Scop): MOA

suppresses nerve traffic in the neuronal pathway that connects the vestibular apparatus of the inner ear to the vomiting center

Scopolamine (Transderm Scop): side effects

-dry mouth

-blurred vision

-drowsiness

-less common urinary retention

-constipation disorientation

Scopolamine (Transderm Scop): dose + route

-oral

-transdermal (behind ear)

-subcutaneous

Alosetron (Lotronex)

very dangerous drug

only used for women with IBD w/ diarrhea as predominant symptom

Alosetron (Lotronex): MOA

selective blockade of type 3 serotonin receptors (5-HT3)

-decrease abd. pain

-increase transit time

-reduce secretions

-increase absorption of water + sodium

Alosetron (Lotronex): considerations

extensive metabolism by cytochrome P450

Alosetron (Lotronex): adverse effects

generally well tolerated

-severe constipation

-impaction

-bowel obstruction

-perforation

-ischemic colitis

death

Azulfidine (sulfasalazine)

class: 5-aminosalicylates

in same family as sulfonamide abx

does not treat infection

Azulfidine (sulfasalazine): indications

-IBD

-rheumatoid arthritis

most effective for acute episodes of ulcerative colitis

can benefit those with Crohn's

Azulfidine (sulfasalazine): MOA

intestinal bacteria metabolize this drug into 2 compounds: 5-ASA and sulfapyridine causing reduced inflammation

Azulfidine (sulfasalazine): adverse effects

-nausea

-fever

-rash

-arthralgia

-agranulocytosis

Palifermin (Kepivance)

1st drug approved for oral muscositis (chemo complication)

synthetic form of human keratinocyte growth factor

increases epithelium cell levels

Palifermin (Kepivance): indication

approved for decreasing incidence and duration of severe mucositis in pts w/ hematological malignancies

**only in those receiving high dose chemo + whole body irradiation

Palifermin (Kepivance): adverse effects

-rash

-erythema

-increased amylase + lipase

-taste distortion

-can affect vision

Palifermin (Kepivance): considerations

-drug binds w heparin, dont give in same line!

-given 24hrs before/after chemo as it can worsen mucositis

-expensive!

Estrogen (Premarin)

Estradiol (Estrace)

supports development + maintenance of female reproductive tract

promotes + suppresses blood coagulation factors and promote fibrin breakdown (more likely to clot)

Estrogen (Premarin)

Estradiol (Estrace): MOA

blocks bone resorption

promotes epiphyseal closure when estrogen levels get high after puberty

reduces LDL and HDL

Estrogen (Premarin): adverse effects

-when used alone potential for endometrial hyperplasia (cancer)

-breast cancer (postmenopausal women)

-CV events (incr. risk over age 60)

menopausal hormone therapy

"hormone replacement therapy"

estrogens given to manage hot flashes + other menopausal s/sx

progestins are given to oppose estrogen-mediated stimulation of endometrium

estrogen in pregnancy

pregnancy risk category X - no legit use in pregnancy

most common adverse effect of estrogen

nausea

Estrogen: patient education

take with food or at night to reduce nausea

birth control

two categories:

-estrogen + progestin

-just progestin "mini pills"

birth control: contraindications

women over 35 who smoke

combo oral contraceptives MOA

reduce fertility primarily by inhibiting ovulation

oral contraceptive benefits

-reduce symptoms of premenstrual disorder

-decrease risk of ovarian cancer, endometrial cancer, ovarian cysts, PID, iron def. anemia, acne

-reduce cramps, reduced menstrual flow, more predictable menses

combo oral contraceptives: contraindications

-pregnancy

-smokers over 35

-abnormal liover fx

-breast cancer

-abnormal vaginal bleeding

-thrombophlebitis

-CVD

-coronary occlusion

estrogen excess s/sx

-NAUSEA

-breast tenderness

-edema

-bloating

-hypertension

-migraine

-polyposis

-cervical mucorrhea

progestin excess s/sx

-incr. appetite

-weight gain

-depression

-tiredness

-fatigue

-hypomenorrhea

-breast regression

-acne

-oily scalp

-hair loss

estrogen deficiency s/sx

-early or midcycle breakthrough bleeding

-incr. spotting

-hypomenorrhea

progestin deficiency s/sx

-late breakthrough bleeding

-amenorrhea

-hypermenorrhea

drugs/herbs that reduce effects of oral contraceptives

-hepatic cytochrome (P450)

-st. john's wort

oral contraceptives decrease benefits of warfarin + hypoglycemic agents

depo-provera

-injected IM or subQ every 3 months

-protects against pregnancy for 3 months by inhibiting gonadotropin secretion

Testosterone

the principal androgen in male + female

Testosterone indication

male hypogonadism

testosterone side effects

-edema

-virlization in females

-prematurely close epiphyseal growth plates in children

-liver toxicity