GI Tract - Prescription University of Hawai‘i Hilo Pre-Nursing Program

NURS 203 – General Pharmacology

Danita Narciso Pharm D

Learning Objectives

• Know what each medication is indicated to treat

• Know drug mechanisms of action

• Know major adverse drug effects (will be discussed)

Drugs to Treat Upset Stomach

(Acid/GERD)/Prevent Ulcers

• Misoprostol

• Proton Pump Inhibitors

• H2 Receptor Antagonists

• Sucralfate

Prostaglandin Analog - MOA

• Misoprostol (Cytotec®) Synthetic prostaglandin E1 analog which places the protective prostaglandins that are consumed by prostaglandin inhibiting

therapies

Parietal

Cell

Parietal

Cell

M

EP3

ATP

EP4

M Mucus

Prostaglandin Analog

• Kinetics

• Absorption – rapid & extensive

• Metabolized – liver

• Protein binding - >90%

• Half life – 20-40 minutes

• Time to peak – 6-22 minutes (fasting)

• Excretion – urine 80%

• ADRs

• Diarrhea, abdominal pain, dyspepsia, flatulence, nausea, & vomiting

• Headache

• Dosing for protection of NSAID induced gastric ulcers

• 200 mcg 4 times daily with food

• Interactions

• Antacids

• Pregnancy category X

Sucralfate - MOA

• Sucralfate (Carafate®) Forms a viscous paste-like adhesive substance by binding with positively charges proteins. Selectively forms a protective coating

along the gastric lining against pepsin, peptic acid, and bile salts

SUCROSE – ALUMINUM - SULFATE

Sucralfate

• Kinetics

• Absorption – oral is minimal

• Distribution – acts locally at ulcer site

• Duration – up to 6 hours

• Metabolism – none

• Excretion – small amounts in urine as unchanged drug

• Dosing

• Initial treatment – 1 g, 4 times per day on an empty stomach for 4-8 weeks

• Maintenance – 1 g BID

• ADRs

• Constipation

• Interactions

• Can decrease the absorption & concentration of many drugs

• Pregnancy category B

Proton Pump Inhibitors - MOA

• Omeprazole (Prilosec®)

• Esomeprazole (Nexium®)

• Lansoprazole (Prevacid®)

• Dexlansoprazole (Dexilant®)

• Rabeprazole (Aciphex®)

• Pantoprazole (Protonix®)

Inhibit the hydrogen/potassium adenosine triphosphatase

(ATPase) enzyme of the secretory surface of the gastric

parietal cells.

Parietal

Cell

Proton

Potassium

Proton Pump

Parietal

Cell

PPI PPI Proton Pump Inhibitor

Chloride ion

Proton Pump Inhibitors - Omeprazole • Kinetics

• Absorption – rapid

• Protein binding - ~95%

• Onset – 1 hour, peak (2 hours)

• Duration – 72 hours, 50% max @ 24 hrs, with d/c take 3-5 days for normal return to baseline

• Metabolism – hepatic CYP2C19 Bioavailability – 30-40%, 100% in poor hepatic function, Asians 4fold AUC as compared to Caucasians

• Half life – 0.5-1 hr, hepatic impairment =3

• Excretion – urine 77%, feces

• Dosing

• 40 mg daily for gastric ulcer for 4-8 weeks

• ADRs

• Headache & dizziness

• Abdominal pain, diarrhea, & flatulence

• Interactions

• Inducers & inhibitors of CYP enzymes

• Clopidogrel (Plavix) – Risk X

• Pregnancy category C

H2 Receptor Antagonists - MOA

• Cimetidine (Tagamet®)

• Ranitidine (Zantac®)

• Famotidine (Pepcid®)

• Nizatidine (Axid®)

Competitive inhibitor of the H2 receptor of the gastric parietal

cell. Inhibits gastric acid secretion, gastric volume, & proton

availability

Parietal

Cells

Stomach lumen

H

G

A

H

G

A

Histamine

Gastrin

Acetylcholine

H2 Receptor Antagonists - Ranitidine

• Kinetics

• Absorption – 50% oral, IM – rapid

• Distribution

• Half life

• Metabolism – hepatic (minor)

• Time to peak – oral 2-3 hrs, IM < 15 mins

• Dosing

• 150 mg BID or 300 mg daily with evening meal

• ADRs

• AV block with rapid IV administration

• Abdominal pain, constipation, diarrhea, nausea, & vomiting

• Interactions

• May decrease the concentrations of other medications through drug effect or enzyme interactions

Increased with reduced

kidney function

Drugs to Treat Nausea & Vomiting

• 5HT3 Antagonists

• Dopamine Antagonists

• Antihistamines/Anticholinergics

• Substance P Antagonists

5HT3 Antagonists - MOA

• Ondansetron (Zofran®)

• Dolasetron (Anzemet®)

• Granisetron (Kytril®)

• Palonosetron (Aloxi®)

5 HT3 antagonist peripherally at vagal nerve terminals and

centrally at chemoreceptor trigger zone

5HT3

Receptor

S

S Serotonin

Sodium

5HT3

Receptor

S

5HT3 Antagonist - Ondansetron

• Kinetics

• Absorption – Well absorbed from GI tract

• Onset – 30 minutes

• Protein binding – 70-76%

• Metabolism – extensive hepatic w/ CYP involvement

• Half life – considerable increase in hepatic impairment, (3hr, 12hr, 20hr)

• Excretion – mostly urine as metabolites

• Dosing

• Varies depending on indication

• Dose adjust in severe hepatic impairment

• ADRs

• Headache, fatigue, & drowsiness

• Constipation

• Hypoxia

• Interactions

• May increase or decrease concentrations of other drugs

Dopamine Antagonists - MOA

• Prochlorperazine (Compazine®)

• Chlorpromazine (Thorazine®)

Blocks dopamine receptors in chemoreceptor trigger zone &

anticholinergic effect blocking the release of hypothalamic

hypophyseal hormones

Blocks

H1

M1

Inner ear

Decrease in

nausea &

vertigo

Blocks

D2

CTZ

Decrease

in

vomiting

Dopamine Antagonist - Prochlorperazine

• Kinetics

• Absorption – Rapid

• Onset – IM 15 mins, oral 30-60 mins

• Protein binding – 92-97%

• Metabolism – extensive hepatic

• Half life – 2 hours, 30 hours (biphasic)

• Excretion – urine

• Dosing

• 10-25 mg every 4-6 hours

• IM and IV dosing available

• ADRs

• Parkinsonian-like syndrome, tartive dyskinesia

• Dizziness, drowsiness

• Constipation, nausea

• Breast enlargement

• Interactions

• Many – avoid with anticholinergics

MOA Antihistamines

• Cyclizine (Marezine®) OTC

• Hydroxyzine (Vistaril®)

• Promethazine (Phenergan®)

• Diphenhydramine (Benadryl®)

Anticholinergics

• Scopolamine (Hyoscine)

Competes with histamine for H1 receptor site on effector cells

Antagonizes histamine & serotonin

Additional Information

Antihistamines - Promethazine • Dosing

• 12.5-25 mg Q 4-6 hours PRN

• ADRs

• Bradycardia

• Agitation, akathisia, tartive dyskinesia

• Constipation

• Blurred vision

• Interactions

• Other anticholinergics, CNS depressants

• Pregnancy category C

Anticholinergics • Dosing

• 1 patch Q 72 hours

• ADRs

• Dry mouth

• Bradycardia

• Constipation

• Blurred vision

• Interactions

• CNS depressants, other anticholinergics

• Pregnancy category C

Substance P Antagonists - MOA

• Aprepitant (Emend®)

• Fosaprepitant (Emend Inject®)

Inhibits the substance P/neurokinin 1 (NK1) receptor;

augments the antiemetic activity of 5-HT3 receptor

antagonists and corticosteroids to inhibit acute and delayed

phases of chemotherapy-induced emesis

Substance P Antagonist

• Kinetics

• Distribution – Vd ~70 L, crosses BBB

• Protein binding – 95%

• Metabolism – Extensively hepatic CYP3A4 (major) & other CYP enzymes

• Half life – 9-13 hours

• Time to peak – 3 hrs adults, 4 hours children

• Dosing

• 125 mg 1 hour prior to chemo, 80 mg daily on days 2&3

• ADRs

• Fatigue

• Nausea, constipation, hiccups

• Weakness – muscular

• Interactions

• Inhibitors/inducers/substrates of CYP enzymes

Drugs to Treat Slowed Gastric Motility

• Prokinetic Agents

Prokinetic Agents - MOA

• Metoclopramide (Reglan®) Blocks dopamine receptors and (when given in higher doses) also blocks serotonin receptors in chemoreceptor

trigger zone of the CNS. Enhances response to

acetylcholine

Increase GI

motility

D2 antagonist

Cholinergic

agonist

Decrease nausea

& vomiting

5HT3 antagonist

5HT4 agonist

D2 receptor

antagonist

Prokinetic Agents - Metoclopramide

• Kinetics

• Onset – 30-60 mins

• Absorption – oral, rapid

• Bioavailability – 65-95%

• Half life – 5-6 hrs adults, 4 hrs children

• Time to peak 1-2 hrs

• Excretion – urine 85%

• Dosing

• Varies depending on indication

• DM gut – 10 mg 4 times per day prior to meals & bed for 2-8 weeks

• GERD – 10-15 mg 4 times per day prior to meals & bed

• > 12 weeks not recommended

• ADRs

• Drowsiness & dystonic reaction

• Interactions

• Other dopaminergic drugs & anticholinergic drugs

Questions