DPT IV Exam 3- SHATANAWI

Used to tx opioid-induced constipation

naloxegal

produced by H pylori and responsible for its survival in the acidic medium

ureace

nurokinun 1 receptor antagonist

rolapitant

transmural inflammatory condition can span the entire depth of the intestinal wall

crohns

GI Mucosal protective agents

sucralafate

neurotransmitter that promotes GI relaxation

norepinephrine

prodrug cleaved by bacterial enzyme azoreductase ibn the colon to sulfapyridine and 5 aminosalicylic acid

sulfasalazine

selective JAK1 inhibitor

upadacitinib

neurotransmitter that promotes GI contraction

acetylcholine

partial agonist at 5HT4

tegaseroa

5HT3 recpetor antagonist

zofran

reduces the surface tension of oil water interface of the stool resulting in enhanced incorporation of water and fat allowing for stool softening

docusate

common cause of PUD

NSAIDs

possible ADR of PPIs

CKD

PGE1 analog

misoprostol

H2 receptor antagonist with anti-androgenic activity

cimetidine

drug that promotes GI motility with dopamine (D2) receptor antagonist

metoclopramide

gastric cells that secrete alkaline mucus whihc protects epithelium

mucus

humanized monoclonial antibody binds to alpha4 integrin expressed on the surface of all leukocytes

natalizumab (Tysarbi)

what causes contraction in the GI

Ach, 5HT, Substance P, motilin

what causes relaxation in the GI

NE, endogenous opiod, dopamine, VIP, NO, ATP

cholinergic muscarinic recpeptors (M3), B2, mu, 5HT3/4

increases contractility and motility

what is the most impprtant part of the stomach

digestion

partial cells

secrete HCL

G cells

secrete gastrin that increases HCl secretion and motility

Chief Cells

secrete pepsin as an inactive zymogen called pepsinogen

mucus cell

secrete alkaline mucus which protects epithelium

enterochromaffin like cells (ECL)

secrete histamine

gastric mucus

mucuous cells (Goblet cells)

a protective layer of the stomach

acid in the stomach is mediated by

histmine, acetylcholine, gastrin

acid secretion in the stomach is inhibited by

PG and ST

pepsin activity is inactivated by ______ pH and destroyed by ______

4 and 7

PUD gastric ulcer is more common in

women over the age of 60

PUD duodeneum ulcer is more common in

men 30-50 (4x)

what results between an imbalance of agressive and protective factors

PUD

3 main causes of PUD

H Pylori

NSIAD

Stress

h pylori

gram negative, flagella bacteria

produces urease enzyme

what is linked to MALT lymphoma, gastric cancer, IDA, gastrtitis, and ulcers

h pylori

urease catalyzes urea to

ammonia creating a neutral environment for HP causing epithelial damage

cox1

increases blood flow, increase mucus secretion, decrease acid secretion

inhibiton leads to increase risk and GI bleeding

cox2

induced at sites of inflammation

selective inhibition may lower risk of ulcers and GI bleeding

dudoenal ulcer

food often relieves pain, returns 1-3h after eating

nocturnal epigastric pain

gastric ulcer

food will cause pain

are H2RAs recommended for HP eradication

NO

cimetidine

anti adrogenic and p450 inhibition

cimetidine MOA

both basal and food stimulated gastric acid secretion

H2RA common ADRs

diarrhea, headache, fatigue, myalgia, constipation

long term: tachyplaxasi

dexlansaproazole

dual delayed release, provides extended acid suppression all are effective foir short term

PPI MOA

irreversibly inhibit H/K/ATPase

results in long lasting

GERD TX PPI

once daily for non erosive and erosive reflux

indications of PPI

gerd, ulcer prevention, NSAID induced ulcers, HP

what enzyme is PPI metabolized by

CYP2c19

ADR of PPI

headache, diarrhea, abdominal pain

concerns with PPIs

gastritis, acid rebound, apsiration, c diff, none fracture, hypomganesium, nephritis

Vonoprazan MOA

Potassium-competitive acid blocker which inhibits the H+, K+-ATPase enzyme system to suppress gastric acid secretion of parietal cells

what is diff about vonoprazan than PPI

can be taken with or without food

ADR with vonprazan

GI upset, headache, fatigue

antimuscarinic agents

atropine, glycopyyrolate

MOA of antimuscarinics

decrease acid secretion by inhibiting cholinergic (vagal) input (rearley used alone, as adjunct)

constipation and antiacids

aluminin salts and ca carbonate

diarrhea and antiacids

mag salts

what do antaicids interact with

iron, digoxin, isoniazid, ketoconalzole, fluroquinolones, tetracyclines

carafate

requires acidic pH avoud with acid reducing agents. can cause constipation

Misoprostol MOA

analog of PEG1, combines acid inhibitory and mucuosal protective effects, bicarbonate and mucus secretion, enhances blood flow

indication of Misoprostol

NSAID induced ulcer prevention and tx

GERD

abnormal reflux gastric contents into esophagus, oral cavity, and lings causing mucosal damage

composition of refluxate

acid, pepsin plus bile, and trypsin in dueodengoastricreflux

Barrett's esphagus

replacement of squamous cells with columnar cells increases risk of strictures and esophageal adenocarnicoma

what drug classes promote GI motility

muscaranic activatros (metaclopromaide)

Acetylcholine inhibitors (neostigmine)

Metoclopramide MOA

D2 receptor antagonist.

agonist on 5ht4 and antagonist at 5ht3 recepotrs

enhances upper GI motility and increases LES tone

metoclopramide ADR

extrapyramidal side effevts, worseing Parkinson's, tardive dyskinesia

Boxed warning for metoclopramide

may cause tardive dyskinesia

UC

lympocyte migration via a4B7 and MAdCAM1

toxic megacolon

major complication fo UC

aminosalicylates

cleaved by azoreductase in colon into sulfapyridine and ASA

MOA of sulfasazine

prodrug, inihibts B cell prolifertation suppresses inflammatory cytokines

sulfasalazine ADR

reversible infertility in men

mesalamine MOA

5-ASA to reduce inflam in IBD, variois forms

TNF alphas

infliximab

adalumab

golimumab

certolizumab

azathioprine and meracptopurine ADR

bone marrow supression and liver fcn abnormalities

never combine allopurinolol with azathripone

inhibits XO leading to toxic metabolite causing severe bone marrow supression

methotrexate

folic acid anaologue. inhibits DHFR block purine biosynthesis and cytokine production prevents DNA synthesis and cell proliferation

ADR Methotrexate

hepatoxicity and teratogenicity

toxicity antidote for mehtotrexate

leucovorin

cyclosprine MOA

inhibits IL2 and T lymph

ustekinumab

IL12/IL23i

reduces NK cell activation and CD4+ T cell differentation

vedolizumab and natalizumab

binds a4B7 integrin preventing MAdCAm1

Upadcitinib (rinvoq) and Tocafitinib (Xeljanz)

JAKi

etrasimod (velsipity)

binds to S1P receptors reducing lymphocytes egress decreases inflamamtion

cyp2c8i

mirikizumab (omvoh)

binds p19 subunits of IL23

Alosetron (Lotronex)

5HT3 receptor antagonist used for IBS-D

TCA

inhibit 5HT and NE transporters and increases NE levels and 5HT to relieve abdominal pain and GI hypersensitivity

anticholinergics

dicyclomanine, hyoscyamine, glycoprryloate, methscoplamine

anticholinergic MOA

non selctive muscaranic receptor antagonism inhibits GI smooth muscle contractiliuty and motility

linaclotide (linzess) and Plecantide MOA

guanlytae cyclase c (GC-C) stimulates chloride and bicarbonate secretion into the intestinal lumen increased fluid and accelrated transit used for IBS-C

tenpanor

inhibits NHE3 in intestine -> reduces sodium absorption -> increases water content in stool -> releives constipation

eluxadoline MOA

reduxes bowel contraxtion and modulates pain signaling in gut for IBS-D

stimmulant senna

6-12hr stool

stimulant bisacodyl (oral)

stimulats peristalsis, fluid accumulation

6-12hr stool

stool softner dosucate

think of soap (reduces tension)

1-3d