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Anti-Secretory AgentsGroup Drugs Mode of Action Side Effects RandomH2 Blockers Cimetidine

RanitidineFamotidineNizatidine

Competitiveantagonist of H2receptors.

Most associated w/ cimetidineInhibits cytochrome P-450(Prolongs t warfarin/phenytoin)Anti-androgenic (High Doses)[Libido loss, gynecomastia &impotence in men, galactorrheab/c prolactin in women] CNS disturbancesHematologic effects (All 4)Nausea, diarrhea, myalgia,rashes, & itching.

Potency:Famotidine (40mg) > Ranitidine & Nizatidine (300mg) >Cimetidine (800mg)

Tablets (One @ bedtime) & IV.Single bedtime dose as effective as multiple day doses. dose used for maintenance.Efficacy: 80-90% in 4-6 weeks

Proton PumpInhibitors

Oral:OmeprazoleLansoprazoleRabeprazole

IV Pantoprazole

Irreversiblybinds to thesulfhydrylgroups (cysteineresidues of proton pumps).

Nausea, diarrhea, cramps 3%Headache, dizziness, rashes,somnolenceHypergastrinemaNocturnal Acid Breakthrough Bacterial Overgrowth in GIInhibits cytochrome P-450(in vitro) (rare)

Substituted Benzimidazoles (weak bases)Prodrugs, only active at acidic pH (

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Cytoprotective AgentsDrug Mode of Action Side Effects RandomProstaglandins Cytoprotective: release of gastroduodenal

mucus & bicarb.Antisecretory: Reduces cAMP levels,

inhibiting histamine-stimulated acid releaseby parietal cells.

Abortifacient Ab. CrampingDiarrhea (dose-dependent/self limited)

Ex.: Misoprostol Synthetic PGE1 analog- Prevents NSAID-induced gastric ulcers- Protective, BUT at doses that acid release

Sucralfate - Acid turns it into sticky slurry that binds tohemoglobin & pepsin & acts as a barrieragainst further acid-pepsin damage.- tissue levels of prostaglandins & mucus.

ConstipationDry MouthReduces bioavailability of tetracycline, phenytoin, digoxin,cimetidine

Non-absorbable Al salt of octasucrose.No acid neutralizing capacity.Dose: 4g a day (Usually 1g 4x a day)Same healing rate as H2-blockers & antacids.Limited use due to efficacy of other agents.Used in ICU to prevent stress-induced GI bleeds.

BismuthCompounds

- Binds to ulcer crater & protects it fromdamage- May stimulate mucus production &prostaglandin synthesis- Anti-H. pylori activity.

Black stool, dark tongue.Risk of bismuth & subsalicylatetoxicity.ie. encephalopathy

Pepto-BismolBismuth subsalicylate & bismuth subcitrate.

Antimicrobials (Anti-H. pylori therapy)Therapy Antibiotic RandomTriple Therapy PPI Amoxicillin

MetronidazoleClarithromycinTetracycline

(2 of these)

PPI agents may have some antimicrobial actions.90% cure rate 2 week regimenFirst -line therapy Lower ulcer reoccurrence rate than H2 or PPI

(10%vs90%)QuadrupleTherapy

Triple Therapy +Tinizadole 90% duodenal ulcers (But requires good patient compliance) 2 week regimen & cheapTetracycline + Metronidazole + Bismuth + H2-antagonist (or PPI)

Other Combos Ranitidine bismuth citrate(Tritec)

AmoxicillinMetronidazoleClarithromycinTetracycline(2 of these)

Omeprazole + Amoxicillin + LevofloxacinThere are metronidazole & clarithromycin-resistant H. pylori.

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Treats Constipation

Group Mode of Action Side Effects RandomBulk-formingagents (DietaryFiber)

-Absorbs water- growth of intestinal bacteria-fermentation by bacterial actionproduces metabolites that alter colonichandling of fluid and electrolytes.-Digestion by bacterial action tometabolites that increase stoolosmolality Pulls water & ions into GI

Minimal- Intestinal Gas

Safest/Least expensivePlant Cell wallsPatient should drink lots of water to prevent impaction.Expect increased initially.- Bran, Rice & psyllium (Metamucil)

Saline (Osmotic)Laxatives

-Poorly absorbed, osmotically activesalts which increase water in colon

Very NON-toxicFluid Loss

Onset: 3-4 hoursOften used in prep for surgeriesMg Salts, Lactulose, Sorbitol, Osmotic lavage fluids

Stimulant Laxatives

- secretion of H 2O & electrolytes into GI- colonic motility

Abuse can lead tocathartic colon

Rectal Onset 1-2 hr.Oral Onset 6-12 hr.Ex. Castor Oil, Bisacodyl, Senna

Lubricants (StoolSofteners)

- Acts as lubricants- Emulsified in stool & softens it.

Ex. Docusate sodium (Detergent), Mineral Oil ( fat solublevitamin absorption) & Glycerin (suppository).

Treat DiarrheaGroup Drugs Mode of Action Side Effects Random

Bulk Forming Agents - Water absorption( bowel fluidity & bulk)

Adsorbents/Demulcents

Kaopectate: kaolin (Al) & pectin (fruit)Donnagel: attapulgite (= kaolin)

Bind intestinal bacteria &toxins

Less effective thanother diarrheals

Bismuth Compounds Adsorbent to bacteria, toxins,& virusesAnti Microbial

Abuse Bismuthsubsalicylate(Pepto-bismol)Relieves milddiarrhea

Opiates Loperimide: Poor CNS penetrationDiphenoxylate w/ atropineDifenoxin w/ atropine: activemetabolite of diphenoxylate

Act via and opiatereceptorsSlow GI motility ( AChrelease).

Ab. pain, emesis,constipation, fatigue,drowsiness.

Mainstay drug

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AntiemeticGroup Drug Mode of Action Side Effects RandomDopamineAntagonist

Prochlorperazine -Blocks dopamine receptors inCTZ & GI

Dystonias PhenothiazineNot effective against motion sickness, orpatients achieving chemo

Metoclopramide -Blocks dopamine receptors inCTZ and GI-GI motility and emptying:prokinetic (viacholinomimetic action)

Dystonias, Parkinsonism,somnolence, nervousness,galactorrhea ( prolactin);diarrhea.

Benzamide

Anticholinergic Scopolamine act centrally (CTZ) &peripherally (vestibularapparatus)

Sedation and dry mouth(therapeutic doses) 4Confusion and memory loss

Prevents motion sickness.Given orally, by injection, or transdermalpatch

Antihistamines(H1 Blockers)

CyclizineMeclizineDimenhydrinatePromethazine

Blocks H1 receptors Promethazine Most effective, but sedatingPrevents motion sickness (Also is anti-cholinergic)Control Post-Op EmesisLittle Potency against chemo-inducedemesis

SerotoninAntagonists

OndansetronDolasetronGranisetron

Blocks 5-HT3 receptors in CTZ& Vagal terminals

ConstipationDiarrheaHeadache

Available by injection or tablet General Anti-emeticNOT effective against motion sicknessOriginally used against cisplatin effects.

Substance P(Neurokinin 1)Antagonists

Aprepitant Blocks NK-1 receptor in emesiscenter Generally well tolerated, but:Fatigue (most common),anorexia, constipation,diarrhea.

Aprepitant is metabolized byP-450; potential druginteractions

Approved in 2003Used as adjunct to standard antiemetics tocontrol emesis from highly emetogenicchemo.

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Mode of Action Side Effects Random

Benzamides MetoclopramideCisapride (Nolonger available)

Cholinomimetics -ACh release fromenteric neurons &response to Ach

Extrapyramidal effects Used to increase gastric motility and emptyingTreats GERDdopamine-blocking effect may contribute toprokinetic effect

Cisapride (Nolonger available)

Cardiotoxic effects (I k block) whencoadministered with drugs/foodswhich metabolism:- QT interval- arrhythmias- cardiac arrest

NO dopamine blockageNO extrapyramidal effectsProlongs action potentialsMay contribute to use as heartburn drug byenhancing contractions of esophagealsphincter