Xenobiotics affecting gastrointestinal function

XENOBIOTICS AFFECTING GASTROINTESTINAL FUNCTION

Table of contents :

anti-acids
prokinetics (gastrointestinal motility-altering agents)
antiemetic drugs
anti-diarrhoic
anti-constipation (evacuants / purgatives / aperients)
anti-flatulents

Anti-acids (vs. peptic disease )

reducing H⁺ secretion by parietal / oxyntic cells

proton pump inhibitors (PPI) (well tolerated even for > 10 yrs of chronic use) : omeprazole works for 2-24 hrs (partly up to 72 hrs). High cost. Side effects : diarrhea, nausea, leukopenia (omeproazole), transaminitis, abdominal pain, headache, sleepiness
H₂ antagonists (side effect : lower stomach pH and facilitate colonization by normophilic Bacteria; histamine is released by mast cells and ECL cells) :

cimetidine 400 mg 2 times a day or 800 mg at evening. Side effects : increased half-life of dicumarol, teophylline, pheytoin, propanolol, quinidine, TCAs
ranitidine : 150 mg 2 times a day or 300 mg at evening; 6-folds more powerful than cimetidine, doesn't inhibits CYPs; also marketed in combination with the antibacterial bismuth citrate (Elicadyr); 95% of patients treated with ranitidine only relapse within 3 years

M₁ antagonists
M₃ antagonists (many side effects; ACh is released by vagus nerve : past therapies included peripheral selective vagotomy)
CCK₂ antagonists
EP₃ agonists

cytoprotective agents

sucralfate / octasulfate of sucrose + Al(OH)₃ (Carafate^®, Gastrogel^®) in environments with pH < 4 undergoes extensive cross-linking and polymerization to produce a viscous, sticky gel that adheres strongly to epithelial cells for 6 hours. It binds biliary salts (also used for therapy of halitosis in elderlies with cholalemia) and pepsin, inducing gastroprotective prostaglandins. It should be assumed 1 hours before meals and before going sleeping. It has a bad taste. It should not be combined with proton pump inhibitors (PPIs) because no longer works at higher pH.
rebapimide / 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]-propionic acid
ecabet / 12-sulfodehydroabietic acid monosodium
carbenoxolone
Bi compounds : side effect : black pigmentation of tongue and stools

milk of bismuth / bismuth magma : a suspension of bismuth hydroxide and bismuth subcarbonate in water, yielding 5.2–5.8% bismuth trioxide; used as an astringent and antacid

mineral antacids

Mg (OH)₂ : side effect from magnesium : diarrhea; from aluminum ; constipation. It should be assumed far from meals and 30 minutes before going at bed.

milk of magnesia / magnesia magma : a suspension of 7.0–8.5% of magnesium hydroxide used as an antacid and cathartic

CaCO₃

Maalox Quick Dissolve^®
Tums-Ex^®

Al (OH)₃+ Mg(OH)₂

Gelusil II^®
Kudrox^®
Maalox TC^®
Mylanta Extra Strength^®

Mg (OH)₂ + CaCO₃

Mylanta^®
Rolaids^®

magaldrate / pentaaluminum-decamagnesiumhentriacontahydroxide-bis(sulfate)-hydrate (Al ₅Mg ₁₀(OH)₃₁(SO₄)₂) (Dynese^®, Riopan Plus Double Strength^®, Rioplus^®)
almagate (Al ₂Mg ₆(OH)₁₄(CO₃)₂^. 4 H₂O; Almax^®) and almagcit are composed of hydrotalcite (Mg ₆Al ₂CO₃(OH)₁₆^. 4 H₂O), magnesium hydroxycarbonate, and/or magnesium carbonate and amorphous aluminum hydroxide.

Prokinetics (gastrointestinal motility-altering agents)

M₂ agonists
M₃ agonists
AChE inhibitors
hydrophilic D₂ antagonists
5-HT₃ antagonists
5-HT₄ agonists
MTLR1 agonists
CCK₁ antagonists
SST₂ agonists
GABA_B agonists

Antiemetic drugs

Anti-diarrhoic

intraluminal agents

bulk-forming and hygroscopic agents / hydrophilic colloids

Bran

dietary fibers

lignin

cellulose

hemicellulose

mucilages

gums

pectins

polycarbophil (Fibercon^®, Fiberall^®, ...)
methylcellulose (Citrucel^®, ...)
carboxymethylcellulose
kaolin (a hydrated aluminum silicate; + pectin in Kaopectolin^®)
attapulgite (magnesium aluminum disilicate) (Diasorb^®)
Plantago ovata (a.k.a. ispaghul, blond psyllium)-based :

psyllium husk (Metamucil^®, ...) is a mixture of neutral and acid polysaccharides containing galacturonic acid with a ratio of soluble/insoluble fibre of 70/30^ref
Fibrolax^®
Mucivital^®
Planten^®
Psyllogell^®

cholestyramine
Bi compounds

Bi subsalicylate (Pepto-Bismol^®)
Bi subcitrate

antimotility and antisecretory agents

peripherally acting m agonists : loperamide has vertigo as a side effect
CB₁ agonists^ref
enkephalinase inhibitors
a₂ agonists
SST₂ agonists
L-type voltage-dependent Ca²⁺ channels blockers (CCB)
5-HT₃ antagonists
CaM inhibitors
berberine
nicotinic acid

Anti-constipation (evacuants / purgatives / aperients)

laxatives : promoting evacuation of formed fecal material from the rectum
cathartics : promoting evactuation of unformed, usually watery fecal material from the entire colon

luminally active agents

bulk-forming and hygroscopic agents / hydrophilic colloids
osmotically active agents (nonabsorbable) => osmotically mediated water retention stimulates peristalsis. Laxative or catharctic effect depending on dose.

saline laxatives

magnesium sulfate
magnesium hydroxide (Magnesia San Pellegrino^®)
magnesium citrate
sodium phosphate (Fleet Phospho-Soda^®)
sodium picosulfate (Dulcolax^®drops, Dulcolax^®pearls, Guttalax^®)

sugars

glycerin (Verolax^®)
lactulose (Cephulac^®, Chronulac^®, ...)
sorbitol
mannitol

polyethylene glycol (PEG) 3350-electrolyte solutions (Colyte^®, Golytely^®, Isocolan^®, MiraLax^®, SELG^®, ...) for the treatment of occasional constipation. This product should be used for 2 weeks or less or as directed by a physician. Most common adverse events : nausea, abdominal bloating, cramping, and flatulence. High doses may produce diarrhea and excessive stool frequency, particularly in elderly nursing home patients. Patients taking other mediations containing polyethylene glycol have occasionally developed urticaria suggestive of an allergic reaction. Contraindications : patients with known or suspected bowel obstruction and/or allergy to PEG. It should be administered dissolved in approximately 8 ounces of water, juice, soda, coffee, or tea. Safety and effectiveness in pediatric patients has not been established. It should only be administered to a pregnant woman if clearly needed. Toxicity

stool-wetting agents (surfactants) and emollients

docusate / dioctyl sulfosuccinate sodium (Colace^®, Doxinate^®, ...), calcium (Surfak^®, ...) or potassium (Kasof^®)
mineral oil (a mixture of aliphatic hydrocarbons obtained from petrolatum)

nonspecific stimulant or irritant laxatives (with effects on both fluid secretion and motility) => increase PAF and NO

diphenylmethane derivatives

bisacodyl (Dulcolax^®tablets)
phenolphthalein (Agarbil^®, Agarol^®, SB Strong-Lax^®, Confetto Falqui^®, Confetti Lassativi Giuliani^®, Crisolax^®, Euchessina^®, Ormobyl^®, Purgestol^®, Reolina^®, Schias^®, Verecolene^®) (=> drug lupus )
oxyphenisatin (side effect : chronic active hepatitis)

anthraquinone derivatives : the active agents share a tricyclic anthracene nucleus with hydroxyl, methyl, or carboxyl groups to form monoanthrones, such as rhein and frangula. Monoanthrones are irritant to the oral mucosa; however, the process of aging or drying converts them to more innocuous dimeric (dianthrones) or glycoside forms. This process is reversed by bacterial action in the colon with the formation of the active forms.

sennoside A + sennoside B (X-Prep^®, Pursennid^®)

confection of senna : a mild laxative containing powdered senna with other ingredients.

barbaloin
chrysaloin

triglyceride of ricinoleic acid / castor oil

prokinetic agents (acting primarily on motility)

5-HT₄ agonists
EP₃ agonists
peripherally acting m antagonists

enemas (tap water, hypo- or hypertonic solution) => bowel distention => evacuation reflex

Warning : symptoms suggestive of bowel obstruction (nausea, vomiting, abdominal pain or distention) should be ruled out before initiating therapy.
Precautions : patients should be evaluated for bowel obstruction or metabolic, endocrine, or neurogenic disorders, and medications.

Anti-flatulents (carminative : a medicine that relieves flatulence and assuages pain)

activated charcoal (the residue from the destructive distillation of various organic materials, treated to increase its adsorptive powers; used as a general purpose antidote)
dimethicone : a silicone oil consisting of dimethylsiloxane polymers with viscosities from 0.65 to 3,000,000 centistokes at 25°C. The term is used with a numeric suffix which indicates the approximate viscosity of the various grades in centistokes, e.g., the viscosity of dimethicone 200 in centistokes is 190 to 210. Dimethicones are used as ingredients of ointments and other preparations for topical application to protect the skin against water-soluble irritants

activated dimethicone / simethicone / dimethylpolysiloxane (Mylicon^®, Phazyme^®; Flatulex^® in combination with activated charcoal; Imodium Plus^® with loperamide ; Maalox Plus^®, Mylanta II^® in combination with aluminum hydroxide/magnesium hydroxide) : a mixture of dimethicones and silicon dioxide, with a molecular weight between 14,000 and 21,000, occurring as a translucent, gray, viscous fluid. It is administered orally as an antifoaming agent in gastroscopy, and is also used as an antiflatulent and as a releasing agent in pharmaceutical preparations. It is used in veterinary medicine in the treatment and prevention of bloat in cattle.

Cite this page!

Search
for