A33. Drugs used in constipation (laxatives) and diarrhea. Drugs promoting digestion. Pharmacology of liver and biliary tract Flashcards
Name some liver toxic and lover protective agents.
Liver Toxic Agents: 1.halothane 2. high-dose iron 3. paracetamol 4. alcohol Liver Protective Agents: 1. N-acetyl-cysteine: very high dose used as antidote for paracetamol poisoning 2. Silibinin, silymarin: milk thistle component. Seems to be liver protective, has been attempted in Amanita phalloides (death cap mushroom) poisoning 3. Vitamin B complex: B1, B2, B5, B6.
What are the indications of bile acid supplementation?
Bile acid supplementation: can be done in chronic liver disease, primary biliary cirrhosis, or to treat gallstones
bile acid binding resins **
Bile-acid binding resins: - cholestyramine causes ↓ enterohepatic circulation + ↑ fecal excretion of bile; used to ↓ cholesterol levels and treat diarrhea due to upper small intestine resection
what are the drugs promoting digestion?
Drugs promoting digestion: 1. HCl - 10% HCl solution for supplementation in gastric hypoacidity; drink with straw to avoid dental damage 2. Pancreatic Enzymes (“Pancrelipase”) - taken orally to treat impaired digestion in steatorrhea, etc.; contain amylase, lipase, protease.
Diarrhea **
Diarrhea: anti-diarrhea drugs only for mild/moderate acute diarrhea • most effective are opioids and opioid derivatives w/ minimal CNS effect • diphenoxylate, loperamide: meperidine analogs w/o analgesic effect o diphenoxylate formulated w/ antimuscarinics (e.g. atropine) to reduce likelihood of abuse. loperamide is formulated alone, but gets pumped out of CNS by glycoprotein P • kaolin + pectin: absorbs bacterial toxins and fluid, resulting in decreased stool liquidity. can cause constipation and interfere w/ absorption of other drugs o kaolin is natural hydrated magnesium aluminum silicate o pectin: indigestible carbohydrate from apples • octreotide: somatostatin analog can be used to treat diarrhea associated with carcinoid syndrome • do NOT use antidiarrheals if: bloody diarrhea, high fever, systemic toxicity. These are signs of infection, and anti- diarrheals can worsen underlying problem • not mentioned in book or practical, but oral rehydration therapy (ORT) should probably be mentioned as the main treatment for life-threateningly severe diarrhea (e.g. cholera infection)
Name examples of Stool softeners that are used.
Stool softeners: 1. paraffin oil. takes 6-12 hours. this is like a lubricant…“stool slips out” - “so pleasant that someone can get addicted to it” - but chronic use maybe causes “paraffin granuloma.”
Name some bowel irritants. **
Bowel irritants: 1. Lactulose fits here too 2. Sennoside A, B: plant-derived drugs that act more slowly 3. Rebarbara: also plant-derived. this and sennoside cannot be used in pregnancy 4. phenolphthalein: Hungarian synthetic version, not licensed in many countries bc maybe arrhythmogenic. otherwise “fairly pleasant.” takes about 8 hours. 5. Bisacodyl: synthetic. long delay too. absorbs and then is re-excreted by the bile, and a conjugate is excreted which acts. 6. castor oil: most brutal laxative, not used much. prodrug, metabolized in bowel wall → strong irritation. tastes really bad too. can “purge the whole bowel” and then don’t have stool for several days.
salt/osmotic laxatives **
salt/osmotic laxatives: salts that don’t absorb or slowly absorb sulfates: MgSO4, Na2SO4 • absorb only very slowly, so wash through the GI. can control effect by the volume that you drink. • avoid Na2SO4 if renal function problem, might have too much salt absorbed o Lactulose: sugar with double effect • osmotic action: not digested, osmotic effect • but may be ingested by bacteria → bowel irritant → increased water secretion → further contributes. excellent in terms of controlling the bowel movement. small amount can normalize, high causes diarrhea, farting o glycerol: usually used as a suppository. hygroscopic, collects water from everything. can use if there is a dry stool stuck in the rectum. common in very young or very old people.
What is bulk laxatives and examples?
Bulk laxatives (“stool normalizers”) o fiber: eat a lot of cellulose. o methylcellulose: similar to normal fiber o if you eat too much, can cause obstructive ileus
What are laxatives and when are they used?
Laxatives: used to stop constipation. Constipation can come from not moving, low fiber, psychological problem, stress (either diarrhea or constipation). Chronic use of laxatives can cause constipation (“habituation” - not quite same as addiction bc doesn’t resolve reward center)
Bowel irritants **
Bowel irritants
Name bile acid supplementations and their MOA.
Drugs: Ursodiol is one bile acid derivative that can be used. MOA: Bile acids dissolve cholesterol gall stones; decrease hepatic cholesterol secretion. toxicity is uncommon. Used to be used more to prevent cholecystectomy, but it takes something like 2 years to work. Nowadays cholecystectomy is preferred, even for asymptomatic stones.
