B.25

Question 1

Drugs used in constipation (laxatives) and diarrhea. Drugs promoting digestion. Pharmacology of liver and biliary tract

Answer 1

Drugs used in constipation:
- Drugs increasing stool volume: Plant fibers
- Osmotic laxatives: MgSO4 (magnesium sulfate), Lactulose
- Stool softeners: Paraffin oil
- Laxatives stimulating the bowel wall: Sennoside, Bisacodyl
Drugs used in diharrea:
- Adsorbant agents: Active charcoal kaoline
- Motility/secretion inhibitors: Diphenoxylate, Loperamide
Drugs acting on the liver: Ursodeoxycholic acid, Acetylcysteine, Silymarin (active compound=Silibinine)

Question 2

Plant fibers

Answer 2

MOA: drugs increasing the stool volume (↑bowel wall tension, ↑motility);
IMP: drink plenty of water to prevent dehydration!;
SEs: safest laxatives, in large doses can cause abdominal discomfort

Question 3

MgSO4 (magnesium sulfate)

Answer 3

OA: inorganic salts, Osmotic laxatives;
IND: Before surgery/colonoscopy

Question 4

Lactulose

Answer 4

MOA: non-absorbed carbohydrates Osmotic laxative (→metabolized to lactate by intestinal bacteria→ lactate decreases the pH in the intestines→ in low pH NH3 is converted to NH4+→NH4+ is not absorbed→↓hepatic encephalopathy);
IND: patients with liver failure to decrease hepatic encephalopathy;
Extra: glycerin (given per rectum) works in similar way

Question 5

Paraffin oil

Answer 5

MOA: Stool softener (does NOT cause fluid loss!→safe for elderly/newborns/pregnant patients);
Kinetics: p.o adm.;
SEs: long term use leads to deacreased lipid soluble vitamins absorption (DEAK)

Question 6

Sennoside, Bisacodyl

Answer 6

MOA: Laxatives stimulating the bowel wall (→↑electrolyte secretion→↑water secretion);
Kinetics: Naturally occuring- Sennoside (=Senna-glycoside), Synthetic- Bisacodyl, fast onset, causes more electrolyte/fluid loss

Question 7

Diphenoxylate, Loperamide

Answer 7

MOA: peripheral weak μ-OR agonists (mainly inhibits motility);
IND: diarrhea

Question 8

Active charcoal, Kaoline

Answer 8

MOA: adsorbs water, toxins and bacteria→firmer stools→reduced fluid loss from diarrhea;
IND: upset stomach and diarrhea

Question 9

Ursodeoxycholic acid

Answer 9

MOA: naturally occuring bile acid that is used to dissolve cholesterol gallstones, it is acting on the liver→ ↑bile acid production, ↓cholesterol/bile acid ratio (→↓gallstones);
IND: Cholesterol gallstones, PBC (primary biliary cholangitis)

Question 10

Acetylcysteine

Answer 10

MOA: mechanism not fully understood, can reduce disulfide bonds, also antioxidant;
IND: expectorant (decreases mucus viscosity via disulfide bond reduction), paracetamol overdose

Question 11

Silymarin (active compound=Silibinine)

Answer 11

MOA: Hepatoprotective drug, doesn’t have a scientific proof, may reduce the uptake of certain mushroom toxins by liver cells;
IND: currently being tested for treatment of severe intoxications with hepatotoxic substances such as death cap (Amanita phalloides) poisoning

Question 12

Mechanisms of diarrhea

Answer 12

1. Motility disturbance (e.g. vegetative neuropathy)
2. Inflammatory (e.g. infections by Shigella, Ulcerative colitis)
3. Secretory (e.g. bacterial infection or cholecystectomy)
4. Osmotic: (e.g. lactose intolerance

Question 13

Which cause of diarrhea can we distinguished

Answer 13

Motility disturbance, Inflammatory, Secretory, Osmotic
Osmotic->stop eating whatever it is causing the diarrhea→if it stopped its osmotic diarrhea, if it didn’t →other cause