Drugs that affect Water Balance

Question 1

What are five classes of drugs that affect Chloride secretion?

Answer 1

CIC-2, GC-C, CFTR inhibitors, Somatostatin analogues, Bismuth Subsalicylate

Question 2

What CIC-2 drug do you need to know?

Answer 2

Lubiprostone

Question 3

What is the MOA for Lubiprostone?

Answer 3

Activates CIC2 which increases Cl secretion.

Question 4

What is the therapeutic use for Lubiprostone?

Answer 4

Chronic constipation, Constipation - IBS

Question 5

What are side effects of Lubiprostone?

Answer 5

Diarrhea, Nausea, HA, Increased fetal loss making it a Class C drug

Question 6

What about Lubiprostone’s absorption?

Answer 6

Poorly absorbed so almost no systemic effects.

Question 7

What GC-C drug do you need to know?

Answer 7

Linaclotide

Question 8

What is the MOA for Linaclotide?

Answer 8

Activates guanylyl cyclase C which increases cGMP and activates CFTR and increases Cl- secretion which increases water in lumen.

Question 9

What is the therapeutic use for Linaclotide?

Answer 9

Chronic constipation, Constipation-IBS

Question 10

What are the side effects of Linaclotide?

Answer 10

Diarrhea, Increased maternal death which makes it a Class C drug, Inc. mortality in juvenile mice.

Question 11

Who should you NOT give Linaclotide to?

Answer 11

DO NOT give to kids.

Question 12

What about Linaclotide’s absorption?

Answer 12

Very little systemic absorption.

Question 13

What CFTR inhibitor do you need to know?

Answer 13

Crofelemer

Question 14

What is the MOA for Crofelemer?

Answer 14

Voltage dependent inhibition of CFTR and another Cl- channel which leads to decreased Cl- secretion and decreased Na+/H2O excretion and firm stools

Question 15

What is the therapeutic use for Crofelemer?

Answer 15

Diarrhea due to HIV drug treatment.

Question 16

What about the absorption of Crofelemer?

Answer 16

Very little systemic absorption.

Question 17

What Somatostatin Analogue do you need to know?

Answer 17

Octreotide

Question 18

What is the MOA of Octreotide?

Answer 18

Dec. fluid secretion. Low dose increases motility and high dose decreases motility.

Question 19

What is the therapeutic use for Octreotide?

Answer 19

Off label use of severe diarrhea due to Dumping syndrome, short bowel syndrome, Vagotomy and AIDs

Question 20

What side effects are associated with Octreotide?

Answer 20

Impaired pancreatic secretion (dec. fat absorption which leads to VitaADEK defeiciency). Decreased GI motility (dose dependent - nausea, pain, flatulence), Decreased Gallbladder contractility (gallstones - 50 percent and acute cholecystitis (rare)), Insulin/glucagon imbalance, hypothyroidism and bradycardia.

Question 21

What should you know about the synthetic somatostatin analogue (Octreotide)?

Answer 21

Longer half life (SS 1-5 hrs, Oct 6-12 hours)

Question 22

What is the MOA of Bismuth Subsalicylate?

Answer 22

Salicylate decreases PG and Cl- secretion in large intestine. Antimicrobial, binds enterotoxin.

Question 23

What is the therapeutic use of Bismuth Subsalicylate?

Answer 23

Prevention/treatment of Traveler’s diarrhea. Opiates are a better choice once diarrhea has started.

Question 24

What are the side effects of Bismuth Subsalicylate?

Answer 24

Black stool, Black tongue, High dose - salicylate toxicity like tinnitus, acid/base disturbances, etc.

Question 25

What six drugs are osmotic cathartics?

Answer 25

Lactulose, Magnesium, Hydroxide, Sodium phosphate, Polyethylene glycol, Electrolyte solution

Question 26

What is the MOA for Osmotic Cathartics?

Answer 26

Not absorbed which increases H2O in lumen by osmosis.

Question 27

What is the therapeutic use of Osmotic Cathartics?

Answer 27

Constipation - especially when enteric NS is disrupted.

Question 28

What are the side effects of Lactulose?

Answer 28

Dec. plasma [Ammonia] which leads to portal systemic encephalopathy. Its metabolized by microbiome which leads to severe cramps.

Question 29

What are the side effects of Osmotic Cathartics?

Answer 29

Most are safe in most patients.

Question 30

What are the side effects of Mg(OH)2?

Answer 30

Hypermagnesium in patient with kidney failure.

Question 31

What can happen if Osmotic laxatives are absorbed systemically?

Answer 31

All can cause intravascular volume depletion and electrolyte imbalance (inc. PO4, dec. Ca2+, inc. Na, dec. K)

Question 32

What are the Bile Acid Binding Resins?

Answer 32

Cholestyramine, Colestipol

Question 33

What is the MOA for Bile Acid Binding Resins?

Answer 33

BABR bind unabsorbed bile acides and dec. H2O secretion.

Question 34

What is the therapeutic use for BABRs?

Answer 34

Dec. reabsorption of bile sales which leads to secretory diarrhea in Crohn's disease and resection of terminal ileum.

Question 35

What are the side effects of BABRs?

Answer 35

Frequent "untoward" GI effects like bloating, gas, constipation, fecal impaction. Impaired absorption of other drugs and ADEK.