(STILL USE)Lesson 89: common drugs for the liver and pancreas

Glossary of disorders

Management of disorders

Overview of drugs acting on the liver

S-adenosylmethionine: Methylation support

donates CH₃ groups for phosphatidylcholine synthesis →stabilizes hepatocyte membranes and promotes bile flow

S-adenosylmethionine: Glutathione synthesis

increases intracellular glutathione (GSH) → major antioxidant protection

S-adenosylmethionine: Mitochondrial protection

maintains membrane potential and reduces apoptosis in hepatocytes

S-adenosylmethionine: Detoxification

enhances conjugation reactions and reduces oxidative and drug-induced injury

S-adenosylmethionine therapeutic uses

S-adenosylmethionine contraindications

Severe hepatic encephalopathy

Hypersensitivity or intolerance

Gastrointestinal disorders

Ursodeoxycholic Acid (UDCA) therapeutic uses

Cholestatic Liver Diseases

Immune-Mediated and Inflammatory Hepatopathies

Secondary (Reactive) Hepatopathies

Supportive Therapy in Drug- Induced Hepatotoxicity - Intrahepatic Cholestasis in Cats

Ursodeoxycholic Acid (UDCA) contraindications

Complete extrahepatic bile duct obstruction (risk of bile retention and hepatocellular injury)

Use cautiously in animals with severe acute hepatic failure

Silymarin: membrane stabilization

prevents entry of toxins (e.g., amanitin)

Silymarin: Antioxidant effect

scavenges free radicals (ROS) and increases intracellular glutathione

Silymarin: Protein synthesis stimulation

enhances ribosomal RNA formation, promoting hepatocyte regeneration

Silymarin: Antifibrotic and anti-inflammatory actions

inhibits lipid peroxidation and cytokines such as TNF-α, reducing inflammatory and fibrotic processes

Silymarin: Immunomodulation

modulates T-cell and Kupffer cell activity, decreasing immune-mediated injury

N-Acetylcystein Indications

Acetaminophen(paracetamol) toxicity

Other hepatotoxicities(sagopalm, aflatoxicosis, xylitol, NSAIDs, phenobarbital…)

Choleretics

UDCA

(SAMe)

Herbal extracts

Cholagogues

Cholecystokinin (CCK) or CCK analogs

Magnesium sulfate

Certain bitters or oils

Dietary fat

Always exclude extrahepatic biliary obstruction before?

giving any choleretic or cholagogue

Antioxidants and supportives: vitamins

Vitamin E, Vitamin K1-B-complex, Vitamin C, (Vitamin A and D)

Antioxidants and supportive: minerals and others

Zinc, Selenium, L-carnitine

Phosphatidylcholine, Methionine

Taurine (esp. Cats)

Hepatic diets

High- quality, highly digestible protein and carbs(restriction in hepatic encephalopathy)

Increased antioxidants (especially vitamin E), Zinc and L-carnitine supplementation

Adequate caloric density, Moderate fat levels, Copper restriction

Copper Storage Disease therapy

Chelators: D-Penicillamine &Trientine

Zinc salts(acetate/gluconate)

Iron Storage Disease therapy

Deferoxamine (Desferal)

Dietary management

Periodic blood removal

S-adenosylmethionine: target, MOA, effect

Silymarin(milk thistle): target, MOA, effect

Ursodeoxycholic acid (UDCA): target, MOA, effect

N-acetylcystein: target, MOA, effect

Penicillamine, Trientine: target, MOA, effect

Zinc: target, MOA, effect

Treatment approaches for Sago palm toxicity

Overview of drugs acting on the pancreas

Enzyme Replacement Therapy purpose and MOA

Replaces missing digestive enzymes (lipase, amylase, protease) in animals with exocrine pancreatic insufficiency (EPI)

Mechanism: Exogenous enzymes act in the intestinal lumen, digesting food nutrients when pancreatic secretion is deficient

Enzyme replacement therapy: forms and administration

Main substance: Pancrelipase (from porcine pancreas)

Powder mixed with food (most effective); tablets or capsules may be used → Always given with each meal to ensure enzyme–food contact

Adverse effects: Oral irritation if powder not mixed; rare vomiting or diarrhea

Acute pancreatitis: Analgesia

Methadone, Fentanyl, Hydromorphone(avoid NSAIDs)

Acute pancreatitis: Antiemetics/anti-nausea

Maropitant, Ondansetron, Metoclopramide

Acute pancreatitis: Gastroprotection

Omeprazole, pantoprazole, Sucralfate

Acute pancreatitis: other

Nutrition helpers (if needed): mirtazapine (cats), Capromorelin (dogs)

Antimicrobials (sometimes): e.g., amoxicillin–clavulanate, Metronidazole

Overview of therapy of acute and chronic pancreatitis

Antidiabetic agents

Insulin preparations: replace or supplement endogenous insulin(Can insulin, Glargine, Detemir etc.)

Oral hypoglycemics(cats): Require residual β-cell function(Glipizide- stimulates insulin release from pancreatic β-cells)

Some other (occasional or experimental): Insulin sensitizers (Thiazolidinediones/pioglitazone), incretin drugs…

Bexacat(Bexagliflozin):

Blocks SGLT2 transporters in the kidneys → Prevents glucose reabsorption

Causes glucose to be excreted in urine(glucosuria) → decreased blood glucose levels

Exocrine pancreas drugs

Endocrine pancreas drugs

Feline triaditis

clinical condition in cats characterized by concurrent inflammation across three organ systems:

• Biliary system / Liver: Cholangitis or cholangiohepatitis

• Pancreas: Pancreatitis (acute or chronic)

• Intestine: Inflammatory bowel disease (IBD) of the small intestine

Therapeutic management of feline triaditis

Antibiotics (if a bacterial infection is detected)

Anti-nausea meds, Appetite stimulants (Mirtazapine, Capromorelin)

Gastrointestinal protectants; painkillers (Buprenorphine)

Steroids (to reduce IBD impact)

UDCA, SAMe, vitamin B12