Pharmacology of Disorders of the Pancreas Flashcards
Clinical use of Pancrelipase.
For exocrine pancreatic insufficiency
What can exocrine pancreatic insufficiency be caused by?
- cystic fibrosis
- chronic pancreatitis, or
- pancreatic resection
When secretion of pancreatic enzymes falls below 10% of normal, fat and protein digestion is impaired and can lead to what?
steatorrhea, azotorrhea, vitamin malabsorption, and weight loss.
Describe what coats pancreatic enzymes in order for them to not be broken down in the stomach?
enteric coated preparations
What should a patient take with non-enteric coated preparations of pancreatic enzyme supplements?
They should take concomitantly with acid suppression therapy to reduce acid mediated destruction of the drug within the stomach
How should one take pancrelipase?
should take with each meal and snack
What are some side effects of pancrelipase?
Oropharyngeal mucositis - so capsules should be swallowed, not chewed
Excessive doses may cause diarrhea and abdominal pain
high purine content of pancreas extracts may lead to hyperuricosuria (Gout) and renal stones
Several cases of colonic strictures were reported in patients with cystic fibrosis who received high doses of pancrelipase with high lipase activity
How does acute pancreatitis present?
midepigastric abdominal pain and tenderness.
What are some of the major causes of acute pancreatitis?
- an alcoholic or someone with gallstones.
ØHypertriglyceridemia, Trauma, Infection, ERCP
ØMedications such as: ACE inhibitors (captopril ,enalapril etc), thiazides,
didanosine, stavudine, or azathioprine
What does therapy for acute pancreatitis consist of?
§ No feeding (bowel rest)
§ Hydration
§ Pain medications
§ We do not have a medication to reverse pancreatitis.
Necrotic Pancreatitis
§ When the CT shows > 30 percent necrosis of the pancreas, the patient should receive antibiotics such as imipenem.
What are some important lab findings that may clue you into the fact that one has acute pancreatitis?
§Serum, urine amylase, 3-5x normal (↑: 6h,↓: 5d)
§Serum lipase (earlier and more prolonged increase↑)
§Sebi↑, ASAT/ALAT↑
§Leukocytosis, CRP
§Hyperglycaemia (insulin↓, glucagon, adrenalin↑) §Triglyceride↑ (reason and cause)
Is a majority of cases of acute pancreatitis self-limited?
yes; subsides within y days of therapy
What is the best therapy for chronic pancreatitis?
- Diet: alcohol abstinency, protein rich, low fat diet
- Pain killers: NSAID, nitrate, spasmolytics (epidural).
- Exocrine (enzyme support: Pancrelipase ) endocrine (insulin) ,H2 blocker
- Therapy of complications:
§Surgery: pseudocyst resection, to solve stenosi
What are the best pharmaceutical therapies for pancreatic cancer?
FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin combination);
GEMOXEL (gemcitabine, oxaliplatin and capecitabine)
What are the side effects of 5-FU?
BMS (bone marrow supression)
N+V
mucositis (lining digestive tract becomes inflamed
diarrhea
hand foot syndrome (redness, swelling and blistering on palms of hands and soles of feet)
MOA of 5-FU.
MOA - Prodrug
Ø After activation to FdUMP it inhibit thymidylate synthase, leading to “thymidine less death” of cells inhibiting DNA synthesis
ØActivation to FUTP – inhibit RNA synthesis