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Recurrent acute pancreatitis probably secondary to lisinopril.



Objectives: Few data exist about the incidence of drug-induced acute pancreatitis acute pancreatitis Inflammation of the pancreas of abrupt onset, often with gallstones and alcohol ingestion Epidemiology 109,000 hospitalizations, 2251 deaths–US; 10-fold ↑ from 1960s to 1980s–reason unclear;  in the general population. Although angiotensin-converting enzymes are generally well tolerated, acute pancreatitis has been reported in a few subjects treated with captopril captopril /cap·to·pril/ (kap´to-pril) an angiotensin-converting enzyme inhibitor used in the treatment of hypertension, congestive heart failure, and post–myocardial infarction left ventricular dysfunction. , enalapril, and lisinopril. However, to our knowledge, there is no published data regarding recurrent pancreatitis secondary to lisinopril. Herein, we report the case of a 54-year-old man who developed recurrent acute pancreatitis after starting lisinopril.

Clinical Presentation: A 54-year-old man with a longstanding history of hypertension, treated with lisinopril 10 mg once daily, presented with acute pancreatitis. Other causes of the disease were ruled out. After cessation of lisinopril, his condition improved and his amylase amylase (ăm`əlās'), enzyme having physiological, commercial, and historical significance, also called diastase. It is found in both plants and animals. Amylase was purified (1835) from malt by Anselme Payen and Jean Persoz.  level decreased. This was his third episode of acute pancreatitis since lisinopril had been started in 2002. After discontinuing lisinopril and beginning treatment with amlodipine 10 mg/d, the patient was well at follow-up examination and has not had another episode of pancreatitis during the subsequent 7 months.

Conclusion: This case report demonstrates additional evidence of acute pancreatitis associated with an ACE inhibitor ACE inhibitor (ā'sē'ē`, ās) or angiotensin-converting enzyme inhibitor (ăn'jēōtĕn`sĭn) .

Key Words: lisinopril, pancreatitis, ACE inhibitor-induced pancreatitis

**********

Medication-related pancreatitis occurs in approximately 1.4 to 2% of patients, (1) and the use of angiotensin-converting enzyme (ACE) inhibitors for the treatment of heart failure and hypertension is increasing. There have been several published reports (1,2) of ACE inhibitor-associated pancreatitis. The offending agents have included captopril, enalapril, quinapril, ramipril, perindopril and lisinopril. (1-7) This case report demonstrates additional evidence of acute pancreatitis associated with an ACE inhibitor. We describe the case of a 54-year-old man who developed recurrent acute pancreatitis after taking lisinopril.

Case Report

A 54-year-old man presented to the gastroenterology department with a 1-day history of sudden onset, severe abdominal pain radiating to the back, plus nausea. He had no previous medical or surgical history, no history of alcohol use, no history of trauma. Before admission, his medication regimen consisted only of lisinopril 10 mg b.i.d. for arterial hypertension for 25 months. He had two previous episodes of acute pancreatitis after starting the lisinopril. His first acute episode of pancreatitis was 4 months after beginning lisinopril, and the second occurred 10 months later. Previous investigations included abdominal ultrasonography ultrasonography /ul·tra·so·nog·ra·phy/ (-so-nog´rah-fe) the imaging of deep structures of the body by recording the echoes of pulses of ultrasonic waves directed into the tissues and reflected by tissue planes where there is a change in  and endoscopic retrograde cholangiopancreatography Endoscopic Retrograde Cholangiopancreatography Definition

Endoscopic retrograde cholangiopancreatography (ERCP) is a technique in which a hollow tube called an endoscope is passed through the mouth and stomach to the duodenum (the first part of the
, which had ruled out common causes of pancreatitis.

On physical examination, the patient's abdomen was distended distended Medtalk Enlarged, bloated. Cf Nondistended.  and diffusely tender. His bowel sounds bowel sounds
pl.n.
Abdominal sounds caused by the products of digestion as they move through the lower gastrointestinal tract, usually heard on auscultation.
 were reduced. Blood tests revealed an amylase of 997 IU/mL (reference range: 0-180 IU/mL), lipase lipase (lī`pās), any enzyme capable of degrading lipid molecules. The bulk of dietary lipids are a class called triacylglycerols and are attacked by lipases to yield simple fatty acids and glycerol, molecules which can permeate the membranes  1368 U/L U/L Upload
U/L Uplink
U/L Universal/Local
U/L Units/Litre
 (reference range: 40-110), a raised white cell count of 14,000 (reference range: 4,500-11,000) and a moderately elevated C-reactive protein C-Reactive Protein Definition

C-reactive protein (CRP) is a protein produced by the liver and found in the blood.
Purpose

C-reactive protein is not normally found in the blood of healthy people.
 level at 82 mg/L (reference range: 0-10 mg/L). The other laboratory tests, including serum calcium, lipids, thyroid, renal, and liver function tests Liver Function Tests Definition

Liver function tests, or LFTs, include tests for bilirubin, a breakdown product of hemoglobin, and ammonia, a protein byproduct that is normally converted into urea by the liver before being excreted by the kidneys.
, were normal. Abdominal ultrasonography showed pancreatic edema edema (ĭdē`mə), abnormal accumulation of fluid in the body tissues or in the body cavities causing swelling or distention of the affected parts. , whereas the rest of the pancreas was normal. The biliary tree was not dilated dilated

a state of dilatation.


dilated cardiomyopathy
see congestive cardiomyopathy.

dilated pupil syndrome
see feline dysautonomia (Key-Gaskell syndrome).
 and no gallstones Gallstones Definition

A gallstone is a solid crystal deposit that forms in the gallbladder, which is a pear-shaped organ that stores bile salts until they are needed to help digest fatty foods.
 were seen. The patient was diagnosed with acute pancreatitis. Occult biliary disease biliary disease Surgery Any pathology that affects the gallbladder and its conduits, commonly cholecystitis, cholelithiasis, cholesterolosis, etc  (microlithiasis) or damage to the ampullary region and congenital variation of the pancreatic duct system was excluded by endoscopic retrograde cholangiopancreatography. The only significant factor in our patient's history was the three episodes of acute pancreatitis since beginning the lisinopril.

The patient's clinical status quickly and spontaneously improved within 3 days of lisinopril cessation. His serum amylase level returned to normal on day 3 after discontinuing lisinopril. The patient was discharged from the hospital 4 days after admission. After discontinuing lisinopril, he was well at his follow-up visit with amlodipine 10 mg/d. The patient has not had another episode of pancreatitis during the subsequent 7 months.

Discussion

Drug-induced pancreatitis has no distinguishing features. The occurrence of reported cases of pancreatitis secondary to ACE inhibitors is relatively rare and mostly associated with captopril, enalapril, quinapril, ramipril, perindopril and lisinopril. (1-9) ACE inhibitors are first line agents in cardiovascular disease. Time intervals between the start of ACE-inhibitor treatment and the onset of acute pancreatitis varies and ranges between 1 day to 2 years, but generally occurs early in the course of therapy. (1-3) The severity of acute pancreatitis is usually mild. The pathogenesis of drug-induced pancreatitis may be caused by an allergic response or by a direct toxic effect. Pancreatitis associated with ACE inhibitors is thought to reflect localized angioedema of the gland. (1-3) Angioedema due to ACE inhibitors appears to be linked to the decreased degradation of bradykinin bradykinin /brady·ki·nin/ (-ki´nin) a nonapeptide kinin formed from HMW kininogen by the action of kallikrein; it is a very powerful vasodilator and increases capillary permeability; in addition, it constricts smooth muscle and  because ACE, also known as kininase II, not only activates angiotensin I but also inactivates bradykinin. Angiotensin II receptors are thought to be important in the regulation of pancreatic secretion and microcirculation microcirculation /mi·cro·cir·cu·la·tion/ (-sir?ku-la´shun) the flow of blood through the fine vessels (arterioles, capillaries, and venules).microcirculato´ry

mi·cro·cir·cu·la·tion
n.
, and this may have an additive effect on pathogenesis. (1-3,8) Proving the association with a particular drug may not always be straightforward, even in suspected cases. Thus, patients restarted on their medications should be closely monitored and the drug promptly discontinued if symptoms recur, as in our patient. (1) Use of the Naranjo probability scale indicates a probable relationship between recurrent acute pancreatitis and lisinopril in this patient. (4) The adverse reaction appeared after lisinopril was initiated, resolved promptly on withdrawal of the drug, and as the patient was on no other regular medications, lisinopril was the most likely etiologic agent. Reintroduction of lisinopril therapy resulted in the recurrence of pancreatitis, which strongly supports this association. Despite the low incidence of drug-induced pancreatitis, all patients with acute pancreatitis of unknown etiology should be carefully questioned regarding their medication history. In addition to monitoring for efficacy and commonly reported adverse effects, clinicians need to be aware that acute pancreatitis may occur in patients taking ACE inhibitors. If pancreatitis is suspected, the drug should be stopped and replaced to reduce the possibility of further episodes of pancreatitis.

This case suggests that when ACE-inhibitor treatment is started, clinicians should be vigilant in monitoring for signs and symptoms of pancreatitis.

References

1. Kanbay M, Korkmaz M. Yilmaz U, et al. Acute pancreatitis due to ramipril therapy. Postgrad Med J 2004;80:617-618.

2. Iliopoulou A, Giannakopoulos G, Pagoy H. et al. Acute pancreatitis due to captopril treatment. Dig Dis Sci 2001;46:1882-1883.

3. Muchnick JS, Mehta JL. Angiotensin converting enzyme Noun 1. angiotensin converting enzyme - proteolytic enzyme that converts angiotensin I into angiotensin II
angiotensin-converting enzyme, ACE

peptidase, protease, proteinase, proteolytic enzyme - any enzyme that catalyzes the splitting of proteins into
 inhibitor induced pancreatitis. Clin Cardiol 1999;22:50-51.

4. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-245.

5. Arjomand H, Kemp D. Quinapril and pancreatitis. Am J Gastroenterol 1999;94:290-291.

6. Gallego-Rojo FJ, Gonzalez Calvin JL, Guilarte J. et al. Perindopril-induced acute pancreatitis. Dig Dis Sci 1997;42:1789-1791.

7. Standridge JB. Fulminant ful·mi·nant
adj.
Occurring suddenly, rapidly, and with great severity or intensity, usually of pain.



ful
 pancreatitis associated with lisinopril therapy. South Med J 1994;87:179-181.

8. Kanbay M, Selcuk H, Yilmaz U, et al. Acute pancreatitis associated with combined lisinopril and atorvastatin atorvastatin /ator·va·stat·in/ (ah-tor?vah-stat´in) an antihyperlipidemic agent that acts by inhibiting cholesterol synthesis, used as the calcium salt in the treatment of hypercholesterolemia and other forms of dyslipidemia.  therapy. Dig Dis 2005;23:92-94.

9. Tosun E, Oksuzoglu B, Topaloglu O. Relationship between acute pancreatitis and ACE inhibitors. Acta Cardiol 2004;59:571-572.

Mehmet Kanbay, MD, Haldun Selcuk, MD, Ugur Yilmaz, Prof, and Sedat Boyacioglu, Prof

From the Departments of Internal Medicine and Gastroenterology, Baskent University Faculty of Medicine, Ankara, Turkey.

Reprint requests to Mehmet Kanbay, MD, 35. Sokak, 81/5, Bahcelievler, 06490, Ankara, Turkey. Email: drkanbay@yahoo.com

Accepted April 20, 2006.

RELATED ARTICLE: Key Points

* Lisinopril might be a cause of recurrent acute pancreatitis.

* Physicians should keep ACE inhibitors in mind when considering the differential diagnosis of recurrent pancreatitis.

* Physicians should be vigilant in monitoring for signs and symptoms of pancreatitis when their patients are on ACE inhibitors.
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Title Annotation:Case Report
Author:Boyacioglu, Sedat
Publication:Southern Medical Journal
Article Type:Clinical report
Date:Dec 1, 2006
Words:1239
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