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Author: either Koga Miyun District Hospital this article is the author's permission NMT Medical publish, please do not reprint without authorization
.
Introduce a rare case of liver injury caused by drugs
.
Case introduction: A 74-year-old female patient weighing 50 kg.
She developed cough and yellow sputum every winter and after catching cold since more than 40 years ago
.
Symptoms can be improved by self-administering cephalosporin antibiotics and anti-tussive and phlegm drugs, without systemic diagnosis and treatment .
This time, he experienced worsening cough, increased yellow sputum, with wheezing, no fever, no hemoptysis, night sweats, chest pain, no oliguria or edema.
He went to Beijing Anzhen Hospital and diagnosed “acute attack of chronic bronchitis, lung Ministry of infection"
.
Give mezlocillin to fight infection for 2 weeks
.
The bronchoscopy was improved, the secretion culture showed MRSA, and the combination of teicoplanin was given for 1 week.
The cough and sputum were improved, and he was transferred back to our hospital for further consolidation
.
There is no teicoplanin in our hospital.
On November 4, I was given vancomycin hydrochloride 0.
5g q12h for injection to continue the anti-infective treatment.
At the same time, he was given ambroxol hydrochloride and sodium chloride injection 30mg bid, intravenously; acetylcysteamine Acid capsule 0.
2g tid, oral expectorant; given 1 tablet of valsartan and amlodipine, qd, oral antihypertensive
.
On November 7, the patient developed acid reflux heartburn and was given pantoprazole tablets 40 mg qd orally
.
The patient had a history of cerebral arterial insufficiency for several years and a history of hypertension for 5 years
.
On November 5th, he was admitted to the hospital for liver function examination: ALT 39.
3 U/L, AST 31.
3 U/L; on November 9th, liver function was rechecked: ALT 537.
90 U/L, AST 213.
7 U/L, and severe liver function damage occurred
.
Please consult with the Department of Infectious Diseases to exclude liver damage caused by liver disease.
Considering the possibility of drug-induced liver damage, the patient’s lung infection condition improves, and the doctor discontinues the suspicious drugs vancomycin, acetylcysteine, and pantoprazole
.
In addition, hepatoprotective therapy was given to give 3 injections of compound glycyrrhizin, intravenously, once a day; 1.
2 g of reduced glutathione for injection, intravenously, once a day
.
Liver function was reviewed on November 13: ALT was 115.
5 U/L, AST was 21.
2 U/L, which was significantly improved compared to before
.
On November 14th, considering that the patient's infection was controlled and his liver function improved, he agreed to take medicine and leave the hospital
.
After discharge from the hospital, he orally took glucurolactone 100 mg tid and continued the enzyme-lowering treatment
.
Re-examination of liver function after 1 week: ALT 165.
5 U/L, AST 146.
5 U/L
.
The changes of liver function indexes measured before and after treatment are shown in Table 1 below
.
Table 1 Changes in liver function indicators Table 2 Table of drug treatment during hospitalization of patients 1.
Discussion of drug treatment during hospitalization 1.
After admission to the hospital, patients with drugs that cause liver damage began to use ambroxol hydrochloride injection, vancomycin hydrochloride for injection, and acetylcysteine Capsules, pantoprazole sodium enteric-coated tablets, budesonide suspension for inhalation and other medications
.
After suspected drug-induced liver injury, the doctor stopped vancomycin hydrochloride for injection, acetylcysteine capsules, and pantoprazole sodium enteric-coated tablets
.
And ask clinical pharmacists to help rule out suspicious drugs: (1) Acetylcysteine is a precursor of reduced glutathione and is mainly used for early treatment of liver failure.
Its main pharmacological effect is to increase blood flow and oxygen supply capacity.
Improve the microcirculation, and at the same time eliminate the liver damage caused by oxygen free radicals in the body, and achieve an effective reduction of inflammation and the level of inflammatory factors, so acetylcysteine capsules can be eliminated
.
(2) Pantoprazole sodium enteric-coated tablets have been taken since November 7th, and they have been taken for only 2 days.
Although they occurred after the medication, the time is short and it is not proportional to the increase in the index of abnormal liver function
.
(3) Liver function damage occurred 5 days after administration of vancomycin hydrochloride for injection, and ALT and AST decreased significantly after stopping the drug and carrying out hepatoprotective treatment; refer to the literature for similar reports of vancomycin-induced liver damage; please consult the Department of Infectious Diseases The doctor's consultation ruled out the possibility of liver damage caused by the disease
.
Based on the above judgment, the possibility of drug-induced liver damage caused by vancomycin is high
.
2.
Related research on drug-induced liver injury caused by vancomycin MRSE) and other severe infections [1]
.
Vancomycin adverse reactions include shock, allergy-like symptoms; acute renal insufficiency, interstitial nephritis; multiple blood cell reductions (less than 0.
1%), agranulocytosis, thrombocytopenia; liver damage, jaundice [2]
.
Clinicians are familiar with kidney damage caused by vancomycin, but clinicians know less about liver damage caused by vancomycin
.
At present, it is believed that there are two main mechanisms of drug-induced liver injury, namely, direct liver toxicity and adverse immune response [3]
.
In most cases, drug-induced liver injury is caused by the direct action of drugs that may cause liver cell damage, or the active metabolites of drugs
.
The damage of liver cells may also trigger the cellular activity of the innate immune system (such as kupffer cells and natural killer cells) to cause inflammatory response and/or activation of the adaptive immune response [4-5]
.
The mechanism by which vancomycin causes the increase in serum transaminase levels may be due to one of the pathways, or a combination of both
.
According to Sun Tao and other 980 cases using vancomycin, the incidence of abnormal liver function is 1.
33%
.
According to the frequency standard of adverse drug reactions established by the International Committee of Medical Sciences Organizations, vancomycin-induced liver function abnormalities are common (≥1%, <10%) adverse reactions, and clinicians should pay attention to them in clinical practice
.
Therefore, before applying vancomycin, medical staff should evaluate the safety of patients in all aspects, strictly control the interval and dose of medication, and need to monitor various biochemical indicators
.
If conditions permit, the blood concentration of vancomycin should be monitored to effectively reduce the adverse effects of vancomycin
.
If abnormal liver function occurs, the drug should be discontinued, and appropriate treatment measures should be given according to the patient's condition to ensure the safety of the patient's medication and avoid the physician's occupational risks
.
References: [1] Zhou Li, Xing Wei.
Analysis of 36 cases of vancomycin clinical application[J].
Anti-infective Pharmacy, 2009, 6(4): 270-273[2] Eli Lilly Japan KK, Seishin Laboratories.
Injection Instructions for using vancomycin hydrochloride (stable and reliable)[S].
2006-11-14.
[3]Cadle RM, Mansouri MD, Darouiche RO.
Vancomycin-induced elevation of liver enzyme levels [J] .
Ann Pharmacother, 2006, 40(6):1186-1189.
[4]Holt MP,Ju C.
Mechanisms of drug-induced liver injury [J].
AAPSJ, 2006, 8(1):E48-E54.
[5]Naisbitt DJ, Farrell J , Wong G, et al.
Characterization of drug-specific T cells in lamotrigine hypersensitivity [J].
J Allergy Clin Immunol, 2003, 111(6).
.
Introduce a rare case of liver injury caused by drugs
.
Case introduction: A 74-year-old female patient weighing 50 kg.
She developed cough and yellow sputum every winter and after catching cold since more than 40 years ago
.
Symptoms can be improved by self-administering cephalosporin antibiotics and anti-tussive and phlegm drugs, without systemic diagnosis and treatment .
This time, he experienced worsening cough, increased yellow sputum, with wheezing, no fever, no hemoptysis, night sweats, chest pain, no oliguria or edema.
He went to Beijing Anzhen Hospital and diagnosed “acute attack of chronic bronchitis, lung Ministry of infection"
.
Give mezlocillin to fight infection for 2 weeks
.
The bronchoscopy was improved, the secretion culture showed MRSA, and the combination of teicoplanin was given for 1 week.
The cough and sputum were improved, and he was transferred back to our hospital for further consolidation
.
There is no teicoplanin in our hospital.
On November 4, I was given vancomycin hydrochloride 0.
5g q12h for injection to continue the anti-infective treatment.
At the same time, he was given ambroxol hydrochloride and sodium chloride injection 30mg bid, intravenously; acetylcysteamine Acid capsule 0.
2g tid, oral expectorant; given 1 tablet of valsartan and amlodipine, qd, oral antihypertensive
.
On November 7, the patient developed acid reflux heartburn and was given pantoprazole tablets 40 mg qd orally
.
The patient had a history of cerebral arterial insufficiency for several years and a history of hypertension for 5 years
.
On November 5th, he was admitted to the hospital for liver function examination: ALT 39.
3 U/L, AST 31.
3 U/L; on November 9th, liver function was rechecked: ALT 537.
90 U/L, AST 213.
7 U/L, and severe liver function damage occurred
.
Please consult with the Department of Infectious Diseases to exclude liver damage caused by liver disease.
Considering the possibility of drug-induced liver damage, the patient’s lung infection condition improves, and the doctor discontinues the suspicious drugs vancomycin, acetylcysteine, and pantoprazole
.
In addition, hepatoprotective therapy was given to give 3 injections of compound glycyrrhizin, intravenously, once a day; 1.
2 g of reduced glutathione for injection, intravenously, once a day
.
Liver function was reviewed on November 13: ALT was 115.
5 U/L, AST was 21.
2 U/L, which was significantly improved compared to before
.
On November 14th, considering that the patient's infection was controlled and his liver function improved, he agreed to take medicine and leave the hospital
.
After discharge from the hospital, he orally took glucurolactone 100 mg tid and continued the enzyme-lowering treatment
.
Re-examination of liver function after 1 week: ALT 165.
5 U/L, AST 146.
5 U/L
.
The changes of liver function indexes measured before and after treatment are shown in Table 1 below
.
Table 1 Changes in liver function indicators Table 2 Table of drug treatment during hospitalization of patients 1.
Discussion of drug treatment during hospitalization 1.
After admission to the hospital, patients with drugs that cause liver damage began to use ambroxol hydrochloride injection, vancomycin hydrochloride for injection, and acetylcysteine Capsules, pantoprazole sodium enteric-coated tablets, budesonide suspension for inhalation and other medications
.
After suspected drug-induced liver injury, the doctor stopped vancomycin hydrochloride for injection, acetylcysteine capsules, and pantoprazole sodium enteric-coated tablets
.
And ask clinical pharmacists to help rule out suspicious drugs: (1) Acetylcysteine is a precursor of reduced glutathione and is mainly used for early treatment of liver failure.
Its main pharmacological effect is to increase blood flow and oxygen supply capacity.
Improve the microcirculation, and at the same time eliminate the liver damage caused by oxygen free radicals in the body, and achieve an effective reduction of inflammation and the level of inflammatory factors, so acetylcysteine capsules can be eliminated
.
(2) Pantoprazole sodium enteric-coated tablets have been taken since November 7th, and they have been taken for only 2 days.
Although they occurred after the medication, the time is short and it is not proportional to the increase in the index of abnormal liver function
.
(3) Liver function damage occurred 5 days after administration of vancomycin hydrochloride for injection, and ALT and AST decreased significantly after stopping the drug and carrying out hepatoprotective treatment; refer to the literature for similar reports of vancomycin-induced liver damage; please consult the Department of Infectious Diseases The doctor's consultation ruled out the possibility of liver damage caused by the disease
.
Based on the above judgment, the possibility of drug-induced liver damage caused by vancomycin is high
.
2.
Related research on drug-induced liver injury caused by vancomycin MRSE) and other severe infections [1]
.
Vancomycin adverse reactions include shock, allergy-like symptoms; acute renal insufficiency, interstitial nephritis; multiple blood cell reductions (less than 0.
1%), agranulocytosis, thrombocytopenia; liver damage, jaundice [2]
.
Clinicians are familiar with kidney damage caused by vancomycin, but clinicians know less about liver damage caused by vancomycin
.
At present, it is believed that there are two main mechanisms of drug-induced liver injury, namely, direct liver toxicity and adverse immune response [3]
.
In most cases, drug-induced liver injury is caused by the direct action of drugs that may cause liver cell damage, or the active metabolites of drugs
.
The damage of liver cells may also trigger the cellular activity of the innate immune system (such as kupffer cells and natural killer cells) to cause inflammatory response and/or activation of the adaptive immune response [4-5]
.
The mechanism by which vancomycin causes the increase in serum transaminase levels may be due to one of the pathways, or a combination of both
.
According to Sun Tao and other 980 cases using vancomycin, the incidence of abnormal liver function is 1.
33%
.
According to the frequency standard of adverse drug reactions established by the International Committee of Medical Sciences Organizations, vancomycin-induced liver function abnormalities are common (≥1%, <10%) adverse reactions, and clinicians should pay attention to them in clinical practice
.
Therefore, before applying vancomycin, medical staff should evaluate the safety of patients in all aspects, strictly control the interval and dose of medication, and need to monitor various biochemical indicators
.
If conditions permit, the blood concentration of vancomycin should be monitored to effectively reduce the adverse effects of vancomycin
.
If abnormal liver function occurs, the drug should be discontinued, and appropriate treatment measures should be given according to the patient's condition to ensure the safety of the patient's medication and avoid the physician's occupational risks
.
References: [1] Zhou Li, Xing Wei.
Analysis of 36 cases of vancomycin clinical application[J].
Anti-infective Pharmacy, 2009, 6(4): 270-273[2] Eli Lilly Japan KK, Seishin Laboratories.
Injection Instructions for using vancomycin hydrochloride (stable and reliable)[S].
2006-11-14.
[3]Cadle RM, Mansouri MD, Darouiche RO.
Vancomycin-induced elevation of liver enzyme levels [J] .
Ann Pharmacother, 2006, 40(6):1186-1189.
[4]Holt MP,Ju C.
Mechanisms of drug-induced liver injury [J].
AAPSJ, 2006, 8(1):E48-E54.
[5]Naisbitt DJ, Farrell J , Wong G, et al.
Characterization of drug-specific T cells in lamotrigine hypersensitivity [J].
J Allergy Clin Immunol, 2003, 111(6).