Ischemic hepatitis

The authors speculated about the role of rosiglitazone, suggesting that it may have precipitated congestive cardiac failure, which then led to ischemic hepatitis. A direct hepatotoxic effect was thought to be unlikely. 

Kamiyami, T., Miyakawa, H., Tajiri, K., Marumo, F., Sato, C. Ischemic hepatitis in cirrhosis. Clinical features and prognostic implication. J. Clin. Gastroenterol. 1996 22 126-130... 

Hepatotoxicity with cibenzoline has been rarely reported. There has been a report of slight rises in the activities of serum transaminases (16), and one of ischemic hepatitis (26). 

Gutknecht J, Larrey D, Ychou M, Fedkovic Y, Janbon C. Ischemic hepatique grave apres prise de cibenzohne. [Severe ischemic hepatitis after taking cibenzohne.] Ann Gastroenterol Hepatol (Paris) 1991 27(6) 269-70. 

Dufour DR, Teot L. Laboratory identification of ischemic hepatitis (shock liver). Clin Chem 1988 34 1287. 

Ischemic hepatitis Other causes of jaundice Other causes of liver failure Other liver infections [6]... 

Ward, J., et al., Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis. Proc NatlAcadSci USA, 2014. 111(33) p. 12169-74. 

Santra S, McKiernan P, Lander A, Dalzell AM, Baillie C, Beath S, Gupte GL. Ischemic hepatitis is a risk factor for progression of liver disease associated with parenteral nutrition in intestinal failure. J Pediatr Gastroenterol Nutr 2008 47(3) 367-9. 

Ticlopidine inhibits the P2Yj2 platelet ADP receptor, thus inhibiting ADP-dependent activation of the GP Ilb/IIIa receptor. It has a slow onset of action and takes 3-7 days to reach its maximal antiplatelet effect. It is inactive in vitro and must undergo activation by the hepatic cytochrome p450 enzyme system. Secondary prevention trials have found that ticlopidine-treated patients have an estimated RRR of 33% for the composite endpoint of stroke, myocardial infarction, or vascular death after ischemic stroke. Significant adverse effects include bone marrow depression, rash, diarrhea, and thrombotic thrombocytopenic purpura. No clinical trials have studied ticlopidine for the treatment of stroke in the acute phase. 

Altered cardiac, hepatic, and renal function resulting from ischemic damage during the arrest warrant special attention. 

Cardiac index and blood pressure must be sufficient to ensure adequate organ perfusion, as assessed by alert mental status, creatinine clearance sufficient to prevent metabolic azotemic complications, hepatic function adequate to maintain synthetic and excretory functions, a stable heart rate and rhythm, absence of ongoing myocardial ischemia or infarction, skeletal muscle and skin blood flow sufficient to prevent ischemic injury, and normal arterial pH (7.34 to 7.47) with a normal serum lactate concentration. These goals are most often achieved with a cardiac index greater than 2.2 L/min/m2, a mean arterial blood pressure greater than 60 mm Hg, and PAOP of 25 mm Hg or greater. 

Contraindications to treatment include autoimmune hepatitis, decompensated liver disease, women who are pregnant or patients whose female partners are pregnant, hemoglobinopathies, creatinine clearance <50 mL/ min, hemodialysis, or ischemic cardiovascular or cerebrovascular disease. 

Hypersensitivity reactions While taking -blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction. Renal/Hepatic function impairment Rarely, use of carvedilol in patients with CHF has resulted in deterioration of renal function. Patients at risk appear to be those with low blood pressure (systolic BP less than 100 mm Hg), ischemic heart disease. 

Uses Acute migraine Action S otonin 5-HTi rec tor antagonist Dose 1—2.5 mg PO once r eat PRN in 4 h 5 mg/24 h max -1- in mild renal/hepatic insuff, take w/ fluids Caution [C, M] Contra Sev e renal/hepatic impair, avoid w/ angina, ischemic heart Dz, uncontrolled HTN, cerebrovascular synds, CTgot use Disp Tabs SE Dizziness, sedation, GI upset, paresthesias, ECG changes, coronary vasospasm, arrhythmias Interactions T Effects W/ MAOIs, SSRIs T effects OF CTgot drugs X effects W7 nicotine EMS May T PR or CyT int val, monitor ECG OD May cause profound HTN and cardiac ischemia symptomatic and supportive... 

Contraindications Cerebrovascular accident (CVA), ischemicheart disease (including angina pectoris, history of Ml, silent ischemia, and Prinzmetal s angina), severe hepatic impairment, transient ischemic attack, uncontrolled hypertension, use within 14 days of MAOls, use within 24 hr of ergof amine preparations... 

Flecainide Sodium channel (INa) blockade Dissociates from channel with slow kinetics no change in action potential duration Supraventricular arrhythmias in patients with normal heart do not use in ischemic conditions (post-myocardial infarction) Oral hepatic, and kidney metabolism half life 20 h Toxicity Proarrhythmic... 

It also appears that the incidence of hepatic adenomas is increased in women taking oral contraceptives. Ischemic bowel disease secondary to thrombosis of the celiac and superior and inferior mesenteric arteries and veins has also been reported in women using these drugs. 

Contraindications to interferon alfa therapy include hepatic decompensation, autoimmune disease, and history of cardiac arrhythmia. Caution is advised in the setting of psychiatric disease, epilepsy, thyroid disease, ischemic cardiac disease, severe renal insufficiency, and cytopenia. Alfa interferons are abortifacient in primates and should not be administered in pregnancy. Potential drug-drug interactions include increased theophylline levels and increased methadone levels. Co-administration with didanosine is not recommended because of a risk of hepatic failure, and co-administration with zidovudine may exacerbate cytopenias. 

Occasionally toxic compounds can directly damage the hepatic sinusoids and capillaries. One such toxic compound is monocrotaline, a naturally occurring pyrrolozidine alkaloid, found in certain plants (Heliotropium, Senecio, and Crotolaria species). Monocrotaline (Fig. 7.7) is metabolized to a reactive metabolite, which is directly cytotoxic to the sinusoidal and endothelial cells, causing damage and occlusion of the lumen. The blood flow in the liver is therefore reduced and ischemic damage to the hepatocytes ensues. Centrilobular necrosis results, and the venous return to the liver is blocked. Hence, this is known as veno-occlusive disease and results in extensive alteration in hepatic vasculature and function. Chronic exposure causes cirrhosis. 

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