Muscle transaminases

While considerable amounts of both GOT and GPT are found in cardiac muscle, skeletal muscle and kidney, differential diagnosis is aided by the fact that the liver shows a much higher total GPT activity. An important clinical application of measurements of transaminase activity is the detection and diagnosis of viral... 

The answer is a. (Hardman, pp 885-8870 Lovastatin should not be used in patients with severe liver disease. With routine use of lovastatin, serum transaminase values may rise, and in such patients the drug may be continued only with great caution. Lovastatin has also been associated with lenticular opacities, and slit-lamp studies should be done before and one year after the start of therapy There is no effect on the otic nerve. The drug is not toxic to the renal system, and reports of bone marrow depression are very rare There is a small incidence of myopathy, and levels of creatinine kinase should be measured when unexplained muscle pain occurs. Combination with cyclosporine or clofibrate has led to myopathy There is no danger in use with bile acid sequestrants. 

A group of enzymes which is particularly important in amino acid metabolism in the liver (and also in muscle) is the transaminases, (also called aminotransferases). These are vitamin B6 (pyridoxine) dependent enzymes which transfer an amino group from an amino acid to an oxo (keto) acid, thus ... 

The calorific capacity of amino acids is comparable to that of carbohydrates so despite their prime importance in maintaining structural integrity of cells as proteins, amino acids may be used as fuels especially during times when carbohydrate metabolism is compromised, for example, starvation or prolonged vigorous exercise. Muscle and liver are particularly important in the metabolism of amino acids as both have transaminase enzymes (see Figures 6.2 and 6.3 and Section 6.4.2) which convert the carbon skeletons of several different amino acids into intermediates of glycolysis (e.g. pyruvate) or the TCA cycle (e.g. oxaloacetate). Not all amino acids are catabolized to the same extent... 

Significant adverse reactions include fatigue headache drowsiness paresthesias difficulty in micturition diarrhea reversible increases in serum transaminases dyspnea bronchospasm asthenia muscle cramps nausea vomiting fever with aching and sore throat toxic myopathy rashes systemic lupus erythematosus vision abnormality hypoesthesia ventricular arrhythmias intensification of AV block mental depression scalp tingling. 

Disp Tabs, susp SE D, dizziness, rash, eosinophilia, T transaminases Interactions T Nephrotox W/ aminoglycosides, loop diuretics T effects W/probenecid i effects W/ antacids, chloramphenicol EMS T Risk of nephrotox w/ loop diuretics monitor for signs of electrolyte disturbances and hypovolemia d/t D monitor pt for super Infxn OD May cause NA /D, Szs, muscles spasms symptomatic and supportive... 

Papaverine Papaverine, molecular formula C20H21NO4, is an isoquinoline alkaloid isolated from poppy seeds Papaver somniferum, family Papaveraceae). This alkaloid is used mainly in the treatment of spasms and of erectile dysfunction. It is also used as a cerebral and coronary vasodilator. Papaverine may be used as a smooth muscle relaxant in microsurgery. In pharmaceutical preparations, papaverine is used in its salt form, e.g. hydrochloride, codecarboxylate, adenylate and teprosylate. The usual side-effects of papaverine treatment include polymorphic ventricular tachycardia, constipation, increased transaminase levels, hyperbihr-unemia and vertigo. 

Adverse Reactions Adverse events with a higher incidence in fiuvastatin-treated patients than placebo patients Arthropathy Exercise-related muscle pain Sinusitis Bronchitis Dyspepsia Diarrhea Abdominal pain Nausea Insomnia Fatigue Abdominal pain Asthenia Constipation Diarrhea Dyspepsia Flatulence Nausea Headache Upper respiratory tract infection Headache Constipation Flatulence Dyspepsia Abdominal pain Arthralgia Myalgia Bronchitis Pruritus Rhabdomyolysis Increases in serum transaminases and CPK... 

Transaminases participate in metabolism of most of the amino acids, over 60 different enzymes have been identified.142163 Best studied are the aspartate aminotransferases, a pair of cytosolic and mitochondrial isoenzymes which can be isolated readily from animal hearts. Their presence in heart muscle and brain in high concentration is thought to be a result of their functioning in the malate-aspartate shuttle... 

The adverse effects associated with the use of nevirapine include rash, mild macular or papular eruptions, pruritus, elevated hepatic transaminases and hypersensitivity reaction. There is also a risk of hepatitis/hepatic failure, which may be associated with muscle ache, fatigue, malaise and/or renal dysfunction. The use of nevirapine is rarely associated with Stevens-Johnson syndrome but is potentially fatal. 

A 59-year-old man took troglitazone 400 mg/day for 6 months and alcohol about 40 g/day. He developed weakness and muscle pain. He had mild liver damage. His HbAic concentration was 9.0%. All his muscles were tender, his creatine kinase activity was 10 570 IU/ml, and his myoglobin, aldolase, and aspartate transaminase were raised. Troglitazone was withdrawn. He improved biochemically and clinically. 

Nicotinic acid is also a potent vasodilator, probably by a direct action on smooth muscle cells. It produces cutaneous vasodilatation, itching of the skin, facial flushing, a sensation of feeling hot, pounding in the head, gastric irritation, diarrhea, raised transaminases, hyperglycemia, and hyperuricemia. These unpleasant adverse effects limit its acceptability for many patients. Nicotinic acid as such is not used in the treatment of vascular disorders, but some of its derivatives are, albeit with poor evidence of clinical efficacy. 

In a placebo-controlled study of 1142 hypercholestero-lemic patients treated with pravastatin for 8-16 weeks, the numbers of adverse drug experiences were similar in the treated and untreated individuals (1). Rash was the only adverse clinical event that was different (4.0 versus 1.1%). However, in the same patients withdrawal of therapy during follow-up was thought to be necessary in 3.2% of those given pravastatin alone. Myopathy was observed in one instance only, and increases in creatine kinase activity in those taking pravastatin did not differ significantly from controls. There were marked persistent increases in transaminases in 1.1%, with no cases of symptomatic hepatitis. Pravastatin is believed to have a particularly low potential for nervous system-related adverse effects, as it has not been shown to enter the cerebrospinal fluid, and clinical experience suggests that muscle toxicity occurs less often with pravastatin than with lovastatin (2). 

A 75-year-old-man taking simvastatin 80 mg/day and diltiazem 240 mg/day developed extreme weakness and diffuse muscle pain. All drugs were withdrawn and he underwent hemodialysis. Within 3 weeks his muscle pain disappeared and he regained function in his legs. The activities of creatine kinase and transaminases gradually returned to normal, but he continued to need hemodialysis. 

Owen, T.G. and Hochachka, P.W. (1974). Purification and properties of dolphin muscle aspartate and alanine transaminases and their possible roles in the energy metabolism of diving mammals. Biochemical Journal 143,541-553. 

Glucocorticoids also increase the activity of transaminases (aminotransferases), especially in the skeletal muscle. Aminotransferases serve to transfer the amino groups from amino acids to be metabolized to a-keto acids, especially pyruvate. In the latter case, the alanine thus formed is transported from the muscle into the bloodstream and extracted from there by the liver. In the liver, alanine is converted to glucose, and glucose may then return to the muscle as it does in the Cori cycle (Figure 18.4). This is the alanine cycle, and more about this is discussed in Chapter 20. Branched-chain amino acids are the principal donors of nitrogen to pyruvate in the muscle and are thus important actors in the alanine cycle. 

Q4 Cardiac enzymes are released into the blood following heart muscle damage during a heart attack. Creatine kinase, particularly its MB isoenzyme, is one of the most specific of these enzymes, which reaches a peak 24 hours after infarction. It rises and then falls within the first 72 hours of the heart attack. Aspartate transaminase is also released, but levels of this enzyme can be raised in several other conditions, so it is less specific than creatine kinase MB. Troponin T is also specific for myocardial damage and is raised for approximately two weeks following infarction. Finding a high concentration of these enzymes in a patient s blood therefore supports the evidence obtained from the ECG and confirms that the patient has suffered a myocardial infarction. 

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