Liver patient-related factor

Finally, do not forget to consider all of the non-liver-related factors about your patient - contraindications to therapy, concomitant disease, age, etc. At the end of this process you should be able to come to some sort of conclusion about the use of a specific drug in your patient. It is often not a definitive answer but an educated guess based on the available evidence. At the very least you should be able to give advice to reduce the risks of side effects and provide guidance on the relevant monitoring parameters. 

Most opioids are metabolised in the liver and have a high intrinsic clearance/high first-pass effect. Therefore, when liver metabolism is impaired or when there is decreased blood flow through the liver (e.g. cirrhosis), clearance of opioids may be reduced, resulting in a prolonged duration of action and possible toxicity. Portal hypertension may also increase the oral bioavailability and hence the toxicity risk of opioids, as first-pass metabolism will be reduced. The probability of toxicity occurring is additionally dependent on a number of other patient and drug-related factors. 

Although the average weekly dose of warfarin is between 30 and 40 mg, some patient-related variables are associated with a lower than usual dose advanced age (>65 years), elevated baseline INR, poor nutritional status, liver disease, hyperthyroidism, and concurrent use of medications known to enhance the effect of warfarin (Table 19-12). Prior to initiating therapy, the clinician should screen for the presence of contraindications to anticoagulation therapy and risk factors for... 

All patients admitted to a hospital during 6 months who had taken at least one dose of metformin were retrospectively evaluated for susceptibility factors for metformin-associated lactic acidosis (8). There were 263 hospitalizations in 204 patients. In 71 admissions there was at least one contraindication, such as renal or liver disease, renal dysfunction, congestive cardiac failure, metabolic acidosis, or an intravenous iodinated contrast medium given within 48 hours of metformin. In 29 (41%) metformin was continued despite the contraindication. The most frequent contraindication was a raised serum creatinine, but in only eight of the 32 admissions was metformin withdrawn. Of nine patients using metformin who died (not necessarily directly related to metformin), six had an absolute contraindication. In two patients who died and in one who survived, blood lactate was increased and this was temporally related to the use of metformin. 

Alcoholics with chronic liver disease may have disorders of fluid and electrolyte balance, including ascites, edema, and effusions. These factors may be related to decreased protein synthesis and portal hypertension. Alterations of whole body potassium induced by vomiting and diarrhea, as well as severe secondary aldosteronism, may contribute to muscle weakness and can be worsened by diuretic therapy. Some alcoholic patients develop hypoglycemia, probably as a result of impaired hepatic gluconeogenesis. Some alcoholics also develop ketosis, caused by excessive lipolytic factors, especially increased cortisol and growth hormone. 

Dose-related toxicities of azathioprine or 6-mercaptopurine include nausea, vomiting, bone marrow depression (leading to leukopenia, macrocytosis, anemia, or thrombocytopenia), and hepatic toxicity. Routine laboratory monitoring with complete blood count and liver function tests is required. Leukopenia or elevations in liver chemistries usually respond to medication dose reduction. Severe leukopenia may predispose to opportunistic infections leukopenia may respond to therapy with granulocyte stimulating factor. Hypersensitivity reactions to azathioprine or 6-mercaptopurine occur in 5% of patients. These include fever, rash, pancreatitis, diarrhea, and hepatitis. 

Relatively innocuous factors can also sometimes influence liver enzyme activity. For example, the metabolic elimination of the bronchodilator theophylline has been reported to be prolonged in patients with influenza A or adenovirus infections. In 1990, an influenza epidemic in Seattle resulted in the admission of 11 children with high serum levels of theophylline and confirmed drug toxicity. These effects appear to be confined to cytochrome P450-based drug biotransformation. They may be related to the generation of interferons as a result of these infections, which, presumably, are causally related to the inhibitory effect on hydroxylases and demethylases. 

It is important to monitor peak and trough plasma levels (see p. 20) of gentamicin, tobramycin, netilmicin, and amikacin to avoid concentrations that cause dose-related toxicities (Figure 31.7). [Note Peak levels are defined as those obtained 1/2 to 1 hour after infusion. Trough levels are obtained immediately before the next dose.] Patient factors, such as old age, previous exposure to aminoglycosides, gender, and liver disease, tend to predispose patients to adverse reactions. The elderly are particularly susceptible to nephrotoxicity and ototoxicity. 

Osteoporosis is also common in those on long-term corticosteroid therapy (for example patients with autoimmune hepatitis or coexisting inflammatory bowel disease). Patients with chronic liver disease may also have other risk factors for osteoporosis related to their disease state. These include vitamin D deficiency, excessive alcohol consumption, poor diet, physical inactivity and low body mass index. Oestrogen deficiency in the postmenopausal stage further increases the risk. 

Liver-disease patients often display white spots on the skin, which are the size of a lentil (sometimes as large as 0.5-1.0 cm in diameter). They can be detected chiefly in the area of the arms, on the back and on the buttocks. Upon cooling of the skin, white spots appear or become more pronounced, so that a cold-related vasocontrac-tion is assumed to be the causative factor. In the predilection area of the spider naevi, the white spotting of the skin can be deemed a preliminary stage of liver star within the round white spot, a central red dot is formed, from which the typical spider naevus develops with a white areola. 

An increase in the retention of sodium occurs in the early stages of severe liver disease, particularly in liver cirrhosis, without any disruption of the water balance. This early tendency towards sodium retention can be detected using the NaCl-tolerance test. The retention of sodium reduces the sodium excretion rate in the urine to < 10 mval/day (normal rate 120 to 220 mval/day). Diuresis is not primarily restricted patients with ascites and oedema react to an excessive intake of water with an adequate excretion of diluted urine, albeit in the virtual absence of sodium excretion. The limited sodium excretion derives from increased, mainly proximal tubular reabsorption of sodium and not from diminished glomerular filtration. Overall maintenance of the liver architecture is usually accompanied by undisturbed sodium excretion, despite existing portal hypertension (such as in primary biliary cirrhosis). Marked sodium retention is, however, usually found in alcoholic-toxic cirrhosis. For this reason, such patients are not only the ones most frequently affected by ascites and oedema, but as a rule they display the most serious forms. This is probably also due to additional biochemical and hormonal factors which are present to a greater degree in patients with alcohol-related liver disease. 

Toklta, H., Mnrai, S., Kamltsukawa, H., Yagnra, M., Harada, H., TakahasU, M., Okamoto, H. High XT virus load as an independence factor associated with the occurrence of hepatocellular carcinoma among patients with hepatitis C virus-related chronic liver disease. J. Med. Virol. 2002 67 501-509... 

Guptan, R.C., Thakur, V., Kazlm, S.N., Sarin, S.K. Efficacy of granulocyte-macrophage colony-stimulating factor or lamivudine combination with recombinant interferon in non-responders to interferon in hepatitis B virus-related chronic liver disease patients. J. Gastroenterol. Hepatol. 2002 17 765-771... 

The figures and observations relating to the epidemiology and frequency of HCC are almost exclusively the result of individual or combined risk factors. The extent of risk regarding HCC correlates with (7.) aetiology, (2.) duration, and (5.) inflammatory activity of the liver disease. In 10-15% of patients, no risk factor could actually be determined in the development of HCC. (s. tab. 37.4)... 

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