In addition to the drug-drug  interactions just reviewed, drug-disease  interactions can occur.  These include interactions between certain drugs and specific disease states.  Severe liver disease can be associated with reduced metabolic clearance and higher plasma levels of drugs extensively metabolized by the liver.{Brouwer}  Although liver disease reduces drug clearance on average, the change is relatively small and usually not clinically relevant except in patients with near terminal liver disease.  The effects of renal disease on elimination of drugs that are primarily cleared renally are more predictable, and well-established guidelines exist for dosage of many drugs in renal disease.{Lam}  Heart failure reduces liver blood flow and causes a reduction in clearance for drugs such as lidocaine or propranolol that are usually extensively cleared by the liver,{Shammas}  and acute myocardial infarction reduces clearance of some drugs, such as lidocaine, as well.{Pieper}  Acute viral infection and changes in thyroid function have been associated with altered clearance for some drugs, such as theophylline and warfarin.{Pokrajac}{Stephens}{Yamaguchi} However, the results are so variable between individuals that it is hard to predict who is at risk, and these changes are usually only clinical important in cases of extremely impaired  organ function.

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