In psoriasis, liver function tests, including serum albumin, should be performed periodically prior to dosing but are often normal in the face of developing fibrosis or cirrhosis. These lesions may be detectable only by biopsy. The usual recommendation is to obtain a liver biopsy at 1) pretherapy or shortly after initiation of therapy (2 to 4 months), 2) a total cumulative dose of grams, and 3) after each additional 1 to grams. Moderate fibrosis or any cirrhosis normally leads to discontinuation of the drug; mild fibrosis normally suggests a repeat biopsy in 6 months. Milder histologic findings such as fatty change and low grade portal inflammation, are relatively common pretherapy. Although these mild changes are usually not a reason to avoid or discontinue methotrexate therapy, the drug should be used with caution.
Bleomycin is a nonribosomal peptide that is a hybrid peptide - polyketide natural product . The peptide / polyketide / peptide backbone of the bleomycin aglycon is assembled by the bleomycin megasynthetase, which is made of both nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) modules. Nonribosomal peptides and polyketides are synthesized from amino acids and short carboxylic acids by NRPSs and PKSs, respectively. These NRPSs and PKSs use similar strategies for the assembly of these two distinct classes of natural products. Both NRPs and type I PKSs are organized into modules. The structural variations of the resulting peptide and polyketide products are determined by the number and order of modules on each NRPS and PKS protein.
Digoxin is classified in FDA pregnancy risk category C, although digoxin is considered by many cardiologists to be one of the safest antiarrhythmics for use during pregnancy. Digoxin readily passes to the fetal circulation; however, this drug has been used safely and effectively off-label for decades to treat both maternal and fetal arrhythmias. No teratogenic effect has been reported in humans. The typical dosage in pregnancy is similar to that given a non-pregnant woman. There may be difficulty, particularly in the third trimester, in interpreting serum digoxin levels as a result of an increase in an endogenous digoxin-like substance that may interfere with the digoxin assays. Thus, digoxin levels may give the impression of supratherapeutic dosing; clinicians should interpret the results in accordance with the clinical status of the mother and fetus before making dosage adjustments based on levels alone. As with most drugs, the use of digoxin during pregnancy should be avoided unless the potential benefit of digoxin therapy to the fetus or mother outweighs the potential risk to the fetus.