text: what is the "first-pass effect" of drugs? how po (oral) drugs are affected? the first pass effect is the change (more commonly, decrease) in activity of the drugs in the body after being ingested orally. this is because after absorption in the intestines, the drugs are carried directly to the liver where they are metabolized to other substrates, either more active or inactivated forms of the drug. to avoid this phenomenon, drugs are administered via different routes, like iv and sublingual. sublingual administration does not decrease the drug effect because the drugs are not carried directly to the liver.