How does binding to tissue proteins affect drug distribution?

As drugs can accumulate in tissues, they may be bound to lipids, proteins or nucleic acids or may be actively transported to the tissue. So tissue binding can prolong drug action or cause local toxicity Ex: Digoxin accumulates at muscles acts as a reserve to make a balance into blood when drug is reduced prolonging the effect. Ex: Acrolein (cyclophophamide) can cause hemorrhagic cystitis as it accumulates in bladder