drug accumulation
Drug accumulation is what happens when you give the next dose before the body has finished clearing the last one: a little leftover drug carries over each time, and the level builds up dose after dose. Imagine topping up a bucket faster than it drains — the water rises until it eventually settles at a new, higher steady level.
Whether and how much a drug accumulates depends on the relationship between the dosing interval and the half-life. If the interval is short relative to the half-life, much of the previous dose remains and accumulation is large; if the interval is several half-lives long, almost nothing carries over and little accumulates. Accumulation is the flip side of building up to steady state, and it plateaus once input and elimination balance.
Some accumulation is intended and harmless — it is simply how a drug reaches its therapeutic steady-state level. The danger arises when accumulation is unexpected, as when kidney or liver disease slows clearance, lengthening the half-life so that a normal regimen piles up into toxic territory. This is a common cause of preventable adverse drug reactions in the elderly and the organ-impaired.
Digoxin, with its long half-life and renal elimination, readily accumulates to toxic levels in patients whose kidney function declines, causing nausea, visual disturbance and arrhythmias.
Declining renal function tips digoxin into toxicity.
Accumulation is large only when the dosing interval is short relative to the half-life. A suddenly longer half-life (renal or hepatic failure) turns a safe regimen into a dangerous one.