Pharmacokinetics questions.

Answer: About four to five, whatever the dose given

Each half-life closes half the remaining gap to steady state, so you reach about 97% after five. The counter-intuitive part is that the dose does not change this: a larger dose gives a higher steady state but arrives there at the same time, which is exactly why a loading dose exists.

Answer: It avoids extensive first-pass hepatic metabolism

Drug absorbed from the gut passes through the liver before reaching the systemic circulation, and GTN is almost entirely removed on that first pass. Veins under the tongue drain into the superior vena cava rather than the portal vein, so the drug bypasses the liver and arrives intact.

Answer: Volume of distribution, since it sets the space

A loading dose fills a space, so it depends on how large that space is, which is what volume of distribution measures. A maintenance dose replaces what is being removed, so it depends on clearance. Confusing the two is the most common pharmacokinetics error in exams.

Answer: They follow zero-order kinetics once saturated

Most drugs are cleared at a rate proportional to their concentration, so doubling the dose doubles the level. These three saturate their metabolic enzymes at therapeutic concentrations, after which a fixed amount is cleared per hour regardless of level, and a small dose rise can be dangerous.

Answer: Induces CYP enzymes over several days to weeks

Induction works by increasing the amount of enzyme made, which requires transcription and translation, so the effect builds over days and takes as long to disappear after stopping. That delay is what catches people: it does not appear on day one nor vanish when the course ends.

Answer: Cannot cross membranes to reach its receptor

Binding is reversible and does not change the drug chemically, but an albumin complex is far too large to cross capillary walls or membranes. The bound portion is therefore a reservoir rather than an inactive form, and it releases drug as the free concentration falls.

Answer: Extensively in tissue and poorly cleared by dialysis

Volume of distribution is the theoretical volume needed to hold the whole dose at the measured plasma concentration, so a large value means most of the drug has left the plasma for tissue. Dialysis only cleans blood, so it can do little about a drug that is mostly somewhere else.

Answer: 100%, because it enters the circulation directly

Bioavailability measures the proportion of an administered dose reaching systemic circulation unchanged, and an intravenous dose is placed there directly. It is the reference standard against which every other route is compared, which is why oral bioavailability is a fraction of it.

Answer: It estimates filtration, and so renal drug removal

Creatinine is produced at a fairly steady rate and cleared mainly by filtration, which makes its clearance a usable proxy for glomerular filtration. For a drug eliminated by the same route, that proxy tells you how fast the patient removes it, and therefore how far the dose must fall.

Answer: Inhibiting CYP3A4 within the intestinal wall

The effect happens in the gut wall rather than the liver, where CYP3A4 normally metabolises a proportion of the drug before it is ever absorbed. Removing that pre-systemic loss increases how much gets through, so the interaction is largest for drugs with a big intestinal first pass.