Transport of drugs to the tissues

Drugs are transported to the tissues, via the circulation, partly in solution and partly attached, or bound, to plasma proteins, particularly albumin. Only the unbound part of the drug is small enough to get out of v the circulation and into the tissues through the capillary walls and thus exert an effect. The binding value of a particular drug is lowered in a person suffering from a disorder involving a deficiency of plasma proteins. Lower than normal doses are then necessary.

Drug-binding can also prolong the action of a drug by forming a store that releases the drug slowly. Some sulphonamides and the heart drug digitoxin are examples of drugs administered to act slowly over a period of time.

Plasma-binding is also important to bear in mind when more than one drug is being administered. For example, someone may be given an oral anticoagulant (an anti-blood-clotting drug) that is extensively bound to plasma protein and slowly released. But if a drug such as indomethacin is then given, its high plasma-binding property causes the anticoagulant to be displaced, thus resulting in a high risk of haemorrhage. Drug doses must therefore be considered when there is competition for plasma protein binding sites. The ease with which drugs reach the tissues varies between drugs and between tissues. For example, the brain has a ‘blood-brain’ barrier around it that is selective about which drugs it lets through from the capillaries that supply the brain. The antibiotic penicillin is slow to cross the barrier and would thus need to be given in large doses to be effective. In contrast, another antibiotic, chloramphenicol, crosses the barrier readily and is more likely to be effective at lower doses.

In pregnancy, the placenta provides the growing foetus with a protective barrier. But this is only true to a limited extent.

Several drugs can cross the barrier easily, as was tragically discovered with the use of the drug thalidomide. Drugs should be avoided in pregnancy unless their use is absolutely safe and approved by a doctor.