Pharmacokinetics - Prolonging drug action

Prolonging drug action

Action of a drug may be prolonged to

1.  Reduce the frequency of administration

2.  Avoid large fluctuations in plasma concentration

3.  Maintain drug effect overnight without disturbing sleep.

This can be achieved by

1.  Delaying absorption - It is desirable to delay absorption, either to reduce the systemic actions of drugs that are being used to produce a local effect or to prolong systemic action. Addition of epinephrine or norepinephrine to local anaesthetic delays absorption due to vasoconstriction. This prolongs the anaesthetic effect and in addition reduces systemic toxicity. From the subcutaneous or intramuscular administration sites, absorption can be delayed by using a relatively insoluble 'slow-release' form. A poorly soluble salt, ester or complex -  injected either as an aqueous solution or an oily solution will have delayed absorption. Procaine penicillin is a poorly soluble salt of penicillin which when injected is slowly absorbed. Esterification of steroid hormone delays absorption. Physical characteristics of a preparation may also be changes so as to influence the rate of absorption. Examples include insulin zinc suspension. Another method of achieving slow and continuous absorption is by using subcutaneous implants. The rate of absorption is proportional to the surface area of the implant. Sustained release tablets, spansules etc. wherein the drug particles are coated with resins, plastic material or other substances that temporarily disperse the release of the active ingredient in the gastrointestinal tract. Transdermal delivery system in which the drug is impregnated in adhesive patches releases the drug slowly over a prolonged period of time.

2.  By increasing the plasma protein binding - Congeners have been prepared which are highly bound to plasma protein and are slowly released in the free active form to have a prolonged duration of action like sulphamehtoxypyridaiazine.

3.  By reducing the rate of metabolism - Small chemical modifications may markedly affect the rate of metabolism without affecting the biological action. Inhibition of specific enzymes by one drug can prolong the action of the other drug. For example physostigmine prolongs the action of acetylcholine by preventing its metabolism.

4.  By reducing renal excretion -Tubular secretion of drug being an active process, it can be suppressed by a competing substance. Example - Probenicid prolongs the duration of action of penicillin and ampicillin.