Therapeutic Relevance : Providing answers

    The questions of How much? How often? How long?? and many more are answered by the drug's pharmacokinetic and pharmacodynamic studies. This will in turn result in better and safer use of drugs for treatment.

credit: theconversation.com

   

Empirical Approach in Designing Dosage Regimen

    Earlier the dosage regimen of drugs was established through trial and error by adjusting factors such as dose, dose interval etc and then observing its effects. With this a regimen can be set up but with excessive side effects and ineffective therapy. It also doesn't explain the apparent difference in regimes for different drugs, nor the principles underlying that leads to effective dosage of other drugs.


Empirical Approach to Designing Drug Design Regimen


Rational Approach

    With advancement, its now understood that its the concentrations at the active site that drive the responses rather than the dose and to obtain and sustain the response, appropriate exposure-time profile of the drug within the body needs to be generated. This requires proper understanding of the factors that control this exposure profile.

The input-response relationship ( a.k.a. dose-response) has a pharmacokinetic and a pharmacodynamic phase.

1. Pharmacokinetic phase : covers relationship between drug input ( includes adjustable factors like- dose, dosage form, route and frequency of administration etc.) and the concentration achieved with time; i.e. in simple terms- how the body handles the drug.

2. Pharmacodynamic phase : covers relationship between concentration and effects ( both desired and adverse) produced with time; or simply, how the drug affects the body.


Rational Approach to Designing Drug Dosage Regimen

Therapeutic Window

Some basic ideas have helped to rationalise drug administration better. 

  • The intensity of effects increases as exposure to drug increases, but only to a threshold value above which the response cant increase even with increase in exposure.
  • Drugs act on different parts of the body and its effect produced varies from one another even if the measured response is same.
  • Drugs can have multiple effects - be it desired or undesired. 
    So very low exposure lead to inadequate desired response and too high exposure can increase the adverse effects. There exists an optimal range of exposure between the extremes which is referred to as the therapeutic window in which desired therapeutic response without much adverse effects. Some drugs have very narrow therapeutic window and thus has a small margin of safety, while some others have wide ones.

Therapeutic Window


Comments

Post a Comment

Popular posts from this blog

A for Absorption !

Image
Absorption is the movement of drug from its site of administration into the circulation. Not only the fraction of the administered dose that gets absorbed, but also the rate of absorption is important.  Routes of drug administration and absorption of drugs (sr: Rang and Dale's Pharmacology) Except when given intravenous, the drug has to cross biological membranes. Other factors influencing absorption are: Aqueous solubility : Drugs given in the solid form must dissolve in aqueous biophase before they are absorbed. A drug given as watery solution is absorbed faster.  Concentration : Passive diffusion depends on concentration gradient : concentrated drug solution is absorbed faster. Area of absorbing surface : Larger it is, faster the absorption. Vascularity of the absorbing surface : Blood circulation removes drug from site of absorption and maintains concentration gradient. Route of administration : Main routes include oral, sublingual, rectal, topical application, inhalat...
Read more

TESTING FOR TOXICITY,MUTAGENICITY & GENOTOXICITY

Image
Testing for Toxicity Both short-term or acute and long-term or chronic toxicity testing are carried out to determine the toxic effects of the drug and mortality in animal models.All these tests are carried out under a standard procedure of "GOOD LABORATORY PRACTICE" to safeguard the quality, integrity, and safety of the preclinical trials.  Drug Development: Drugs must be approved by the FDA before they can be marketed in the US.  Long, costly, and inherently risky: only 1 of 10-15,000 reach FDA approval.  Toxicology testing is required to demonstrate that drugs are safe before they can be given to humans. Testing of Mutagenicity:- Mutagenicity :- Mutagenicity refers to the induction of permanent transmissible changes in the amount or structure of the genetic material of cells or organisms. These changes may involve a single gene or gene segment , a block of genes or chromosomes. Testings: - Carcinogenicity:- Ames test   is used as one of the initial screen...
Read more

EVOLUTION OF DRUGS

Image
  Definition  Berries of coffee plant     A drug is defined as any chemical agent that affects the living protoplasm. Drug invention vs Drug discovery A drug discovery is not intentional. A drug invention   is defined as the intentional process Poisonous mushroom by which the drug is sculpted by experimentation &   optimization of individual properties .  Early experiences in chemistry Goats went insane after eating the berries of coffee plant  Professional poisoners used mushrooms and Belladona  Atropa belladona source: www.fs.fd.usa Curare was used by South American tribes for hunting Poppy  was used to relieve pain Chinese herb Ma Huang was used as a circulatory stimulant Rise of Organic chemistry PAUL EHLRICH worked on dyes  He invented arsphenamine named as  Salvarsan - Salvation of humankind  PAUL EHLRICH Father of chemotherapy curare   poppy                 ...
Read more