09 HIGH ON LIFE

                                                                               Perhaps, If Tom would have known what's in there and what does it do to him he would not have been this much afraid of the situation. 😕      We all would have faced the same fearful situation 😫 when we were young👶, even we did not know at that time what PHARMACOKINETICS really is and how we are overcoming sickness 😊 !!!      PHARMACOKINETICS is defined as the process of how drug concentrations changes with time in one or more different regions of the body in relation to dosing       For a drug to be utilized in the body it has to overcome various barriers before reaching the target of action.. Mechanisms by which a drug cross these barriers along with their physicochemical properties also play a major role in their movement. Source: John Wiley & Sons.Inc The fluid compartments of the body are divided into Intracellular and extracellular fluids. The extracellular fluid  is further composed of 80%

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 screens for potential dru

Preclinical research   After validation----> Drug molecule is noted for its                                    ✅ Affinity and selectivity                                     ✅ ADME properties                                     ✅ Pharmacokinetic properties  Potency of drug is checked in      ☆Rodents      ☆Non Rodents (usually Rabbit)   《Unwanted effect --- off-Target effect      Desirable effect   --- on-Target effect》      Before testing in Humans  ●File an application  called Investigative new drug(IND) to FDA seeking permission  ●The efficacy, pharmacology, toxicity & plan to conduct trials in Humans should  be submitted  Role of FDA  FDA is a federal agency that ensures public health by regulating the foods,human &Vetrinary drugs,biological products and medical devices etc. 1906 - Only associated with interstate  transport 1938 - Elixir sulfanimide caused deaths in children - Regulated laws for safety  1962 - Thalidomide caused fused limbs in new born - Efficacy        

Small Molecules as our Drugs     I nitially, most drugs are small organic molecules, typically of molecular weight less than 500 Da. Screening of a "library" of chemicals to find the compound with your features of interest is the usual approach for invention of small molecule drugs. These libraries contain millions of compounds which are screened according their interaction with the specific target or its property to produce a biological response.  Some of the more than 3,000 drugs at Johns Hopkins. Credit (Brendan Smialowski for The New York Times) From serendipitous discovery to high throughput screening of libraries, drug discovery has taken a modern approach. The ideal target molecules are of human origin made via transcription and translation of human genes. The 'hit' drugs thus are to react with the human proteins itself rather than their animal counterparts.      Most of the screened hits require its derivatives to be synthesised for better structure- activity

  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                                                                            Organic arsenicals was used for the treatment of syphilis