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Kind attn Trupti

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Hi

This issue was discussed by Dr Trupti Swain.

hence I leave the question for her to answer, before the next

discussion picks up.

Over to you Trupti.

Vijay

groupie

> >

> > I am thankful to the very less number of respondents for their

participation.

> >

> > I believe that the future lays in our GENES and off course the

use of drugs as per our Genetic Make up.

> >

> > The era of amplichip is today.

> >

> > Tomorrow it will be the time for " GENECHIP " or we can call it

the " GENECARD " .

> >

> > Very personal, very unique to each one.

> >

> > And hence the most rational tool for therapy…leading to the most

rational way of therapy..

> >

> > I would like to thank the contributors of discussion who had

done valuable inputs to our discussion " The Role of PGNX in RUM " .

> >

> > Dr Swapnil for providing us the

> >

> > definition of RUM that is given by WHO as, " Patients receive

medications appropriate to their clinical needs, in doses that meet

their OWN INDIVIDUAL REQUIREMENTS, for adequate period of time, and

at the lowest cost to them and their community. "

> >

> > Dr Mangesh for giving us very comprehensive view on

Pharmacogenomics as follows,

> >

> > " According to a famous ancient quote " what is medicine to some

may be the fierce poison to others. " The same drug and in the same

dosage may produce beneficial effects in many patients but can

produce adverse effects in few. We already have data regarding the

number of hospital admissions and deaths due to adverse drug

reactions. We also know that the most important factor for such

variable response to medicines is the genetic differences between

the individuals.

> > Pharmacogenomics is the new field that is bridging the gap

between pharmacology, drug treatment and the patients.

Pharmacogenomics associates individual's genetic make up with drug

metabolism and treatment response. It takes into consideration all

the causes of differences in the drug response which includes genes

controlling the drug metabolizing enzymes, transporter proteins,

signaling and cellular response pathways and cellular targets.

Pharmacogenomcis holds the promise to use the current drugs more

rationally, finding of the new drug targets, and development of new

drugs. Now, how the knowledge of the molecular action of drug and

genetic determinants of the drug response is to going to achieve the

goal of giving the right drug at the right dose to the right patient

and at the right time (RUM)?

> > By looking at the genetic profile of the patients, the genes

responding to a given drug by over-expression, down-regulation or no

response at all can be easily identified. So by this we can tell

which are the genes involved in the drug response and expected side

effects of the drug.

> > Treatment strategies based on the population's genetic profiles

can be developed so that we can predict which are responders, non-

responders and poor responders, also the patients who are prone to

side effects. In conclusion, pharmacogenomics will be very helpful

for the RUM:

> > By looking at the genetic profile, best drug for the patient can

be selected.

> > Dosage adjustment can be made according to person's genetics so

avoiding the risk of adverse effects.

> > Early selection of the optimal therapy will definitely increase

the patient's compliance to therapy. "

> >

> > And also about the ethical aspects in PGNX as follows,

> > Though the development of personalized medicine is

scientifically and clinically seems very useful to mankind, there

are few ethical concerns:

> > The pharmacogenomic data of the population may be utilized for

the exclusion of the patients which are either adverse drug reaction

prone or not responding to research medicine, thus neglecting these

patients from the clinical trial.

> > As vast amount of the pharmacogenomic data will be available,

maintenance of the confidentiality of it will be the most

challenging task. Genetic profile of the patient will disclose the

disease predisposition of that person, family members or entire

ethnic group and abuse of such data can harm patient as well as

entire population.

> > Also, if the patient's profile discloses any rare genetic

disorder for which no treatment is available, then that may be the

worst scenario for the patient.

> >

> > Further I would like to mention the contribution of Dr. S. Ziaur

Rahman regarding

> >

> > 1. Pharmacogenetics is generally regarded as the study of

genetic variation that gives rise to differing response to drugs,

while pharmacogenomics is the broader application of genomic

technologies to new drug discovery and further characterization of

older drugs.

> >

> > 2. History as In the early 1950s, two interesting findings –

prolonged muscle relaxation after curarization with suxamethonium in

patients with congenital cholinesterase deficiency and acute

hemolysis induced by antimalarial drugs (like primaquine) in

patients with low G-6 PD activity set the stage for new

developments. By the end of 1980s and 1990s, the causal genes coding

for debrisoquine hydroxylase, or CYP2D6 had been cloned and

characterized, inaugurating a new field of Pharmacogenetics and

Pharmacogenomic

> >

> > 3. the role of PGNX in RUM would greatly enhance our approach to

unanticipated drug toxicity and would narrow the risk/benefit margin

of drug therapy. Such an integrative strategy is a key element

directed towards the promotion of optimal drug therapy. The concept

of PGNX is not only a rational (RUM) but also profitable during drug

discovery process (can earn 5 billion USD/year). The risk like 1 out

of 10 pass clinical trials to market and 1 out of 20 recover

development costs may maximally be minimized.

> > Researches in this direction are being done in many places of

clinical pharmacology. I know few scientists who are involved

directly in this field such as Dr. Gaidgek (of USA who first

time worked in gene deletion that explains slow metabolism),

Professor Leif Bertilsson (of Clinical Pharmacology Dept, Karolinska

Inst, Huddinge University Hospital, Sweden), Dr. Collen Masimirembwa

(He has now started his own lab in Nairobi, Kenya. Earlier he was in

AstraZeneca) , Professor Olavi Pelkonen (of Dept of Pharmacology and

Toxicology, University of Oulu).

> > With the passage of time, we may take the advantage of this

novel drug targeted PGNX; if not now, then our successors will

definitely devour its fruits. PGNX as a part of RUM will improve

human health. It will be helpful in both infectious diseases and

noninfectious diseases, microbial drug resistance, where there is

treatment failure, and in non-responders (30-60% of patients do not

respond to treatment by available drugs). It will also help in drug

intellectual property.

> >

> > Dr. Shilpa Jadav

> >

> > For providing an important article on

> > The concept of personal drugs in the undergraduate pharmacology

practical curriculum. Indian J Pharmacol 2007;39:165- 7

> >

> > Dr Surendiran for enlightening us regarding funding agencies as

> >

> > There are enough agencies to fund research projects on genomics,

which are remaining unutilized. These depot of resources like DBT,

DST, ICMR, CEFIPRA etc are to be utilized by various institutions

all over the country and set up pharmacogenetic labs with personnel.

This has a long way to go, with the current rate of progress in

research.

> >

> > Dr. Buch

> >

> > For adding the link of following article from NEJM As

> >

> > http://content. nejm.org/ cgi/content/ full/358/ 2/105?query= TOC

> >

> > Volume 358:105-107 January 10, 2008 Number 2

> > Letting the Genome out of the Bottle — Will We Get Our Wish?

> >

> > And lastly, the group owner Dr Vijay Thawani for giving me the

apportunity to moderate on this forum.

> >

> > Thanks to all readers too.

> >

> > Regards,

> > Dr Kiran Chaudhari

> > Lecturer, Pharmacology,

> > GMC, Nagpur.

> >

> >

> >

> > ---------------------------------

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> >

>

>

>

>

>

>

> ---------------------------------

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