Introduction
With the information available about human genome and human proteome, it is now well understood that there are a lot of variations between individuals. These minor variations account for many differences like adverse drug reactions, which are responsible for many hospitalizations and casualties. The observed variable effect of drug is due to difference in sensitivity as some people need higher dose and some need lower dose to get similar therapeutic effect, but in some people drug has no therapeutic effects and in some it shows strong adverse reactions.
Call Now ☎ 9999965857 !! Call Girls in Hauz Khas Escort Service Delhi N.C.R.
Pharmacogenomics, Pharmacogenetics and Pharmacokinetics
1. Pharmacogenomics, Pharmacogenetics and Pharmacokinetics
Introduction
With the information available about human genome and human proteome, it is now well
understood that there are a lot of variations between individuals. These minor variations account
for many differences like adverse drug reactions, which are responsible for many hospitalizations
and casualties. The observed variable effect of drug is due to difference in sensitivity as some
people need higher dose and some need lower dose to get simil
people drug has no therapeutic effects and in some it
Figure 1: The figure shows the variable effect of the same drug on different individuals
suffering from the same disorder
Pharmacogenomics, Pharmacogenetics and Pharmacokinetics
With the information available about human genome and human proteome, it is now well
understood that there are a lot of variations between individuals. These minor variations account
for many differences like adverse drug reactions, which are responsible for many hospitalizations
and casualties. The observed variable effect of drug is due to difference in sensitivity as some
people need higher dose and some need lower dose to get similar therapeutic effect, but in some
people drug has no therapeutic effects and in some it shows strong adverse reactions.
The figure shows the variable effect of the same drug on different individuals
suffering from the same disorder
1
With the information available about human genome and human proteome, it is now well
understood that there are a lot of variations between individuals. These minor variations account
for many differences like adverse drug reactions, which are responsible for many hospitalizations
and casualties. The observed variable effect of drug is due to difference in sensitivity as some
ar therapeutic effect, but in some
shows strong adverse reactions.
The figure shows the variable effect of the same drug on different individuals
2. Some of these effects are due to environmental causes, the individual’s ability to absorb or
metabolize a drug may be altered, or multiple drug interaction can occur (in people taking
multiple drugs). Pharmacogenetics is th
whereas
Pharmacogenomics
Pharmacogenomics is the study of how an individual’s genetic makeup affects the body’s
response to drugs. Pharmacogenomics or personalized medicine or a recen
medicine is helping to device stra
biotechnology and medical institute
treatment of the patient with the correct dose of the suitable medicine which is based u
genes of the individual. With the expanded knowledge of the molecular basis of cance
known that significant differences in gene expression patterns can guide therapy for a variety of
solid tumors and hematologic malignant neoplasms.
Figure 2: The figure shows advantages of pharmacogenomics studies which lead to complete
benefit of the drug to the patients
ese effects are due to environmental causes, the individual’s ability to absorb or
metabolize a drug may be altered, or multiple drug interaction can occur (in people taking
multiple drugs). Pharmacogenetics is the study of the roles of specific genes in t
Pharmacogenomics is the study of how an individual’s genetic makeup affects the body’s
Pharmacogenomics or personalized medicine or a recent term given precision
is helping to device strategies for the coming generation pharmaceutical companies,
biotechnology and medical institutes, and academic medical centers. The primary aim is the
treatment of the patient with the correct dose of the suitable medicine which is based u
With the expanded knowledge of the molecular basis of cance
cant differences in gene expression patterns can guide therapy for a variety of
solid tumors and hematologic malignant neoplasms.
figure shows advantages of pharmacogenomics studies which lead to complete
benefit of the drug to the patients
2
ese effects are due to environmental causes, the individual’s ability to absorb or
metabolize a drug may be altered, or multiple drug interaction can occur (in people taking
c genes in these effects,
Pharmacogenomics is the study of how an individual’s genetic makeup affects the body’s
t term given precision
tegies for the coming generation pharmaceutical companies,
The primary aim is the
treatment of the patient with the correct dose of the suitable medicine which is based upon the
With the expanded knowledge of the molecular basis of cancer, it is now
cant differences in gene expression patterns can guide therapy for a variety of
figure shows advantages of pharmacogenomics studies which lead to complete
3. It is assumed that variability to drug responsiveness (effi
maintenance dose) is due to individuals’ own gene
Figure 3: The figure shows that all these individuals are suffering from the same disease; thus,
they were given similar drug with the similar dose. Drug response is variable due to genetic or
environmental factors; however, individuals in green were responders with best effects of drug,
and individuals in yellow were responsive for the drug, but drug had some adverse side effects in
them; thus, they require lower dose; individuals in blue had no effect, no ADRs, but
responsiveness, disease might become
did not got any benefit from the drug but suffered from serious ADRs requiring hospitalization
or sometimes drug might be fatal
more than 1 lakh deaths worldwide.
These days, genome-wide association studies (GWAS) are quiet beneficial for survey of the
entire genome for association with drug response phenotype.
ty to drug responsiveness (efficacy, adverse effects, toxicity,
individuals’ own genetic makeup and becomes very serious
The figure shows that all these individuals are suffering from the same disease; thus,
they were given similar drug with the similar dose. Drug response is variable due to genetic or
however, individuals in green were responders with best effects of drug,
and individuals in yellow were responsive for the drug, but drug had some adverse side effects in
them; thus, they require lower dose; individuals in blue had no effect, no ADRs, but
, disease might become problematical and difficult to control; individual
t from the drug but suffered from serious ADRs requiring hospitalization
or sometimes drug might be fatal where it is responsible for many admissions in the hospital and
more than 1 lakh deaths worldwide.
wide association studies (GWAS) are quiet beneficial for survey of the
on with drug response phenotype. The results for the studies a
3
cacy, adverse effects, toxicity, and
and becomes very serious.
The figure shows that all these individuals are suffering from the same disease; thus,
they were given similar drug with the similar dose. Drug response is variable due to genetic or
however, individuals in green were responders with best effects of drug,
and individuals in yellow were responsive for the drug, but drug had some adverse side effects in
them; thus, they require lower dose; individuals in blue had no effect, no ADRs, but due to no
cult to control; individuals in red
t from the drug but suffered from serious ADRs requiring hospitalization
e for many admissions in the hospital and
wide association studies (GWAS) are quiet beneficial for survey of the
The results for the studies are
4. 4
highly encouraging that once genetic association or association of genes are identified for a
particular side effects or adverse effects with a specific drug, the results are immediately helpful
for the practitioner. These studies also help to evaluate the dose of the drug, depending upon the
metabolizationcapabilities of the individuals. Another issue pertaining to the need of research in
pharmacogenomics is that the effect size for many genetic associations identified to date for
pharmacogenomic traits is larger than that of complex diseases. This stronger effect has helped
in the identification of pharmacogenomic association with a small size of the samples where
association of complex traits requires very large sample size. It is quite well known that drug
response is complex phenotype, which is affected by genetic factors (through regulation of drug
metabolizing enzymes) as well as dosage, diet, age, lifestyle, health condition, environmental
status, and socioeconomic condition. The studies have been extremely helpful for some of the
drug. The drug administered can be pro-drug, which requires conversion to active component, or
the drug which itself mediates effects and afterward it is detoxified and secreted. In some of the
drugs which are well characterized with their mechanism of action known, the studies are simple
where their potential targets are genotyped, whereas drug with unknown mechanism of action
requires complex and many studies to reach to a meaningful conclusion.
Pharmacogenetics
The study of single genetic variant with analysis on responders and nonresponders to the drug or
having adverse side effects of the drug (drug toxicity) is the pharmacogenetics. The relationship
between genetic defect and abnormal drug response was termed as pharmacogenetics by Vogel
in 1959. The response of an individual to a drug differs as it depends upon the genetic and
nongenetic factors. These factors may be variations in the target of the drug, genes responsible
for the disease, the enzymes that metabolize the drug, and finally clearance of the drug. All these
5. 5
factors may predict the efficacy or toxicity of the drug. Now nearly millions of genetic markers
of single nucleotide polymorphism (SNP) type are available for genotyping and phenotyping
studies. Their usage can generate clinically useful data, as it can predict the response of an
individual because of the presence or absence of a particular genetic variant. In 1999 a
consortium to discover human SNPs was formed. Probably high-resolution SNP map would help
in the identification of genes for complex diseases such as asthma, diabetes mellitus,
atherosclerosis, and psychiatric disorders. SNP technology has been in use in oncology where the
efforts for the detection and predisposition for cancer and predicting toxic responses to drugs and
selecting the best individual and combination anticancer drugs may be very useful.
Pharmacokinetics
Pharmacokinetics refers to what the body does to a drug, whereas pharmacodynamicsdescribes
what the drug does to the body. Once administered through one of several available routes, four
pharmacokinetic properties determine the speed of onset of drug action, the intensity of the
drug’s effect, and the duration of drug action
1. Absorption: First, drug absorption from the site of administration permits entry of the
therapeutic agent (either directly or indirectly) into plasma
2. Distribution: Second, the drug may then reversibly leave the bloodstream and distribute into
the interstitial and intra cellular fluids
3. Metabolism: Third, the drug may be biotransformed by metabolism by the liver, or other
tissues
4. Elimination: Finally, the drug and its metabolites are eliminated from the body in urine, bile,
or feces.
6. Pharmacokinetic parameters allow the clinician to design and optimize
including decisions as to the route of administration for a specificdrug, the amount and frequency
of each dose, and the duration of treatment.
Figure 4: Schematic representation of drug absorption, distribution, metabolism, and
elimination.
Pharmacokinetic parameters allow the clinician to design and optimize treatment regimens,
including decisions as to the route of administration for a specificdrug, the amount and frequency
of each dose, and the duration of treatment.
Schematic representation of drug absorption, distribution, metabolism, and
6
treatment regimens,
including decisions as to the route of administration for a specificdrug, the amount and frequency
Schematic representation of drug absorption, distribution, metabolism, and