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UNIT 1: INTRODUCTION
 

Intended Learning Outcomes

a. Discuss the scope of drug development including screening through
ethnographic research in relevant databases
b. Relate the basic biology of disease in generating hypothesis in the design,
development and testing potential new therapies in the laboratory
 
Introduction
Drug discovery can be described as the process of identifying chemical entities that have
the potential to become therapeutic agents. This module discusses the basic knowledge that
the students need to understand on issues and topics on drug discovery and development.
A key goal of drug discovery is the recognition of new molecular entities that may be of
value in the treatment of diseases that qualify as presenting unmet medical needs. The
importance of drug discovery is vital due to the arising modern and diverse development
of diseases in and out of the body.
Drug development comprises all the activities involved in transforming a compound from
drug candidate to a product approved for marketing by the appropriate regulatory
authorities. It is the process of bringing a new drug molecule into clinical practice. In its
broadest definition this encompasses all steps from the basic process of finding suitable
molecular target to supporting the commercial launch of the drug.

 
Drug Discovery and Development
Drug  a chemical substance of known structure, other than a nutrient or an essential
dietary ingredient, which, when administered to a living organism, produces a biological
effect.
Discovery phase  is the identification of a new chemical entity as a potential therapeutic
agent.
Development phase  the compound is tested for safety and efficacy for one or more
clinical indications, and in suitable formulations and dosage form.
In the past, drugs were discovered as natural products and used as such. Now, drugs are
sculpted and brought into being by pharmacologists in air conditioned laboratories.
New Drug Definition (CDSCO)
According to Rule 122 E:

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(a) A new substance of chemical, biological or biotechnological origin; in bulk or prepared

dosage form; used for prevention, diagnosis, or treatment of disease in man or animal;
which, except during local clinical trials, has not been used in the country to any significant
extent; and which, except during local clinical trials, has not been recognized in the country
as effective and safe for the proposed claim.
(b) A drug already approved by the licensing authority, which is now proposed to be
marketed with modified or new indications, dosage forms (including SR dosage form) and
route of administration.
(c) A fixed dose combination of two or more drugs, individually approved earlier, and now
proposed to be combined for the first time in a fixed ratio, or of the ratio of ingredients in
an already marketed combination is proposed to be changed, with certain claims, viz.
indications, dosage form (including SR dosage form) and route of administration.

Stages of the New Drug Synthesis:

 Drug discovery: candidate molecules are chosen on the basis of their

pharmacological properties
 Preclinical development: non-human studies (e.g. toxicity testing, pharmacokinetic
analysis and formulation) are performed
 Clinical development: the selected compound is tested for efficacy, side effects and
potential dangers in volunteers and patients

Figure source: nebiolab.com, 2020

Ethnopharmacology and Natural Product Research

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Ethnopharmacology has already re-emerged as an innovative approach for drug discovery.

Ethnopharmacology  the study of the chemistry and physiologic actions of (primarily plant)
medicines used by native populations.
Ethno = denotes cultural group
Pharmacology = the science of drug sources, activities, and uses
Natural product – anything that is produced by life, and includes biotic material or any
organic compound synthesized by a living organism.
Natural products have high structural diversity and unique pharmacological or biological
activities due to the natural selection and evolutionary processes that have shaped their
utility over hundreds of thousands of years. Thus, natural products have been utilized in
both traditional and modern medicine for treating diseases. Currently, natural products are
often used as a starting points for drug discovery followed by synthetic modifications to
help reduce side effects and increase bioavailability.

Biology of the Disease (Ahmed, Dawson, Smith, Wood 2007)

Biology of Disease is concerned with the scientific study of disease, and is one of the
foundations of medical science and practice. It encompasses all aspects of disease, including
knowledge of the causes and effects of disease, and the organism's response to disease. The
cause of a disease is often an injurious agent, but defects and deficiencies may also cause
disease. Knowledge of how an organism responds to disease is important, as sometimes
disease may arise as a result of an innate response of the organism to injury or infection. 
Disease can be defined as any abnormality or failure of the body to function properly and
this may require medical treatment. Every disease has a distinct set of features that include
a cause, associated clinical symptoms and a characteristic progression, with associated
morphological and functional changes in the patient.

Characteristic Features of Diseases

Every disease has a number of characteristic features. These features allow diseases to be
categorized and allow a better understanding of the disease, its diagnosis and management.
A correct diagnosis should mean that appropriate treatment is given.
Etiology
Etiology refers to the cause of a disease. Etiological agents can be endogenous, in other
words originating from within the body, or exogenous, coming from outside the body.
Endogenous agents include genetic defects and endocrine disorders, while exogenous

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agents include microorganisms such as viruses, bacteria and fungi that cause infections,
chemicals, physical trauma and radiation. Many diseases are said to be predictable and
arise as a direct consequence of exposure to the causative agent. Other diseases are
considered probable in that they may be a consequence of the causative agent but the
development of illness is not inevitable. An individual can be infected with a pathogenic
microorganism but the outcome of the disease may depend on other factors such as the
nutritional and immune status of the affected person. Some diseases have more than one
etiological agent and may, indeed, be caused by a range of factors. Such diseases are said to
be multifactorial in origin. Many diseases are of unknown cause and are said to be
idiopathic. An example of this is hypertension, where more than 90% of cases are of
unknown cause. The treatment of idiopathic diseases is restricted to alleviating the
symptoms. Some conditions are caused by the effects of treatment and are called iatrogenic
diseases (from the Greek word iatros, doctor). Predisposing factors are conditions or
situations that make an individual more susceptible to disease. They include age, sex,
heredity and environmental factors. For example, the immune system in a newborn is not
fully developed and, as a consequence, babies are more susceptible to infections. However,
during aging the immune system undergoes a progressive decline in function making the
elderly also more susceptible to infections. Sex may also be a predisposing factor: men are
more likely to suffer from gout than women whereas osteoporosis is more common in the
latter.

Pathogenesis
Every disease has a pathogenesis that describes the development of the disease or, more
specifically, how the etiological agent(s) acts to produce the clinical and pathological
changes characteristic of that disease. Some examples of how diseases undergo
pathogenesis include inflammatory reactions in response to harmful agents and
carcinogenesis where the formation of tumors occurs as a result of exposure to carcinogens
(cancerinducing substances). Diseases have ‘natural histories’ that describe the typical
patterns of how each disease usually progresses, its effects and its duration. The effects of
the disease on the patient are referred to as morbidity.
Manifestations of Diseases
The etiology of a disease and its pathogenesis produce clinical manifestations that include
signs and symptoms of the disease. A symptom is an indication that a disease is present
and something of which the patient complains, for example, nausea, malaise or pain. A
sign is something that the clinician specifically looks or feels for, such as redness or
swelling of the skin, when examining the patient.

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Outcome of a Disease
The prognosis of a disease is its likely outcome. Prognoses can vary considerably between
different diseases and, of course, can be influenced by treatment. Hence when giving a
prognosis, it is necessary to clarify if the disease is following its natural course or whether
there is, or needs to be, medical or surgical intervention. A viral disease such as German
measles (rubella) will normally resolve of its own accord, whereas a broken leg or a heart
attack needs treatment. With some diseases, especially some cancers, patients may go
through a period of good health with a reduction or disappearance of the symptoms and
the disease is said to be in remission. However, a relapse may occur with a return of the
disease symptoms following this period of apparent recovery.

CLASSIFICATION OF DISEASES
Some diseases share common features and can be grouped together in a classification
system. One way of classifying diseases is on the basis of their cause. This is by no means
perfect as some diseases have multiple causes and there is likely to be an overlap between
the different categories. Infectious diseases are caused when microorganisms such as
viruses, bacteria, fungi, protozoa and helminths enter and spread within the body.
Immunological diseases occur in circumstances in which the immune system can cause
damage to the body’s own tissues. In autoimmune conditions, for example autoimmune
thyroiditis, antibodies are produced that attack the body’s own tissues. Alternatively, there
are diseases associated with immunodeficiency that increase the susceptibility of the
patient to infectious agents. Endocrine diseases arise from the over- or underproduction of
hormones or from resistance to a particular hormone perhaps because the cellular receptor
is absent as the result of a mutation. Homeostatic diseases arise when mechanisms for
controlling homeostasis are disrupted. Nutritional diseases result from an inadequate
intake of nutrients, such as proteins (which supply essential amino acids), carbohydrates,
essential fatty acids, vitamins or trace elements. Toxic diseases are caused by the ingestion
of a variety of poisons that may be encountered in the environment. Ingestion may be
accidental or deliberate. Genetic diseases arise due to defects in the genes or chromosomes
of individuals. Congenital diseases are present at birth and may or may not have been
inherited. They may arise due to a developmental defect of known or unknown cause.
Thus, a newborn may suffer from fetal alcohol syndrome, a congenital condition arising as
a consequence of excessive alcohol intake by the mother during pregnancy. Neoplastic
diseases are characterized by the uncontrolled and abnormal growth of cells. Traumatic
diseases are caused by physical injury and include mechanical trauma, extremes of heat or
cold, electrical shock and radiation. Apart from the obvious problems caused by extensive
damage to tissues, traumatic diseases may render an individual more prone to infection by
compromising the immune system. Degenerative diseases involve the progressive loss of

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body tissues and impairment of their functions usually associated with aging. Psychogenic
diseases originate in the mind. They may have a significant psychological or emotional
component as seen, for example, in schizophrenia. Iatrogenic diseases arise as a
consequence of treatment. For example, patients who are receiving drugs, such as thiazide
diuretics to control their blood pressure, may suffer from low serum K+ caused by an
excessive renal loss. Finally, idiopathic diseases are those of unknown cause.

Assessment
In a one whole sheet of yellow paper, write your name, subject, and the name of your
Instructor and answer the following questions.
1. List down and explain some reasons why there is a need to discover and develop
drug.
2. Make a diagram of the complete process of drug discovery and development. (drug
candidate to market)
3. Make a table on the classification of diseases and give at least 5 examples of each and
the treatment regimen of each diseases.
Note: You have 3 weeks to finish your output. Submit your outputs on your respective
municipality coordinators upon delivery of the next LPs. Failure to follow the given
schedule may affect your performance for this subject. For more query, you may contact
this number 09173073682.
 
References

Drug discovery and development in http://innovation.org

(http://cmidd.northwestern.edu/files/2015/10/Drug_RD_Brochure-12e7vs6.pdf)
Doogue, M. P., & Polasek, T. M. The ABCD of clinical pharmacokinetics
FDA Circular No. 2012-007 - Recognition of Ethical Review Board/Committee (ERB/ERC)
For Purposes of the
Conduct of Clinical Trials on Investigational Medicinal Products in the Philippines
and for Other Purposes
Benjamin Blass. Basic Principles of Drug Discovery and Development, Elsevier
Raymond Hill, Drug Discovery and Development, ISBN: 978-0-7020-4299-7
Jayaram, P., & Bhushan, K. (2000). Bioinformatics for better tomorrow. Indian Institute of
Technology, Hauz Khas, New Delhi.

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K. Roy et al., A Primer on QSAR/QSPR Modeling. SpringerBriefs in Molecular Science,

DOI 10.1007/978-3-319-17281-1_2
The clinical trial of the future. PharmaTimes magazine- October 2016.
http://www.pharmatimes.com/magazine/2016/october/the_clinical_trial_of_the_future
A precision medicine approach to clinical trials. http://scipol.duke.edu/content/precision-
medicine-approach-clinical-trials

 
Acknowledgment
 
The images, tables, figures and information contained in this module were
taken from the references cited above.

DISCLAIMER

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C. M. D. Hamo-ay