C ollege of

N ursing
OVERVIEW OF DRUG
P harmacy & DISCOVERY
A llied
H ealth
S ciences
Gemrose Contiveros, RPh
 The Main Stages in Drug Discovery
Department of Pharmacy

• EARLY DRUG DISCOVERY

• PRECLINICAL RESEARCH
• CLINICAL DRUG DEVELOPMENT PROCESS
• REGULATORY APPROVAL
• OTHER IMPORTANT STEPS
• INVESTIGATIONAL NEW DRUG IND APPLICATION
• TOXICITY TESTING
• LEAD IDENTIFICATION AND OPTIMIZATION
• MAIN MOLECULE OPTIMIZATION
Department of Pharmacy

• EARLY DRUG DISCOVERY

- Finding drug targets
- Drug discovery research involves finding new medications. Initially, this
process relied on identifying active ingredients from traditional remedies or
by chance. Later, chemical libraries of small molecules, natural products,
and plant extracts were tested for therapeutic effects through classical
pharmacology. With the sequencing of human DNA, reverse pharmacology
now helps identify treatments for existing diseases through modern testing
methods.
- Today the steps in drug discovery and development involve screening hits,
iterative medicinal chemistry, and optimization of hits to reduce potential
drug side effects (increasing affinity and selectivity). Efficacy or potency,
metabolic stability (half-life), and oral bioavailability are also improved in
these steps of the drug development process.
Department of Pharmacy

• STEPS IN EARLY DISCOVERY

- Target Identification And Validation: Target identification finds a
gene or protein (therapeutic agent) that plays a significant role in
disease.
- Hit Discovery Process: identifying "hit" compounds that interact
effectively with a specific biological target, such as a protein or
enzyme linked to a disease. These hit compounds show initial
promise in modulating the target’s activity and can serve as starting
points for further drug development.
- Assay Development And Screening: evaluate the effects of the new
drug candidate at the cellular, molecular, and biochemical levels.
Department of Pharmacy

- High Throughput Screening: drug discovery method used to rapidly

test thousands to millions of chemical compounds for their potential
interactions with a biological target, such as a protein, enzyme, or
cell receptor associated with a disease.
- Hit To Lead:a stage in drug discovery that involves optimizing initial
"hit" compounds identified in high-throughput screening (HTS) into
"lead" compounds. Leads are chemically refined versions of hits with
improved therapeutic properties that make them more suitable for
further drug development.
- Lead Optimization: the lead compounds discovered in the H2L
process are synthesized and modified to improve potency and reduce
side effects. Lead optimization conducts experimental testing using
animal efficacy models and ADMET tools, designing the drug
candidate
Department of Pharmacy

- Active Pharmaceutical Ingredients: are biologically active

ingredients in a drug candidate that produce desired effects. High
Potency Active Pharmaceutical Ingredients (HP APIs) are
molecules that are effective at much smaller dosage levels than
standard APIs. They are classified based on toxicity,
pharmacological potency, and occupational exposure limits
(OELs), and used in complex drug development involving more
than ten steps.
Department of Pharmacy

• PRECLINICAL RESEARCH: Once a lead compound is found,

preclinical phase of drug development begins with in vivo
research to determine the efficacy and safety of the drug.
Researchers determine the following about the drug:
❑ Absorption, distribution, metabolization, and excretion information
❑ Potential benefits and mechanisms of action
❑ Best dosage, and administration route
❑ Side effects/adverse events
❑ Effects on gender, race, or ethnicity groups
❑ Interaction with other treatments
❑ Effectiveness compared to similar drugs
Department of Pharmacy

- Absorption, Distribution, Disposition, Metabolism, & Excretion: a

Pharmacokinetic (PK) process of measuring the ways the new drug
affects the body.
- Proof Of Principle / Proof Of Concept:
Proof of Concept establishes that the basic idea behind a treatment
strategy works in a real-world setting. In drug development, PoC
studies typically involve: Testing in Animal Models or Cell Cultures and
Limited Human Testing Phase I and II
Proof of Principle is a step further, providing initial evidence that the
drug not only works as expected but also produces a meaningful
therapeutic outcome. In this phase: more comprehensive studies and
focus on mechanism of action.
Department of Pharmacy

- In Vivo, In Vitro, And Ex Vivo Assays:In vivo, preclinical research

examples are the development of new drugs using mice, rat, and dog
models. In vitro is research conducted in a laboratory. Ex vivo uses
animal cells or tissues from a non-living animal
- In Silico Assays: are test systems or biological experiments
performed on a computer or via computer simulation.
- Drug Delivery: New drug delivery methods include oral, topical,
membrane, intravenous, and inhalation. Drug delivery systems are
used for targeted delivery or controlled release of new drugs.
Physiological barriers in animal or human bodies may prevent drugs
from reaching the targeted area or releasing when they should. The
goal is to prevent the drug from interacting with healthy tissues
while still being effective.
Department of Pharmacy

- Formulation Optimization & Improving Bioavailability: focused

on refining the drug’s form and how it is absorbed in the body to
ensure maximum therapeutic effect and safety.
FORMULATION OPTIMIZATION IMPROVING BIOAVAILABILITY

ENHANCING STABILITY ENHANCING SOLUBILITY

IMPROVING SOLUBILITY AND DISSOLUTION RATE BYPASSING FIRST-PASS METABOLISM

CONTROLLED RELEASE USE OF PERMEATION ENHANCERS

PATIENT CONVENIENCE AND COMPLIACE ENCAPSULATION TECHNIQUES

Department of Pharmacy

• CLINICAL DRUG DEVELOPMENT PROCESS

- Complexity Of Study Design, Associated Cost &
Implementation Issues: The complexity, cost, and
implementation challenges of clinical trial design can impact
trials. Trials must ensure safety, efficacy, and adherence to the
development budget, with a methodology confirming the drug’s
effectiveness for its intended use. Proper setup and a large
volunteer enrollment are essential for success.
Department of Pharmacy

- Phase I (Healthy Volunteer Study) This phase is the first time

the drug is tested on humans; less than 100 volunteers will help
researchers assess the safety and pharmacokinetics, absorption,
metabolic, and elimination effects on the body, as well as any
side effects for safe dosage ranges.
- Phase II and III (Studies in patient population)
Phase II assesses drug safety and efficacy in an additional
100-500 patients, who may receive a placebo or standard drug
previously used as treatment.
Phase III enrolls 1,000-5,000 patients, enabling medication
labeling and instructions for proper drug use.
Department of Pharmacy

- Biological Samples Collection, Storage & Shipment

- Pharmacodynamic (PD) Biomarkers: are measurable indicators
that provide information about a drug's biological effects on a
patient, revealing how the drug interacts with its target and
affects disease processes. Examples: blood pressure, glucose
size, tumor size
- Pharmacokinetic Analysis: is an experimental trial that
determines the theory of how a new drug behaves in the
human body. The volume of distribution, clearance, and
terminal half-life are defined through compartmental modeling.
Department of Pharmacy

- Bioanalytical Method Development And Validation: focuses on

creating and confirming analytical techniques to measure drug
concentrations and their metabolites in biological samples. Key steps
are method development: analytical techniques, method validation:
specificity-sensitivity-accuracy-precision-linearity-stability,
- Drug (Analyte) & Metabolite Stability In Biological Samples: making
sure metabolites are stable and not degraded which can affect the
integrity of the study
- Blood, Plasma, Urine & Feces Sample Analysis For Drug And
Metabolites
- Patient Protection – GCP, HIPAA, & Adverse Event Reporting
Department of Pharmacy

• REGULATORY APPROVAL (FDA): Once the new drug has been

formulated for its best efficacy and safety, and the results from
clinical trials are available, it’s advanced forward for wholistic FDA
review. At this time, the FDA reviews and approves, or does not
approve, the drug application submitted by the drug development
company.
- Regulatory approval timeline: approval timeline may be up to an
year.
- IND application (investigational new drugs): are submitted to the
FDA before starting clinical trials. If clinical trials are ready to be
conducted, and the FDA has not responded negatively about the
drug, developers may start the trials.
Department of Pharmacy

- NDA / ANDA / BLA Applications: submitted to the FDA after clinical trials
demonstrate drug safety and efficacy.
- Orphan Drug: a pharmaceutical agent developed specifically to treat rare
medical conditions, often referred to as orphan diseases. These diseases
typically affect a small percentage of the population, which makes
developing treatments less commercially viable for pharmaceutical
companies without additional incentives.
- Cystic Fibrosis: ivacaftor (Kalydeco), lumacaftor/ivacaftor (orkambi)
- Huntington’s: tetrabenazine (Xenazine)
- Gaucher: imiglucerase – Cerezyme
-Accelerated Approval: New drugs may be granted accelerated approval if
there is strong evidence of positive impact on a surrogate endpoint instead
of evidence of impact on actual clinical benefits the drug provides.
Expedition of approval means the medication can help treat severe or
life-threatening conditions.
Department of Pharmacy

- Reasons for Drug Failure

• Toxicity
• Efficacy
• PK Properties or Bioavailability
• Inadequate Drug Performance
Department of Pharmacy

• POST-MARKET MONITORING: Following drug approval and manufacturing, the FDA

requires drug companies to monitor the safety of its drug using the FDA Adverse Event
Reporting System (FAERS) database
• OTHER RELEVANT DRUG DEVELOPMENT CONCEPTS
- Drug Master File: a submission to the FDA used to provide confidential, detailed
information about facilities, processes, or articles used in the manufacturing, processing,
packaging, and storing of a human drug.
- Drug for pediatric use
- Drug for veterinary use
- Small molecule vs biologics
- Process scale-up differences and difficulties: Drug development involves generating
progressively larger medicine batch sizes, and changes in processes for different-sized
batches may cause unexpected difficulties. Use of the right pharmaceutical equipment can
be helpful, as well as the discovery of parameters that affect critical process parameters
(CPPs).
 ETHNOPHARMACOL
OGY AND NATURAL
C ollege of PRODUCT
N ursing
P harmacy & RESEARCH
A llied
H ealth
S ciences
 Ethnobotany
Department of Pharmacy

• Ethnobotany is the study of the relationships between people

and plants, focusing on how different cultures use plants for
various purposes, including food, medicine, rituals, and other
cultural practices.
• This interdisciplinary field combines aspects of botany,
anthropology, ecology, and pharmacology to understand the
cultural significance and practical applications of plant species.
 Key aspects of ethnobotany
Department of Pharmacy

• Cultural practices: societies utilize plants in their daily lives, rituals, and
traditions, providing insight into cultural identity and heritage
• Medicinal use: study traditional medicine practices to identify plants with
potential therapeutic properties, contributing to drug discovery and
pharmacological research
• Food and nutrition: role of plants in local diets, including the cultivation,
preparation, and preservation of food, as well as the cultural significance of
specific foods
• Conservation and sustainability: many indigenous cultures possess
knowledge about local ecosystems and sustainable practices that have
been developed over generations
• Ethnopharmacology: This branch of ethnobotany focuses specifically on
the medicinal properties of plants and their use in traditional healing
practices, often leading to the discovery of new pharmaceuticals
Department of Pharmacy

• Traditional Medicine is tapping nature and indigenous

knowledge to advance modern medicine (WHO)
• Sweet Wormwood (Artemisia annua): Malaria
• Willow Bark (Salix spp.): pain relief and anti inflammatory conditions
• Madagascar Periwinkle (Catharanthus roseus): cancer; vinblastine and
vincristine are used for treating cancer
• Hawthorn (Crataegus spp.): Cardiovascular disease and hypertension
• Foxglove (Digitalis purpurea): Heart disease (used to treat various
heart conditions)
• Star Anise (Illicium verum): Influenza (shikimic acid from star anise is
used to manufacture Tamiflu)
Department of Pharmacy

• Wild Mexican Yam (Dioscorea villosa): Used in the formulation of

contraceptive pills (norethindrone)
• Sunlight (for jaundice treatment)
• Variolation (ancient practice for smallpox)
-dates back to ancient practices in Asia and Africa, with evidence of its use
as early as 200 BCE. It was notably practiced in regions such as China, India,
and Persia.
-The practice gained more widespread attention in the early 18th century,
particularly after Lady Mary Wortley Montagu observed it among Turkish
women and introduced it to England. Variolation laid the groundwork for
Edward Jenner's development of the first true smallpox vaccine in 1796, which
used material from cowpox lesions instead of smallpox.
• Yoga and Acupuncture: Chronic pain, particularly non-specific lower back
pain
Department of Pharmacy
Department of Pharmacy

• Study Focus: The research aims to document the medicinal

plants used by the Panay Bukidnon in Lambunao, Iloilo, as little
is known about their ethnobotanical knowledge due to limited
written records and a lack of recent research.
• Methodology: Semi-structured interviews were conducted with
75 key informants over a period from June 2020 to September
2021 to gather information on the therapeutic uses of medicinal
plants in traditional medicine.
Department of Pharmacy

• Findings on Medicinal Plants: A total of 131 medicinal plant

species were identified, belonging to 121 genera and 57
families. These plants were used to treat 91 diseases across 16
different disease categories. The Fabaceae family was the most
represented with 13 species, followed by Lamiaceae (9 species)
and Poaceae (8 species).
DISEASE PLANT
(arrange in alphabetical order)
Department of Pharmacy

• Commonly Used Parts and Preparation Methods

leaf was the most frequently used plant part.
decoction method was the preferred form of preparation for
medicinal use.
• Diseases and Symptoms: respiratory system and injuries,
poisonings, and other external causes
Department of Pharmacy

• Importance of the study

• Cultural Significance
• Dependence on Medicinal Flora
• Key Medicinal Species
• Need for Further Research: The therapeutic efficacy of these key
species requires further pharmacological investigation and validation,
as they have been historically used worldwide to treat various
diseases.
• Novel Therapeutic Uses: Comparative studies with other
ethnobotanical research have revealed novel and additional
therapeutic uses, enriching the traditional knowledge and practices in
the Philippines.
Department of Pharmacy

• Oral Tradition of Knowledge: Indigenous knowledge about medicinal

plants is primarily passed down orally, influenced by cultural and
religious beliefs.
• Urgency for Documentation: There is an urgent need to document this
indigenous knowledge before it is lost due to environmental and social
challenges, including species extinction, climate change,
modernization, and a lack of interest among younger generations.
• Preservation of Cultural Heritage: The results of the study contribute
to preserving cultural heritage, providing ethnopharmacological bases
for future drug research, and promoting biological diversity.
 Ethnopharmacology
Department of Pharmacy

• Ethnopharmacology is at the intersection of the medical,

natural, and social sciences. Despite its interdisciplinary
nature, most ethnopharmacological research has been
based on the combination of the chemical, biological, and
pharmacological sciences.
• It provides insights into potential new drug candidates based on
traditional uses of plants, helping to bridge the gap between
ancient knowledge and modern drug development.
Department of Pharmacy
Historical context of
ethnopharmacology
• Traditional Medicine: Many cultures have utilized plants for
healing long before the advent of modern medicine. These
practices have been documented across various civilizations,
highlighting the importance of ethnobotanical knowledge.
• Contributions to Modern Medicine: Numerous modern drugs
have origins in traditional medicine, such as quinine from
cinchona bark for malaria and morphine from opium poppies
for pain relief
Department of Pharmacy

• ETHNOPHARMACOLOGY’S ROLE IN THE DRUG DISCOVERY

PROCESS:
• provide leads by identifying plants with therapeutic potential
that may target specific diseases based on traditional
applications.
 Mechanisms of Action
Department of Pharmacy

• Active Compounds: Many medicinal plants contain bioactive

compounds that exert pharmacological effects. Understanding
these compounds is crucial in drug development.
• Synergy in Traditional Use: Traditional practices often involve
using whole plants or combinations of plants, which may
enhance efficacy through synergistic effects. This holistic
approach can inform modern pharmacology.
Department of Pharmacy
Methodological Approaches in
Ethnopharmacology
• Field Studies: Ethnopharmacologists often conduct field
studies, engaging with indigenous communities to document
traditional practices and medicinal plant use.
• Laboratory Analyses: After identifying potential plants,
researchers analyze them for active compounds, using
techniques like chromatography and bioassays to validate
traditional claims.
 Challenges and Considerations
Department of Pharmacy

• Ethical Issues: The appropriation of indigenous knowledge

without proper consent or benefit-sharing is a significant
concern in ethnopharmacology. Respecting intellectual property
rights is essential.
• Sustainability: Overharvesting of medicinal plants can threaten
biodiversity. Sustainable practices must be prioritized in drug
discovery to preserve ecological balance.
 Future Directions
Department of Pharmacy

• Integrative Approaches: There is a growing trend to integrate

ethnopharmacological knowledge with modern scientific
methods, enhancing the drug discovery process.
• Personalized Medicine: Understanding the genetic and cultural
factors influencing the efficacy of traditional remedies could
lead to the development of personalized medicine strategies.
 Basic Biology of Disease
C ollege of
N ursing
and Hypothesis Generation
P harmacy & in Drug Discovery
A llied
H ealth
S ciences
 Biology of Disease
Department of Pharmacy

• The biology of disease is the study of how diseases develop in

organisms, including the causes, effects, and the body's response
• Causes: Diseases can be caused by infectious agents like
bacteria, viruses, fungi, and parasites, or by defects in normal
cellular processes
• Effects: Diseases can cause cells to replicate out of control,
organs to fail, and immune systems to be overwhelmed.
• Response: The body can respond to disease in innate or
adaptive ways. For example, people who have been previously
infected with a disease may be immune to it in the future.
Department of Pharmacy

• Understanding the basic biology of disease is essential for

developing targeted therapies that can effectively treat specific
conditions while minimizing side effects.
• BACTERIAL INFECTIONS
• Basic Biology: occur when pathogenic bacteria invade host tissues,
leading to inflammation and tissue damage. Bacteria can produce
toxins, evade the immune system, and form biofilms, complicating
treatment. Common examples include strep throat and pneumonia.
• Targeted Therapies: antibiotics or vaccine development
Department of Pharmacy

• INFLAMMATION
• Basic biology: a natural immune response to injury or
infection characterized by redness, swelling, heat, and pain.
It involves various immune cells, cytokines, and signaling
pathways. While acute inflammation helps heal injuries,
chronic inflammation is linked to diseases like arthritis,
cardiovascular disease, and cancer.
• Targeted therapies: anti inflammatory drugs, biologics
Department of Pharmacy

• CANCER CELL PROLIFERATION

• Basic Biology: results from uncontrolled cell division due to genetic
mutations that disrupt normal cell cycle regulation.
• Targeted therapies: inhibit mutated proteins or disrupted pathways,
immunotherapy

• AUTOIMMUNE DISEASE
• Basic Biology: immune system mistakenly attacks the body’s own
tissues.
• Targeted therapy: immunosuppressant, biologic agents
 Hypothesis generation
Department of Pharmacy

• Hypothesis generation is a key step in the drug discovery

process, where a disease mechanism is created to predict
the relationship between a target molecule and a
disease. A well-formulated hypothesis helps guide the
design and testing of new compounds, and ensures that
resources are focused on the most promising areas of
research
Department of Pharmacy

• Identifying biological targets

-understanding pathophysiology: knowledge of the underlying mechanisms
of diseases allows researchers to identify critical biological targets such as
proteins, genes, or pathways that play a central role in disease progression.
For example, in cancer, mutations in specific oncogenes or tumor suppressor
genes can be targeted for therapy. For example, if a particular enzyme is
found to be overactive in cancer cells, researchers can hypothesize that
inhibiting this enzyme could slow tumor growth.
• Formulating hypotheses
- Insights into disease mechanisms help researchers formulate hypotheses
about how targeting specific pathways or molecules may alter disease
outcomes. For instance, if a signaling pathway is known to promote
inflammation in autoimmune diseases, a hypothesis could be developed that
inhibiting this pathway will reduce symptoms and tissue damage.
Department of Pharmacy

• Designing Drugs: Knowledge of the molecular structure of

biological targets facilitates structure-based drug design.
Understanding the biological pathways involved in disease helps
researchers design drugs that are selective for their targets,
reducing off-target effects. Knowledge of disease mechanisms
can lead to the development of combination therapies that
target multiple pathways simultaneously.
• Personalized Medicine: Identifying biomarkers that can predict
response to therapy. tailored to the genetic or molecular profile
of a patient’s disease, improving treatment outcomes and
minimizing adverse effects.
Department of Pharmacy

• Preclinical and Clinical Testing: Testing hypotheses regarding the

effectiveness of new drugs. Evaluating Drug Mechanisms of
Actio, In clinical trials, understanding the mechanisms of action
helps evaluate the drug's effects, side effects, and interactions
with other treatments.
 Drug Screening
Department of Pharmacy

• Drug screening is a systematic process used in drug discovery to

identify and evaluate potential therapeutic compounds that
could be developed into effective medications.
• The process involves testing a wide array of chemical
substances to assess their biological activity against specific
targets, such as proteins, enzymes, or cellular pathways
associated with diseases
Department of Pharmacy

• The scope of new drug screening includes a variety of

activities, such as:
• Screening: Compounds are screened for therapeutic activity,
usually based on a specific rationale. For example, a screening
might target a specific receptor.
• Molecular modification: A lead compound is improved through
molecular modification to create a more effective agent
• Drug design: New methods and applications are used in drug
design, including computer-aided drug discover
• Biological Evaluation: Novel compounds are designed,
synthesized, and biologically evaluated
• Drug delivery: Dosage forms, release mechanisms, and in vivo
testing are designed and characterized
Department of Pharmacy

• Preclinical development: Preclinical development studies are

conducted
• Toxicology studies