Pre-Clinical Studies Flashcards
(129 cards)
1
Q
Involve experiments conducted on living organisms, typically animals, to observe the effects of a drug in a whole-body system.
A
In Vivo Testing
2
Q
Involves experiments performed on isolated cells, tissues, or organs outside of a living organism, providing a simplified model for studying drug effects.
A
In Vitro Testing
3
Q
INTRODUCTION TO IN VIVO DRUG SAFETY TESTING
In vivo studies provide valuable insights into how a drug interacts with a living organism, including its absorption, distribution, metabolism, and excretion.
A
Understanding Drug Behavior
4
Q
INTRODUCTION TO IN VIVO DRUG SAFETY TESTING
These studies assess the potential for a drug to cause adverse effects, such as organ damage, reproductive issues, or carcinogenicity.
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Evaluating Toxicity
5
Q
INTRODUCTION TO IN VIVO DRUG SAFETY TESTING
The data from in vivo studies helps researchers design safer and more effective clinical trials in human participants.
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Informing Clinical Trials
6
Q
REGULATORY REQUIREMENTS FOR IN VIVO STUDIES
Drug safety evaluations must comply with guidelines set by organizations
A
Global Regulatory Bodies
7
Q
REGULATORY REQUIREMENTS FOR IN VIVO STUDIES
Global regulatory bodies:
- FDA
- EMA
- OECD
A
- Food and Drug Administration
- European Medicines Agency
- Organisation for Economic Co-operation and Development
8
Q
REGULATORY REQUIREMENTS FOR IN VIVO STUDIES
In vivo studies must adhere to strict animal welfare regulations and protocols to minimize suffering.
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Ethical Considerations
9
Q
REGULATORY REQUIREMENTS FOR IN VIVO STUDIES
Regulatory agencies provide standardized study designs and methods to ensure consistent, high-quality data.
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Standardized Protocols
10
Q
REGULATORY REQUIREMENT: PHILIPPINE SETTING
The primary agency responsible for regulating animal use in drug development in the Philippines is the ___ , which is under the Department of Agriculture (DA).
A
Bureau of Animal Industry (BAI); Department of Agriculture (DA)
11
Q
The BAI oversees and implements the ___ , which provides the legal framework for the humane treatment of animals used in research and development.
A
Animal Welfare Act of 1998 (Republic Act No. 8485)
12
Q
What BAI does: (4)
A
- Issue permits
- Monitor and Inspect
- Investigate Complaints
- Promote ethical practices
13
Q
In addition to the BAI, other agencies that may be involved in regulating animal use in drug development in the Philippines include: (3)
A
- Department of Health (DOH)
- Department of Science and Technology - Philippine Council for Health Research and Development (DOST - PCHRD)
- Institutional Animal Care and Use Committees (IACUCs)
14
Q
The ___ may be involved in setting standards for the use of animals in biomedical research.
A
Department of Health (DOH)
15
Q
The ___ may provide guidelines and ethical review for research involving animals.
A
DOST - Philippine Council for Health Research and Development (PCHRD)
16
Q
Are established within research institutions (university) to review and approve animal use protocols.
A
Institutional Animal Care and Use Committees (IACUCs)
17
Q
They play a crucial role in the development and testing of new drugs. By studying how drugs impact different species, researchers can gain valuable insights into safety, efficacy, and potential side effects before human trials.
A
Animal models
18
Q
Rodent models (3)
A
- Mice
- Rats
- Guinea Pigs
19
Q
Non-Rodent models (4)
A
- Primates
- Pigs
- Dogs
- Rabbits
20
Q
Rodents that are small size, short lifespan, easy to breed and handle.
A
Mice
21
Q
Rodents that are larger size, longer lifespan, more robust physiology.
A
Rats
22
Q
Rodents that are similar to humans in terms of vitamin C requirements.
A
Guinea pigs
23
Q
Non-rodents that are closest to humans in terms of physiology and genetics, valuable for studying diseases like HIV and Alzheimer’s.
A
Primates
24
Q
Non-rodents that are used for studying organ transplantation and cardiovascular research, similar size and anatomy to humans.
A
Pigs
25
Non-rodents that are large animal models for studying cancer, diabetes, and cardiovascular diseases, long lifespan allows for chronic studies.
Dogs
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Non-rodents that are used for studying reproductive and developmental toxicology, convenient size and relatively low cost.
Rabbits
27
Are widely used in drug research due to their physiological similarities to humans. Understanding different ___ strains is crucial for selecting the most appropriate model for specific research questions. Their names are from *research centers*
Rats
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Types of Rats: (5)
- Wistar Rats
- Sprague Dawley Rats
- Long-Evans Rats
- Spontaneously Hypertensive Rats (SHR)
- Zucker Diabetic Fatty Rats (ZDFR)
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An albino strain characterized by their white fur and pink eyes.
Wistar rats
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They are known for their rapid growth and adaptability, making them suitable for various research purposes.
Wistar rats
31
Applications in Drug Studies
Wistar rats are commonly used in ___ , ___ , and ___ .
toxicology,
cancer research,
behavioral studies
32
Their predictable responses to drug treatments make them valuable models for evaluating drug efficacy and safety.
Wistar rats
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Wistar physical characteristics: (3)
- Long ears
- Tail length shorter than body length
- Wider head
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Are a popular strain known for their docile nature, rapid growth rate, and high reproductive rate.
Sprague Dawley rats
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These qualities make Sprague Dawley rats suitable for various studies, including ___ , ___ , and ___ .
toxicology,
pharmacology,
safety testing
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Kinds of rats with consistent physiology which allows for reliable data collection and interpretation.
Sprague Dawley rats
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Researchers often use Sprague Dawley rats for general ___ and to evaluate ___ .
toxicity testing,
drug efficacy
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Are known for their hooded coat pattern, featuring a darker, pigmented area on the head and shoulders.
Long-Evan rats
39
This strain is also recognized for its relatively larger size compared to other commonly used rat strains.
Long-Evan rats
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Long-Evans rats are cross between a ___ and a ___ .
Female albino,
Wild male (Rattus norvegicus)
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Long-Evans rats are often used in behavioral research due to their well-documented behavioral patterns and responses. They are also valuable models for studying ___ and ___ .
neurological disorders,
drug-induced behavioral changes
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Are genetically predisposed to hypertension, characterized by elevated blood pressure.
Spontaneously Hypertensive Rats (SHR)
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Spontaneously Hypertensive rats are commonly used in research on cardiovascular diseases, including ___ , ___ , and ___ .
stroke,
heart failure,
hypertension
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Spontaneously Hypertensive rats are valuable models for evaluating new drugs for ___ and other ___ . Their sensitivity to *** makes them particularly useful for testing the efficacy of antihypertensive drugs.
hypertension,
cardiovascular disorders
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Are genetically predisposed to obesity and type 2 diabetes.
Zucker Diabetic Fatty (ZDF)
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These rats are characterized by their distinctive white fur and tendency to develop insulin resistance.
Zucker Diabetic Fatty (ZDF)
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ZDF rats are valuable models for studying ___ , ___ , and related ___ . Researchers utilize ZDF rats to evaluate the efficacy and safety of new drugs for managing *** and ***.
diabetes,
obesity,
metabolic disorders
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Considerations in rat selection: (6)
- Genetic background
- Age
- Sex
- Health status
- Environmental factors
- Ethical consideration
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Types of In Vivo Pre-Clinical Studies: (9)
- Acute Toxicity Studies
- Subchronic Toxicity Studies
- Chronic Toxicity Studies
- Reproductive Toxicity Studies
- Genetic Toxicity Studies
- Pharmacokinetic Studies
- Efficacy Studies
- Safety Pharmacology Studies
- Immunogenicity Studies
50
ACUTE TOXICITY STUDIES
A single, high dose of the drug is given to assess immediate, short-term effects.
Dose Administration
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ACUTE TOXICITY STUDIES
Animals are closely monitored for signs of toxicity, such as changes in behavior, physiology, and mortality.
Observation Period
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ACUTE TOXICITY STUDIES
Detailed examination of organ tissues to identify any damage or abnormalities.
Pathology Analysis
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SUBCHRONIC TOXICITY STUDIES
The drug is administered for a longer period, typically 28-90 days, to assess medium-term effects.
Exposure Duration
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SUBCHRONIC TOXICITY STUDIES
Multiple dose levels are tested to determine the threshold for toxicity and establish safe dosing ranges.
Dose Levels
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SUBCHRONIC TOXICITY STUDIES
In-depth analysis of clinical chemistry, hematology, and histopathology to identify potential organ-specific toxicity.
Comprehensive Evaluation
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CHRONIC TOXICITY STUDIES
The drug is administered for an extended period, typically 6 months to 2 years, to assess long-term effects.
Long-Term Exposure
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CHRONIC TOXICITY STUDIES
Gradually increasing the dose over time to identify the maximum tolerable dose and potential cumulative toxicity.
Dose Escalation
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CHRONIC TOXICITY STUDIES
In-depth evaluation of organ function, histopathology, and any other adverse effects that may develop.
Comprehensive Assessment
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REPRODUCTIVE TOXICITY STUDIES
Assessing the drug's impact on mating, conception, and sperm/egg production.
Fertility
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REPRODUCTIVE TOXICITY STUDIES
Evaluating the drug's effects on the developing embryo and fetus during pregnancy.
Embryonic/Fetal Development
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REPRODUCTIVE TOXICITY STUDIES
Monitoring the growth and development of offspring exposed to the drug in utero.
Postnatal Development
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REPRODUCTION TOXICITY STUDIES
Examining the drug's effects over multiple generations to identify any heritable changes.
Multi-Generation Studies
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GENETIC TOXICITY STUDIES
Assessing the drug's potential to cause permanent changes in the genetic material of cells.
64
GENETIC TOXICITY STUDIES
Evaluating the drug's ability to induce chromosomal breaks, rearrangements, or other abnormalities.
Clastogenicity
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GENETIC TOXICITY STUDIES
Analyzing the drug's impact on the integrity and repair of genetic material.
DNA Damage
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PHARMACOKINETIC STUDIES (4)
- Absorption
- Distribution
- Metabolism
- Excretion
67
EFFICACY STUDIES
Demonstrates the drug's ability to achieve its intended effect.
Proof-of-Concept
68
EFFICACY STUDIES
Determines the optimal dosage for efficacy.
Dose-Response
69
EFFICACY STUDIES
Identifies the range of doses that provide benefit without excessive toxicity.
Therapeutic Window
70
EFFICACY STUDIES
Assesses the drug's effectiveness over extended periods.
Long-Term Effects
71
SAFETY PHARMACOLOGY STUDIES
Assess effects on heart rate, blood pressure, and rhythm.
Cardiovascular
72
SAFETY PHARMACOLOGY STUDIES
Evaluate impact on breathing rate, depth, and lung function.
Respiratory
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SAFETY PHARMACOLOGY STUDIES
74
SAFETY PHARMACOLOGY STUDIES
Examine effects on behavior, cognition, and motor function.
Central Nervous System
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SAFETY PHARMACOLOGY STUDIES
Assess impact on digestion, absorption, and bowel movements.
Gastrointestinal
76
IMMUNOGENICITY STUDIES (2)
- Immunomodulation
- Immunosuppression
77
IMMUNOGENICITY STUDIES
Measure the production of antibodies against the drug or its components.
Antibody Response
78
IMMUNOGENICITY STUDIES
Evaluate the activation of immune cells like T cells, which can directly attack cells expressing the drug.
Cell-Mediating Immunity
79
IMMUNOGENICITY STUDIES
Analyze the levels of various immune signaling molecules (cytokines) in blood or tissues.
Cytokine Profile
80
IMMUNOGENICITY STUDIES
Examine tissue samples under a microscope to assess the presence of immune cells and inflammation.
Histopathology
81
DATA ANALYSIS AND INTERPRETATION OF IN VIVO STUDY RESULTS
Applying rigorous statistical methods to identify significant drug-related effects and trends.
Statistical Analysis
82
DATA ANALYSIS AND INTERPRETATION OF IN VIVO STUDY RESULTS
Evaluating how changes in dose affect the magnitude and incidence of observed effects.
Dose-Response Relationships
83
DATA ANALYSIS AND INTERPRETATION OF IN VIVO STUDY RESULTS
Carefully translating animal data to predict potential safety and efficacy in human clinical trials.
Extrapolation to Humans
84
Ethical Considerations on Animal Models in Drug Development
The 3 R's
- Replacement
- Reduction
- Refinement
85
Seek to replace animal models with alternative methods such as in vitro or in silico approaches whenever possible.
Replacement
86
Design studies to minimize the number of animals used while maintaining scientific validity.
Reduction
87
Continually improve procedures to enhance animal welfare and minimize pain, distress, and suffering.
Refinement
88
EVALUATING THE SCIENTIFIC MERIT AND NECESSITY OF ANIMAL STUDIES
Ensure that the study design and methodology is robust and can yield meaningful, reproducible results.
Scientific Validity
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EVALUATING THE SCIENTIFIC MERIT AND NECESSITY OF ANIMAL STUDIES
Carefully weigh the potential benefits of the research against the risks and suffering imposed on animals.
Minimizing Harm
90
EVALUATING THE SCIENTIFIC MERIT AND NECESSITY OF ANIMAL STUDIES
Continually seek and implement alternative methods that can replace animal models when feasible.
Alternative Exploration
91
EVALUATING THE SCIENTIFIC MERIT AND NECESSITY OF ANIMAL STUDIES
Require rigorous ethical review and approval before conducting any animal research studies.
Ethical Review
92
MINIMIZING ANIMAL SUFFERING
Utilize appropriate anesthetic agents to eliminate pain and distress during procedures.
Anesthesia
93
MINIMIZING ANIMAL SUFFERING
Provide analgesics to manage pain and discomfort before, during, and after experiments.
Analgesia
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MINIMIZING ANIMAL SUFFERING
Ensure humane and painless methods of euthanasia when animals must be sacrificed.
Euthanasia
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ENSURING PROPER ANIMAL WELFARE
Provide appropriate, spacious, and enriched environments to support the animals' natural behaviors.
Housing
96
ENSURING PROPER ANIMAL WELFARE
Ensure that animals receive a balanced and nutritious diet to maintain their health and well-being.
Nutrition
97
ENSURING PROPER ANIMAL WELFARE
Establish comprehensive veterinary oversight to monitor the animals' health and address any issues promptly.
Veterinary Care
98
LIMITATIONS OF IN VIVO STUDIES
Animal welfare is paramount, necessitating strict ethical guidelines and regulatory oversight to minimize animal suffering.
Ethical Considerations
99
LIMITATIONS OF IN VIVO STUDIES
Results from animal models may not fully translate to humans due to physiological and metabolic variations.
Species Difference
100
LIMITATIONS OF IN VIVO STUDIES
In vivo studies involve significant financial investments and time to conduct, especially for long-term studies.
High Cost and Time Commitment
101
LIMITATIONS OF IN VIVO STUDIES
Individual animal responses can vary, influencing the reliability of study results and requiring careful statistical analysis.
Limited Control over Variables
102
BALANCING SCIENTIFIC PROGRESS AND ETHICAL CONSIDERATIONS
Maintain an open and constructive dialogue between researchers, ethicists, and the public.
Ongoing Dialogue
103
BALANCING SCIENTIFIC PROGRESS AND ETHICAL CONSIDERATIONS
Continuously strive to enhance animal welfare and seek alternatives to reduce reliance on animal models.
Continual Improvement
104
BALANCING SCIENTIFIC PROGRESS AND ETHICAL CONSIDERATIONS
Ensure that animal research is conducted with the highest ethical standards and scientific rigor.
Responsible Research
105
Evaluating the safety and efficacy of new drug compounds is a critical step in the drug development process. In vitro testing using cell-based models and advanced organ-on-a-chip systems provides an essential foundation for understanding a drug's potential toxicity before further clinical trials.
Drug Safety Evaluation In Vitro
106
ADVANTAGES OF IN VITRO STUDIES
In vitro studies provide a fast and efficient way to screen potential drug candidates, enabling quicker identification of promising leads.
Rapid Screening
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ADVANTAGES OF IN VITRO STUDIES
In vitro studies are generally less expensive to conduct than in vivo studies, reducing overall drug development costs.
Cost0Effectiveness
108
ADVANTAGES OF IN VITRO STUDIES
In vitro studies allow for precise control of variables, minimizing external factors that can influence experimental outcomes.
Controlled Environment
109
ADVANTAGES OF IN VITRO STUDIES
In vitro studies do not involve living organisms, eliminating ethical concerns associated with animal welfare.
Ethical Considerations
110
CELL-BASED ASSAYS
Choosing the appropriate cell line is crucial, as it should be representative of the target tissue or disease state.
Cell Line Selection
110
Types of In Vitro Drug Studies: (6)
1. Cell-Based Assays
2. Genotoxicity and Mutagenicity Testing
3. Receptor Binding Assay
4. Biochemical/Enzyme Activity Assays
5. Permeability Studies
6. Metabolic Stability Studies
111
CELL-BASED ASSAYS
Cell-based assays can measure various cellular responses, such as proliferation, differentiation, or signaling pathway activation.
Functional Readouts
112
CELL-BASED ASSAYS
These assays can assess the cytotoxic effects of drug candidates on cells, helping identify potential safety concerns.
Toxicity Evaluation
113
GENOTOXICITY AND MUTAGENICITY TESTING
Detecting mutagenic potential using bacterial reverse mutation assays.
Ames Test
114
GENOTOXICITY AND MUTAGENICITY TESTING
Measuring DNA strand breaks and alkaline-labile sites in individual cells.
Comet Assay
114
RECEPTOR BINDING ASSAYS
These assays determine the selectivity of a drug candidate for its intended receptor target, versus off-target receptors.
Receptor Specificity
114
GENOTOXICITY AND MUTAGENICITY TESTING
Evaluating chromosomal damage and aneuploidy in mammalian cells.
Micronucleus Assay
114
RECEPTOR BINDING ASSAYS
Receptor binding assays quantify the strength of the interaction between a drug candidate and its target receptor.
Binding Affinity
115
RECEPTOR BINDING ASSAYS
Some receptor binding assays also measure the ability of a drug candidate to activate or inhibit the receptor's downstream signaling pathways.
Functional Activation
116
BIOCHEMICAL/ENZYME ACTIVITY ASSAYS
These assays determine the ability of a drug candidate to inhibit the activity of a target enzyme, which can be a potential mechanism of action.
Enzyme Inhibition
117
BIOCHEMICAL/ENZYME ACTIVITY ASSAYS
Enzyme activity assays can provide information on the kinetic parameters of an enzyme-drug interaction, such as the rate of catalysis or inhibition.
Enzyme Kinetics
117
PERMEABILITY STUDIES
Measures the ability of a drug candidate to passively diffuse across cell membranes, which is crucial for oral bioavailability.
Passive DIffussion
117
BIOCHEMICAL/ENZYME ACTIVITY ASSAYS
Enzyme activity assays are well-suited for high-throughput screening of large chemical libraries to identify potential drug candidates.
High-Throughput Screening
118
PERMEABILITY STUDIES
Assesses the likelihood of a drug candidate to cross the blood-brain barrier and reach the central nervous system.
Blood-Brain Barrier
118
PERMEABILITY STUDIES
Evaluates the potential for a drug candidate to be a substrate or inhibitor of membrane transporter proteins.
Active Transport
119
METABOLIC STUDIES
These studies identify the major metabolic pathways and enzymes involved in the biotransformation of a drug candidate.
Metabolism Pathways
120
METABOLIC STUDIES
Metabolic stability assays can provide a comprehensive understanding of the drug's metabolic fate and potential metabolite-mediated effects.
Metabolite Profiling
121
METABOLIC STUDIES
The rate of drug metabolism is crucial for determining the appropriate dosing regimen and predicting in vivo pharmacokinetics.
Half-Life Determination
122
"Animal research and testing has played a part in almost every medical breakthrough of the last century. It has saved hundreds of millions of lives worldwide"
Jean Ryan
