2 | Overview of DDD Flashcards
(158 cards)
1
Q
Majority of research at this stage is publicly funded at universities, colleges and independent research institutions in every state
A
Basic Research
2
Q
Once a disease target is identified, drugs are designed and tested.
A
Clinical trials
3
Q
T/F: Both public and privately funded research are involved in clinical trials.
A
True
4
Q
Human trials are completed including FDA approval
A
Regulatory approval
5
Q
Industry is responsible for bringing a drug to market
A
Regulatory approval
6
Q
T/F: Safety and evaluation does not continue after regulatory approvals
A
False
7
Q
Practice of Pharmacy
A
Patient Care
8
Q
Deals with drug formulations and dosage forms
A
Pharmaceutics
9
Q
Deals with pharmacotherapeutics and clinical pharmacy
A
Pharmaceutical Chemistry
10
Q
Clinical trials include how many phases?
A
Three
11
Q
Basic research is involved in?
A
Medicinal Chemistry
12
Q
Therapeutic concept is also known as
A
Objective
13
Q
Pertains to finding a protein responsible for disease development
A
Target Selection
14
Q
Steps involved in Discovery
A
- Target selection
- Target validation
- Lead finding
- Lead optimization
15
Q
Lead finding
A
Lead compound
16
Q
Lead optimization
A
Candidate drug
17
Q
Steps involved in Development
A
- Preclinical development
- Clinical development
- Regulatory approval
- Registration
18
Q
Commercialization involves
A
- Clinical development
- Regulatory approval
- Registration
- Product
19
Q
biomolecule to which the drug will bind (through a specific binding site)
A
Target
20
Q
Often responsible for (or related to) the disease chosen for the research
A
Target
21
Q
T/F: Majority of drugs target nucleic acids and lipids, although a protein molecule is occasionally targeted too
A
False
22
Q
Blockbuster drug that targets beta-adrenergic receptors
A
Salbutamol
23
Q
Blockbuster drug that targets alpha-adrenergic receptors
A
Phenylephrine
24
Q
Blockbuster drug that targets muscarinic receptors
A
Atropine
25
Blockbuster drug that targets serotonin transporters
Sertraline
26
Blockbuster drug that targets calcium channels
Nifedipine
27
Blockbuster drug that targets angiotensin converting enzyme
Enalapril
28
Blockbuster drug that targets acetylcholinesterase
Neostigmine
29
Drug that acts as HMG CoA reductase inhibitor
Atorvastatin
30
Possess an opposite effect as compared to atropine
Physostigmine
31
Medication category of Nifedipine which lowers BP
CCBs
32
Requires molecular biology techniques to allow testing of multiple candidate targets
Target Identification and Validation
33
Use of microarray plates to find which proteins are responsive to a disease
Target Identification and Validation
34
Found between target validation and lead finding
Compound preparation
35
Prepares compound found in the boundary of target identification and target finding
Compound preparation
36
T/F: DDD projects can start without the presence of a series of compounds to test
False
37
A series of compounds also pertain to
A compound library
38
Cycle of prepare, test, prepare, test, prepare...
Compound preparation
39
Series of trials and errors
Compound preparation
40
For _________________ projects, simple modifications to make a handful of compounds is enough
small scale
41
For ___________________, synthetic strategies can produce thousands to millions of compounds
pharmaceutical companies
42
Small scale project (e.g, academic research) is usually funded by?
Government
43
molecules with potential to be selected as leads
Hit
44
generated during the initial screening process
Hit
45
type of hit that is chosen during lead finding to become leads
most active hits
46
contains toxicity, not refined
Hit
47
can be a candidate for a drug compound
Hit
48
selected hits that can have not only potency but also safety and other qualities wanted in a drug
Leads
49
less toxic than hit, but is not considered safe due to lack of animal testing done
Leads
50
How does a molecule become a hit?
Needs to have confirmed activity
51
Requirements to become a lead
1. Must have confirmed activity
2. Show evidence of desired selectivity
3. Have activity in cellular systems
4. Stability in biologic systems
5. Free from toxicity alerts
52
T/F: If a lead becomes toxic, it should be stopped
True
53
hits are validated, then tested to assess if they can become leads
Lead generation/ identification/ finding
54
The stage of finding hits to finding leads
Lead generation/ identification/ finding
55
Stage done just before optimization and is sometimes combined to the term H2L generation
Lead generation/ identification/ finding
56
H2L generation means
hit-to-lead generation
57
Requires selection and validation of target first
Lead generation
58
generated during the initial screening process
Hit
59
closer but still not perfect, so they undergo an extra process
Lead
60
Leads are closer but still not perfect, so they undergo an extra process called
lead optimization
61
Improvement of a lead’s PD, PK, and toxicity profiles suitable for future stages of the DDD pipeline
lead optimization
62
T/F: Already-existing leads will never be perfect for very specific purposes
True
63
The first and only stage in discovery where synthesis is intentional and not a mere guessing game
lead optimization
64
May involve improvements in potency, efficacy, or safety profile of a drug
lead optimization
65
Converts “close enough” leads to “certain” drug candidates
lead optimization
66
biological/ biochemical testing to get initial data
Structure-activity relationship (SAR)
67
Results to diagrams showing how modifying a part of the lead’s/drug’s structure changes it’s activities
lead optimization
68
Gives birth to drug analogues and drug generations
lead optimization
69
Potent activity against gram-positive
1st generation cephalosporin
70
Mediocre activity against gram-negative bacteria
1st generation cephalosporin
71
Example of a 1st generation cephalosporin
Cephalotin
72
1st generation cephalosporin became available for use during [year]
1964
73
Expanded spectrum of activity
2nd generation cephalosporin
74
Better cell penetration
2nd generation cephalosporin
75
Increased resistance to Beta-lactamases
2nd generation cephalosporin
76
Slightly less potent against gram-positive
2nd generation cephalosporin
77
Considerable more active against gram-negative
2nd generation cephalosporin
78
Example of a 2nd generation cephalosporin
Cefuroxine
79
2nd generation cephalosporin became available for use during [year]
1983
80
Improved activity against gram-negative
3rd generation cephalosporin
81
Like a 2nd gen cephalosporin, it also has better cell penetration
3rd generation cephalosporin
82
Higher binding towards bacterial arget
3rd generation cephalosporin
83
Example of a 3rd generation cephalosporin
Ceftazidime
84
3rd generation cephalosporin became available for use during [year]
1985
85
Improved resistance to beta-lactamases
4th generation cephalosporin
86
Wider spectrum of activity
4th generation cephalosporin
87
Higher activity against both gram-positive and against gram-negative
4th generation cephalosporin
88
Example of a 4th generation cephalosporin
Cefepime
89
4th generation cephalosporin became available for use during [year]
1994
90
Approved for tx of critical infections (e.g., hospital-acquired pneumonia)
5th generation cephalosporin
91
Example of a 5th generation cephalosporin
Ceftobiprole
92
5th generation cephalosporin became available for use during [year]
2013
93
T/F: Discovery is shorter, but development is more expensive.
True
94
Studies involving animals extensive toxicity studies in animals
Preclinical testing
95
Done to predict the risks that will be associated with administering the drug to humans
Preclinical testing
96
May not reveal all of the adverse effects that will be found in human subjects
Preclinical testing
97
the first occasion at which a compound is tested in live organisms
Preclinical PK study
98
Compounds targeted as oral therapies are administered as?
IV and PO
99
Why are compounds targeted as oral therapies are administered as both IV and PO?
to compute bioavailability
100
residence time in lung is considered for?
inhaled/topical drugs
101
high solubility is given even more importance for
IV drugs
102
Concurrent to pharmaceutical development
Preclinical testing
103
proper dosage form, delivery system, and route of administration for the final product
Pharmaceutical development
104
Pharmaceutical development involves two phases
1. Preformulation studies
2. Formulation phase
105
Preparatory analysis
Preformulation studies
106
Utilizes pharmaceutical analysis and physical pharmacy tests
Preformulation studies
107
In Preformulation studies, ________ is tested all the time to assess shelf life
Stability
108
actual formulation of the product
Formulation phase
109
Requires good background of excipients and drug manufacturing
Formulation phase
110
Includes a complete description of the drug, results of preclinical studies, and description of the proposed clinical studies and the qualifications of the investigators
Investigational New Drug (IND) Application
111
Pharmacokinetic properties and safety of an IND in healthy human subjects
Phase I IND
112
Efficacy on diseased subjects not yet measured
Phase I IND
113
First studies on human subjects who have the particular disease the IND is targeting
Phase II IND
114
Small number of patients only
Phase II IND
115
Employ a larger group of subjects (hundreds to thousands)
Phase III IND
116
Multiple centers, wide variation of study methods
Phase III IND
117
Final phase before approval
Phase III IND
118
Toxicity testing is still significant further into the preclinical and clinical phases of the DDD pipeline
Safety
119
Post-Development includes
1. New Drug Application (NDA)
2. Postmarketing Surveillance
120
Includes the results of all preclinical and clinical studies, as well as the proposed labeling and clinical indications for the drug
New Drug Application (NDA)
121
Last hurdle before reaching the market
New Drug Application (NDA)
122
Also referred to as Phase IV
Postmarketing Surveillance
123
Some drugs are found to have other clinical uses after the drug has been introduced to the market
Postmarketing Surveillance
124
Covered by the pharmacovigilance sector
Postmarketing Surveillance
125
In some cases, old drugs are revisited for new purposes
Postmarketing Surveillance
126
Within the glass
In vitro
127
Use of isolated tissue/ cell samples for testing
In vitro
128
Versatile and applicable on a wide range of tissues
In vitro
129
Approximation to the normal functioning of the tissue
In vitro
130
In vitro
Activity depends on permeation through the membrane for?
Compounds acting on intracellular activity
131
In vitro
T/F: A very wide range of physiologic responses can be addressed by studies on isolated tissues
True
132
Concentration-effect relationships can be accurately measured, and design of the experiments is flexible
In vitro
133
In vitro shortcomings
T/F: Tissues does not normally have to be obtained from small laboratory animals
False (normally)
134
In vitro shortcomings
T/F: Preparations often survive for more than a day, allowing only short-term experiments
False (rarely survive)
135
Within the living
In vivo
136
Uses animals that express similar physiology/ pathology relevant to the research
In vivo
137
time-consuming, technically demanding and expensive
In vivo
138
Subject to considerable ethical and legal constraints, and face public opposition
In vivo
139
Use today is much more limited, especially to later stages
In vivo
140
In vivo
T/F: Imaging technologies are increasingly being used for studies on whole animals
True
141
In vivo
T/F: Physiology of disease processes and drug metabolism differs markedly in different species
True
142
Nevertheless is essential part of every major drug discovery project and represents a valuable link in the chain of evidence
In vivo
143
intended to mimic certain manifestations of the clinical disorder
Acute models
144
Histamine- induced bronchoconstriction, hotplate test for inflammation, elevated maze for anxiety, etc. are examples of?
Acute models
145
Involve use of agents that induce an abnormality similar to the clinical conditions
Chronic models
146
Alloxan- induced DM1, administration of dependence-inducing drugs, cholesterol feeding for atherosclerosis, etc. are examples of?
Chronic models
147
Allowed inbred strains to be produced that over- or under-express particular genes that lead to conditions (e.g., inborn disease) that allow testing to take place
In vivo
148
In vivo
T/F: Use of transgenic animal models has led to an increase, rather than decrease, in animal experimentation
True
149
When used in DDD context, is often called
computer-aided drug design (CADD)
In silico/Virtual
150
Computational programs that generate “models” to separate molecules that are likely to work vs. those that are less likely to work
In silico/Virtual
151
Used early in the discovery phase to avoid costs from using in vitro methods
In silico/Virtual
152
Considered dry lab experiments as it does not use actual reagents or lab apparatuses (traditional wet lab)
In silico
153
though with altruistic and commercial aims in their mission statements, the profit necessarily takes priority
Industry
154
In Industry:
Freedom is ___________________, teamwork ______________, and has little room for the lone genius
more limited; obligatory
155
In Industry:
Publication means compromising ________________, and compromising _____________
patent; profit
156
researchers are substantially constrained to work on projects that attract funding support; more free to publish
Academia
157
In Academia:
Under much more pressure to do so since _____________ are their measure of research achievement
publications
158
Publish or perish culture
Academia
