Lecutre 1

Question 1

What is a disease?

Answer 1

A condition which alters or interferes with the normal state of an organism and is usually characterized by the abnormal functioning of one or more of the host’s systems, parts or organs.

Question 2

According to Stedman’s medical dictionary, a disease is a morbid entity which is characterized by at least 2 of which 3 criteria?

Answer 2

1. recognized aetiologic agents
2. identifiable groups of signs and symptoms
3. consistent anatomical alterations

Question 3

What is FDA’s definition of a drug?

Answer 3

active ingredient to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of a disease

Question 4

What is the difference between OTC drug and ethical drug?

Answer 4

OTC drug: can be purchased from pharmacies without prescription

Ethical drug: prescribed drug that requires prescription by physicians
–> generics
–> new drugs

Question 5

What are ‘new drugs’?

Answer 5

novel prescribed drugs covered by patents

Question 6

What are generics?

Answer 6

copies of drugs that have expired patents

Question 7

What are statins?

Answer 7

Statins are drugs that can lower cholesterol

–> inhibit HMG CoA reductase
–> reductase cannot reduce HMG to mevalonate, a precursor for cholesterol

Question 8

What are some pleiotropic effects of statins?

Answer 8

modification of endothelial function, plaque stability, thrombus formation and inflammatory pathways

–> lead to inflammatory disorders

Question 9

What diseases could therapeutic potential of statins extend to?

Answer 9

inflammatory disorders
multiple sclerosis
rheumatoid arthritis
chronic kidney disease
Alzheimer’s dementia
age-related bone loss
prostate cancer etc

Question 10

Give an example where 2 drugs were combined to produce 1 drug

Answer 10

Flovent (fluticasone propionate):
–> the only nasal steroid that has an FDA-
approved non-allergic rhinitis indication

Serevent (salmeterol):
produces bronchodilation by relaxing
bronchial smooth muscle through b2-
adrenergic receptor stimulation

combination in a single inhalation device

Question 11

State an example where a company extended the drug patent by ‘tweaking’ theri existing patented drug

Answer 11

AstraZeneca
-launched Losec in 1988, with the active ingredient omeprazole,

-in late 1999 and 2000, the company
released Nexium, containing only the active S-enantiomer of the active ingredient

Question 12

What type of drug is omeprazole?

Answer 12

a proton pump inhibitor (PPI), to treat diseases related to excess acid in the stomach

Question 13

What stage of the drug development stage requires the largest cash?

Answer 13

clinical trial stage, where hundreds and thousands of human subjects are recruited.

Question 14

What are some regulatory requirements that the drug discovery and development process has to be comply with?

Answer 14

GLP, GMP and GCP

Question 15

What is the importance of drug development on the societal scale?

Answer 15

1. Deliver improved medicine to patients
2. Provide innovative solutions to address unmet medical needs
3. Help to relieve the financial pressure on patients and the society incurred
   by high medical costs

Question 16

What factor is contributing to the rapidly increasing of medical costs?

Answer 16

global aging

–> psoing a financial challenge on states

Question 17

Why do age-related diseases lead to more costs?

Answer 17

Age-related diseases often require long-term care that necessitates large input of
manpower and huge medical spending

Question 18

What are the 2 major approaches of drug discovery and development?

Answer 18

1. irrational approach
2. Rational approach

Question 19

What is the irrational approach of drug development?

Answer 19

Historical method that observes the pharmacological effects from screening of many chemical compounds

Question 20

What is the rational approach of drug development?

Answer 20

–> Requires 3D knowledge of the target structure involved in the disease –>Molecules are designed to interact with the target structure for beneficial response.

Question 21

What are some of the recent trends in drug development?

Answer 21

1. antisense drugs
2. biologics
3. gene therapy
4. stem cell therapy

Question 22

What are anti sense drugs?

Answer 22

Makes modifications to oligonucleotides that can bind to RNA and DNA

Question 23

How do antisense drugs work?

Answer 23

Interferes the disease process by stopping the transcriptional (from DNA) or translational (from RNA) pathways from proceeding.

Question 24

What are biologics?

Answer 24

Mainly protein-based drugs in the form of antibodies, vaccines, and cytokines

–> manufacturing based on recombinant DNA technologies

Question 25

What are biologics manufactured by?

Answer 25

recombinant DNA technologies

Question 26

Describe gene therapy

Answer 26

taking diseased gene out from the patient, fixing it outside the body, and reinserting it back into the body OR Inserts a missing gene to influence disease pathway or to initiate manufacture of the missing proteins or enzymes

Question 27

Describe stem cell therapy

Answer 27

To grow body parts to replace defective human organs and nerves

Question 28

In stem cell therapy, how are stem cells harvested?

Answer 28

from very early embryos or umbilical cord blood

Question 29

Wha is the advantange of stem cell therapy over organ transplantation?

Answer 29

less rejection problems

Question 30

How does lipitor (a statin) work?

Answer 30

1. selectively and competitively inhibits HMG-CoA reductase 2. HMG CoA reductase cannot convert HMG-CoA to mevalonate (precursor of cholesterol) 3. decrease in hepatic cholesterol and increase in uptake of LDL cholesterol

Question 31

Following the identification of drug leads, the lead compounds will enter the stage of Drug Development in which the following major activities take place:

Answer 31

Preclinical testing of the candidate compounds Development and analysis of dosage form Process development for scale-up production Clinical studies Submission of marketing approval documents

Question 32

What are some of the requirements stipulated in GLP?

Answer 32

1. well-trained personnel 2. setting up quality assurance unit 3. Material for studies appropriately tested for identity, purity, stability and uniformity 4. Animals isolated, their health status checked and given proper welfare

Question 33

GMP is set of regulations requiring that ________, ________, and _________ be built into foods, drugs, medical devices, and biological products

Answer 33

quality, safety, effectiveness

Question 34

What guidlines does GCP provide?

Answer 34

1. how clinical trials should be conducted 2. define the roles and responsibilities of clinical trial sponsors, clinical research investigators, and monitors

Question 35

Drug discovery pipeline

Answer 35

Target Discovery Target Validation Assay Development and Optimization Activity Screening Chemical Lead Optimization Preclinical Development Clinical Studies

Question 35

The drug discovery and development process entails:

Answer 35

High-skill working force Sophisticated equipment and technology Highly-controlled environment