Lecutre 1 Flashcards
What is a disease?
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.
According to Stedman’s medical dictionary, a disease is a morbid entity which is characterized by at least 2 of which 3 criteria?
- recognized aetiologic agents
- identifiable groups of signs and symptoms
- consistent anatomical alterations
What is FDA’s definition of a drug?
active ingredient to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of a disease
What is the difference between OTC drug and ethical drug?
OTC drug: can be purchased from pharmacies without prescription
Ethical drug: prescribed drug that requires prescription by physicians
–> generics
–> new drugs
What are ‘new drugs’?
novel prescribed drugs covered by patents
What are generics?
copies of drugs that have expired patents
What are statins?
Statins are drugs that can lower cholesterol
What are some pleiotropic effects of statins?
modification of endothelial function, plaque stability, thrombus formation and inflammatory pathways
–> lead to inflammatory disorders
What diseases could the pleitropic effects of statins lead to?
inflammatory disorders
multiple sclerosis
rheumatoid arthritis
chronic kidney disease
Alzheimer’s dementia
age-related bone loss
prostate cancer etc
Give an example where 2 drugs were combined to produce 1 drug
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
State an example where a company extended the drug patent by ‘tweaking’ theri existing patented drug
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
What type of drug is omeprazole?
a proton pump inhibitor (PPI), to treat diseases related to excess acid in the stomach
What stage of the drug development stage requires the largest cash?
clinical trial stage, where hundreds and thousands of human subjects are recruited.
What are some regulatory requirements that the drug discovery and development process has to be comply with?
GLP, GMP and GCP
What is the importance of drug development on the societal scale?
- Deliver improved medicine to patients
- Provide innovative solutions to address unmet medical needs
- Help to relieve the financial pressure on patients and the society incurred
by high medical costs
What factor is contributing to the rapidly increasing of medical costs?
global aging
–> psoing a financial challenge on states
Why do age-related diseases lead to more costs?
Age-related diseases often require long-term care that necessitates large input of
manpower and huge medical spending
What are the 2 major approaches of drug discovery and development?
- irrational approach
- Rational approach
What is the irrational approach of drug development?
Historical method that observes the pharmacological effects from screening of many chemical compounds
What is the rational approach of drug development?
–> Requires 3D knowledge of the target structure involved in the disease –>Molecules are designed to interact with the target structure for beneficial response.
What are some of the recent trends in drug development?
- antisense drugs
- biologics
- gene therapy
- stem cell therapy
What are anti sense drugs?
Makes modifications to oligonucleotides that can bind to RNA and DNA
How do antisense drugs work?
Interferes the disease process by stopping the transcriptional (from DNA) or translational (from RNA) pathways from proceeding.
What are biologics?
Mainly protein-based drugs in the form of antibodies, vaccines, and cytokines
–> manufacturing based on recombinant DNA technologies
What are biologics manufactured by?
recombinant DNA technologies
Describe gene therapy
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
Describe stem cell therapy
To grow body parts to replace defective human organs and nerves
In stem cell therapy, how are stem cells harvested?
from very early embryos or umbilical cord blood
Wha is the advantange of stem cell therapy over organ transplantation?
less rejection problems
How does lipitor (a statin) work?
- selectively and competitively inhibits HMG-CoA reductase
- HMG CoA reductase cannot convert HMG-CoA to mevalonate (precursor of cholesterol)
- decrease in hepatic cholesterol and increase in uptake of LDL cholesterol
Following the identification of drug leads, the lead compounds will enter the
stage of Drug Development in which the following major activities take place:
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
What are some of the requirements stipulated in GLP?
- well-trained personnel
- setting up quality assurance unit
- Material for studies appropriately tested for identity, purity, stability and uniformity
- Animals isolated, their health status checked and given proper welfare
GMP is set of regulations requiring that ________, ________, and _________ be built into foods, drugs, medical devices, and biological products
quality, safety, effectiveness
What guidlines does GCP provide?
- how clinical trials should be conducted
- define the roles and responsibilities of clinical trial sponsors, clinical research investigators, and monitors
Drug discovery pipeline
Target Discovery
Target Validation
Assay Development and Optimization
Activity Screening
Chemical Lead Optimization
Preclinical Development
Clinical Studies
The drug discovery and development process entails:
High-skill working force
Sophisticated equipment and technology
Highly-controlled environment
