Introduction to Pharmacology and Toxicology- Biopharmaceuticals and gene therapy Flashcards Preview

PM2C: Therapeutics and Patient Care: Autumn > Introduction to Pharmacology and Toxicology- Biopharmaceuticals and gene therapy > Flashcards

Flashcards in Introduction to Pharmacology and Toxicology- Biopharmaceuticals and gene therapy Deck (21):

What is a biological product?

- Includes proteins, antibodies and oligonucleotides and their use as drugs

- Use of nature to be used as therapeutic purposes

- Product on the market in the laboratory or going through clinical trials

- First and second generation biopharmaceuticals


What are first generation biopharmaceuticals?

Mainly copies of endogenous proteins or antibodies produced by recombinant DNA technology


What are second generation biopharmaceuticals?

Engineered to improve the performance of the protein or antibody


What is Recombinant DNA technology?

1. The plasmid is inserted contains cDNA version of mRNA required for protein of interest

2. Inserted into the bacteria

3. Slow production of protein is formed


How are biopharmaceuticals designed and used? What is specifically looked at?

1. Potency
2. Specificity
3. Side effects
These are all the intrinsic properties that you need to target the receptors and transporters you're interested in

4. Delivery- get the intrinsic properties in to have an effect
-Can't be delivered orally (especially peptide/protein)- as the enzymes in stomach will break it down- poor bioavailability

5. Can't/difficult to cross the blood brain barrier- size may be too big- may require surgery

6. Broken down by ubiquitous proteases- injected rapidly to be metabolised


What are the outside considerations you have to take into account for the production of biopharmaceuticals?

1. Manufacture
- Cost more to make than organic chemicals
- Yields may be low
- Purification- cows secrete protein into the milk
- Quality control- pure product and not contaminated with anything that isn't a therapeutic benefit

2. Stability
- Proteins often unstable= sensitive to heat and light etc- think about formulation and how to overcome these
- Storage and shelf life is an issue


What are the different routes of administration for the different forms of insulins?

1. Pulmonary delivery (aerosol, dry powder)- inhalation- inhaler

2. Transdermal delivery (patches, creams and sprays)- across the skin- hydrophilic


What are the main intracellular targets for biopharmaceuticals?

1. Mitochondrial/sub cellular targets- Lyosomal enzymes

2. Nuclear targets- DNA and RNA binding proteins

3. Cytoplasmic targets- kinases

4. Intracellular pathogens- inhibitors or promoters of fusion


What are the Therapeutic Proteins?

1. Peptide hormones- insulin, something to replace something missing which causes it to become dysfunctional

2. Therapeutic enzymes

3. Anti-bodies

4. Extracted from natural sources
- Pigs (insulins)
- Human Cadavers (growth hormone)

5. Recombinant DNA technology- insulin


What are the three examples of proteins that are used to replace a missing factor?

1. Insulin (hormone)- replaces insulin in type I diabetics who have reduced ability to produce insulin

2. Somatotropin (Hormone)- Growth hormone to prevent reduced stature- retarded growth

3. Factor VIII (8) (Coagulation Factor)- For haemophilia replaces a missing clotting factor in the blood


What is the insulin used for, its mechanism of action, how is it administered and what are the types?

Indication: Type I diabetes mellitus

Mechanism of action: Insulin receptor agonist

Administration: Subcutaneous injections (pen devices)

Types: Short acting and long acting- long acting is used to increase half life.


How is insulin produced via recombinant DNA?

1. Human pancreas cell has its insulin DNA producing gene cut out

2. This is implemented into plasmid DNA that's cut with restriction enzymes

3. A recombinant DNA is created and implemented into a bacterium thats put into a fermentation tank

4. Multiplying and producing human insulin- extraction and purification


What stimulates the production of red blood cells in treatment of chronic renal failure and anaemia in association with EPI deficiency?



What factor helps promote wound healing?

Platelet derived growth factor


What influences orthopaedic surgery, bone repair and promotes vertebral fusion?

Bone Morphogenic proteins


What factor influences hepatitis and multiple sclerosis?



What is the role of tPA?

1. Turns plasminogen (inactive) to plasmin (active)

2. This encourages the Thrombus (blood clot) to turn into a proteolytic degradation product


What are monoclonal antibodies?

1. Very specific antagonists
Y proteins
- bind to natural ligand- high degree of specificity
- neutralise effect
- may contain part of receptor

2. Humanised antibodies
- Overcome immune response

3. Disease modifying agents

Example: Infliximab- treatment of Crohn's disease


What are nano bodies?

Anti-bodies that are much smaller in terms of size and can be used for difficult target- this may be drugs for different anti-bodies and individual ion channels.


What is gene therapy?

1. The replacement of a defective gene with a normal healthy gene itself

2. The genetic modification of cells to prevent, alleviate or cure disease


What are some examples of uses of gene therapy?

1. The curing of monogenic diseases such as cystic fibrosis

2. Curing of neurodegenerative diseases and infectious diseases