(PM3B) Biomacromolecules + Biologics Flashcards
What is a biologic?
A biomacromolecule used as a drug
How does a biologic differ from a small molecule? What can be said for their route of delivery?
(1) >1000g/M - instead of <500g/M
(2) Organic (hydrophilic polypeptide) instead of a carbon chain
(3) High complexity, a single protein, moderate heterogeneity (slight mixture)
(4) Both delivered at site of action
Give 3 examples of a biologic.
(1) Flu vaccine
(2) Monoclonal antibodies
(3) Insulin
What is the most common route of administration for biologics?
Injection - parenterally
What 4 categories can biologics be grouped into?
(1) Gene therapy - nucleic acids
(2) Polypeptides - e.g. proteins and peptides
(3) Polypeptides - e.g. monoclonal antibodies
(4) Vaccines
What are some general pharmaceutics challenges for biologics/ biomacromolecules?
(1) Increased complexity
(2) Instable - inherent from biological origin
(3) Limited availability
(4) Immunogenicity - drug hypersensitivity to immune response - can lead to loss of efficacy
Why types of complexity is there for biologics?
(1) Molecular complexity
(2) Functional complexity - more expensive to produce
(3) Composition complexity - manufacturing/ distribution issues
What are biologics/ biomacromolecules unstable?
Formulations can go mouldy/ grow bacteria
Are proteins stable?
No
Inherently unstable
Why are proteins unstable?
(1) 3-4 layers of structure
(2) Polypeptide chain is susceptible to reactions with water/ oxygen
(3) Many changes are irreversible
What are the 3-4 layers of structure of a protein?
(1) Primary structure
(2) Secondary structure - helices/ pleated sheets
(3) Tertiary structure - 3 dimensional structure
(4) Quaternary structure
What is a common problem with biologic/ biomacromolecule drugs?
Often oral unsuitable - digested as food
What type of biologic is insulin?
Polypeptide - proteins/ peptides
How is insulin most often administered?
Subcutaneously
What is the general purpose of a polypeptide biologic?
To emulate an endogenous protein
What are 2 methods of pharmaceutical protein manufacture?
(1) Biotechnology
- Produced in microbial/ animal cell cultures
- Isolated via chromatographic + filtration steps
(2) Isolate from blood
- From blood/ tissue of animal
What is a major downside of isolating biologics from animals’ blood/ tissue?
Transfer of viral infection
What are 3 different types of insulin?
(1) Purified animal insulin
(2) Recombinant human insulin
(3) Variants of human insulin - changes speed of onset/ duration of action
What is a hexema (6-mer)?
6 insulin molecules around a zinc ion
What are 3 possible treatment regimes for Type 1 Diabetes?
(1) 1/2/3 insulin injections per day
- Short or rapid-acting
(2) Multiple daily injections (before meals)
(3) Continuous SC insulin infusion
- Programmable pump
What are the routes of administration possible for insulin?
(1) IV
(2) SC
What would be the advantages/ disadvantages of needle-free injectors?
(1) Fewer needles
(2) Complex to use + can cause bruising
Why can insulin not be administered transdermally?
Poor bioavailability - due to high Mr and hydrophilicity
What route of administration for insulin is most common in hospitals?
Intravenous injection/ infusion
