Biologics Flashcards
what is meant by biological? and in this context what is considered as biologicals?
any medicinal product manufactured in or extracted from biological sources.
peptides and proteins
which receptor does the alpha-bungarotoxin binds to?
post synaptic nicotinic Ach receptor
name the receptors/channels inhibited by these toxin:
- alpha-conotoxin
- delta-conotoxin
- kappa-conotoxin
- mu-conotoxin
- omega-conotoxin
- inhibits nAchr at nerves and muscles
- inhibits the inactivation of VG Na channels
- inhibits potassium channels
- inhibits VG na channels in muscle
- Inhibits N-type VG Ca channels
what class of drug is captopril? describe its mechanism of action
Angiotensin Converting Enzyme inhibitors.
this inhibition would block the conversion of Ang I to Ang II (potent vasoconstrictor). This would lower arteriole resistance, increase venous capacity, decrease cardiac output and stroke volume -> lower resistance in blood vessel of the kidney -> increased natriuresis -> lower blood pressure
how does a ‘rational drug design’ demonstrated when designing the first catropil
ACE inhibitors isolated from a snake venom and is originally a large peptide -> identified the active region and isolate it -> create drugs which consist of the active region -> simpler form of ACE (therefore it is taking a more complex structure to simpler one)
what is an MMR vaccine?
what is an inactivated vaccines?
what is a recombinant vaccines?
measles, mumps and rubella with attenuated, drastically reduced virulence virus but they are still viable
virus particles that has been inactivated
recombinant vaccines present antigenic proteins from the pathogen in order to stimulate an immune response
why is producing protein in yeast cells is more beneficial than in E.coli?
yeast cells has nucleus and the proteins produced are able to be folded and made into functional protein. in E.coli, the protein is made in the cytoplasm and therefore no folding -> no functional protein
what is the important factor in the formation of disulphide bridges in insulin?
proper folding of the molecule
this demonstrate the importance of protein folding to make a functional one
which disorder uses enzyme replacement therapy?
lysosome storage diseases
- Gaucher’s disease
- Fabry disease
- Hunter syndrome and Battens disease
name the enzymes used in the treatment of lysosome storage disease
- VIMZIM (elosulfase alpha)
- Naglazyme
- Aldurazyme
which fragment of an antibody possesses high degree of variability?
describe the other fragment present in antibody
Fab fragment, where antigen binds
Fc fragment, crystallisable and gives antibody its stability. it interacts with cell surface receptors
what is an antivenin? explain how it works.
antivenin is an antivenin used livestock with venomous bite
toxin obtained from venomous animal injected in small amount to domestic animal. antibodies formed is purified from the blood and made into serum
antibody is able to bind to toxin and soaked it up like sponge
where is the birth place of B cells and how many antibody can it formed?
generated in the bone marrow and it can only give rise to one type of antibody
explain how monoclonal antibodies are formed
- inject mice with a small amount of antigen to provoke an immune response
- B cells producing antibodies complementary to the antigen is harvested from the spleen and isolated
- B cells fused with B cancer cells, myeloma to produce hybrid cell line hybridoma
- starting with one viable Hybridoma, the cell is placed in culture (HAT medium)
- ended up with genetically identical hybridomas producing the same antibody
OXIZU what is this?
suffix for antibodies
- omab: suffix for murine monoclonal antibody
- ximab and zumab: suffix for chimeric and humanised antibody
- umab: suffix for human monoclonal antibody
what is a:
- murine monoclonal antibody
- chimeric and humanised monoclonal antibody
- human monoclonal antibody?
- antibody in which both chains are from a mouse origin.
- chimeric: when the variable region is of a foreign species origin but the constant region is of human origin
humanised: grafting murine variable region into human antibody
humanised: variable region is engineered to be almost identical to the variants in humans
what is TNF-alpha, what does it do and what is the outcome of dysregulation of TNF-alpha
TNF alpha is a cytokine secreted by activated macrophages which regulates immune response.
The dysregulation of TNF alpha results in autoimmune disorder such as rheumatoid arthritis, ankylosing, spondylitis, inflammatory bowl disease, psoriasis and asthma
name two monoclonal antibodies which binds to TNF alpha and neutralises its activity and state which category of monoclonal antibody they fall into
infliximab - chimeric murine monoclonal antibody
adalimumab - humanised monoclonal antibody (human monoclonal)
what is etanercept?
etanercept is a fusion between TNF receptor and antibody constant region. it is not a monoclonal antibody but it binds and inhibits the action of TNF-alpha
what is retuximab and how is it use in anti-cancer therapies?
retuximab is a chimeric murine monoclonal antibody against CD-20 protein found on the surface of B cells. it is use in the treatment of lymphoma cancer, leukemias, transplant rejection and some autoimmune disorder
what is ibritumomab (zevalin) describe its constituents
murine monoclonal antibody against CD-20 conjugated with chelator (tiuxetan) which binds to radioactive isotopes yttrium-90 and indium-111
state what type of antibody is cetuximab and panitumumab, the type of cancer that they treat and their mechanism of action
cetuximab is a chimeric murine monoclonal antibody
panitumumab is a humanised monoclonal antibody from XenoMouse
both treat metastatic colorectal (bowel cancer)
both antibodies bind to EGFR receptor, preventing its activation and tumour growth (no cascade of intracellular signalling)
what is Trastuzumab which cancer does it treat and describe its mechanism of action
Trastuzumab is a humanised monoclonal antibody which treats some type of breast cancer which has over expression of HER2. It binds to HER2 causing down regulation of the receptor
what is an ado-trastuzumab emtansine, which cancer does it treat and describe its mechanism of action
ado-trastuzumab emtansine is an antibody-drug conjugate, covalently linked to cytotoxic agent (mertansine). binds to HER2 and causes internalisation
what is age related macular degeneration?
medical condition where the centre field of vision is blurred or no vision at all, due to damage to the macula of retina
what is the name of the receptor associated with age related macular degeneration and name the ligand
VEGFR 1 and 2, ligand: VEGF-A
name two antibody used in the treatment of age related macular degeneration and state what it targets
Bevacizumab and ranibizumab (monoclonal antibody fragment derived from bevacizumab consisting of the Fab region of bevacizumab). Both antibodies bind to VEGF A, inhibiting its activity (prevent binding to receptors)
describe the structure of alfibercept
it is a recombinant protein, a fusion of VEGFR1 and 2 and Fc of human IgG1
what is Racotumomab?
it is a therapeutic cancer vaccines (anti-idiotype) which raised an immune response against tumour antigen, Neu-glycolyl GM3 ganglioside (over expressed in several solid tumours)
what is omazilumab? what does it treat?
(Xolair) used in reducing sensitivity to allergens. it is a humanised murine monoclonal antibody which specifically binds to human IgE. This particular anti-IgE does not bind to IgE that is already bound to its receptor on the surface of mast cells therefore avoids activation that would relate histamine, leukotrienes and other inflammatory molecules which result in allergy symptoms
what class of drug is motesanib or levatinib?
they are VEGF antagonist and is a tyrosine kinase inhibitors
what are microRNA and siRNA?
what is the difference between the two?
siRNA: double stranded RNA molecule with interferes with specific gene expression
microRNA: non-coding RNA which interferes with post-transcriptional regulation of gene expression
siRNA being double stranded is derived from the double stranded region of RNA transcript whereas microRNA is derived from the region which forms the hairpin loop
