Medicines design Flashcards
What is salbutamol?
- A SABA (short-onset, short duration bronchodilator)
- treating symptoms of asthma and COPD
- provide short-term relief
What are the 4 methods of structural modification for SAR?
- Chain extension
- Conformational restriction
- Group shifting
- Chiral switching
What are the 4 methods of choosing a lead compound?
- Natural receptor ligands (ACh, NA)
- Collection of synthetic compounds
- Existing drugs
- Natural products (muscarine)
What are the 2 types of cholinergic receptor?
Nicotinic
Muscarinic
Whats the difference between b1 and b2 adrenoceptors?
b1 contracts cardiac muscle, found in heart
b2 relaxes smooth muscle, found in airways
What are the 2 enveloped proteins contained in influenza viruses and what do they do?
Haemagglutinin (HA): functions in attachment and penetration
Neuraminidase (NA): a glycoside hydrolase that cleaves glycosidic linkages, and faciliates virus release from infected cells
How does the structure of Haemagglutinin aid its role?
Haemagglutinin protein is comprised of two domains.
- Globular head
- Fibrous stem
The globular head of Haemagglutinin binds to the cell surface receptor sialic acid, the tail is latched to the membrane of the cell
What is the function of neuraminidase?
Neuraminidase (N) protein is an enzyme that breaks down the sialic acid receptor on the cell surface to gain entry.
Many pathogens have acquired neuraminidases to facilitate infection
Once sialic acid is removed from the receptor by neuraminidase, the Heamagglutinin protein no longer binds.
What is the innate response to influenza?
NFκB transcription thus leads to pro-inflammatory cytokine gene expression of TNFα, IFNβ and IL-8.
Chemokines and cytokines produced increase inflammatory response by attracting NK, B and T cells to the infection site.
These cells still continue to produce more inflammatory cytokines to keep the Th1 response cycle going
What is NFκB?
Nuclear factor kappa-light-chain-enhancer of activated B cells.
It is a family of transcription factor protein complexes that controls transcription of DNA, cytokine production and cell survival.
What are the 6 long term responses to influenza infection?
- IFNγ boosts chemokine gene expression, activation of macrophages, antigen presentation and continual development of specific cell-mediated immunity.
- Th2 response
- T cell stimulation
- Antigen Presentation
- B cell maturation
- Antigen-specific IgG production
What is IFNγ?
Interferon-gamma
A cytokine that activates of macrophages to increase phagocytosis and intracellular killing of pathogens.
What are the 4 types of influenza virus?
A, B, C and D.
Human influenza A and B viruses cause seasonal epidemics of disease almost every winter.
Influenza type C infections generally cause a mild respiratory illness and are not thought to cause epidemics.
Influenza D viruses primarily affect cattle and are not known to infect or cause illness in people.
What are influenza A sub-types?
Influenza A viruses are divided into subtypes based the hemagglutinin and neuraminidase
There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes.
Current subtypes of influenza A viruses found in people are influenza A (H1N1) and influenza A (H3N2) viruses.
An IgG antibody will only recognise the ONE sub-type of H or N it was generated against
What is antigenic drift?
Gradual accumulation of amino acid mutations that allow the hemagglutinin to escape neutralizing antibodies
Epidemic strains of influenza are thought to have changes in three or more antigenic sites
Antigenic drift results in a reduced ability of circulating antibodies to recognise the ‘new’ virus.
What is seasonal flu?
- Most common form and usually comprises a variant of a previous strain
- We can anticipate the likely strain to emerge and prepare vaccines in preparedness
- As the new strain is usually derived from a previous strain, much of the population will already have at least partial immune protection
- While seasonal influenza (flu) viruses can be detected year-round, flu viruses are most common during the winter.
- Most of the time flu activity peaks between December and February, although activity can last as late as May.
How are influenza vaccines made?
- These vaccines are produced by growing the bacteria or virus in culture media then inactivating it with heat and/or chemicals (usually formalin).
- Inactivated vaccines are not alive and cannot replicate. The entire dose of antigen is administered in the injection. These vaccines cannot cause disease from infection, even in an immunodeficient person.
- In general, the first dose does not produce protective immunity, but only “primes” the immune system. A protective immune response develops after the second or third dose.
What are the 2 pros and 2 cons of flu vaccines?
Pros:
- Generally safer
- Improved stability
Cons:
- Can be costly
- Hypersensitivity
What are the 4 critical factors of flu vaccines?
Growth potential of seed virus
- The quantity of vaccine that can be produced is limited by the least productive strain
Timing of strain selection
- Available production time is limited due to administering vaccine prior to influenza season, seed require 4 weeks for development
Potency test reagents
- Required to determine the potency of monovalent components prior to formulation of vaccine
- Must be produced/standardized for new strains
Timing of Annual License Supplement Approval
- Required to begin packaging process
