NAPSR Exam, CNPR_Answered_Latest 2023_A+ Rated
CNPR, NAPSR Exam_Answered_Latest
2023_A+ Rated
Drug Discovery
• Unlike small molecule drugs (pharmace... [Show More] uticals), large molecule drugs
(biopharmaceuticals) are mainly protein-based
o These protein-based drugs are similar to natural biological compounds found in
human body or they're fragments that mimic active part of natural compounds
Discovery of Pharmaceuticals
commences w/ scanning hundreds of compounds, whether w/ actual materials
(irrational approach) or virtual simulations (rational approach)
• Pharmaceuticals are new chemical entities (NCE) and are produced (synthesized)
in manufacturing plants using techniques based on chemical reactions of reactants
Discovery of Biopharmaceuticals
researchers have to examine compounds w/in humans
o Ex. Hormones or other biological response modifiers and how they affect
biological processes
o In some cases, study pathogens such as influenza virus or bacteria to derive
vaccines
o In other cases, researchers copy these biological response modifiers and use them
as replacement therapy
o Protein-based drugs are manufactured in biological systems, such as living cells,
producing desired protein molecules in large reaction vessels or by extraction from
animal serum
o Becoming increasingly important
• More potent and specific—more similar to proteins w/in body therefore more
effective in treating our diseases
Areas of Biopharmaceuticals
• Prophylactic→ preventive as in vaccines
• Therapeutic→ antibodies
• Replacement therapy→ hormones, growth factors
Biologics
FDA definition is:
o Biological product subject to licensure under Public Health Service Act is any
virus, therapeutic serum, toxin, antitoxin, vaccine, blood, a blood component or
derivative, allergenic produce, or analogous product, applicable to prevention,
treatment or cure of diseases or injuries to humans. Biological products include,
but are not limited to, bacterial and viral vaccines, human blood and plasma and
their derivatives, and certain products produced by biotechnology, such as
interferons and erythropoietins. Biologics encompass many different protein-based
drugs, and include blood products such as clotting factors extracted from blood.
Vaccines
• Basis of vaccination is that administering small quantity of a vaccine (antigen that
has been treated) stimulates our immune system and causes antibodies to be
secreted to react against foreign antigen
• Later in life, when we encounter another exposure to same antigen, our immune
system will evoke a memory response and activate defense mechanisms by
generating antibodies to combat invading antigen
• Contains antigenic components that are obtained from or derived from pathogen
o Include mainly viruses, bacteria, parasites and fungi
o Research has shown that part of pathogen that causes disease (virulence) can be
decoupled from protective part (immunity)
• Development focuses on means to reduce virulence factor while retaining
immunity stimulation
• Oral or parenteral
Vaccine Preparations
Attenuated Vaccines
Killed or Inactivated Vaccines
Toxoids
Attenuated Vaccines
• Virulence of pathogen that can be reduced in number of ways
• By chemical treatment, by temperature adaptation, or by growing pathogen in
specified other than natural host (passaging)
• Advantages are low cost preparation, elicit desired immunological response, and
normally single dose is sufficient
• Disadvantages are potential to revert to virulence and limited shelf life
Killed or Inactivated Vaccines
• Chemical and temperature treatment are normally used to kill or inactivate
pathogen
• Formaldehyde treatment most common method
• Other chemicals used are phenol and acetone
• Another method is to irradiate pathogen to render it inactive
• Advantages are non-reversal to virulence and relatively stable shelf life
• Disadvantages are higher cost of production, more control is required for
production to ensure reliable processes for complete inactivation and there is
possibility of reduced immunological response due to treatment processes so
multiple booster vaccinations may be required
Toxoids
• Derived from toxins secreted by pathogen
• Advantages and disadvantages similar to killed or inactivated
vaccines(advantages: non-reversal to virulence and relatively stable shelf life;
disadvantages: higher cost of production, more control is required for production to
ensure reliable processes for complete inactivation and there is possiblity of
reduced immunological response due to treatment processes so multiple booster
vaccinations may be required)
New Vaccines
• Advances in genomics, molecular biology and recombinant technology has
provided new directions for discovery, development and manufacture of vaccines
• Current approach is minimalist strategy to decouple virulence and immunity
functions
• Aim is to use only immunity part to confer protection, so vaccine is safe to be
administered
• Approach can be divided into subunit, vector-based, DNA and peptide vaccines
Subunit Vaccines
• Use only part of bacteria or virus instead of entire pathogen
• Part is derived from outside envelope protein of pathogen
• Requires knowledge of genome sequence of pathogen by identifying open
reading frames (ORF) that potentially encode novel antigenic surface proteins
known as epitopes, which bind to antibodies
• When identified, ORFs are cloned to express protein epitopes using self-
replicating plasmids
• Binding properties of epitopes can be studied using enzyme linked
immunosorbent assay (ELISA) or fluorescent activated cell sorter (FACS)
• Leading candidates of epitopes are injected into animals to determine whether
they elicit any antibody response
o Those that work are selected and optimized to become vaccine candidates w/
further tests before human clinical trials
o Also working on multiple epitope subunit vaccines which can provide different
antigenic binding sites
Vector-based Vaccines
• Viruses and bacteria are detoxified and used as vehicles to carry vaccines
• Subunit vaccines are being delivered by carrier vehicles to elicit immune
response
• Multiple types of envelope proteins can be delivered w/ this method
• Clinical trials w/ this type of vector-based vaccines are being investigated
DNA Vaccines
• Aka nucleic vaccines or genetic immunization
• Host (patient) is directly injected w/ selected viral genes which contain
engineered DNA sequences that code for antigens
• Hosts own cells take up these genes and express antigens which are then
presented to immune cells and activate immune response
Peptide Vaccines
• Chemically synthesized and normally consist of 8-24 amino acids
• Relatively small
• Aka peptidomimetic vaccines as they mimic epitopes
• Complex structures of cyclic components, branched chain or other configurations
can be built into peptide chain
• They possess conformations similar to epitopes and can be recognized by
immune cells
• An in silico vaccine design approach has been used to find potential epitopes
• Critical aspect of peptide vaccines is to produce 3D structures similar to native
epitopes of pathogen
Adjuvant
• Vaccines formulated w/ certain substances to enhance immune response
• Latin adjuvare→ to help
• Most common adjuvants for humans are aluminum hydroxide, aluminum
phosphate and calcium phosphate
• Others include bacteria and cholesterol
• Mineral oil emulsions normally adjuvants used in animal studies
• Adjuvant known as Freund's Complete Adjuvant consists of killed tubercle bacilli
in water-in-mineral oil emulsion
• Freund's Incomplete Adjuvant is water-in-oil emulsion
• Both effective in stimulating immune response but cause unacceptable side
effects in humans
3 Mechanisms Adjuvants Help Immune Response
• Adjuvants help immune response by forming reservoirs of antigens and providing
sustained release of antigens over long period
• Adjuvants act as non-specific mediators of immune cell function by stimulating
or modulating immune cells
• Adjuvants can serve as vehicles to deliver antigen to spleen and/or lymph nodes
where immune response is initiated
Alzheimer's Disease
• Vaccine being tested contains small protein called B amyloid (AB)
o This protein forms abnormal deposits or "plaques" in the brains of individuals w/
Alzheimer's
o It's believed that AB deposition Causes loss of mental fxn by killing brain
neurons
o AB vaccination stimulates immune system to clean up plaques and prevent
further AB deposits
o Phase II clinical trial was halted because 15 of 360 patients developed severe
brain inflammation
• Studies showed that AB did generate desired antibody response
• Acceptable vaccine may still be possible by modifying epitope to reduce
inflammation effects
Pneumococcal
• In Oct 2006, FDA approved use of Prevnar for immunization of infants and
toddlers against otitis media middle ear infection
o Prevnar is pneumococcal seven-valent conjugate vaccine
• Formulated w/ sterile solution of saccharides conjugated to antigen
Cancer
• In cancer, immune system doesn't recognize changes in cancer cells
• Cancer vaccines seek to mimic cancer-specific changes by using synthetic
peptides to challenge immune system
o When these peptides are taken up by T cells, immune system is activated
o T cells search for cancer cells w/ specific markers and proceed to kill them
• Vaccines being tested are peptide called B-defensin 2 which activates immune
system against tumor activity and outer coat protein of human papilloma virus act
as vaccine against cervical cancer
AIDS
• Caused by HIV infection
• HIV belongs to large family of retroviruses, Lenti virus
• HIV genome is w/in RNA
• RNA genome of HIV is reverse-transcribed into DNA and integrated w/in human
cell
• HIV undergoes frequent mutation and therefore highly variable
• Technique for producing AIDS vaccine is to reproduce, using recombinant
technology, the surface proteins on HIV
o 2 particular envelope proteins being investigated
• gp120 and gp41
• trimeric protein and held together by 3 transmembrane gp41 proteins
• Vaccines based on these proteins can induce antibody responses to different
strains of HIV
• Other AIDS treatments are use of antiviral (AZT, reverse transcriptase inhibitor)
drugs, drugs (indinavir) that target and inhibit production of HIV protease, and
enzyme required to assemble new virus particles and gene therapy—control of
viral genome expression through use of synthetic oligonucleotides
Malaria
• Major disease in tropical countries
• According to WHO, 300-500million individuals are infected w/ malaria
o Death tolls are 1.5-3.5million people yearly
• 4 species of malaria parasites that infect humans
o plasmodium falciparum
• predominant malarial parasite found in Africa and most virulent
o P. vivax
o P. ovale
o P. malariae
• Vaccine strategies are of 3 types:
o Pre-erythrocytic
o Blood stage
o Transmission-blocking stage
Chicken Pox
• Highly contagious viral infection that causes rash-like blisters on skin surface and
mucous membranes
• mild and not normally life-threatening
o can be deadly to pregnant women, people w/ leukemia, or immunosuppressed
patients
• Varivax from Merck tested on about 11,000 children and adults and was
approved by FDA as chicken pox vaccine
Human Immune System [Show Less]
