Nur 552 Midterm Questions With Complete Solutions
1980s... Introduction of modern biologics based on recombinant
DNA technology and monoclonal antibodies that transformed
medicine Correct Answers • 1982 First approval of a rDNA
Insulin
- Lilly recombinant human insulin (HUMULIN-R). First human
healthcare product from recombinant DNA technology to reach
the market
• 1984: Nobel Prize awarded to Niels K. Jerne, Georges J. F.
Köhler and César Milstein
- Theories concerning the specificity in development and control
of the immune system and the discovery of the principle for
production of monoclonal antibodies
• 1985: First approval of a monoclonal antibody for use in
humans
- Anti-CD3 antibody muromonab-CD3 receives U.S. FDA
approval for use in preventing transplant rejection
• Biologics drug development was in its nascent stage
1980s were at the early stages of biologics whereas small
molecules were very well-known
1980s....small molecules Correct Answers • Drug Price
Competition and Patent Term Restoration Act enacted
- "Hatch-Waxman Act": how a generic drug is established and
used
• Abbreviated New Drug Application (ANDA)
,• Defined "Bioequivalence"
• Small molecule drug development was established
- well-understood that if the active ingredient has the same PK
profile, it had the same therapeutic effect
- how generics could be approved
Additional clinical examples of erythrocyte-based delivery
Correct Answers • Enzyme replacement for lysosomal storage
diseases (Gaucher's disease)
- difficult to treat
- macrophages rely heavily on lysosome for their activity
• Depletion of macrophages by targeting toxin- loaded RBC to
alleviate acute graft injury after transplantation
• Covalent attachment of tPA, urokinase or other anti
thrombolytic agents for treatment or prevention of blood clotting
• Sustained administration of enzymes—e.g., Adenosine
deiminase for ADA
Advantages of Liposomes Correct Answers - Drugs are
delivered intact to various tissues and cells and released when
the liposome is destroyed, enabling prolonged and/or site
specific and targeted delivery
- Tissues and cells are protected from the drug until released,
thus reducing toxicity
- Liposomes are biocompatible
- Can be administered in many ways, skin, lungs, IV, eye
--> don't take liposome orally because it won't survive in the GI
environment
--> so administer through IV and make sure it's small enough
that it remains intact
,Advantages of Modified/Sustained Release Correct Answers -
Reproducible rate, prolonged delivery
- Less frequent administration
- Better patient compliance
- Increased convenience
- Reduced side effects because an effective
--> Concentration is maintained
- Targeting can eliminate damage to non- target organs
- Less drug used
- Re-patenting without new drug development
Advantages of Polymers Correct Answers - Versatile-may be
used for small molecules and macromolecules (protein, DNA,
RNA)
- Administered dose can be subdivided into smaller units
- Release rate can be delayed or controlled/sustained
- Various dosage forms-Can be implanted
- Example: KCl is very irritating to the GI tract, so if it's spread
out it can cause less irritation
Advantages to biologics Correct Answers • Availability of
well established and broadly applicable methods for antibody
generation and optimization
• A growing repertoire of technologies to re-design antibodies
with modified or new properties to enhance their clinical
potential
• High success rate compared to other drugs
- up to 32% from FIH to regulatory approval
, • Often well tolerated by patient
- less side effects because *of high specificity towards target*
- healthy tissue either won't have target or will be less expressed
- small molecules don't distinguish between normal tissues and
abnormal tissues so you get toxic effects
• Broad experience and expanding knowledge
Aemcolo or rifamycin Correct Answers - for traveller's
diarrhea
- delay release into colon for better therapeutic effect
- drug crystallized inside tablet with excipients around and a
delayed released layer on top, so it doesn't get released into the
colon until it's needed
Afrezza Correct Answers - Mannkind insulin inhaler and
approved from FDA in 2014
- small, easily portable
- particle size is different
- MannKind claims that Afrezza is significantly different,
mainly because Exubera used a clunky foot-long inhaler and
was linked to a higher lung cancer risk that Pfizer just couldn't
overcome
- However, after the first sales in 2015, the market has lagged
considerably behind the corresponding performance of Exubera
a decade earlier
- still on market though
Antibody Drug Conjugates for Oncology Correct Answers
ADC = Targeting Antibody + Cytoxic Drug and Linker
1980s... Introduction of modern biologics based on recombinant
DNA technology and monoclonal antibodies that transformed
medicine Correct Answers • 1982 First approval of a rDNA
Insulin
- Lilly recombinant human insulin (HUMULIN-R). First human
healthcare product from recombinant DNA technology to reach
the market
• 1984: Nobel Prize awarded to Niels K. Jerne, Georges J. F.
Köhler and César Milstein
- Theories concerning the specificity in development and control
of the immune system and the discovery of the principle for
production of monoclonal antibodies
• 1985: First approval of a monoclonal antibody for use in
humans
- Anti-CD3 antibody muromonab-CD3 receives U.S. FDA
approval for use in preventing transplant rejection
• Biologics drug development was in its nascent stage
1980s were at the early stages of biologics whereas small
molecules were very well-known
1980s....small molecules Correct Answers • Drug Price
Competition and Patent Term Restoration Act enacted
- "Hatch-Waxman Act": how a generic drug is established and
used
• Abbreviated New Drug Application (ANDA)
,• Defined "Bioequivalence"
• Small molecule drug development was established
- well-understood that if the active ingredient has the same PK
profile, it had the same therapeutic effect
- how generics could be approved
Additional clinical examples of erythrocyte-based delivery
Correct Answers • Enzyme replacement for lysosomal storage
diseases (Gaucher's disease)
- difficult to treat
- macrophages rely heavily on lysosome for their activity
• Depletion of macrophages by targeting toxin- loaded RBC to
alleviate acute graft injury after transplantation
• Covalent attachment of tPA, urokinase or other anti
thrombolytic agents for treatment or prevention of blood clotting
• Sustained administration of enzymes—e.g., Adenosine
deiminase for ADA
Advantages of Liposomes Correct Answers - Drugs are
delivered intact to various tissues and cells and released when
the liposome is destroyed, enabling prolonged and/or site
specific and targeted delivery
- Tissues and cells are protected from the drug until released,
thus reducing toxicity
- Liposomes are biocompatible
- Can be administered in many ways, skin, lungs, IV, eye
--> don't take liposome orally because it won't survive in the GI
environment
--> so administer through IV and make sure it's small enough
that it remains intact
,Advantages of Modified/Sustained Release Correct Answers -
Reproducible rate, prolonged delivery
- Less frequent administration
- Better patient compliance
- Increased convenience
- Reduced side effects because an effective
--> Concentration is maintained
- Targeting can eliminate damage to non- target organs
- Less drug used
- Re-patenting without new drug development
Advantages of Polymers Correct Answers - Versatile-may be
used for small molecules and macromolecules (protein, DNA,
RNA)
- Administered dose can be subdivided into smaller units
- Release rate can be delayed or controlled/sustained
- Various dosage forms-Can be implanted
- Example: KCl is very irritating to the GI tract, so if it's spread
out it can cause less irritation
Advantages to biologics Correct Answers • Availability of
well established and broadly applicable methods for antibody
generation and optimization
• A growing repertoire of technologies to re-design antibodies
with modified or new properties to enhance their clinical
potential
• High success rate compared to other drugs
- up to 32% from FIH to regulatory approval
, • Often well tolerated by patient
- less side effects because *of high specificity towards target*
- healthy tissue either won't have target or will be less expressed
- small molecules don't distinguish between normal tissues and
abnormal tissues so you get toxic effects
• Broad experience and expanding knowledge
Aemcolo or rifamycin Correct Answers - for traveller's
diarrhea
- delay release into colon for better therapeutic effect
- drug crystallized inside tablet with excipients around and a
delayed released layer on top, so it doesn't get released into the
colon until it's needed
Afrezza Correct Answers - Mannkind insulin inhaler and
approved from FDA in 2014
- small, easily portable
- particle size is different
- MannKind claims that Afrezza is significantly different,
mainly because Exubera used a clunky foot-long inhaler and
was linked to a higher lung cancer risk that Pfizer just couldn't
overcome
- However, after the first sales in 2015, the market has lagged
considerably behind the corresponding performance of Exubera
a decade earlier
- still on market though
Antibody Drug Conjugates for Oncology Correct Answers
ADC = Targeting Antibody + Cytoxic Drug and Linker
