BPS MODULE 6 EXAM QUESTIONS
AND ANSWERS
What helps control dissolution of insulin drug - Answer-Crystal form
- At 10^-3 M, the insulin is in its oligomeric form
- When injected, hexamers precipitate at injection site, slowly dissolving and providing
approximate basal concentrations
When did insulin pumps become practical - Answer-In late 1990's with a cell phone
Insulin pump - Answer-- Small pump with an insulin reservoir ( computer controller)
- Delivers constant supply of small amounts of insulin (mimics basal action)
- Can be adjusted for bolus delivery (short duration for meals
Why is insulin not an ideal drug - Answer-- Concentrated solution
- Injection site variation
- Variation in precipitation and dissolution
- Basal concentration variability
- Slow onset
Use of fast acting insulin - Answer-- Designed for use before a meal
- Crystals dissolve quicker
Use of slow (long) acting insulin - Answer-- Designed to mimic basal levels
- Slow, even dissolution rate
Creation of fast acting insulin - Answer-1. Modify amino acids to speed dissolution
2. Insulin-like growth factor 1 (IGF-1) has similar amino acid sequence to insulin
- Order of Pro (B28) and Lys(B29) reversed
- protein tends not to oligomerize
- Dissolves quickly
3. Switch the ordr of amino acids at positions B28 and B29 in insulin!
What drug is fast acting insulin - Answer-Lispro
Lispro characteristics - Answer-- Does not self-associate well
- Zinc crystals break up quickly ( dissolves 300x faster than injected human insulin)
, - Good for bolus injections before meals
Aspart (2017) drug - Answer-- Proline at position B28 replaced by asparatic acid
creating a charge repulsion and a less stable crystal
- crystal dissolves quickly
- Good for bolus injections before meals
What speeds dissolution - Answer-Charge repulsion
Long lasting insulin - Answer-- Slow dissolution increases time between injections
- Less variation in blood amounts
- Achieve by lower solubility ( crystals take longer to dissolve)
Glargine (2000) - Answer-- Designed as a long lasting insulin
- Two arginines added to B chain ( now 32 amino acids)
- Lowers the soluility
Isoelectric point - Answer-- The Ph at which overall charge on a zwitterionic molecule is
zero
- In proteins, determined by pKa's of N-terminus, C-terminus and side chain groups
Fatty acid attachment to insulin - Answer--Lowers water-solubility (slower dissolution)
- Drug becomes soluble in subcutaneous fat (slow release and even rate of dissolution)
Advantages of genetic manufacturing - Answer-- Less risk of contamination (allergy and
viruses)
- Large quantities easily available (lower cost)
- Possible to modify protein properties to make them more "drug-like"
Diabetes - Answer-Family of metabolic disorders characterized by high (or low) blood
sugar concentrations
- cardiovascular problems
- Kidney disease
- Skin Ulcers
- Eye damage
How many people are affected by diabetes - Answer-greater than 170 million affected
Diabetes yearly death rate - Answer-3.2 million deaths per year
What is responsible for the regulation of blood glucose concentrations - Answer-Insulin
Insulin - Answer-Hormone produced by the pancreas
What are the roles of protein - Answer-1. Regulate metabolism of carbohydrates, fat
and protein
AND ANSWERS
What helps control dissolution of insulin drug - Answer-Crystal form
- At 10^-3 M, the insulin is in its oligomeric form
- When injected, hexamers precipitate at injection site, slowly dissolving and providing
approximate basal concentrations
When did insulin pumps become practical - Answer-In late 1990's with a cell phone
Insulin pump - Answer-- Small pump with an insulin reservoir ( computer controller)
- Delivers constant supply of small amounts of insulin (mimics basal action)
- Can be adjusted for bolus delivery (short duration for meals
Why is insulin not an ideal drug - Answer-- Concentrated solution
- Injection site variation
- Variation in precipitation and dissolution
- Basal concentration variability
- Slow onset
Use of fast acting insulin - Answer-- Designed for use before a meal
- Crystals dissolve quicker
Use of slow (long) acting insulin - Answer-- Designed to mimic basal levels
- Slow, even dissolution rate
Creation of fast acting insulin - Answer-1. Modify amino acids to speed dissolution
2. Insulin-like growth factor 1 (IGF-1) has similar amino acid sequence to insulin
- Order of Pro (B28) and Lys(B29) reversed
- protein tends not to oligomerize
- Dissolves quickly
3. Switch the ordr of amino acids at positions B28 and B29 in insulin!
What drug is fast acting insulin - Answer-Lispro
Lispro characteristics - Answer-- Does not self-associate well
- Zinc crystals break up quickly ( dissolves 300x faster than injected human insulin)
, - Good for bolus injections before meals
Aspart (2017) drug - Answer-- Proline at position B28 replaced by asparatic acid
creating a charge repulsion and a less stable crystal
- crystal dissolves quickly
- Good for bolus injections before meals
What speeds dissolution - Answer-Charge repulsion
Long lasting insulin - Answer-- Slow dissolution increases time between injections
- Less variation in blood amounts
- Achieve by lower solubility ( crystals take longer to dissolve)
Glargine (2000) - Answer-- Designed as a long lasting insulin
- Two arginines added to B chain ( now 32 amino acids)
- Lowers the soluility
Isoelectric point - Answer-- The Ph at which overall charge on a zwitterionic molecule is
zero
- In proteins, determined by pKa's of N-terminus, C-terminus and side chain groups
Fatty acid attachment to insulin - Answer--Lowers water-solubility (slower dissolution)
- Drug becomes soluble in subcutaneous fat (slow release and even rate of dissolution)
Advantages of genetic manufacturing - Answer-- Less risk of contamination (allergy and
viruses)
- Large quantities easily available (lower cost)
- Possible to modify protein properties to make them more "drug-like"
Diabetes - Answer-Family of metabolic disorders characterized by high (or low) blood
sugar concentrations
- cardiovascular problems
- Kidney disease
- Skin Ulcers
- Eye damage
How many people are affected by diabetes - Answer-greater than 170 million affected
Diabetes yearly death rate - Answer-3.2 million deaths per year
What is responsible for the regulation of blood glucose concentrations - Answer-Insulin
Insulin - Answer-Hormone produced by the pancreas
What are the roles of protein - Answer-1. Regulate metabolism of carbohydrates, fat
and protein
