Lecture 5 Peptide and Protein Flashcards
Describe the use of Peptides and Proteins as therapeutics.
Peptides and Proteins are used to replace deficient or abnormal proteins, augment existing pathways, provide novel functions, interfere with molecules or organisms, deliver compounds, act as vaccines, and assist in clinical decision-making.
Define the advantages of Peptides and Proteins as pharmaceuticals.
Advantages include:
* highly complex functions not mimicked by small molecules,
* high specificity reducing interference with normal processes,
* natural production for good tolerance,
* and effective replacement therapy for mutated or deleted genes.
How have advances in technology overcome the limitations of Peptides and Proteins as pharmaceuticals and what does this mean for medicine
Advances in recombinant DNA, protein engineering, and tissue culture techniques have helped in producing these molecules, reducing immunological responses, and improving therapeutic outcomes.
Do Peptide and Protein drugs face challenges in delivery?
Yes, challenges include low systemic availability when administered orally, due to factors like low solubility, degradation by GI enzymes, and poor uptake, among others.
Describe the challenges of Peptide and Protein drug delivery via subcutaneous administration.
Challenges include low systemic availability, but benefits include higher bioavailability (50-80%), better patient compliance, and depot-based formulations reducing dosing frequency.
How are absorption kinetics of Peptides and Proteins limited by capillaries or the lymphatic system?
Absorption kinetics are limited by physical barriers like structural proteins of the extracellular matrix and the maximum injectable volume versus the amount needed for therapeutic efficacy.
Describe the enzymatic barriers for protein/peptide delivery.
Enzymatic barriers involve proteolytic enzymes that break down peptides and proteins, including endopeptidases and exopeptidases.
How can peptides be rendered resistant to proteolytic attack?
Peptides can be made resistant by co-administration of protease inhibitors, substitution of (L) amino acids for (D) amino acids, and incorporation of non-cleaved peptide bond isosters.
Define physicochemical barrier in protein/peptide delivery.
Physicochemical barriers refer to the challenges faced by hydrophilic peptides and proteins in partitioning into cell membranes due to varying limitations in absorption by different mucosae.
What are the different classes of absorption enhancers for protein/peptide delivery?
- Chelators, (pronounced=keylaters)
- synthetic surfactants,
- natural and semi-synthetic surfactants,
- fatty acids and their derivatives,
- cell-penetrating peptides (CPP)
Describe the occurrence of proteolytic enzymes in the body.
Proteolytic enzymes occur in the:
* stomach (pepsin),
* GI luminal enzymes (pancreatic protease),
* brush-border membrane-bound (enteropeptidase),
* and liver enzymes (ALT, AST, ALP, GGT).
How does permselectivity affect the transportation of peptides and proteins?
Permselectivity refers to the selective ability of the epithelium for charged molecules, impacting the absorption of peptides and proteins by affecting the permeability of the epithelium.
Describe the dual dose-dependent effect ofadotropin-releasing hormone on theuitary gland.
In low doses, GnRH activates gonadotropin (LH & FSH) secretion, while larger, repeated doses block pituitary and gonadal function, leading to a down-regulation of gonadotropin secretion.
What are the primary clinical applications of GnRH?
The primary clinical applications GnRH include induction of ovulation and treatment of endometriosis.
How does bioavailability change with increasing hydrophobicity in GnRH analogues?
Bioavailability increases with increasing hydrophobicity in GnRH analogues.
