Phar 323 - Peptide Drugs

Front 1

What are the characteristics of Small Molecules? (4)

Back 1

1) MW <500 Daltons

2) Favours Oral Bioavailability

3) Simple Administration

4) Good Patient Compliance

5) Reduced target selectivity

Front 2

What are the characteristics of Peptide Drugs? (3)

Back 2

1) High MW >700 Daltons

2) Defined as <50 amino acids

3) High Hydrophilicty

Front 3

What are the characteristics of Biologics? (4)

Back 3

1) Exquisite potency and selectivity

2) MW >5000 Daltons

3) Not orally bioavailable

4) Fewer side effects

Front 4

What are the advantages of Peptide drugs relative to Small Molecules? (3)

Back 4

1) Often greater efficacy and selectivity

2) Low accumulation in tissues

3) Minimal systemic toxicity

Front 5

What are the advantages of Peptide drugs relative to Biologics? (4)

Back 5

1) Better penetration into tissues

2) Lower manufacturing costs

3) Higher activity per unit mass

4) Often less immunogenic

Front 6

What are the disadvantages of Peptide drugs relative to Small Molecules? (4)

Back 6

1) Poor metabolic stability

2) Poor membrane permeability

3) Low oral bioavailability

4) Efficient hepatic and renal damage

Front 7

What are the disadvantages of Peptide drugs relative to Biologics? (2)

Back 7

1) Less specific

2) Short half-life

Front 8

What are the advantages of Oral Delivery Systems? (1)

Back 8

Avoids pain and discomfort

Front 9

What are the advantages of Injection Delivery Systems? (1)

Back 9

Avoids GI tract and first pass metabolism

Front 10

What are the advantages of Pulmonary Delivery Systems? (2)

Back 10

1) High absorption via alveolar epithelium

2) Avoids GI degradation and first pass metabolism

Front 11

What are the advantages of Transdermal Delivery Systems? (2)

Back 11

1) Avoids GI degradation and first pass metabolism

2) Excellent barrier for large hydrophilic compounds

Front 12

What are the advantages of Nasal Delivery Systems? (3)

Back 12

1) High permeability of epithelium

2) Rapid absorption (similar to IV)

3) Proteolytic enzymes present in mucosal cavity

Front 13

What are the disadvantages of Oral Delivery Systems? (3)

Back 13

1) Strong gastric environment

2) High proteolytic activities

3) High intestinal barrier to permeability(size)

Front 14

What are the disadvantages of Injection Delivery Systems? (3)

Back 14

1) Potential to be costly

2) Can be painful

3) Leads to poor patient compliance

Front 15

What are the disadvantages of Pulmonary Delivery Systems? (2)

Back 15

1) Low efficiency

2) Potential irritation and irreversible damage

Front 16

What are the disadvantages of Transdermal Delivery Systems? (1)

Back 16

Low efficiency

Front 17

What are the disadvantages of Nasal Delivery Systems? (1)

Back 17

Possibility of Irritation/damage

Front 18

What are the only 3 peptide drugs that can be taken orally?

Back 18

1) ACE Inhibitors: Enalapril, Lisinopril

2) CNS: Taltirelin

3) Cyclosporin A: Sandimmune, Neoral

Front 19

What are the characteristics common with orally compatibile peptide drugs? (3)

Back 19

All these drugs have a MW<500 Daltons (di/tripeptides) They all have some chemical chemical modifications that allow them to resist degradation They have sufficient oral bioavailbility

Front 20

What are the 3 structural key features of Cyclosporin A?

Back 20

1) Cyclic Backbone (Protects against degradation) 2) Hydrophobic side chains

3) N-mthylation of amide bonds

Front 21

"Cyclosporin A's soft gelatin capsules have higher bioavailability than micro emulsion" True or False?

Back 21

False

Front 22

How is Desmopressin delivered to the patient?

Back 22

Drug delivered as a Nasal spray saline solution with preservatives

Front 23

What are the effects of structural changes (D-Arg, loss of amine from Cys) to Desmopressin?

Back 23

Enhances anti-diuretic activity but decreases other effects

Front 24

What is the use of Leuprolide for patients?

Back 24

For Palliative care for prostate cancer as it reduces testosterone levels

Front 25

What is the half-life for Leuprolide in blood?

Back 25

3 hours

Front 26

What are the characteristics of Leuprolide Lupron?

Back 26

PLA poly (DL Lactide) microspheres loaded with drug, 8um in diameter

Front 27

What is the benefit to using Leuprolide Lupron over regular Leuprolide?

Back 27

Less Injections therefore better compliance for patients

Front 28

What are the characteristics of Leuprolide Eligard?

Back 28

PLGA poly (D,L Lactide co glycolide) as a gel formulation which forms an in situ implant

Front 29

What are the characteristics of Leuprolide Vidur?

Back 29

Non-biodegradable implant, with a polyurethrane rate-controlling membrane

Front 30

"Leuprolide Vidur subcutaneous implants must be removed/replaced" True or False?

Back 30

TRUE

Front 31

What are the characteristics of of Histrelin Vantas Implant?

Back 31

Non-biodegradable hydrogel inserted subcutaneously into the arm and must be removed/replaced.

Front 32

What are the characteristics of Octreolitide?

Back 32

Mimics somatostatin, inhibits growth hormone. Used for GI tumors/acromegally

Front 33

How is Sandostatin LAR Depot administered to the patient?

Back 33

Suspensions distributed within microspheres for monthly injection (IM, Intragluteal)

Front 34

What are the future aspects of Peptide drugs? (3)

Back 34

1) Conjugated to Sugars - Improve solubility/ Protect from degradation and conformational changes

2) Conjugated to PEGS+LIPIDS - Improves uptake and permeability

3) Conjugated to Abs - Improves targeting