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Pharmaceutics - Test 3 > Proteins & Peptides (Classes 19-20) > Flashcards

Proteins & Peptides (Classes 19-20) Flashcards

1
Q

Give an example of a commonly used protein drug?

A

Insulin

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2
Q

What are some benefits of protein therapy?

A

High specificity, target any defective gene, broad range, easier FDA approval

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3
Q

Give an example of an anti-cancer protein therapy (besides monoclonal antibodies)?

A

Herceptin

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4
Q

What is the largest class of therapeutic proteins?

A

Antibodies

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5
Q

Name 4 ways protein therapies deliver their therapeutic effects to the body.

A

Replace a deficient or abnormal protein, Augment existing pathway, provide novel function, Interfere with a molecule or pathway, Deliver a therapeutic payload

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6
Q

What are some classes of protein therapies?

A

Enzymes, antibodies, blood factors, hormones, interferons, interleukins

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7
Q

What are some clinical conditions that protein therapies are used for?

A

Diabetes, Cancer, Transplant rejection, Crohn’s disease

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8
Q

What classifies a peptide drug vs a protein drug?

A

Peptide - 50 Aas or less; Protein - 100 to 1000s of Aas

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9
Q

What is the major disadvantage of protein therapy?

A

Maintaining stability & high dosing; efficacy requires maintaining 3D structure/high dosing can lead to aggregation or precipitation

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10
Q

What are 4 ways to cause denaturation of proteins (not the chemical rxns)?

A

Adjust temp, Adjust pH, agitation, Use solvents

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11
Q

What are 3 physical issues that can affect protein stability/efficacy (other than denaturation & not chemical reactions)?

A

adsorption, aggregation, precipitation

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12
Q

What are 4 chemical reactions that can affect protein stability/efficacy?

A

Deamidation, Oxidation, hydrolysis, racemisation, Isomerisation, disulfide exchange

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13
Q

What are 2 common sites of attack for protein oxidation (think amino acid residues)?

A

methionine & cysteine

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14
Q

What are four ways to cause oxidation in proteins?

A

Irradiation, Air pollutants, Inflammation, Reactive Oxygen Species

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15
Q

What amino acid residues are affected in deamidation?

A

asparagine & glutamine

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16
Q

What are 2 ways to cause deamidation in a protein?

A

change pH, change temp

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17
Q

What does TRAIL do on a molecular level?

A

Induces cell death via TNFa

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18
Q

What is TRAIL used for clinically?

A

Kill cancer cells

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19
Q

What is the goal of transfection?

A

Transfer DNA into a cell

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20
Q

In recombinant DNA tech, what do you use to cleave the host plasmid?

A

Restriction Endonucleases

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21
Q

In recombinant DNA tech, what is the name of the process of closing the 2 ends of the open plasmid after you have inserted new DNA?

A

Annealing

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22
Q

In recombinant DNA technology, what do you use to put a plasmid with your new gene inside a host cell?

A

transfection reagent

23
Q

What is the major challenge of recombinant DNA technology (other than being expensive)?

A

Scaling up; Requires scaling of producer cells in sterile environment

24
Q

What is one challenge to using bacterial cells for recombinant DNA technology?

A

bacteria cannot perform post-translational modifications to proteins

25
Q

Can protein therapies have generic versions?

A

No. Only biosimilar versions.

26
Q

Procrit and Eprex are examples of what kind of protein therapy?

A

EPO replacement

27
Q

What is the origin of paclitaxel (ie where does it come from)?

A

Pacific Yew bark

28
Q

What are some problems with using cremophor as a dissolution agent?

A

axon degeneration/demyelination; Rash, chest pain, tachycardia, peripheral neuropathy

29
Q

What challenge did the use of human albumin overcome in the development of paclitaxel drug for breast cancer?

A

hydrophobicity/solubility challenge

30
Q

What is the drug Abraxane comprised of?

A

paclitaxel and human albumin

31
Q

What is Abraxane used for?

A

Metastatic cancer (study was on metastatic breast cancer)

32
Q

What are 4 things proteins are susceptible which make protein therapies a challenge?

A

Aggregation, Fragmentation, Oxidation, Deamidation

33
Q

What is a major challenge for protein therapy in liquid or subQ formulations?

A

Requires high dose for delivery

34
Q

Name 3 ways to prevent protein breakdown

A

lyophilization, polymer encapsulation, cell-based delivery system, virus-based delivery system

35
Q

What are 4 ways to prevent protein aggregation in a protein therapy?

A

lower temp, adjust pH, add stabilizing agents, Add detergents

36
Q

What do detergents do to protect proteins?

A

Shield hydrophobic regions

37
Q

What is the process of freeze-drying and dehydrating a protein therapy called?

A

lyophilization

38
Q

How much residual water should remain in a lyophilized protein?

A

1-8%

39
Q

What is the key to rehydration after lyophilization of a protein therapy?

A

Slow rate of rehydration; too fast and the protein will not regain native conformation

40
Q

What is one way to provide a continual delivery system of protein based therapies?

A

Cell-based delivery system

41
Q

Name 3 requirements for cell-based therapies

A

Must be engineered in genome, must be secreted or expressed across membrane, Must be a protein therapy (not a small molecule)

42
Q

What is the term used to describe when a cell used in cell-based therapy navigates to the site of pathology?

A

homing

43
Q

How does viral gene delivery work?

A

Gene is engineered into genome, Virus delivered into target cells, cell starts producing proteins that initiate curative effect

44
Q

What are the roles of the variable and constant regions of an antibody?

A

Variable -> binds the epitope; Constant -> initiates immune response

45
Q

What are 4 uses for antibody therapies in targeting cancer cells?

A

block cancer-promoting receptors, localize lethal drugs to specific cells, localize radioactive molecules to kill cancer, localize drug-loaded nonoparticles

46
Q

What are some mouse (murine) antibody drawbacks?

A

allergic reactions, short half-lives, inefficient targeting

47
Q

What is the term for a mouse antibody and what is its suffix?

A

Murine; momab/monab

48
Q

What is a term for a mouse Fab region grafted onto a human backbone antibody called? Suffix?

A

Chimeric; Ximab

49
Q

What is the term for a mouse hypervariable region grafted onto a human backbone antibody called? Suffix?

A

Humanized; Zumab

50
Q

What is the suffix for a fully human antibody?

A

Umab

51
Q

What antibody type has the longest half-life?

A

Recombinant Humanized

52
Q

What are some challenges of monoclonal antibodies?

A

low potency, difficult/expensive to develop, low patient compliance with dosage form/admin schedule, hypersensitivity/immune rxns, Formulation/stability issues

53
Q

What humanized monoclonal antibody therapy is used for brain tumors?

A

Bevacizumab

54
Q

What is cetuximab used for?

A

Cancer

Pharmaceutics - Test 3 (3 decks)

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