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Drug Development Flashcards

1
Q

Define drug development

A

Process of bringing a new pharmaceutical drug to the market

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2
Q

Outline the four main stages of the drug development model

A
  1. Drug discovery
  2. Pre-clinical development
  3. Clinical development
  4. Regulatory approval
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3
Q

How many phases are there in clinical development

A
  1. Effect on body
  2. Safety in humans
  3. Effectiveness at treating diseases
  4. Larger scale safety and effectiveness
  5. Long-term safety
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4
Q

Roughly how long does drug development take

A

12-15 years

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5
Q

Define druggability

A

The ability of a protein target to bind small molecules with high affinity

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6
Q

What proportion of the human genome is draggable

A

10-15%

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7
Q

What four key structures are interacted with by drugs

A
  1. G protein coupled receptors
  2. Nuclear hormone receptors
  3. Ion channels
  4. Kinases
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8
Q

Name examples of where we can find drugs

A
  1. Medicine from plants
  2. Inorganic elements
  3. Organic molecules
  4. Bacteria
  5. Stereoisomers
  6. Immunotherapy antibodies
  7. Gene therapy
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9
Q

What plant alkaloid is morphine extracted from

A

Poppy

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10
Q

What plant alkaloid is atropine extracted from

A

Deadly nightshade

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11
Q

What plant alkaloid is vincristine extracted from

A

Periwinkle

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12
Q

Name on anaesthetic

A

Isoflurane

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13
Q

Name an antiseptic

A

Chlorhexidine

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14
Q

What does Humira monoclonal antibody target

A

TNF alpha

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15
Q

When is Infliximab prescribed

A

Rheumatoid arthritis

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16
Q

How does Infliximab effect rheumatoid arthritis

A

Chemical inhibition by extracellular neutralisation of TNF alpha

Inhibits lymphocyte proliferation

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17
Q

How is Infliximba delivered

A

Every 6-8 weeks

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18
Q

Structure of Etanercept

A

Dimeric fusion protein of TNF type II receptor

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19
Q

When is Etanercept prescribed

A

Rheumatoid arthritis and psoriasis

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20
Q

What are infliximab and etanercept examples of

A

Chimeric antibodies

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21
Q

What is an example of a human antibody used for pharmaceutical treatments

A

adalimumab

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22
Q

How does Adalimumab

A

Inhibits lymphocyte proliferation, down regulates inflammatory reactions associated with autoimmune disease

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23
Q

How is adalimumab injected

A

Subcutaneously - fortnightly

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24
Q

Why is IgG not filtered by the kidney

A

Too big molecular weight

25
Role of FcRn receptors
Systemic receptors which absorb IgG into cells protecting them from metabolism
26
Problem with using mouse antibodies for human FcRn
Shorter half-life than human antibodies
27
The three step process in Zmapp production for Ebola treatment
1. Mouse genes extracted from hybridomas 2. Chimeric conversion to humanised gene 3. Transfect with viral vector into tobacco plant
28
What iz ZMapp's structure
THREE chimeric monoclonal antibodies
29
Stturtcure of insulin
2 peptide chains joined by disulphide bridges derived from a single sequence of proinsulin
30
Describe recombinant human insulin process
1. Plasmid isolated from bacterial cell 2. Restriction endonuclease recognises specific site 3. Break DNA to give sticky ends 4. Same enzyme cuts out gene of interest from human DNA 5. Ligase joins the two pieces together by complementary base pairing (forms phosphodiester bonds) 6. Bacteria secrete insulin and it's collected
31
How does Insulin Lispro function and made
Made: Switches lysine and proline residues Function: and prevents insulin dimer formation
32
Why do we use Insulin Lispro
Faster onset, shorter duration of action Inject before a meal
33
How is slow insulin produced
Protein binding: Substitute lysine (B29) with myristic acid binds to albumin Micro crystals: Asparagine substitution with glycine + 2 Arginines. Aggregates due to neutral pH following subcutaneous injection
34
Half-life of protein binding long acting insulin
5-8 hours
35
When are micro crystals soluble
Acidic pH
36
Half-life of slow release insulin produced as micro crystals
18-24 hours
37
What is the advatanage of long acting insulin
Lower risk of nocturnal hypoglycaemia
38
Problems of long-acting insulin
Mammary tumours
39
Adverse effects of mineralocorticoids
1. Hypertension 2. Fluid retention 3. K/Ca loss
40
Adverse effects of glucocorticoids
1. Diabetes 2. Osteoporosis 3. Muscle wasting 4. Peptic ulcers
41
Role of Calcineurin
Phosphatase enzyme which activates NF-AT (T cell activation precursor)
42
How does Nf-AT activate T cells
Binds to promotor site for IL-2 transcription
43
Role of IL-2
Lymphocyte activation
44
When are calcineurin inhibitors given
Skin inflammation
45
Name two calcineurin inhibitors
Ciclosporin | Tacrolimus
46
What can folic acid deficiency lead to
Anaemia and worsens leukaemia
47
Role of methotrexate
Inhibits dihydrofolate reductase to increase levels of folate in blood
48
Why is THf important
Required to incorporate carbon atoms to form purine rings and precursor of guanine and adenine bases
49
How do azathioprine work
Blocks incorporation of thiopurine analogues into the DNA structure, causing chain termination and cytotoxicity
50
How do cyclophosphamide work
Causes irreversible DNA cross-links = apoptosis
51
Name a protein kinase inhibitor
Vemurafinib
52
What three ways does gene therapy prevent disease
1. Replacing mutated genes 2. Inactivating a mutated gene 3. Introducing a new gene in th body
53
Result of Lipoprotein lipase deficiency
Cause severe pancreatitis
54
How do we treat lipoprotein lipase deficiency
Glybera delivers intact copy of human lipoprotein lipase gene
55
How is Glybera delivered for treatment
Delivered to non-diving cells
56
How does high-throughput creeping work
Compares results to libraries of thousands of compounds
57
Define rational drug design
Process of dining new medications based on the knowledge of a biological target
58
What does rational drug design rely on
1. Computer modelling techniques | 2. Knowledge of 3 dimensional structures of the bimolecular targett is known as a sturcture-absed drug design

Year 2 (155 decks)

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