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Year 2 > Drug Development > Flashcards

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
Q

Role of FcRn receptors

A

Systemic receptors which absorb IgG into cells protecting them from metabolism

26
Q

Problem with using mouse antibodies for human FcRn

A

Shorter half-life than human antibodies

27
Q

The three step process in Zmapp production for Ebola treatment

A
  1. Mouse genes extracted from hybridomas
  2. Chimeric conversion to humanised gene
  3. Transfect with viral vector into tobacco plant
28
Q

What iz ZMapp’s structure

A

THREE chimeric monoclonal antibodies

29
Q

Stturtcure of insulin

A

2 peptide chains joined by disulphide bridges derived from a single sequence of proinsulin

30
Q

Describe recombinant human insulin process

A
  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
Q

How does Insulin Lispro function and made

A

Made: Switches lysine and proline residues

Function: and prevents insulin dimer formation

32
Q

Why do we use Insulin Lispro

A

Faster onset, shorter duration of action

Inject before a meal

33
Q

How is slow insulin produced

A

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
Q

Half-life of protein binding long acting insulin

A

5-8 hours

35
Q

When are micro crystals soluble

A

Acidic pH

36
Q

Half-life of slow release insulin produced as micro crystals

A

18-24 hours

37
Q

What is the advatanage of long acting insulin

A

Lower risk of nocturnal hypoglycaemia

38
Q

Problems of long-acting insulin

A

Mammary tumours

39
Q

Adverse effects of mineralocorticoids

A
  1. Hypertension
  2. Fluid retention
  3. K/Ca loss
40
Q

Adverse effects of glucocorticoids

A
  1. Diabetes
  2. Osteoporosis
  3. Muscle wasting
  4. Peptic ulcers
41
Q

Role of Calcineurin

A

Phosphatase enzyme which activates NF-AT (T cell activation precursor)

42
Q

How does Nf-AT activate T cells

A

Binds to promotor site for IL-2 transcription

43
Q

Role of IL-2

A

Lymphocyte activation

44
Q

When are calcineurin inhibitors given

A

Skin inflammation

45
Q

Name two calcineurin inhibitors

A

Ciclosporin

Tacrolimus

46
Q

What can folic acid deficiency lead to

A

Anaemia and worsens leukaemia

47
Q

Role of methotrexate

A

Inhibits dihydrofolate reductase to increase levels of folate in blood

48
Q

Why is THf important

A

Required to incorporate carbon atoms to form purine rings and precursor of guanine and adenine bases

49
Q

How do azathioprine work

A

Blocks incorporation of thiopurine analogues into the DNA structure, causing chain termination and cytotoxicity

50
Q

How do cyclophosphamide work

A

Causes irreversible DNA cross-links = apoptosis

51
Q

Name a protein kinase inhibitor

A

Vemurafinib

52
Q

What three ways does gene therapy prevent disease

A
  1. Replacing mutated genes
  2. Inactivating a mutated gene
  3. Introducing a new gene in th body
53
Q

Result of Lipoprotein lipase deficiency

A

Cause severe pancreatitis

54
Q

How do we treat lipoprotein lipase deficiency

A

Glybera delivers intact copy of human lipoprotein lipase gene

55
Q

How is Glybera delivered for treatment

A

Delivered to non-diving cells

56
Q

How does high-throughput creeping work

A

Compares results to libraries of thousands of compounds

57
Q

Define rational drug design

A

Process of dining new medications based on the knowledge of a biological target

58
Q

What does rational drug design rely on

A
  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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