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PH2503- formulations > Overview of the drug development process > Flashcards

Overview of the drug development process Flashcards

1
Q

contents

A 
Drug discovery- key routes
-Natural products 
-Adaptations 
-Side effects 
-Mechanism- based design 
-Serendipity 
\+All of these lead into synthesis 
Patient protection
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2
Q

Drug discovery

A

Synthesis (serendipity, natural products, adaptations, side effects, mechanism based)
Pharmacological screening
QSAR
(all in a triangle)–> these all lead to large scale synthesis
-12-15yrs to go from drug discovery to MA

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3
Q

Large scale synthesis

A
  • Analysis (NMR, IR,MS, UV)
  • Pharmacology
  • Toxicology
  • Biochemistry
  • Formulation
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4
Q

Natural products 1)

A
  • Digoxin

- Originally isolated from digitalis purpurea

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5
Q

Natural products 2)

A
  • Atropine
  • Originally isolated form atropa belladonna
  • Greek goddess, atropa, who cut the tread of life
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6
Q

Natural products 3)

A
  • Paclitaxel and docetaxel
  • Paclitaxel (taxol) isolated from the pacific yew (taxis brevifolia)
  • Docetaxel (taxotere) isolated form the English yew
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7
Q

Natural products 4)

A
  • Isolated from a strain of aspergillum terreus

- Fungi

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8
Q

Adaptations (analogues) 1.

A
  • Opiate analgesics
  • Morphine
  • Nalorphine
  • Naloxone
  • Methadone
  • Pethidine
  • Dextromethorphan
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9
Q

Analogues 2.

A

Pro-drugs- to overcome limertations of stability (degradation) or solubility

  • Ampicillin
  • Pivampicillin (is pro-drug)
  • Ramapril is converted into ramaprilat= therapeutic action
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10
Q

Side effects

A
  • Sildenafil (Viagra)
  • Developed for treatment of angina
  • Adverse effects noticed in early-phase clinical trial
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11
Q

Side effects

A
  • Minoxidil (loniten)
  • Vasodilator used to treat severe hypertension
  • Bald men noticed increased hair growth
  • Marketed for male pattern baldness (regaine)
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12
Q

Mechanism-based design

A
  • HIV-1 protease
  • HIV directs infected cells to make viral proteins
  • Cleaved into smaller units by HIV-1 protease (prevented)
  • These are used to build more virus particles
  • replication and propagation of virus
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13
Q

Mechanism-based design

A

HIV protease inhibitors

  • Block activity of HIV-1 protease, thereby inhibiting viral replication
  • Saquinavir (invirase); Indinavir (Crixivan); Ritonavir (Norvir)
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14
Q

Mechanism-based design

A 
Numerous other examples:
-ACEI (e.g. enalapril) 
\+prevent conversion fo angiotensin | to ||
\+Used in the treatment of hypertension 
-H2 antagonists (e.g.ranitidine) 
\+inhibits histamine at H2 receptors (dec gastric) 
\+Decrease gastric acid secretion 
-SSRI's (sertraline) 
\+inhibit re-uptake of 5-HT in CNS 
\+Used in the treatment of depression
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15
Q

Serendipity Penicillin

A
  • Discovered by chance
  • Alexander flemming
  • Penicillium mould killed bacterial cultures
  • Large-scale testing of soil micro-organisms lead to the development of many other antibiotics:
  • Streptomycin, neomycin, gentamicin, erythromycin and the tetracyclines
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16
Q

Serendipity Tamoxifen

A
  • Developed as an oral contraceptive, but found to induce (rather than inhibit) ovulation
  • Found to lower breast cancer incidence in lab animals
  • Prevents oestrogen binding to receptors in breast tissue
17
Q

Outline of product development

A
  • New chemical entity –>
  • Pre-clinical studies –>
  • Clinical trials –>
  • Marketed drug
18
Q

Patent protection

A

-Typical patent lasts for 20 years
+BUT usually take out near start of discovery
+Effective patent life is much shorter
-In 2010, patents on 50% of top branded drugs expired, THEN:
+Generic companies flooded market with cheaper copies
+Major Pharma may lost 70% of scales
-Supplementary protection certificates (SPC’s)
+May be granted for up to 5 years if development has been difficult

19
Q

What can big Pharma do?

A

-Maximise regulatory protection (e.g. SPCs)
-Adding value to product
+New formulations; new delivery systems; new indications
+Can add 10 years to patent life
-Defend patent rights
+Use courts to defend any patent infringement
+Not all patents are defensible in law
-Competing after patent expiry
+POM to OTC switch
+Market own-brand generic products
-Life-cycle management
+Balanced portfolio of products in development
+Not dependent upon sale of one product

20
Q

Tricks of the trade

A

-Loratidine (clarityn; schering plough) withdrawn
+Replaced by desloratidine- 1 year before patent expired
+because desloratidine was a better product
-Doxazosin (Pfizer) 4mg withdrawn
+No need for a standard and modified release system
+Because the MR formulation is a cheaper and better option
-Esomeprazole (Nexium)
+S-isomer of omeprazole extended patent to 2014

PH2503- formulations (18 decks)

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