Big Pharma Flashcards
How long does drug development take? With pre-clinical and clinical trails
Average 12 to 15 years
-50% incident in 60 to 69-year-olds
-Damages vasculature
-Sustained increase in blood pressure (>140/90 mmHg) (ideal is <120/80 mmHg)
Hypertension
Force during beat
Systolic blood pressure
Force between beats
Diastolic blood pressure
-decreased or loss of blood flow to part of the heart
Myocardial infraction (heart attack)
- 500,000 US deaths per year
-$27 billion healthcare costs
-Decreased cardiac output
-increase, sympathetic, nervous system activation
-increased blood volume
-In adequate tissue supply leads to fluid retention (oedema), fatigue, and shortness of breath
Congestive heart failure
-Insufficient oxygen supplied to heart
-myocardial ischaemia
>9 million Americans
Angina (pictoris)
Fat plaques buildup on artery walls
Narrows blood vessel
Increase blood pressure
Plaque rupture releases, clotting factors
Atherosclerosis
Introduced in 1979, US FDA approval in 1990
> 6 million patients per year
Type two diabetes
Increases AMP dependent protein kinase enzyme activity
Decreases glucose release from liver
Increases glucose uptake into skeletal muscles and fat cells
Decreases glucose uptake from intestines
A biguanide drug
-Target ID & validation
* What causes the disease
*How can symptoms be controlled
-Compound screening
*ID chemical classes that interact with target
-Lead generation & optimization
*Medicinal chemistry
*ADME
*Stability
-Efficacy & safety testing
-Disease models
*Cell & animal
-On-target toxicity
-multiple species
Pre-clinical trials
-Investigate new drug application (IND)
*Food & drug administration (FDA)
*Health Canada
-Phase 1
*20-80 healthy volunteers
*safety
*Dose-finding
Blood levels
Urine levels
Psychological effects
-Phase 2
*100-125 patients
*efficacy & safety
*Large patient studies
Clinical trail
-biological Liscense application (BLA)/ New drug application (NDA)
*FDA
manufacturing
Chemical composition
Rouse if administration
Fillers, psalter form, vehicles
Packaging
Safety/efficacy data
6-12 months
-phase 5 - post approval monitoring
*compliance
*drug-drug and drug-food interactions
Market approval
-20 years
-protection filed at compound screening stage
*chemical family
*uses
-5-7 years protected marketing
*break even/recoup development costs of 10,000 compounds
*disease market
-generic vs. Name brand
*generic; no development costs
Patent protection
-sex differences
*aloestron for IBD in women only
-ethnic differences
*BiDil for congestive heart failure in African-Americans
-Genetic testing
* already exists to limited extent
Her2+ Breast cancer
Herceptin
Chronic Myeloid leukaemia sub types
Imatinib
HIV treatments
Abacavir
Lethal side effects 6% Caucasians, 2.5% African-Americans
Personalized medicine
-Effects of genetics on the drug responses
*> 250 approved drugs contain pharmacogenetic label info
- polymorphism’s in drug targets
-drug metabolisms
* cytochrome P450 enzymes
Codeine
* alcohol metabolism
-DNA for ancestry
Pharmacogenetics
