Biologics vs Small Molecules Flashcards
What drugs are considered small molecules?
<500 Da in size
Single defined structure
What drugs are considered large molecules/biologics?
> 500 Da in size
Complex structure
Advantages of small molecules
The drug can pass through cell membranes to reach intracellular targets
Flexible formulation
Less time-consuming
Stable = easier to store and transport
The low Mr and simple structure results in predictable PK and PD and lead to simpler dosing protocols
Able to cross BBB
Disadvantages of small molecules
Can develop resistance
Doesn’t differentiate between healthy and diseased cells
More likely to have DDIs
Shorter half-life
Susceptible to generic competition = negatively impact profit gain after patent life
Examples of resistance mechanisms
Enzyme mutation
Efflux
Drug target mutations
Inactivation of the drug
Disadvantages of biologics
Difficult to synthesize as they are complex structures
Unstable = sensitive to environmental conditions = difficult storage and transport
Expensive
Time-consuming
Difficult to make a profit as they are designed for one individual
Unpredictable chemical properties
Inability to cross BBB
Immunogenic potential
Why can’t biologics be administered orally?
Subject to enzymatic degradation
Polar
Heat sensitive
Membrane impermeable
Biologics ADME
A - Bypass absorption
D - Limited vol of dist = don’t distribute around the
body to same extent as a small molecule + long
time to reach peak conc.
M - Therapeutic proteins are broken down into
amino acids which are then recycled by the body
E - Longer half-life
Small molecules ADME
A - GI absorption
D - higher vol of dist
M - metabolised in the liver
E - eliminated by the kidneys
Quality control of biologics
More rigorous than small molecules to avoid possible errors
Advantages of biologics
Very potent
Low toxicity
Low accumulation in tissues
Fewer side effects
More security around the drug as the manufacturing is more complex and difficult to for competitors to manufacture identical biologic
Treat serious illness
