Types & Origins Of Drugs Flashcards
What are the sources of lead compounds in the natural world?
- plantlife e.g. flowers, trees, bushes
- microorganisms e.g. bacteria, fungi
- animal life e.g. snakes, scorpions
- biochemicals e.g. hormones, neurotransmitter
- marine chemistry e.g. corals, bacteria, fish
What are the sources of lead compounds in the synthetic world?
- chemical synthesis
- combinatorial synthesis
What is the main source of lead compounds in the virtual world?
- computer aided drug design
What is the active principle?
- a compound isolated from a natural extract
- principally responsible for the extract’s pharmacological activity
- often used as lead compound
What are some drugs developed from venoms and toxins?
- teprotide - isolated from Brazilian viper- used to make captopril used to treat hypertension
- tubocurarine - from curare- lead for atracurium a neuromuscular blocker
What are the steps involved in computer aided drug design?
- choose a verified biological target
- find a key metabolic or functional event for it
- determine the 3D structure of the critical point in this
- design ligands to modulate events by blocking this critical 3D site
What is the strategy employed by structure-based drug design?
Carry out drug design based on the identified interactions between the lead compound and the target binding site
What are are the main considerations when establishing test procedures?
- choosing the right bioassay
- test should be simple, quick, cost-efficient and relevant
What are the two main challenges associated with establishing testing procedures?
- sufficient activity against the desired target
- minimal activity against any other targets to reduce off-target effect
What are in vitro tests?
- tests carried out on target molecules, whole cells, isolated tissues or isolated organs
What is in vivo testing?
Tests carried out on living systems such as animals are human volunteers
What are the aims of enzyme assay?
- to evaluate the level of enzyme inhibition
- to evaluate the mode of inhibition e.g. competitive or non-competitive
- to measure IC50
What are the aims of enzyme inhibition tests?
- identify type of inhibition i.e. competitive or non-competitive
- strength of inhibition measured as IC50
What is IC50?
- corresponds to the concentration of inhibitor required to reduce enzyme activity by 50%
Define affinity in terms of testing with receptors.
The strength with which compounds bind to a receptor
Define efficacy in terms of testing with receptors.
A measure of the maximum biochemical effect resulting from binding of a compound to a receptor
Define potency in terms of testing with receptors.
The code traction an agonist required to produce 50% of the maximum possible effect
- the smaller the does required to achieve the biological effect, the more potent the agonist
What are some advantages associated with in vitro testing?
- more suitable for routine testing
- used in high throughput screening
- measures the interaction a drug with the target
- can be used to test for pharmacokinetic properties of drug candidates
- results are easier to rationalise as there are less factors involved
What are some limitations associated with in vitro testing?
- does not evaluate the ability of the drug to reach the target
- does not demonstrate a physiological or clinical effect
- does not identify possible side effects
- does not identify effective prodrugs
What are some of the advantages associated with in vivo testing?
- measures an observed physiological effect
- measures a drug’s ability to interact with its target
- measures a drug’s ability to react its target
- can identify possible side effects
What is a disadvantage associated with in vivo testing?
- rationalising may be difficult due to the number of factors involved.
What are three in vivo tests?
- using transgenic animals - genetically modified animals
- drug potency
- therapeutic ratio/ index
What is therapeutic ratio/ index?
It compares the dose level of a drug required to produced a desired effect in 50% of the test sample (ED50) versus the dose level that is lethal to 50% of the sample (LD50)
What are the main source of lead compounds?
- natural world
- synthetic world
- virtual world
