Drug Design Flashcards
4 classifications of drugs
- Psychopharmaceutical agents acting on CNS
- Pharmacodynamic agents
- Chemotherapeutic agents
- Metabolic agents (eg, treatment of diabetes)
what are primary effects?
desired therapeutic effects
what are secondary effects?
side effects, e.g. drowsiness, loss of appetite
define an agonist
a drug/substance that binds to a receptor and initiates the same action as the substance that normally binds to the receptor
define an antagonist
a drug/substance that binds to a receptor and blocks or suppresses a normal biological response
why do we need new drugs?
- less side effects
- prevent drug resistance and tolerance
- improve treatment of a new disease
- treat new diseases
- to give specific action on new targets for treating a disease
9 stages of drug development
- Extraction of lead compound (usually a natural product)
- Check for activity
- Determine molecular structure
- Synthesize new related compounds with similar structures to determine responsible molecular features
- Check new compounds for activity
- Deduce molecular features responsible for activity
- Synthesize new compounds to optimise activity
- Test new compounds
- Select suitable compounds for development
what is meant by pharmacokinetics?
it refers to the study of how a drug is absorbed, distributed, metabolized and eliminated by the body (ADME).
advantages of small molecules when compared to macromolecules
Small molecules diffuse easily, easy to synthesize, cheap (£1 a day)
90% of therapeutics in pharmaceutical market are small molecules
Rapid diffusion
aims in drug design (7)
- The drug should have a good selectivity for its target
- The drug should have a good level of activity for its target
- The drug should have minimum side effects
- The drug should be easily synthesized
- The drug should be chemically stable
- The drug should have acceptable pharmacokinetics properties
- The drug should be non-toxic
give an example of a drug that is neither specific or selective
antihistamines have many targets and many effects, e.g. drowsiness and dry eyes, etc.
define a lead structure
“in medicine, a chemical compound that shows promise as a treatment for a disease and may lead to the development of a new drug. This molecule may letter be optimised to produce the final drug.”
what is a the goal of structural optimisation in drug development?
- to increase efficacy of potency
- to reduce toxicity and side effects - LD50
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2 approaches to drug discovery
ligand based and target based
define ligand based drug design
ligand based drug design is lead by finding a molecule that expresses the wanted pharmacological effect without knowing its target.
- structure of ligand is known, target structure is unknown
define target based drug design
- AKA rational or direct or structure-based drug design
- involves identifying a specific target, such as a receptors or enzyme that is involved in a disease process
what are the important considerations for preclinical trials?
Not teratogenic (causing birth defect)
Carcinogenic
LD50
Optimal route of administration
how do we carry out preclinical testing of compounds?
in vitro (cell-based) and in vivo (animal-based) models
what is preclinical testing?
an essential step in the drug development process that involves evaluating the safety, efficacy, and pharmacokinetic properties of potential drug candidates before they can proceed to clinical trials in humans.
what is in vivo testing?
involves evaluating the compound’s effects in living organisms (animals) to provide a more comprehensive understanding of its pharmacokinetics, efficacy, safety, potential toxicities
what is in vitro testing?
involves the studying the effects of the compound on isolated cells or cellular components in a controlled laboratory setting
aim of lead optimisation
aims to maximize the interactions of a drug with its target binding site in order to improve activity, selectivity and to minimise side effects
what are the principle phases of drug action?
Pharmaceutical phase - determines amount of drug available for absorption
Pharmacokinetic phase - determines amount of drug available for action
Pharmacodynamic phase - determines induction of therapeutic effect
define potency
- refers to the concentration or dose of a drug required to produce a specific effect
- measured as EC50 or IC50
- represents the drug’s strength or activity at a given receptor or target
define efficacy
- refers to the maximum response that a drug can produce regardless of dose or concentration
- represents the drug’s ability to elicit a therapeutic effect or desired outcome
define IC50
inhibitory concentration 50% - the concentration of a drug needed to inhibit a specific biological process target by 50%
define GI50
(Growth Inhibition Concentration 50%):
GI50 is a measure of the concentration of a drug or compound required to inhibit the growth of cells, typically in cell-based assays or in cancer research.
define LD50
(Lethal Dose 50%):
LD50 refers to the dose or concentration of a drug or compound that is lethal and causes death in 50% of the individuals or experimental subjects tested.
It is a measure of acute toxicity and is typically determined in preclinical studies using animal models.
Factors influencing how drug reaches target?
- Hydrophilic/hydrophobic character
- Ionisation
- Size
- Chemical and metabolic stability
why does hydrophobicity/hydrophilicity matter?
Drug must be hydrophobic enough to pass membrane, but not too much as it will sit in membrane and is toxic.
If drug is too hydrophilic then it cannot move through membrane at all.
