Definition of Pharmacology and the Related Subjects. Drug development Flashcards
Definition and Goals of Pharmacology
Study of effects of drugs on the function of living systems
Goal
To understand what drugs do to living organisms and how their effects can be applied to therapeutics
Subcategories: Pharmacology
Neuro CV GI Immuno Respiratory
Definition of Pharmacokinetics
Effect of body on the drug
Absorption (sit of admin-> systemic)
Distribution
Metabolism (biotransformation, liver, plasma, gut wall)
Excretion (urine, stool, sweat, resp tract, mothers milk)
Definition of Pharmacodynamics
Effect of drug on body
Activation
Inhibition
Stimulation
Definition of Toxicology
Non desired effects
drug–> effects of overdose
Poisons not drugs; rare exceptions
Definition of Pharmacy
Formation and development of drugs as chemical compounds
Definition of Homeopathy
Ailments treated by minute doses of natural substances that in larger amounts would produce symptoms of the ailment.
Definition of Pharmacoeconomics
‘Cost-benefit’ of therapy
Example
Rituximab is expensive
Definition of Pharmacogenesis
Genetic influences on response to substance
Steps in the Development of Drugs
Choose a disease Choose a drug target Identify a 'bioassay' Find a lead component Synthesis analogues of the lead Identify Structure Activity Relationships (SARs) Detemine toxicity and efficacy in animal models Determine pharmacokinetics and dynamics Design a manufacturing process Carry out clinical trials Market the drug
Choosing a Disease
Tendency towards avoidance of products with small markets
Most research on diseases of ‘first world countries’
Identifying a Drug Target
Specific macromolecule, biological system with which the drug will interact with
Importance of selectivity; not present in mammals or significant structural differences
Combinatorial Chemistry
Process in which large amounts of compounds can be prepped at one time
Computer Assisted Drug Design
Use of computer to design a perfectly fitting ligand to known molecular structure of target
Drawbacks
Ligands id designed and/or docked into active site–> Most programs don’t allow conformational movement in target
Choosing a Bioassay
Bioassay= test to determine biological activity
In Vitro: artificial environment, Test tube or culture media
In Vivo: within living body
Ex Vivo: Test on tissue taken from living organism
In Vitro Testing
Advantages
Speed
Req relatively small amounts of compound
High throughput screening (HTS)
Increase in speed to point where can analyse several
100s compounds per day
REM: results may to translate to living animals
In Vivo Testing
More expensive
Moral debate- animals
Disadvantage
Possible clouding of results by interference with other
biological systems
Finding the Lead
Screen Natural Products
plants, microbes, marine world, animals..
Req quick assay for desired biological activity
Req to be able to separate bioactive component from
other inactive substances
Screen Synthetic Banks
Stored in freezer
Catagorisation and screening of new targets as these
are being identified
Structure- Activity - Relationship (SARs)
Identifying which structural features are resp for a leads biological activity = pharmacophore
Example
Longer chains decrease the effect
Xenobiotics
Foreign substances which are not produced naturally
Goal of body is to remove these
Toxicity: With Thalidomide as Example
Sold 1957-61 mainly as antiemetics for morning sickness
Lead to severe malformations in offspring; incl phocomelia
New Studies, now used in ex: erythema nodosum leprosum
Clinical Trial: Phases
I: Test drug on healthy volunteers
Det: toxicity relative to dose
screen for unexpected SE
II: Test on small group of patients
See if drug has beneficial effect
Determine dose level required for this effect
III: Test on larger group of people
Compare with existing treatments and placebo
IV: Drug is placed on market
Patients monitored for SE
Takes approximately 12 years for the drug to be approved from Phase I-Beg. Phase IV
