Molecular pharmacology Flashcards
Crystal structure of receptors
Important as it lets you look at the receptor structure and what might be able to bind to (increase or inhibit) it
Gpcrs
3% of all genes in body encode for these.
The endogenous ligand has been identified for approx 210. Grpcs.
Good drug targets.
Knockout/knockdown models give clue to receptor function.
3 major classes.
3 major classes of GPCRs
Family A - ligand known 180, orphaned 110, rhodopsin is an example, almost all drugs target this family.
Family B - ligand known 25, orphaned 40, secretin is an example.
Family C - ligand known 11, orphaned 5, mGluR is an example.
Adverse drug reactions
An unintended event that occurs at drug doses used in humans for prophylaxis, diagnosis, therapy or modification of physiological functions. This definition excludes intentional or deliberate overdose or drug abuse.
Today method of drug therapy
Get sick Go to doctor Doc checks symptoms Doc orders tests Determines cause of sickness Prescribes one-for-all drugs 30-60% respond to drug 40-70% remain sick Try New drug til fixed or treat symptoms but not illness
Hope for future drug therapy
Patient gets sick Goes to doctor Doc checks symptoms Doc orders test Determines cause of sickness Uses genetics to prescribe appropriate drugs Patient gets better
Personalised therapy
Optimal efficacy, reduced adverse drug reactions
Pharmacogenomics
The influence of genetic variation on drug response in patients by correlating gene expression or presence of snps with a drugs eficacy/toxicity.
Non-synonymous mutation
Mutation that ultimately results in a change in protein sequence
SNP
Single nucleotide polymorphism
A single base that differs at the same genetic location between diferent chromosomes, either within an individual or between individuals of the same species. Most common type of genetic variation.
Must affect at leats 1% of population to be classified as an SNP
Responsible for 90% of all human genetic variation
Thought to be biomarkers for identifying genes associated with disease
Silent mutations
Occur in coding and regulatory regions
Have no known ill-effects
Can influence benign individual characteristics such as eye colour, stature, body shape
Variations causing harmful changes
Specific variations in coding and regulatory regions can result in harmful effects
These changes alter function or expression of important proteins needed for health.
Variations causing latent changes
Coding and regulatory region variations that are not harmful on their own.
Changen in each gene only becomes apparent if the eventually cause person to be at higher risk of disease but only after ecposure to environmental factors.
May explain differing drug response interindividually.
How can SNPs be used to inform drug treatment?
Entrance/exclusion from clinical trials
Understanding variability in pharmacokinetics and clinical trial dose response
Drug revival if their limited effectivesness can be mapped to a niche population
Will defrease drug discovery time
