Week 1 Flashcards
Absorption
movement of drug from site of admin to systemic circulation
Active drug
takes effect immediately- morphine
Adverse drug reaction-
unintended harmful reaction to medicines
Allele
one of two or more forms of a single gene- one from each parent
Base pair
2 complementary nucleotides
Candidate gene
predicted to be associated with particular trait (adverse reaction)
Cytochrome p450
group of enzymes involved in drug metabolism found in high levels in liver- metabolism many drugs for excretion
DNA
deoxyribonucleic acid
Enzyme
biological catalyst that speeds up rate of a specific chemical reaction
Efficacy
maximum beneficial or therapeutic response that a drug can produce and isa. Measure of clinical effectiveness
Excretion
irreversible removal of a drug in the unchanged form
Polymorphism
variant that has two or more alleles and present at a frequency of at least 1%
Prodrug
precursor of a drug- must undergo chemical conversion by metabolic processes before becoming active
Gene
basic physical unit of inheritance
Genotype
individuals collection of genes
GWAS
genome wide associate study- assess common genetic variations across entire genome of a large population of individuals
Haplotype
collection of genetic variants such as SNPS that travel together on same allele
Heterozygosity
when two different alleles are present on chromosome pair
Homozygosity
when two identical alleles present on the chromosome pair
Poor metabolizer-
two non-functional alleles and therefore have little to no enzyme activity
Intermediate metabolizers-
one nonfunctional allele so decreased enzyme activity
Extensive metabolizers
2 normally functioning- normal enzyme activity
ultra rapid-
one or more alleles which result in increased enzyme activity compared to extensive
SNP
single nucleotide polymorphism- single base pair substitution
Nucleotides
building blocks of Dna ATCG
Pharmacodynamics
biochemical and physiological effects of drugs particularly those that define drugs mechanism of action one the body
Pharmacokinetics
absorption, distribution, metabolism and excretion of bioactive drugs following admin
Pharmacogenetics
identification of genetic variants and their association with variations in drug treatment response
Pharmacogenemocs
incorporation of multiple pharmacogenetic results to develop gene based phenotypic characterization- identifying responsiveness or side-effect prone patients in clinical practice and in drug development trials
Phase I metabolism-
small chemical changes making more hydrophilic so can be eliminated adding or unmasking-a. Hydroxyl group or amine- hydrolysis, oxidation or reduction
Phase II purpose
if phase I is insufficient to clear or if I generates reactive metabolite
Conjugation
adding large polar group such as glucuronide to further increase compounds solubility usually by transferase
Phase III-
involves drug transporters influence effect of ADME across cellular barriers can target site of accumulation
Phenotype
observable physical characteristic
Efficacy
maximum therapeutic response- measure of clinical effectiveness- % who show response at standard dose
Toxicity
to what extent show adverse- percentage of showing
Optimal dose
greatest efficacy and lowest toxicity
Extreme drug responders
non responders and adverse responders-
Cancer development
accumulation of multiple mutations in certain genes in cell acting together to disrupt normal check-uncontrolled cellular proliferation
Conventional chemo problems
to achieve reasonable efficacy have to make very toxic and have lots of adverse side effects-
Herceptin
Ab based therapeutic used for treatment of HER2 positive breast cancers- high levels of HEGF- 20% of cancers
Herceptin action
Herceptin competitively binds blocking Growth factor binding preventing replication by HER2 binding
