Transduction:
The translation of receptor binding to biological effect
4 examples of receptors are
Ligand-gated ion channels
G-Protein couple receptors
Enzyme
linked receptors
Intracellular receptors
3 membrane bound receptors
Ligand-gated ion channels
g-protein couple receptors
Enzyme-linked
Intracellular receptors are
Lipids/lipid soluble
Nicotinic receptors are stimulated by
Acetylcholine
Nicotinic agonists leads to
sodium influx and potassium efflux
Ionized molecules cannot move through the cell wall without
a channel
G-protein receptors have an agonist, which is also called a
First messenger
First messengers are also called
signaling molecules
Second messenger processes are also called
cascades
pKa is
Ionization constant
Bioavilability is calculated as
AUC
AUC is
Area under curve
Vd is
Volume of distribution
Volume of distribution is
the fluid volume required to contain the entire drug in the body at the same time.
tolerance
no change in ligand binding, you have less receptor
desensitization
same amount of receptor, just not as responsive to drug
Currently how many drugs are on the market with pharmacogenomic information in their drug label?
<100
Changing metabolism changes:
clearance
Changing clearance changes
plasma concentration
Changing plasma concentration changes
Efficacy
Genetic variations can alter
Drug metabolism, efficacy (Emax), therapeutic effects
Allele
Two or more alternate forms of DNA at a given location (gene)
Geneotype
The genetic constitution of an individual (combination of two alleles for a gene)
Single Nucleotide Polymorphism
SNP
SNP has two types
synonymous
Non-synonymous
SNP
single base pair positions in genomic DNA <1%
SNPs are identified by their position in the gene sequence
521T-C SNP
+ means
protein coding
- means
in sequence
521 T -> C means
At
521 position
Arrow denotes change
T turns into
C
T is major, C is minor
521T - Allele 1 (*1a) means
...
Alleles are given star numbers.
The number doesnt mean anything, just the number they were discovered
Allele is also referenced as
Haplotype
Haplotype also means
Allele
521TC -> *1a/*5
On one chromosome they have T at this position, on another chromosome they have C at this position, T corresponds to 1a, C corresponds to 5
OATP1B1*1a/*5
Gene name followed by genotype is gene nomenclature
Copy number variation
Gene duplication can lead to new variants or multiple copies
CPIC
Clinical pharmacogenetics implementation consortium
Phenotype and ___ found in tables of CPIC
recommendations classified by strength
*2 and *5 pt, what is their recommendation for codeine?
regular dose
Know general concepts. Ultrafast metabolizer, metabolizer groups,
look at graph to identify poor metabolizer
look at graph and identify highest efficacy
look at graph identify highest potency
no math on test
no unit conversions
20% from first lecture
60% PK
heavy on new definitions
phew
Amino acid based, water-soluble hormones receptors
Are on the outside of the cell because they cannot pass through the plasma membrane
Because they cannot pass through the cell wall, what are the most common channels called that proteins use?
G protein-coupled receptors
What do G protein-coupled receptors do to send a message inside the cell?
Use the second messenger system to amplify the effect within the cell.
3 Common second messengers are:
cyclic AMP (cAMP)
Inositol triphosphate
(IP3)
diacylglycerol (DAG)
How does thyroxine tell a cell to do stuff?
Intracellular receptors inside the cytoplasm or nucleus of the target cell.
Steroid hormones often activate
Genes and protein synthesis