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Exam 1

Terms in this set (246)

pharmaceutical sciences
Defined as: pharmacology, pharmaceutics, toxicology, pharmacodynamics, pharmacokinetics, pharmacogenomics, medicinal chemistry, and biophysics and physical chemistry
drug
Defined as: a therapeutic agent; any substance other than food, used in the prevention, diagnosis, alleviation, treatment, or cure of a disease
dried herbs
The name drug is derived from the French word drogue which means _____________.
1. molecular structure
2. pharmacologic/physiological effects
3. mechanism of action
4. target systems
5. company products
Name the 5 ways drugs are classified.
chemical name
What type of drug name is (S)-1-[N2-(1-carboxy-3-phenylpropyl)-L-lysyl]-L-proline?
pharmacological name
What type of drug name is lisinopril?
proprietary name
What type of drug name is Privinil and Zestril?
company code name
What type of drug name is MK-521?
United States Adopted Names Council
Which organization creates a drug's pharmacological name?
the drug company, and gets approval by FDA and US Patent and Trademark Office
Which organization creates a drug's proprietary name?
A drug is a therapeutic agent with an active species and a medicine is a broader term that includes the active ingredient + nonmedicinal agents known as excipients
What is the difference between a drug and a medicine?
oral, sublingual, buccal, nasal, inhalant, ocular, injections, rectal, subcutaneous, transdermal, topical
Name the routes of administration of a drug.
proteins, nucleic acids, lipids, carbohydrates
Name the 4 molecular targets of drugs.
pharmacodyamics
Defined as: what the drug does to the body
pharmacokinetics
Defined as: what the body does to the drug
passive diffusion
Defined as: type of diffusion by high concentration on outside of the cell to low concentration by the inside of the cell via carrier proteins
external surface with hydrophilic molecules and internal layer with hydrophobic molecules
Describe the fluid mosaic model of cell membranes.
paracellular (melts through) or transcellular (goes through holes)
Passive diffusion can be either _____________ or _____________.
active diffusion
Defined as: type of diffusion that requires some energy process to move molecules from outside of cell to inside of cell.
Polar molecules can't cross the BB barrier because the inside is hydrophobic (i.e., Penicillin G).
What's the issue with the blood brain barrier?
concentration of drug in organic phase/concentration of drug in water phase
What is the partition coefficient (P)? Name formula.
The greater the P value, the more hydrophobic the molecule.
Partition coefficient: What are the implications of a large P value?
True
True/False: Compounds with logP>/= 2 cross the BB barrier and therefore there will be CNS effects.
pH
logD is the logP value at different ________.
prodrug
Defined as: a medication that upon administration is converted into a pharmacologically active drug in the body. Example: disguise a drug as polar so it can cross the hydrophobic internal layer of the membrane.
1. A drug binds to a receptor (affinity)
2. conformation change
3. biological response is induced by the change in shape
Describe the 3 steps of drug action in the body.
A - absorption
D - distribution
M - metabolism
E - excretion
T - toxicity
Define ADMET
Excretion means the drug is completely out of the body; there is no activity. Elimination means the drug is no longer in its active form, but it's still there.
What is the difference between excretion and elimination?
potency
Defined as: how much of the drug is necessary to cause a biological response
solubility
Defined as: ability of a drug to dissolve
permeability
Defined as: how the drug gets from one side of the membrane to the other
The in vivo biotransformation of a drug into active or inactive molecular products through enzymatic reactions.
What is drug metabolism?
Phase 1: introduce polar functional groups. Nonpolar parts become polar.
Phase 2: Couple the drug to another polar molecule (conjugation reactions)
Distinguish between phase 1 and phase 2 of drug metabolism.
Drugs enter the liver first and then go into the rest of the body. If a drug can survive that first hit in the liver, the body will have a response. Some drugs cannot be administered orally because of first pass metabolism!
What is first pass metabolism?
proteins located in cell membranes that recognize and bind small molecules called ligands
What are receptors?
receptors binding to ligands
What produces the biological response?
1. Receptors perceive the signals.
2. Transducers transmit the signals.
3. Effectors convert the signals into a biological response.
Describe the 3 steps of the signaling pathway.
Kd
Defined as: dissociation constant for products/reactants or forward reaction/reverse reaction or [D][R]/[RD]
We want the drug to be bound to the receptor. So concentration of the drug-receptor (denominator) should be HIGH.
Why should Kd be a small number?
Ka
The inverse of Kd is ______, or [RD]/[D][R].
large
Ka would be ___________ (large or small) compared to Kd.
Change the orientation, change the way a drug interacts with its receptor. Need 3 contact points as a minimum for selectivity.
Describe the Easson-Stedman Model of drug stereoselectivity.
The greater the drug concentration, the less biological response. You get diminishing returns. If you introduce more drug, you may have toxic effects.
Describe the implications of a dose-response curve.
It is more compact, however mathematically there may be consequences because there is an area where the curve is linear. You need a common reference point when talking about drugs; this is typically 50%, or EC 50 (50% of the effective concentration).
Describe the implications of a logarithmic dose-response curve.
A small molecule, aka ligand, interacts and forms a bond. In forming the bond, it opens up the channel and the ion can go from the outside to the inside.
Describe the mechanism of ion channel receptors.
1. Drug interacts with receptor
2. Conformation change
3. GTP replaces GDP
4. G-protein dissociates itself
5. Alpha subunit interacts with adenylate cyclase and creates a conformational change.
6. ATP is converted to cyclic AMP (a secondary messenger, a messenger that will carry on a response).
Describe the mechanism of *G-protein coupled receptors.
phosphorylations
G-protein coupled receptors: The key to sending on a biological response is through ____________________.
cAMP
Rs and Ri are part of the interaction with __________.
G-protein coupled receptors
Activation of phospholipase occurs via ________.
Outer part recognizes a small molecule. The change in conformation is reflected from the outside to the inside. Then a catalytic reaction occurs where A is converted to B. The signal is amplified.
Describe the mechanism of enzymatic receptors.
a single polypeptide chain with 7 domains that cross the cell membrane
Describe the structure of G-protein coupled receptors.
a single polypeptide chain with 4 domains that can interact with one another and 4 other transmembrane receptors
Describe the structure of ion-channel receptors.
a small molecule interacts with a receptor to create a conformational change that leads to a biological event
Describe the function of agonists.
a small molecule binds to the receptor but there is NO biological effect
Describe the function of antagonists.
a small molecule that binds to the receptor but causes the OPPOSITE biological response (ex: instead of increasing cAMP, you may decrease cAMP)
Describe the function of inverse agonists.
The greater the biological effect, the more receptors are being occupied by the drug.
What is the relationship between the drug-receptor binding and the intensity of the biological effect?
The biological activity is proportional to the number of receptors occupied?
What is the occupation theory?
The proportion of occupied receptors (v) = [D]/[D] + Kd.
What does the Hill-Langmuir Equation describe?
For 50% maximal response, half of the receptors would be occupied (v = 1/2). Thus, the concentration required would be [EC]50 = Kd.
Describe the [EC]50 concept.
May can have a full biological response without all receptors occupied because the signal is being amplified.
What are spare receptors?
potency
Defined as: how strong the drug is
efficacy
Defined as: two different drugs can interact at the same receptor but one has a maximum biological response and the other does not, regardless of how much the other one you add
full
________ agonist reaches 100% biological response.
partial
_________ agonist never reaches 100% regardless of how much agonist you have.
Affinity (step 1) means binding (occupation). Efficacy (step 2) means generating a biological response (activation).
Distinguish between drug affinity and efficacy.
x; y
Potency looks at the _____ axis and efficacy looks at the _____ axis.
competitive antagonist
Defined as: molecule that interacts at the same binding site
noncompetitive antagonist
Defined as: molecule that interacts at a different binding site
functional (physiologic) antagonist
Defined as: an agonist that produce effects that oppose one another
chemical antagonists
Introduce a chemical and it interacts with another compound in the body and through that chemical interaction you have an antagonistic effect.
Without the agonist, a receptor exists in dynamic equilibrium of a resting state OR active state.
Describe the two-state receptor activation model.
Full agonists selectively bind to the active state and shifts the equilibrium to a completely active state.
What does full agonist activation do in two-state receptor activation?
Partial agonists selectively bind to the active state, but not to the same extent as a full agonist.
What does partial agonist activation do in two-state receptor activation?
Inverse agonists selectively bind to the resting state and shift the equilibrium completely to the resting state resulting in decreased biological activity for the receptor.
What does inverse agonist activation do in two-state receptor activation?
Antagonists binds both to the resting and active receptorswith NO shift in equilibrium.
What does antagonist activation do?
genetics
Defined as: the study of inherited variation of traits
genes
Defined as: the units of heredity
DNA
Genes are composed of ________.
genes & environment
Traits are produced by an interaction between _________ and __________.
genome
Defined as: the complete set of genetic information for an organism
all genes present in an organism and other DNA sequences that do not encode genes
The human genomes includes what?
epigenetic
_____________ changes to the chemical groups that associate with DNA that are transmitted to daughter cells after cell division.
-two alpha chains on chromosome 11
-two beta chains on chromosome 16
Describe the components of hemoglobin.
iron
Each of the four globins in hemoglobin surrounds an ________-containing heme group.
two epsilon + two zeta chains
Hemoglobin: describe the subunit makeup of an embryo
two gamma + two alpha chains
Hemoglobin: describe the subunit makeup of a fetus
two beta + two alpha chains
Hemoglobin: describe the subunit makeup of an adult
adult
The ________ type is about 99% of hemoglobins by four years of age.
proteomics
_____________ tracks all proteins made in a cell, tissue, gland, organ, or entire body
based on the relative abundance of each class at different stages of development
How can proteins be charted?
14
How many categories of proteins are there?
immunoglobulins
Which category of proteins is activated after birth?
promoter; extra copies
A gene controls its expression by having a ___________ sequence and ____________ of genes.
1. chromatin remodeling
2. microRNAs
The control of gene expression occurs in two processes. Name them.
on/off
Chromatin remodeling is the __________ switch.
dimmer
microRNAs is the __________ switch.
Histones expose DNA when it has to be transcribed and shields it when it needs to be silenced.
What is the role of histones?
1. acetyl groups
2. methyl groups
3. phosphate groups
Name the 3 types of molecules that bind to histones.
Remove positive charge, DNA less bound to histones, makes DNA more available to be transcribed
Histone binding: describe the purpose of the acetyl groups
Makes the histones a little more hydrophobic, compacts the DNA
Histone binding: describe the purpose of the methyl groups
Activates the DNA
Histone binding: describe the purpose of the phosphate groups
noncoding
MicroRNAs belong to a class of molecules called _____________ RNAs.
21-22
How many bases are in MicroRNAs?
1000;1/3
The human genome has about ___________ distinct microRNAs that regulate at least ________ of the protein-encoding genes.
Translation is prevented.
What happens when a microRNA binds to a target mRNA?
True
True/False: The human genome contains about 20,325 genes.
100,000
The genes in the human genome encode for about __________ mRNAs, which in turn specify more than a million proteins.
introns
____________ are the noncoding regions of DNA and are removed.
exons
____________ are the coding regions of DNA and are spliced together.
1. An intron on template strand may encode protein on a coding strand.
2. post-translational modifications
3. protein can be cut to yield two products (ex: autosomal dominant mutation...DSPP ---> DPP & DSP)
Name 3 ways to maximize genetic information.
True
True/False: Only 1.5% of human DNA encodes protein.
viral DNA, noncoding RNAs, introns, promoters and other control sequences, repeated sequences
What else is the genome made of, since the majority of it does not encode protein?
24,000
The human genome contains about _____________ protein encoding genes.
alleles
Defined as: variants of genes
mutations
Alleles form because of ___________.
sperm; egg
Mutations in _______ or _______ cells are passed on to the next generation.
polymorphisms
Defined as: variations in the DNA sequence that occur in at least 1% of the population; variants of alleles
SNPs
_________ are single base sites that differ among individuals and are important as markers.
DNA & protein
What comprises chromosomes?
nucleus
Where are chromosomes found?
46; 22; 1
Human cells have ________ chromosomes: ________ pairs of autosomes and ________ pair of sex chromosomes.
karyotypes
Defined as : a chart of the chromosomes organized by the size of the chromosome pairs
differentiation
______________ causes cells to differ in appearance and function.
stem cells
Defined as: cells that are less specialized and can become many different cell types
genotype
The __________ of an individual is defined by the alleles they carry.
phenotype
The __________ is the visible trait.
dominant
What kind of alleles are expressed if the individual carries one of two copies of the allele?
recessive
What kind of alleles are expressed if the individual carries two copies of the allele?
pedigree
A _____________ indicates the structure of a family schematically.
population
Defined as: a group of interbreeding individuals
gene pool
This consists of all alleles in a population
evolution
Defined as: the changing allelic frequencies in populations over time.
Mendelian traits
Defined as: traits that are determined by a single gene
multifactorial traits
Defined as: traits that are influenced by 1+ genes and environment
Mendelian, multifactorial, non-inherited
Illnesses can occur in these 3 different forms.
True
True/False: Disease phenotypes almost always depend on more than one gene.
polygenic theory
This theory suggests that phenotype is influenced by more than one gene and accounts for complex multifactorial diseases.
polygenic theory
This theory suggests that phenotype is influenced by more than one gene and accounts for complex multifactorial diseases.
Everyone has the trait but to a different degree.
What is a continuous or quantitative trait?
dichotomous
Single-gene traits are _____________ traits.
continuous/quantitative
Polygenic traits are ____________ traits.
quantitative trait loci (QTLs)
The DNA sequences involved in continuous/quantitative traits are called _______________.
1. predict disease
2. develop treatments
3. family planning
What is the application of genetics in healthcare?
all the DNA in a haploid set of chromosomes
What does the term genome refer to?
the study of genomes
What does the term genomics refer to?
cytogenetic map
Defined as: a map that distinguishes DNA sequences that are at least 5,000 kilobases apart
linkage map
Defined as: a map that distinguishes genes hundreds of kilobases apart
far away
If a gene recombinants frequently, is it close or far away on the genetic map?
close together
If a gene recombinants infrequently, is it close or far away on the genetic map?
physical map
Defined as: a map that distinguishes genes tens of kilobases apart and locates the DNA by recombinant DNA techniques
sequence map
Defined as: a map that depicts the order of bases two sequences apart and uses a computer to compare them
positional cloning
This approach matches single genes to specific diseases. Begins with a phenotype and gradually identifies a causative gene.
muscular dystrophy, CF, Huntington's disease
Positional cloning yielded discoveries of genes that cause diseases such as...?
chain termination/Sanger sequencing
This sequencing method uses chemically altered bases to terminate newly-synthesized DNA fragments at specific bases (either A, C, T, or G). These fragments are size-separated and the DNA sequence can then be read.
pharmacogenomics
Defined as: the study of the role of the genome in drug action
change in a DNA sequence that is present in <1% of a population
What is a mutation?
a genetic change that is present in >1 % of a population
What is a polymorphism?
meiosis
Where do germline mutations originate?
mitosis
Where do somatic mutations originate?
beta globin genes & collagen genes
Name examples of mutations that cause disease.
2 bad Beta globin genes
What does sickle cell anemia result from?
transition
Purine replacing purine is an example of a _____________ mutation. Ex: A to G or G to A
transversion
Purine replacing pyrimidine is an example of a ______________ mutation. Ex: A or G to T or C
missense
A _____________ mutation replaces one amino acid with another. Can be synonymous (changes phenotype) or non-synonymous (doesn't change phenotype).
nonsense
A _____________ mutation changes a codon on an amino acid into a stop codon.
splice site
_____________ mutations alters a site where an intron is normally removed from mRNA.
1. intron is translated (CF mutation)
2. exon is skipped (familial dysautonomia)
How can splice site mutations affect the phenotype?
frameshift
What kind of mutations occur if a nucleotide is not read in multiples of 3?
deletion
Defined as: a mutation that removes genetic material
male infertility
Name an example of a deletion.
insertion
Defined as: a mutation that adds genetic material
Gaucher disease
Name an example of an insertion.
tandem
A _____________ duplication is an insertion of identical sequences side by side.
Charcot-Marie-Tooth disease
Name an example of a tandem duplication.
gene copy number
The _____________ number can affect phenotype.
segregation
Mendel's First Law is the law of ___________, which really observed meiosis and fertilization.
independent assortment
Mendel's Second Law is the law of __________. The inheritance of one does not influence the chance of inheriting the other.
Random alignment of chromosome pairs during metaphase I of meiosis
How does independent assortment happen?
dominant
Huntington disease is a autosomal (dominant or recessive) disease?
recessive
CF is a autosomal (dominant or recessive) disease?
True
True/False: The homozygous dominant phenotype is either lethal or vary rare.
pedigrees
Defined as: symbolic representations of family relationships and the transmission of inherited traits
Most genes do not exhibit simple inheritance, so phenotypes vary.
Why are there exceptions to Mendel's Law?
-multiple alleles
-other nuclear genes
-non-nuclear genes
-gene linkage
-environment
Name "outside-the-gene" influences.
from mother to offspring
How are mitochondrial genes transmitted?
protein synthesis and energy production
Mitochondrial genes encode proteins that participate in...?
mitochondrial myopathies leber optical atrophy
Name diseases that result from mitochondrial mutations.
ooplasmic transfer technique
This technique can help women avoid transmitting a mitochondrial disorder.
heteroplasmy
The condition where the mtDNA sequence is not the same in all copies of the genome, so a mitochondria will have different alleles for the same gene than other mitochondria in the same cell.
phenotype
The ____________ reflects the proportion of mitochondria bearing the mutation.
linked genes
Defined as: genes that are close on the same chromosome and do not assort independently in meiosis
prophase I
During what phase of meiosis do chromosomes recombine?
the percentage of meiotic divisions that result in breakage of linkage between parental alleles
What is frequency of recombination based on?
>1500
How many genes does the X chromosome contain?
231
How many chromosomes does the Y chromosome contain?
ichthyosis, color-blindness, and hemophilia
Name examples of X-linked recessive traits.
Barr body
What is the inactivated X chromosome in mammals called?
epigenetic
X inactivation is an example of an ____________ change. An inherited change that does not alter the DNA base sequence.
XIST gene
What gene encodes a RNA that binds to and inactivates the X chromosome?
phenotype frequency
Defined as: percentage of people who express dominant or recessive phenotype in a population
genotype frequency
Defined as: percentage of AA, Aa, or aa genotypes in a population
allele frequency
Defined as: percentage of A and a alleles in a population
cross-sectional
Study design:
genotype and phenotype from a random sample of the population
ADVANTAGES:
-inexpensive
-estimate of disease prevalence
DISADVANTAGES:
-few affected individuals if disease is rare
cohort
Study design:
genotype, follow disease incidence for a specified time period
ADVANTAGES:
-estimate of disease incidence
DISADVANTAGES:
-follow-up is expensive
-drop-outs
case-control
Study design:
genotype affected and unaffected individuals
ADVANTAGES:
-no need for follow-up
-exposure effects
DISADVANTAGES:
-careful selection of controls
-potential for confounding
incidence
Defined as: the risk of getting the disease over time
prevalence
Defined as: the occurrence of disease at any given time
extreme values
Study design:
genotype individuals with extreme values of a quantitative trait as established from an initial cross-sectional or cohort sample
ADVANTAGES:
-genotype only the most informative individuals, save on cost
DISADVANTAGES:
-no estimate of true genetic effect size
siblings
Study design:
genotype affected individuals and their siblings
ADVANTAGES:
-not affected by population stratification
DISADVANTAGES:
-less powerful than case-control
case-parent triads
Study design:
genotype affected individuals plus their parents
ADVANTAGES:
-not affected by population stratification
DISADVANTAGES:
-less powerful than case-control
case-parent-grandparent septets
Study design:
genotype affected individuals plus their parents and grandparents
ADVANTAGES:
-not affected by population stratification
-and very powerful
DISADVANTAGES:
-grandparents rarely available
candidate gene
genotyping method: genes are selected because of known effect on drug response and disease process
candidate gene
genotyping method: prior knowledge of the function of the gene is essential
candidate gene
genotyping method: tests whether an allele is more frequent in cases v. controls
candidate gene
genotyping method: useful when there is a plausible link between the gene and drug response
candidate gene
genotyping method: results are clear and easy to understand
candidate gene
genotyping method: less expensive, requires smaller sample size
candidate gene
genotyping method: cannot do novel discovery
candidate gene
genotyping method: cannot study an undefined gene
genome wide association studies (GWAS)
genotyping method: surveys common genetic variations for a role in disease or drug response
GWAS
genotyping method: looks at large sets of SNPs across the genome
GWAS
genotyping method: ~12 million common SNPs in the genome
GWAS
genotyping method: tests whether an allele is more frequent in cases vs. controls
GWAS
genotyping method: requires an ethnically similar cohort
GWAS
genotyping method: good tool to discover new function of a gene or new genetic biomarker
GWAS
genotyping method: find novel genetic biomarkers
GWAS
genotyping method: expensive
GWAS
genotyping method: recruiting a sufficient sample size is expensive
-highly sensitive and specific
-cost-effective
What are the 2 requirements for mass genetic screening?
-potentially serious
-can be managed before symptoms occur
-no harm/discrimination
What are the requirements for the genetic disorder you're screening for?
Even single diseases are often not caused by one polymorphism.
What is the biggest problem with mass genetic screening?
1. family history
2. bring other family members in
3. thorough phenotype assessment
4. genetic testing is performed for patient and family
Describe the approach to the individual patient.
pre-symptomatic testing
genetic testing: specific genetic alteration is associated with 100% likelihood of developing disease; ex: Huntington's disease
predisposition testing
genetic testing: specific genetic alteration predicts risk for a disease that is less than 100%; ex: BRCA gene
-some diseases have treatment options and some do not
-anxiety and fear
-can also lead to new information on the patient's family history
What are ethical issues with genetic testing?
-maintenance of privacy
-questionable clinical utility of whole genome scans
-need for genetic counseling
-unintended questions regarding family history
What are the concerns with DTC genetic testing?
You cannot be discriminated *health* insurance when it comes to genetic information. You can't be denied healthhealthot be discriminated *health* insurance when it comes to genetic information. You can't be denied *health* insurance.
What is the basis of the Genetic Non-Discrimination Act?
-OMIM - updated daily
-Genetic Testing Registry - submitted by providers
-Public Health Genomics from the CDC
Name resources for medical genetics information for the healthcare provider.
Genetics Home Reference
Name a resource for medical genetics information for the consumer.
the maximum response produced by a drug
What does the symbol alpha represent?
1
For a full agonist, alpha is ___.
<1
For a partial agonist, alpha is ___.
Gq
This activates phospholipase C in the GCPR.
Gs
This activates adenyl cyclase in the GCPR.
Gi
This inhibits cAMP in the GCPR.
protein kinase A
cAMP activates ______________ in GCPR, which produces a biological effect
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