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60 Cards in this Set
- Front
- Back
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bioavaliability
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free and unbound drug
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oil/water partition coefficient
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determines how fast it will be absorbed into blood
measure the amount of drug the diffuses into the oil vs the water part. |
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lipophilic
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hyrdrophobic
more soluble in the water |
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lipophobic
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more soluble in the water
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naloxone
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is injected into the butt b/c its oil/water partition coefficient is 15...
too lipid solube to use an IV |
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ionization
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charged molecules CANNOT cross membranes easily
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pka
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the pH at which half of a drug is ionized
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aspirin
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has a pka of 3.5, so it is NOT ionized in the stomach (pH 2) and therefore it can diffuse into the blood, but in the blood it becomes ionized (ph 7.4) and is trapped.
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cyp 450 3A
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microsomal enzyme that breaks down about half of the known drugs
can be inhibited by grapefruit juice |
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Barriers
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BBB, PB
drugs must be actively transported or VERY lipid soluble to cross |
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Depot binding
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an impetement to drug distribution
serum albumin fat, bone, and muscle are common proteins that drugs get stuck on |
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compartments
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drugs don't distribute evenly throughout the body, equilibriums are different in each body compartment
blood plasma, IF, fat, cytoplasm, cavity fluids |
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phenytoin (dilantin)
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anti-seizure drug
over 128 known drug interactions b/c it is a serum albumin binder easily displaced by other drugs |
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first order kinetics
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the normal curve
half live can be predicted |
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Phase 1 Biotransformation
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non synthetic
clears most drugs attempts to cleave and breakdown molecules oxidation/reduction/hyrdolysis |
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Phase 2 Biotransformation
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synthetic reactions
helps metabolites to be water soluble and excreted (ionized)A conjugation |
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CYP
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cyp 1,2,3 eliminates most drugs in humans
CYP 3A 4/5 eliminates 50% of the drugs NON SELECTIVE |
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enzyme induction
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when a drug increases the synthesis and activity of an enzyme
for another drug so tegretol can decrease teh level of oral contraceptives |
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enzyme inhibition
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competitive antagonism - compete for binding site
down regulation - decreases synthesis of enzyme leads to increased bioavaliabiltiy |
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genetic polymorpism
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can lead to reduced enzyme expression
cyp 2A6 has an altered binding site and thus cannot break down nicotine as effectively |
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half life rule
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at 6 half lives, 98.4% of the drug is eliminated
if a drug is dosed on the 1/2 life, it will take 6 half lives to reach the peak conc. in a steady state. this time is independent of drug dosage |
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metabolic tolerance
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enzyme induction - drug causes increased production of enzyme for itself
pharmacodynamic - changing the receptor or site of biological action, drug loses its affinity behavior/conditioned-your brain prepares your body for the drug before you ingest it |
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Pharmacodynamic tolerance
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receptors can be desensitized
receptors can be down regulated |
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cellular effect of a drug:
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proportional to DR / R (without drug attached)
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dose-response relationships
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describe the equilibrium concentration of the drug bound to the ligand (DR) and the D/R itself
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ED(50)
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median effective dose
the dose that is effective in 50% of the cases |
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3 things alter potency of drugs
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affinity for receptor
efficacy - how good the drug is at changing the shape of receptor Access to R - if a drug is ionized in the blood then it may be less avaliable to bind |
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therapeutic Index
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TI = TD(50) / ED (50)
a large TI is GOOD |
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agonist
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a drug that binds to a receptor with a biobehavioral effect
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antagonist
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a drug the binds to a receptor with little or no biobehavioral effect
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receptor types
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ionotropic
metabotropic (G protein coupled, use energy) carrier proteins tyrosine kinase |
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what is the RMP in inside of cell
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-70mV
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Where does Na want to go?
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inside the membrane
b/c of electrostatic pressure and concentration gradient |
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Where does K+ want to go?
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out of membrane
is drawn out by conc. gradient, BUT drawn IN by electrostatics |
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Na/K Pump
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3 Na go out and 2 K+ go back in
fights their gradients |
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Peak of Rising Phase
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vNa+ channels get tired
vK+ channels open and and K+ is pushed out by + charge inside the membrane and conc. gradient |
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Why are absolute and relative phases important?
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prevents back propagation
gives Na+/K+ pump time to correct gradient so it DOES take energy to propagate an AP |
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vesicular transporters
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proteins embedded in synaptic vesicles that help pull the NT out of cytoplasm and into vesicle
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Ca++ has two jobs at terminal
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1. initiates exocytosis of NT
2. turns the reserved pool of NT synaptic vesicles into a readily releasable pool -reserve pool vesicles get released from the cytoskeleton and become part of the readily releasable pool |
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scaffold proteins
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proteins in neuron membrane active zones and in the vesicular membranes that bind the vesicle to the membrane and cause it to open, releasing NT
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aterograde transport
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peptide NTs can be packaged in soma and then they "walk" from soma to terminal
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retrograde transport
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packages go from terminal to the soma
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Endorphin example
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it is a peptide NT synthesized in soma.
It is packaged in large granular vesicles and enzyme break it down into usable pieces as it is anterograde transported. the excess protein junk makes the vesicle opaque |
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4 NT criteria
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1. pre-synaptic store
2. has to have an effector site in the synapse 3. must have a synthesizing mechanism - usually in the terminal 4. There must be an inactivating mechanism |
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neuromodulator
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chemical ligand with an effector site in the synapse, but comes from another place, not the same synapse
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neurhormone
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part of its lifespan is spent in blood otherwise same as modulator
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release of NT
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graded
quantal |
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ionotropic receptors
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attached to ion channels
most are 5 protein subunits surrounding a pore |
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partial agonist
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the agonist binds, but it doesn't open the receptor everytime
it looks like an agonist at low doses, but looks like an antagonist at high doses the dose-response curve will NEVER reach 100% with it chantix (and nicotine) is an example of therapeutic use |
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inverse agonist
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binds to receptor, but shuts down/desensitizes the channel
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metabatropic receptors
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most are 1 protein with 7 transmembrane domains
have constitutive activity (are always working to some degree) |
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inverse agonist and metabatropic receptors
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shuts down constitutive activity
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Ion channels and intracellular effects
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have kinase 2nd messengers
leads to CaMK tends to activate receptors, ion channels, gene expression |
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Metabatropic intracellular effects
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G protein coupled
are kinase 2nd messengers too: 1. PKA (protein kinase A) 2. PKC (protein kinase C) |
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PKA
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positive feedback effects
excitatory phosphorylates receptors (can open ion channels) |
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PKC
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negative feedback effects
hyperpolarizes membrane by opening K+ channels inhibitory |
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somatodendritic autoreceptors
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regulate NT release
on pre-synaptic membrane reduce packaging |
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terminal autoreceptors
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in terminal
binds excess NT and causes K+ channels to open and reduce depolarization (hyperpolarize) this is the reason antidepressants take so long to work, these need to be desensitized |
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reuptake
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proteins in pre-synaptic membrane pull NT back into neuron and expells Na into cleft
works against NT conc gradient |
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enzymatic degredation
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enzymes in post synaptic membrae break down NT (AcH)
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