Pharmacodynamics Flashcards
Pharmacodynamics
Effect of a drug on the body
based on the concept of drug receptor binding
Affinity
Kd
D+R <-> DR
Kd= disassociation constant
1. Ratio of rate at which the drug binds to the receptor compared to the rate that a receptor complex disassociates
2. As drug concentration increases the concentration of bound receptors increases and as free receptors inc, bound receptors concentration inc as well
Dose response relationship
certain doses are associated with certain responses
Potency (EC50)
amount of drug that produces a response in 50% of the population
more potent needs lower dose
Efficacy (Emax)
the max response produced by the drug, adding more drug wont produce more response because there is 100% occupancy
Median effective dose (ED50)
amount of drug that produces a response in 50% of the population
Median toxic dose (TD50)
amount of drug that produces a response in 50% of the population
Median lethal dose (LD50)
amount of drug that produces a response in 50% of the population
6 major neurotransmitters
Serotonin
Norepinephrine
Dopamine
Acetylcholine
Glutamate
GABA
5 psychotroptic drug targets
neurotransmitter reuptake
neurotransmitter receptors
neurotransmitter metabolism
Ion channel neurotransmission (2: ligand and voltage gated)
Neurotransmitter reuptake
Prevent recycling of NT like serotonin or dopamine by inhibiting reuptake and storage in neuron and inc levels in the synapse and affect post synaptic neurons
Neurotransmitter receptors
Many drugs interact with these by binding on the same receptor as the NT or may bind allosterically and change the receptor to enhance or inhibit the NT
Neurotransmitter metabolism
Enzymes are another target of drugs as they convert one molecule into another and the enzyme often affect on NT is to break them down
Basically they could inhibit this and allow NT concentrations to circulate
Ion channel (2)
Ligand gated which is opened by NT binding
Voltage gated which opened by charge across the membrane
reuptake
NT released during neurotransmission are in many cases transported back into the presynaptic neurons and allows reuse and once back in are put in vescicles for storage and protection and ready to redploy
presynaptic transporter SERT
for serotonin
presynaptic transporter NET
for norepinephrine and dopamine
presynaptic transporter DAT
for dopamine
presynaptic transporter GABA 1-4
for GABA
presynaptic transporter glycine 1-2
for glycine
presynaptic transporter: excitatory amino acid transporters 1-5
glutamate
aspartate
vesicular transporter VMAT 1-2
serotonin
NE
DA
vesicular transporter VAchT
Ach
vesicular transporter VIAAT
GABA
vesicular transporter V GluT 1-3
glutamate
G-protein linked receptors
second messenger system (NT is the first messenger)
drug can act at NT binding sites or allosteric sites
So NT binds first and changes the receptor allowing the g-protein to bind
The G protein makes another change which preps it for the enzyme that synthesizes the second messenger
Agonist
When a drug binds to the g protein linked receptor it can affect the receptor in different ways than the endogenous NT
Generally produces response similar to the endogenous NT
direct: bind to NT receptor at NT site or allosteric site
indirect: boost levels of NT by blocking inactivation
partial agonist
stabilizers
Hard to understand
Somewhere on spectrum of agonist that fully activates a receptor and an antagonist that doesn’t change signal transduction
Like a light on a dimmer switch
antagonist
Usually blocks what an endogenous NT would do to the receptor
True antagonists are neutral and because they have no actions of their own they are often called silent
Maintain baseline activity
partial inverse agonist
inactivates the receptor
reduces signal transduction
removes baseline activity
Opposite extreme of the agonist in that it neither inc signal transduction or blocks agonist activity like an antagonist
dopamine receptors and associated class
D1
D2
antipsychotics
serotonin receptors and associated class
5HT1A, 2A, 1B/D, 2C, 6, 7
antipsychotics
antidepressants
anxiolytics
norepinephrine receptors and associated class
a-1
a-2
B-2
antidepressant (mirtazapine)
antihypertensives
antipsychotics
Acetylcholine receptors and associated class
M1
M3/M5
antidepressant
antihistamines
antipsychotics
enzymes
convert a substrate into a product
Rx can bind to enzyme inhibitors which can be reversible or irreversible
Only a few drugs are enzyme inhibitors
The ones that bind to inhibitors allow the enzyme to inc interaction with substrate because they inhibit the inhibitor
Examples of enzyme targets
In each case the action of the drug prevents the action of the enzyme that degrades the substrate
Monoamine Oxidase
Acetylcholinesterase
Glycogen synthase kinase (GSK)
Aldehyde Dehydrogenase
Ligand gate is regulated by
receptor gate keeper that hasd the potential to bind an NT or hormone
regulation of a ligand gate produces
a confirmation change that opens the channel and allows the flow of charged molecules
If agonist occupies a binding site on a ligand gate
the frequency at which the channel opens is increased
If antagonist binds to the receptor on a ligand gate
the channel is locked in resting confirmation and similar to if no NT bound
If partial agonist binds to ligand gate
will open but less than if full agonist present
If inverse agonist binds to ligand gate
channel closes and stabilizes it
Allosteric site
It is a site other than which the endogenous ligand binds
Allosteric sites have no activity on their own but when bound at the same time as a ligand
they can enhance or block the ligand activity
if enhance they are positive and
if block they are negative allosteric modulator
a. Pos ex is a benzo
voltage sensitive
Action potential: Electrical impulse in a neuron
Voltage-sensitive sodium channels (VSSCs)
Voltage-sensitive calcium channels (VSCCs)
