Pharmacodynamics Flashcards
What is pharmacodynamics?
biochemical and physiological effect of drugs and their mechanism
What is the mechanism of action?
initial interactions between drug and cellular macromolecules
Most drug receptors have what type of ligand?
endogenous
What are the non-receptor mediated drug actions?
- gastric antacid
- mannitol (osmotic diuretic)
Most drugs have what types of reversible forces?
- ionic
- hydrogen
- hydrophobic
- van der waals
What is the 2 state model?
- agonists bind and stabilizes in the active configuration
- population shifts to the right when agonists are present
When does basal activity occur?
when more receptors are active
An inverse agonist favors which side?
left side
What are the mechanisms needed for signal transduction?
- ion channels
- receptor coupled G-proteins
- receptors with intrinsic enzyme activity
- receptors that are internalized to deliver receptor complexes to intracellular targets
What are the characteristics of nicotinic Ach receptors?
- made of 5 subunits
- every subunit goes through the membrane 4 times
- subunits are higly homologous
- binding of receptor allow Na+ and K+ to flow across membrane
What type of receptor is a partial agonist?
GABA
Binding to a GABA receptor results in what?
pore opening and allowing Cl- ions across the membrane to cause hyperpolarization
What are the drugs that modulate GABA receptors?
barbituates and benzodiazepine
Glycine and glutamate are what type of ligand channels?
glycine: inhibitory
glutamate: excitatory
A transient change in the voltage across membrane can trigger what?
opening of gate allowing Na+ ions across membrane
Where do local anesthetics bind?
to the intracellular domain of voltage-gated Na channel
What is the purpose of receptor coupled G-proteins?
regulate generation of intracellular second messengers
What are the 3 types of G-proteins?
alpha, gamma, beta
What are the enzymes coupled to G-proteins?
- adenylyl
- cyclase
- phospholipase C
What are the channels coupled to G-proteins?
Ca++ and K+
What 2 things can regulate the activity of other enzymes?
cAMP and Ca++
What is a ligand regulated transmembrane enzyme?
tyrosine kinase receptor
What is an intracellular receptor and where does it bind?
steroids; bind inside the membrane
When a durg is more potent, where is it located on the graph?
furthest to the left
Partial agonists have a lower what compared to fulla agonists?
lower efficacy
What is the EC50?
- the conc. that produces 1/2 the max effect
- measures potency
If the drug needs less conc. for same EC50 then?
increase potency
What is an agonist?
drug or ligand that binds to the same site as endogenous ligand and produces a signal
What does a full agonist have affinity for?
ONLY for active state
What does a partial agonist have affinity for?
higher affinity only for active than inactive state
What is efficacy/intrinsic activity?
properties of durgs that bind to the same receptor site but DO NOT produce equal maximum effects
What is the most efficacious agonist?
drug that produces greatest maximum effect
What is an antagonist?
drug that binds to the site used by endogenous ligand and blocks the signal produced by the endogenous ligand
What is the difference between agonists and antagonists when it comes to the binding states?
agonists change the equil. to active while antagonists DO NOT
What are the characteristics of competitive antagonists?
- reversible
- inhibition overcome by increasing the conc. of an agonist
What are the characteristics of noncompetitive antagonists?
- irreversible
- prevents agonist, at any conc., from producing a maximum effect on a given receptor
When looking at a graph, what is the movement of competitive antagonists?
shift from left to right
When looking at a graph, what is the movement of noncompetitive antagonists?
has a decrease, line gets closer to 0
What is an inverse agonist?
reduce constituitive activity of a receptor
An inverse agonist has affinity for what?
ONLY for inactive state (shifts the equil.)
On a graph how would you differenciate between the types of antagonists and agonists?
- full agonist: at the very top
- patial agonist: halfway between 0 and full agonist
- antagonis: at 0
- inverse agonist: below 0
What is receptor desensitization?
when continued exposure ot the same conc. of the drug diminishes the effect as a function of time of exposure to the agonist
Continuous exposure to an agonist can what?
decrease the number of receptors
Continuous exposure to an antagonist can what?
increase the number of receptors
What is responsible for pharmacodynamic tolerance?
receptor desensitization and down regulation
What is required to produce a given magnitude of effect and what is it known as?
increasing doses of drugs; tachyphylaxis
What are spare receptors?
when the max effect is reached with a small fraction of the receptors
What gives the terapeutic index?
ED50
What is ED50?
median effective does that causes 50% of individuals to have an effect
What is LD50?
median lethal does that kills 50% of tested animals
What is TD50?
dose that produces toxic effect in 50% of individuals
For a drug to be safe, what is the ratio we need?
a high TD50 and a low ED50
