Exam1Lec4Pharmacokinetics Flashcards
What are pharmacodynamics?
The study of biochem and physiological effect of drugs and their mechanism of action
what drugs do to body
Pharmacodynamics mechanism of action include ___
- Initial interaction between drug and receptor
- responses
The site of drug action is often at specific protein macromolecules typically termed
receptors
Most receptors have
an endogenous ligand
usuallt agonist,compd that produce effect on receptor
Antagonists can be detected when?
When there is an agonist around
Drug receptors are not always membrane embedded proteins but can also be
- Enzymes (HMG-CO A reductaase, acetylcholinestrase)
- Na+, K+, -ATP ase pump
- structural proteins (tubulin)
- Nucleic acids (for cancer chemotherapeutic agents)
Interaction of drug receptors are
reversible/non convalent
drugs can bind and come off.
Two state model
mostly inactive form but when you add a ligand, it binds to the active form
example of an inverse agonst
antihistamines
AMPA receptor configurations
receptor is “dancing” going from an active to inactive state
receptors are dynamic molecules
what 3 things play an important role in drug/receptor interactions
- Hydrogen bonding
- Ionic
- Hydrophobic
General mechanisms for signal transduction
- Ion channels
- GPCR ( to regulate generation of IC second messengers)
- Intrinsic enzyme activity (tyrosine kinases)
- Receptors internalized (to deliver receptor-complexes to IC targets)
example of ion channels and function
ligand gated
agonist ligand binds to receptor and allow flow of ions (stabalizes channel)
another ex: voltage gated
Ligand gated ion channel examples
- Nicotinic AChR (excitatory)
- GABA (inhibitory)
- Glycine (inhibitory)
- Glutamate (excitatory)
Nicotinic AChR:
excitatory vs. inhibitory?
how many subunits?
leaves how many times?
allows what ions through?
excitatory
Pentamer (2alpha, 1 beta, 1 delta, 1 gamma)
4 times
Na+ & K+
endog ligand=ACh
GABA:
excitatory vs. inhibitory?
how many subunits?
allows what ions through?
inhibitory
pentamer
Cl-
binding of agonsits GABA will result in the openong of the pore allowing Cl- ions to flow across membrane
Example of drugs which modulate GABA receptors
Barbiturates and Benzodiazepines
Local anesthetics bind to the ____ domain of voltage gated ____ channel
intracellular; Na+
GPCR can influence activity of enzymes such as ____ and channels such as ____ thereby incr or decr the lvel of IC seconday messengers such as
1.adenylyl cyclase or phospholipase c
2. Ca2+ and K+
3. cAMP or
Ca2+
cAMP and Ca2+ can then regulate the activity of other enzymes
GPCRs are huge targets for drugs
How many receptors does GPCR have? spanning how many domains?
3 receptors
7 domains
ex: angiotensin, glucagon, histamine,opiod, serotonin, beta-adrenic, beta2-adrenic receptors.
Example of Ligand regulated transmembrane enzymes (intrinsic enzymes)
Insulin and epidermal GFR
(TK receptors)
intrinsic enzymatic activities (aka, they have their own kinase activity)
Intracellular receptors example
steroids (estrogen, androgen) receptors
it can alter gene expression in nucleus
Drug receptor interaction with the following Drug binds to :
GABA receptor
GPCR
Steroid receptor
slide 78
Cl- amplification
cAMP amplification
mRNA amplification
As the [ ] of a drug increase, the magnitude of effect ____
increases
EC50 of a drug is the [ ] that produces _____
1/2 maximum effect (Emax/2)
Explain this graph
which is the most potent and explain why
Which is the least potent and explain why
which one has the most efficacy
Label each one as either full agonist, partial agonsist, or antagonist
this graph represents different drugs on the same receptor.
Muscarine is most potent because it has the lower EC50 ( it takes less concentration to reach 50% of its effect)
Phenoarbital is the least potent because it takes more concetration to reach 50% of its effect
Muscarine and Gaba have the same efficacy, but we need more Gaba to reach this effect
Muscarine and Gaba are both full agonists
Phenoarbiital is a partial agonsit because it does not reach full effect.
Explain this graph
This graph represent the same drug on the receptor. In this case it is an antagonist of GABA, more specifically, competitive antagonist of GABA. Its action can be reveres bc its competing for the same site as gaba. If you incr the concentration of GABA high enough, you can overcome the antagonist and get full effect.
