Pharmacodynamics Flashcards
What is delineated under pharmacodynamics?
Drug receptors Dose-response curves MOA
What is the difference between a hyperbolic and sigmoidal dose-response curve?
Hyperbolic when drug dose vs response Sigmoidal when log of drug dose vs response
What is ED50
dose of drug that produces 50% maximal effect
What is Emax
maximal drug effect
What is a graded response?
Magnitude of response of population mean or single person –> “how much”
What is a quantal response?
frequency of individuals responding to a pre-defined variable
–> does a response occur, in how many yes or no, binary responses
Describe cumulative vs noncumulative quantal dose-response graphs
Cumulative: resposne of individuals to the dose and all doses lower than it
Noncumulative: response of individuals to only one dose
What are ED50, TD50 and LD50 in a cumulative quantal dose-response graph?
ED50: median effective dose
TD50: median toxic dose
LD50: median lethal dose
What is the equation for a therapuetic index?
TD50/ ED50
The higher the TI, the …
safer the drug
What is the therapeutic window?
range of doses that provides safe and effective therapy
Is it better for a drug to have a narrow or high therapeutic window?
High–> more space between therapeutic effect and adverse reaction
What is potency?
amount of drug required to produce specific pharm effect
What represents potency?
ED50
The lower the ED50, the…
more potent the drug
What is efficacy?
maximal pharm effect that a drug can produce
What represents efficacy?
Emax
The greater the Emax, …..
the more efficacious the drug
What relates the total number of receptors available to bind a drug?
efficacy
What kind of bonds do most drugs bind?
non-covalent
Reversible (ionic, hydrogen, hydrophobic)
Why aren’t covalent bonds used with most drugs?
since irreversible bonds, must resynthesize receptor or remove drug via enzyme
Describe relationship of Kd to affinity
inverse
low Kd, high affinity
Describe affinity in terms of drug dose
inverse
high affinity, low drug dose required
What affinity requires more drug due to poor receptor-drug interaction?
low affinity
What is the relationship of Bmax to Emax?
Bmax is maximal binding on a drug-receptor curve
Emax is maximal effect of drug on dose-response curve
BOTH look the same on graph–> Kd=EC50 on x axis
What is the difference between Kd and EC50?
same thing–> Kd used on drug-receptor graph, EC50 used on dose-response graph
What is the relationship of Kd to selectivity?
higher Kd, lower affinity, more selective, affects fewer targets, fewer adverse effects
Do agonists or antagonists have intrinsic activity?
Agonists ONLY
What is intrinsic activity?
ability of drug to change receptor function and produce physiological response on binding
Do antagonists change receptor function?
NO, no intrinsic activity to prevent agonist from binding instead
What types of agonists exist?
Full
Partial
Inverse
Describe full agonists
fully activate receptors
produce maximal effect when all receptors occupied
maximal intrinsic activity
What is a main difference between full and partial agonists?
intrinsic activity
Describe partial agonists
partially activate receptor on binding
produce sub-maximal effect when all receptors occupied
intrinsic efficacy varied (always sub-maximal)
Describe inverse agonists
decrease receptor signaling
decrease response at receptors
intrinsic activity present and related to inhibition of receptor function
opposite of full and partial agonist
What types of antagonists exist?
pharmacologic
chemical
physiologic
Describe pharmacologic (receptor) antagonism
act as same receptor as endogenous ligand or agonists
Describe chemical antagonism
makes another drug unavailable
DOESN’T interact with receptor
Describe physiologic antagonism
1 pathway antagonizes another pathway with different receptors
What types of pharmacologic antagonists exist?
Competitive and Non-competitive
Can competitive antgonist be displaced?
yes if enough drug is there
What are the types of non-competitive antagonists
Irreversible
Allosteric
Why are irreversible antagonists irreversible
they form covalent bonds over binding site
Action of allosteric antagonist
bind to site other than agonist binding site–> prevent or reduce binding OR prevent activation of receptor
EC50 increases
Emax does not change
competitive antagonist
Emax decreases
EC50 does not change
noncompetitive antagonist
Which antagonist is this
competitive antagonist
Which antagonist is this
Noncompetitive
What is the function of a full agonist
mimiks action of endogenous chemicals at receptors
What drugs can block actions of endogenous ligands at receptors?
antagonists
partial agonist
inverse agonist
What are drugs designed to target
important regulatory proteins in signaling pathways
What part of the G-protein receptor has GTPase activity
alpha subunit
What does Gs activate
adenylyl cyclase–> AC activation
What does Gi activate
adenylyl cyclases–> AC INHIBITION
What does Gq activate
phospholipase C–> PLC activation
What does G 12/13 activate
Rho GTPases–> cytoskeletal rearrangements
What downregulates G-protein receptors
beta-arrestin
G-protein coupled receptor kinase
protein phosphatase
What trigger JAK receptors
growth hormone
erythropoietin
leptin
INF-2, 10, 15
Why are receptor tyrosine kinases target for cancer drugs?
oncogenes in growth factor pathways
point mutation sites in cancer
anticancer drugs inhibit upregulated GF signaling
Point mutations in Ras cause what cancer
pancreatic adenocarcinoma
Point mutations in Raf cause what cancer
melanoma
Where are nuclear receptors
cytoplasm
What activate nuclear receptors
lipophilic so can cross into cytoplasm and activate receptor
steroid and thyroid hormones
vitamins D and A
lipid mediators
Why is L-type calcium channel a drug target?
everywhere, can cause arrhythmias, angina, HTN, constipation
