Upgrade to remove ads
Only $2.99/month

8110.05.03-Pharmacodynamics II (Dose-Response Theory)

Terms in this set (46)

Pharmacodynamics
the study of biochemical and physiological effects and the molecular mechanisms of action of drugs
Dose-response Relationship
relationship between dose and intensity of response
maximal efficacy
the largest effect that a drug can produce (y-axis)
relative potency
the amount of drug required to produce a given effect (rarely important clinically) (x-axis)
Law of mass action
as you increase the number of activated receptors, you will increase the response
What shape are response curves?
sigmoidal shape (similar to michelis-menten
Graded Response curve
plots the degree of a given response against the concentration of the drug
Quantal response curve
A particular effect is chosen and the concentration or dose of the drug is plotted against the percentage of a specific population in which the drug produces that specific effect
What is the Y-axis in a Quantal Patient Response Curve
the percentage of patients responding
Drug that produces more efficacy, will have a higher response on which axis of the dose-response curve?
Y-axis
Drug that is more potent produces a greater response on which axis of the dose-response curve?
X-axis
Theories of Drug-receptor interaction
Simple occupancy theory; Modified Occupancy theory
Modified Occupancy theory
Currently used today; Has two components:
1) Affinity- strength of attraction
2) Intrinsic Activity- ability to activate a receptor after binding as reflected by maximal efficacy
Simple Occupancy Theory
As you increase the number of ligands binding to receptor, you increase the response
Do you have to occupy all receptors to produce a response?
NO
Agonist
occupy receptor, conformational change, leads to signaling pathway
Antagonist
engages receptor, but doesn't activate. May create conformational change, but makes receptor stable
Partial Agonist
engages receptor, but only partially activates it. Also considered partial antagonist
What effect do Beta-blockers have on the heart
decrease the heart rate
How do Agonists activate receptors?
bind to receptors and mimic actions of the body's own regulatory molecules
Examples of Agonists
1. Neurotransmitters (epinephrine, norepinephrine, Ach);
2. Hormones (steroids, GH, insulin)
3. Endogenous regulators of receptor function
Isoproterenol
a drug that mimcis action of epinephrine on all beta receptors
Dobutamine
a drug that mimics action of norepinephrine at Beta1 receptors on the heart
Norethindrone
a drug that mimics action of progesterone
Bethanechol
drug that mimics action of ACh on muscarinic receptor
Heart uses which receptors
Beta 1 receptors (only have ONE heart)
Lungs use which receptors
Beta 2 (have 2 lungs)
How do antagonists produce their effects?
by preventing receptor activation by endogenous regulatory molecules and drugs; NO intrinsic activity
What does an antagonist do?
has affinity for receptor, so bind receptor and blocks activation of receptor by agonist
Examples of Antagonists
Propranolol; Prazosin; Tubocurare;
What is the endogenous agonist of Alpha receptors and beta receptors?
norepinephrine
Multiple receptors live in different tissues, therefore, you can synthesize __ neurotransmitter and produce a wide variety of responses by defining the receptors on the target tissue.
1 neurotransmitter
What are the two types of antagonists?
Noncompetitive (irreversible) and Competitive
How do irreversible (noncompetitive) antagonist bind to receptors?
covalently (those receptors no longer able to participate in process; chemically modified, so they can't be engaged)
A truly Noncompetitive antagonist produces a change in what?
both potency and efficacy (bind to, but doesn't interfere with actual engagement of receptor, but with the production of a response)
Irreversible selective antagonist changes what?
efficacy, but not potency
What do Competitive Antagonists change?
They change potency, not efficacy (interfere with agonist ability to engage receptor; done in a reversible fashion)
Which way do competitive agonists shift the curve on the dose-response curve?
to the right
Partial agonist
agonist that has only moderate intrinsic activity; maximal effect is LOWER than that of a full agonist
Can partial agonist also be partial antagonists?
Yes; when it reaches maximum response, 100% of receptors are engaged, so some receptors not activated..by definition it is also an antagonist
Spare Receptors
term used to describe situation in which maximum tissue response occurs, but not all receptors occupied by drug (in reserve)
ED50
Effective dose
The higher the therapeutic index, the safer/ more dangerous the drug
safer
Formula for Therapeutic Index (TI)
TI= LD50/ED50
Certain Safety Factor
Compares dose that produces toxicity in 1% of population to dose that produces effective response in 99% of population.
Formula for Certain Safety Factor (CSF)
LD1/ED99; bigger is better; ratio greater than 1 is safer
THIS SET IS OFTEN IN FOLDERS WITH...