Download - Principles of Pharmacology: Pharmacodynamics
![Page 2: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/2.jpg)
Learning Objectives: Understand the theoretical basis of
drug-receptor interactions. Understand the determinants and
types of responses to drug-receptor interactions.
Know the four major families of receptors.
Define potency and efficacy. Understand how to compare drug
potency and efficacy. Understand the consequences of
receptor regulation Understand measures of drug safety.
![Page 3: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/3.jpg)
Biochemistry:
L+S LS
![Page 4: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/4.jpg)
Biochemistry:
L+S LS (Langmuir equation)
Pharmacology:L+R LR
![Page 5: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/5.jpg)
Biochemistry:
L+S LS
Pharmacology:L+R LR Response
![Page 6: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/6.jpg)
Pharmacodynamics
![Page 7: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/7.jpg)
Drugs: Chemical agents that interact with
components of a biological system to alter the organism’s function. Examples of such components, sites of drug action, are enzymes, ion channels, neurotransmitter transport systems, nucleic acids and receptors. Many drugs act by mimicking or inhibiting the interactions of endogenous mediators with their receptors
![Page 8: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/8.jpg)
Receptors: Regulatory proteins that interact
with drugs or hormones and initiate a cellular response– Ion channels– G-protein coupled receptors– Receptor-enzymes– Cytosolic-nuclear receptors
Act as transducer proteins– Receptor-effector signal transduction– Post-receptor signal transduction
provides for amplification of the signal
![Page 9: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/9.jpg)
Mg++
Ca++
Na+Na+
K+
Ligand-gated Ion Channels
Mg++Ca++
Ca++
![Page 10: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/10.jpg)
Na+
Na+
Na+Na+
Na+
Mg++
Ca++
K+
Ligand-gated Ion Channels Mg++
Ca++
Ca++
Na+
Na+
![Page 11: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/11.jpg)
G-protein coupled receptors
NH3+
COOH-
GTP
agb
![Page 12: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/12.jpg)
G-protein coupled receptors
NH3+
COOH-
GDP
agb
![Page 13: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/13.jpg)
Receptor-enzyme
Catalytic site
![Page 14: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/14.jpg)
Receptor-enzyme
Catalytic site
![Page 15: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/15.jpg)
Cytosolic-Nuclear receptors
![Page 16: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/16.jpg)
Cytosolic-Nuclear receptors
![Page 17: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/17.jpg)
Classical Receptor Occupancy Theory
Ka
L+R LR Stimulus Response
KdL: Ligand (Drug)R: ReceptorLR: Ligand-Receptor ComplexKa: Association rate constantStimulus: initial effect of drug on
receptor
![Page 18: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/18.jpg)
Properties of drugs Affinity: The chemical forces
that cause the drug to associate with the receptor.
Efficacy: The extent of functional change imparted to a receptor upon binding of a drug.
![Page 19: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/19.jpg)
Properties of a biological system Potency: Dose of drug
necessary to produce a specified effect.– Dependent upon receptor density,
efficiency of the stimulus-response mechanism, affinity and efficacy.
Magnitude of effect: Asymptotic maximal response– Solely dependent upon intrinsic
efficacy.– Also called efficacy.
![Page 20: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/20.jpg)
Determinants of Response Intrinsic Efficacy (ε): Power of a
drug to induce a response. Number of receptors in the target
tissue.
![Page 21: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/21.jpg)
Spare receptors Some tissues have more
receptors than are necessary to produce a maximal response.– Dependent on tissue, measure of
response and intrinsic efficacy of the drug.
![Page 22: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/22.jpg)
Active vs Inactive states Receptors in an active state
initiate cell signaling. For any cell, there is an
equilibrium between receptors in active and inactive states. The inactive state usually predominates.
Each state has its own affinity.
![Page 23: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/23.jpg)
Classification of a drug based on drug-receptor interactions: Agonist: Drug that binds to receptors
and initiates a cellular response; has affinity and efficacy. Agonists promote the active state.
Antagonist: drug that binds to receptors but cannot initiate a cellular response, but prevent agonists from producing a response; affinity, but no efficacy. Antagonists maintain the active-inactive equilibrium.
![Page 24: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/24.jpg)
cont. Partial agonists: Drug that, no
matter how high the dose, cannot produce a full response.
Inverse agonist: Drug that binds to a receptor to produce an effect opposite that of an agonist. Stabilizes receptors in the inactive state.
![Page 25: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/25.jpg)
Graded dose-response curves Individual responses to varying doses Concepts to remember:
– Threshold: Dose that produces a just-noticeable effect.
– ED50: Dose that produces a 50% of maximum response. (EC50: blood concentration that produces a 50% of max response)
– Ceiling: Lowest dose that produces a maximal effect.
![Page 26: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/26.jpg)
Dose-response curve
Dose
Resp
ons
e
0
20
40
60
80
100
0 200 400 600 800 1000
![Page 27: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/27.jpg)
Dose-response curve
Dose
Resp
ons
e
0
20
40
60
80
100
0.1 1 10 100 1000 10000
![Page 28: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/28.jpg)
= Agonist
0
20
40
60
80
100
0.1 1 10 100 1000 10000
![Page 29: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/29.jpg)
= Agonist
0
20
40
60
80
100
0.1 1 10 100 1000 10000
![Page 30: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/30.jpg)
= Agonist
0
20
40
60
80
100
0.1 1 10 100 1000 10000
![Page 31: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/31.jpg)
= Agonist
0
20
40
60
80
100
0.1 1 10 100 1000 10000
![Page 32: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/32.jpg)
= Agonist
0
20
40
60
80
100
0.1 1 10 100 1000 10000
![Page 33: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/33.jpg)
= Agonist
0
20
40
60
80
100
0.1 1 10 100 1000 10000
![Page 34: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/34.jpg)
= Agonist
0
20
40
60
80
100
0.1 1 10 100 1000 10000
![Page 35: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/35.jpg)
Dose-response curve
Dose
Resp
ons
e
0
20
40
60
80
100
0.1 1 10 100 1000 10000
Ceiling
ED50
ThresholdED50
![Page 36: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/36.jpg)
Full vs Partial agonists
0
20
40
60
80
100
0.1 1 10 100 1000 10000
Full Agonist
Partial Agonist
Dose
% E
ffec
t
![Page 37: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/37.jpg)
Full vs Partial agonists These terms are tissue dependent
on– Receptor density– Cell signaling apparatus– Other receptors that are present– Drug history
Partial agonists have both agonist and antagonist properties.
![Page 38: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/38.jpg)
Inverse Agonist
Dose
% E
ffec
t
-40
-20
0
20
40
60
80
100
1 1 0 1 0 0 1 0 0 0 1 0 0 0 0
Full agonist
Partial agonist
Inverse agonist
![Page 39: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/39.jpg)
Relative Potency
0
20
40
60
80
100
0.1 1 10 100 1000 10000
A B
Dose
Effec
t
![Page 40: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/40.jpg)
Relative Potency
Dose
Effec
t
0
20
40
60
80
100
0.1 1 10 100 1000 10000
A B
![Page 41: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/41.jpg)
Relative Potency
=ED50B/ED50A
320/3.2=100
![Page 42: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/42.jpg)
Relative Efficacy
0
20
40
60
80
100
0.1 1 10 100 1000 10000
Relative Efficacy
![Page 43: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/43.jpg)
Antagonists Competitive: Antagonist binds to
same site as agonist in a reversible manner.
Noncompetitive: Antagonist binds to the same site as agonist irreversibly.
Allosteric: Antagonist and agonist bind to different site on same receptor
Physiologic: Two drugs have opposite effects through differing mechanisms
![Page 44: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/44.jpg)
= Agonist = Antagonist
0
20
40
60
80
100
120
-10.5 -10 -9.5 -9 -8.5 -8 -7.5 -7 -6.5 -6
![Page 45: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/45.jpg)
= Agonist = Antagonist
0
20
40
60
80
100
120
-11 -10 -9 -8 -7 -6
![Page 46: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/46.jpg)
= Agonist = Antagonist
0
20
40
60
80
100
120
-11 -10 -9 -8 -7 -6
![Page 47: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/47.jpg)
= Agonist = Antagonist
0
20
40
60
80
100
120
-11 -10 -9 -8 -7 -6
![Page 48: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/48.jpg)
= Agonist = Antagonist
0
20
40
60
80
100
120
-11 -10 -9 -8 -7 -6
![Page 49: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/49.jpg)
= Agonist = Antagonist
0
20
40
60
80
100
120
-11 -10 -9 -8 -7 -6
![Page 50: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/50.jpg)
= Agonist = Antagonist
0
20
40
60
80
100
120
-11 -10 -9 -8 -7 -6
![Page 51: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/51.jpg)
Competition
0
200
400
600
800
1000
1200
-11 -10 -9 -8 -7 -6
ID50 or IC50
log [antagonist]
Effec
t
![Page 52: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/52.jpg)
= Agonist = Antagonist
![Page 53: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/53.jpg)
= Agonist = Antagonist
![Page 54: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/54.jpg)
= Agonist = Antagonist
![Page 55: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/55.jpg)
= Agonist = Antagonist
![Page 56: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/56.jpg)
= Agonist = Antagonist
![Page 57: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/57.jpg)
= Agonist = Antagonist
![Page 58: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/58.jpg)
= Agonist = Antagonist
![Page 59: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/59.jpg)
Competitive antagonists
0
20
40
60
80
100
0.1 1 10 100 1000 10000
A CB
Dose
Resp
onse
![Page 60: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/60.jpg)
Noncompetitive antagonists
Dose
Resp
onse
0
20
40
60
80
100
0.1 1 10 100 1000 10000
A
C
B
![Page 61: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/61.jpg)
Allosteric and Physiologic antagonists Response can be irregular
![Page 62: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/62.jpg)
Allosteric Antagonism
![Page 63: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/63.jpg)
Allosteric Antagonism
![Page 64: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/64.jpg)
Allosteric Antagonism
![Page 65: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/65.jpg)
Allosteric Antagonism
![Page 66: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/66.jpg)
Allosteric antagonists 1
0
20
40
60
80
100
0.1 1 10 100 1000 10000
A
Dose
Resp
onse
![Page 67: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/67.jpg)
Allosteric antagonists 2
Dose
Resp
onse
0
20
40
60
80
100
0.1 1 10 100 1000 10000
A
C
B
![Page 68: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/68.jpg)
Quantal Dose-Response Curves
Also known as concentration-percent or dose-percent curves
Used when the dose of a drug to produce a specified effect in a single patient is measured (individual effective dose or concentration.)
The percent of subjects responding at a dose is plotted.
![Page 69: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/69.jpg)
Quantal Dose-Response Curves
1 3.2 10 32 100 320 1000 32000
10
20
30
40
50
60
70
80
90
100
DosePerc
ent
Resp
onde
rs
![Page 70: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/70.jpg)
Cumulative Quantal Dose-Response Curves
1 3.2 10 32 100 320 1000 32000
20
40
60
80
100
120
DosePerc
ent
Resp
onde
rs
![Page 71: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/71.jpg)
Cumulative Quantal Dose-Response Curves
1 10 100 1000 100000
20
40
60
80
100
120
DosePerc
ent
Resp
onde
rs
![Page 72: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/72.jpg)
Receptor regulation Reduced responsivity: Chronic
use of an agonist can result in the receptor-effector system becoming less responsive
– eg. alpha-adrenoceptor agents used as nasal decongestants
Myasthenia gravis: decrease in number of functional acetylcholine nicotinic receptors at the neuromuscular junction.
![Page 73: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/73.jpg)
Receptor regulation Increased responsivity: Chronic
disuse of a receptor-effector system can result in an increased responsiveness upon re-exposure to an agonist.
– Denervation supersensitivity at skeletal muscle acetylcholine nicotinic receptors
– Thyroid induced upregulation of cardiac beta-adrenoceptors
– Prolonged use of many antagonists (pharmacological as well as functional) can result in receptor upregulation
![Page 74: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/74.jpg)
Receptor Upregulation Most receptors are internalized
and degraded or recycled with age and use.
Antagonists slow use-dependent internalization
Inverse agonists stabilize the receptor in the inactive state to prevent internalization.
The cell continues to produce receptors.
![Page 75: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/75.jpg)
Desired vs undesired effects: Indices of drug safety. Safety Index Therapeutic Index
“Potency means nothing. I can always give a bigger pill.”
J. Hunter
![Page 76: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/76.jpg)
Safety index: LD1/ED99
-20
0
20
40
60
80
100
0.000
10.0
01 0.01 0.1 1 10 10
0 1K 10K
100K
Sleep Death
LD1
ED99
![Page 77: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/77.jpg)
Therapeutic index: LD50/ED50
-20
0
20
40
60
80
100
0.000
10.0
01 0.01 0.1 1 10 10
0 1K 10K
100K
Sleep Death
![Page 78: Principles of Pharmacology: Pharmacodynamics](https://reader033.vdocuments.us/reader033/viewer/2022052414/56816713550346895ddb7ec7/html5/thumbnails/78.jpg)
Safety Index vs. Therapeutic Index
1 10 100 1000 10000 1000000
20
40
60
80
100
Dose
Perc
ent
Effec
t
LethalityDesired Effect
LD50ED50 ED99 LD1
Safety Index
Therapeutic Index