Pharmadynamics
·
Drug
:
Any substance that when administered to a
living organism produces ,
a
biological effect
Drug administered
Distribution
Absorption
·
Pharmacology :
The study of how the function of living systems is affected by chemical agents Drug in Tissue
Pharmacokinetics :
The study of ADME (absorption ,
distribution ,
metabolism & excretion) of drugs Drug in Systemic Pharmacan
D Circulation Elimination Drug Metabolizeda
Pharmacodynamics : The study of effects of drugs & their mechanisms of action
Drug g
·
Clinical pharmacology a .
k . a .
Pharmacotherapeutics :
The study of the use of drugs K
Site of
in the prevention & treatment of disease Drug at Action
·
Pharmacotherapy :
use of drugs to treat disease
·
Toxicology :
The study of adverse effects of drugs
Pharmaco
Pharmacologic Effect Clinical Response
Sia
Interactions
Drug Actions
Selectivity
most
size Non-covalent (H-bond hydrophobic)
,shape Charge , ,
ionic , reversible
few Covalent
L
·
Degree of Selectivity
D) Drug target The component of the organism which
drug interacts
rug receptor a k. a w/ most ptns
:
a are
i. e
. Selective on particular types of Ra
.
Useful therapeutic tool majority Physiological Rc : neurotransmitters & hormones
Other classes of ptn
:
enzymes , transport ptn ,
structural ptr
Pharmacologic Effect
Drugs Not Mediated
by Binding to R
. Antacids neutralize acid
:
e
g gastric
Major Types of Drug Targets
.
GPCR 160 % of prescribed drugs Ion Channels alters conductance
e .
.
g
Albuterol :
B2-agonist asthma e .
.
g
Local anaesthetics , sedative-hypnotics antiepileptics ,
e .
.
g Propanolol B2-antagonist :
hypertension
Enzymes Common target
Enzyme Linked Rc ·
Mostly act by inhibiting enzyme activity
NSAID H + pump inhibitor - acid reducer
e .
.
g Aspirin Ibuprofen Omeprazole
, ,
Tyr Kinase largest group e .
.
g Insulin Rc , Epidermal GFR
·
Imp .
in cellular growth & differentiation Transporters many clinically used drugs
GOF targets
·
Tyr R, Cancer · NT transporter drugs psychiatric disorders
-
SSRI
nL
anticancer drugs e .
.
g Imatinib (leukemia e .
.
g Prozac
= Gleevec
Nuclear Rc intracellular Structural Proteins
bind to
·
regulate expression of genes controlling metabolism & development · Anticancer drug tubulin polymerization into MT arrest at metaphase die
e .
. vinblastine
g
e .
.
g Steroid H, Thyroid H ,
Vit D
Dose-Response Curves
Graded [drug] vs .
effect
hyperbolic sigmoid
- - In Vitro
·
[Drug] us .
its effect .
us Whole Animal Experiments
max
.
response produced by drug % E % E
X-axis [drug]
Emax
Emax 100 Emax 100 in vitro :
*
C
E =
C EC505 [drug] that produces 12 Emax
X
+
whole animal
drug dose
:
50 50
·
[Drugbound" to R,J us .
[Free drug EC50
[Drug] log plot EC50 log[Drug]
Brector sumdissociationcont Bma -
% B [ >
Bmax An agonist does not have to
a 100
occupy
B =
all Rc to evoke a full response
2XBmax 50 50
kp I'spare' receptors (
affinity
Affinity tendency :
of a
drug to combine w/ Rc Indicates there is signal amplification
KD Ki
[Drug] log[Drug]
(measure of the strength of the drug-receptor complex
En
Efficacy -
hig her
I
ee
efficacy
·
Efficacy Magnitude :
of the response a
drug produces
· Maximal efficacy (Emax) : Greatest effect a
drug can
produce
Sometimes referred to log[Drug]
simply as
efficacy
Potency
·
Potency :
Measure of concentration or amt of drug necessary to
produce an effect of a
given magnitude
Er
Determined EC5o
using
Depends on both
affinity &
efficacy
log[Drug]
higher potency
, Sia
nL
ee
·
Drug
:
Any substance that when administered to a
living organism produces ,
a
biological effect
Drug administered
Distribution
Absorption
·
Pharmacology :
The study of how the function of living systems is affected by chemical agents Drug in Tissue
Pharmacokinetics :
The study of ADME (absorption ,
distribution ,
metabolism & excretion) of drugs Drug in Systemic Pharmacan
D Circulation Elimination Drug Metabolizeda
Pharmacodynamics : The study of effects of drugs & their mechanisms of action
Drug g
·
Clinical pharmacology a .
k . a .
Pharmacotherapeutics :
The study of the use of drugs K
Site of
in the prevention & treatment of disease Drug at Action
·
Pharmacotherapy :
use of drugs to treat disease
·
Toxicology :
The study of adverse effects of drugs
Pharmaco
Pharmacologic Effect Clinical Response
Sia
Interactions
Drug Actions
Selectivity
most
size Non-covalent (H-bond hydrophobic)
,shape Charge , ,
ionic , reversible
few Covalent
L
·
Degree of Selectivity
D) Drug target The component of the organism which
drug interacts
rug receptor a k. a w/ most ptns
:
a are
i. e
. Selective on particular types of Ra
.
Useful therapeutic tool majority Physiological Rc : neurotransmitters & hormones
Other classes of ptn
:
enzymes , transport ptn ,
structural ptr
Pharmacologic Effect
Drugs Not Mediated
by Binding to R
. Antacids neutralize acid
:
e
g gastric
Major Types of Drug Targets
.
GPCR 160 % of prescribed drugs Ion Channels alters conductance
e .
.
g
Albuterol :
B2-agonist asthma e .
.
g
Local anaesthetics , sedative-hypnotics antiepileptics ,
e .
.
g Propanolol B2-antagonist :
hypertension
Enzymes Common target
Enzyme Linked Rc ·
Mostly act by inhibiting enzyme activity
NSAID H + pump inhibitor - acid reducer
e .
.
g Aspirin Ibuprofen Omeprazole
, ,
Tyr Kinase largest group e .
.
g Insulin Rc , Epidermal GFR
·
Imp .
in cellular growth & differentiation Transporters many clinically used drugs
GOF targets
·
Tyr R, Cancer · NT transporter drugs psychiatric disorders
-
SSRI
nL
anticancer drugs e .
.
g Imatinib (leukemia e .
.
g Prozac
= Gleevec
Nuclear Rc intracellular Structural Proteins
bind to
·
regulate expression of genes controlling metabolism & development · Anticancer drug tubulin polymerization into MT arrest at metaphase die
e .
. vinblastine
g
e .
.
g Steroid H, Thyroid H ,
Vit D
Dose-Response Curves
Graded [drug] vs .
effect
hyperbolic sigmoid
- - In Vitro
·
[Drug] us .
its effect .
us Whole Animal Experiments
max
.
response produced by drug % E % E
X-axis [drug]
Emax
Emax 100 Emax 100 in vitro :
*
C
E =
C EC505 [drug] that produces 12 Emax
X
+
whole animal
drug dose
:
50 50
·
[Drugbound" to R,J us .
[Free drug EC50
[Drug] log plot EC50 log[Drug]
Brector sumdissociationcont Bma -
% B [ >
Bmax An agonist does not have to
a 100
occupy
B =
all Rc to evoke a full response
2XBmax 50 50
kp I'spare' receptors (
affinity
Affinity tendency :
of a
drug to combine w/ Rc Indicates there is signal amplification
KD Ki
[Drug] log[Drug]
(measure of the strength of the drug-receptor complex
En
Efficacy -
hig her
I
ee
efficacy
·
Efficacy Magnitude :
of the response a
drug produces
· Maximal efficacy (Emax) : Greatest effect a
drug can
produce
Sometimes referred to log[Drug]
simply as
efficacy
Potency
·
Potency :
Measure of concentration or amt of drug necessary to
produce an effect of a
given magnitude
Er
Determined EC5o
using
Depends on both
affinity &
efficacy
log[Drug]
higher potency
, Sia
nL
ee
