PHARMACODYNAMICS 2024 Flashcards
- The cellular macromolecule or macromolecule
complex with which the drug interacts to elicit a
cellular response. - Selective
- Modifiable
DRUG RECEPTOR/ DRUG TARGET
Molecules that translate the drug receptor
interaction into a change in cellular activity
EFFECTORS
Binding of ATENOLOL to Beta receptor
stimulates conversion of __
ATP to cAMP
Binding of AMLODIPINE to Calcium Channel.
ION CHANNELS
Binding of RAMIPRIL to its receptor inhibits ACE
Angiotensin Converting Enzyme
ENZYMES
Thiazides (Bendroflumethiazide) block NaCl
transporter at the_____
distal convoluted tubule
In partial agonist, the magnitude of biologic effect is directly related to the fraction of_________
Active state
In reversible equilibrium, it favors the _____
inactive
state.
The strength of the reversible interaction between
a drug and its receptor, as measured by the
dissociation constant
DRUG SPECIFICITY
- Defined as the affinity of one for the other.
- Both the affinity of a drug for its receptor and its
intrinsic activity are determined by its chemical
structure.
DISSOCIATION CONSTANT
A drug that interacts with a single type of receptor
that is expressed on only a limited number of
differentiated cells will exhibit_____
high specificity.
Once the drug binds to the receptor, it produces a
curve – Receptor Occupancy Theory or Dose
Response Curve and this curve is characterized
by
“Hyperbolic Curve”
Response emanates from a receptor occupied by
a drug
RECEPTOR OCCUPANCY THEORY
e maximal response that can
be produced by the drug.
Emax
the concentration that produces
50% of maximal effect.
EC50
refers to the “effect”
EC
refers to
“affinity” of the receptor binding.
Kd
is the total concentration of
receptor sites (ie, sites bound to the drug
at infinitely high concentrations of free
drug).
Bmax
(equilibrium dissociation constant)
represents the concentration of free drug
at which half-maximal binding is
observed.
Kd
If the
Kd is low, binding affinity is_____
high
If there are 100 receptors, the concentration of the
drug wherein 50% of the receptors are bound
Kd
If there are 100 receptors, the concentration
wherein 100% of these receptors are bound
Bmax
Refers to the concentration (EC50) or dose
(ED50) of a drug required to produce 50% of that
drug’s maximal effect
POTENCY
For this drug, potency is at 1μg, wherein 50% of
half maximal effect is seen. If you give a drug that
would increase the heart rate and the maximum
effect of the drug would be increasing the heart
rate by 50, at what dose wherein you would
appreciate a 25 increase in the heart rate? That is
your_____
ED50
In case potency, the lowest dose that produces half maximal effect would be the _____ potent
most
A magnitude of response a drug causes when it
interacts with a receptor.
- Intrinsic Activity
MAXIMAL EFFICACY
The best determinant of which drug to choose
clinical effectiveness depends on_____
maximal efficacy
This parameter reflects the limit of the doseresponse relation on the response axis.
maximal efficacy
Among Potency and Maximal Efficacy, which is
more important in prescribing drugs?
Consider both, but for Clinical Effectiveness,
Maximal Efficacy is more important. When you
prescribe a drug, we are not only after the dosage,
but we’re after the effect of the drug
If you are comparing 2 drugs, for example, ARB
and Irbesartan (HPN drugs); They are both
efficacious, but which among the 2 is more potent
based on the dosage, then ____
Potency
If you are comparing drugs with different
mechanisms and you want to choose which is
better, then
EFFICACY
In determining the drug of choice what will you
consider is it the potency or efficacy?
Efficacy
In Potency, you look for the
ED50
In Efficacy, you look for the
Receptor and
Response.
A 55-year-old woman with hypertension is to be treated with
a thiazide diuretic. Thiazide A in a dose of 5mg produces the
same decrease in blood pressure as 500mg of Thiazide B.
Which of the following statements best describes these
results?
a. Thiazide A is more efficacious than Thiazide B
b. Thiazide A is about 100 times more potent than
Thiazide B
c. Toxicity of Thiazide A is less than that of Thiazide B
d. Thiazide A has a wider therapeutic window that
Thiazide B
Thiazide A is about 100 times more potent than Thiazide B
because it only takes 5mg of Thiazide A to produce the
same efficacy compared to 500mg of Thiazide B.
t is used in computing the therapeutic index.
QUANTAL DOSE EFFECT CURVES
It is the dose at
which 50% of individuals exhibit the specified
quantal effect.
Median Effective Dose (ED50)
It is the dose
required to produce a particular toxic effect in 50%
of individuals
Median Toxic Dose (TD50)
If the toxic effect is
the death of the animal. The amount of
drug/substance that when administered to a group
of experimental animals, will kill 50% of the group
in a specified time
Median Lethal Dose (LD50)
- Dose of a drug required to produce a desired
effect to that which produces an undesired effect
THERAPEUTIC INDEX
TI is Defined as the ratio of the______
TD50 to the ED50
TI formula:
Formula = LD50/ ED50
refers to the range
wherein the half maximal effect is seen as well as
the adverse effect
Therapeutic Window
If TI is_____, a slight change in the dosage
can lead to potential adverse effect.
low/ narrow
If TI is_____, even if there is an increase/
decrease in the dosage of the drug the risk for
adverse effect is lower.
large/ wide
Penicillin is an example of a drug with _____ TI
High
Drugs with Low TI:
▪ Antiarrhythmic Drugs - Digoxin ▪ Diabetes - Insulin ▪ Bronchodilator - Theophylline ▪ Anticoagulant - Warfarin ▪ Antiepileptic - Phenytoin
If ED50 is 0.1 and the TD50 is 10 what will be the
Therapeutic Window?
0.1 to 10 ug
If ED50 is 0.1 and the TD50 is 10 what will be the
Therapeutic Index?
10/ 0.1 = 100
Determines the ability to fully or partially activate
the receptors
INTRINSIC ACTIVITY
If a Full Agonist binds to the receptor and
produces and effect similar to your endogenous
ligand, the Intrinsic Activity is
1
If the drug produces an Intrinsic Activity of 1 and
mimics the effect of your endogenous ligand it is
considered as a
Full Agonist.
For Partial Agonist, they also bind to the receptor
and mimic the effect of your endogenous ligand
however the Intrinsic Activity of your Partial
Agonist is____
above 0 but less than 1.
are also agonists however when
they bind to the receptor, they change the
equilibrium/state of your receptor from active to
inactive
Inverse Agonist
he Intrinsic Activity of your
Inverse Agonist is
below 0.
For Antagonist, the Intrinsic Activity is
0
-because in the absence of agonist your
antagonist will not have any effect.
A ligand that binds to a receptor and produces a
conformational change that initiates an
intracellular signal
Agonist
Continuous administration of agonist after Emax
would lead to
Desensitization
A ligand that binds to a receptor but does not
produce the conformational change that initiates
an intracellular signal
ANTAGONIST
- binding site different from active site that is
bound by endogenous ligand.
Allosteric Site
Antagonist that binds to allosteric are ALL
noncompetitive antagonist
reversible -
Compete to the binding site of endogenous
ligand.
Competitive antagonist
irreversible
because if they bind to active site, they form
covalent bond. Duration of effect will depend
on the regeneration of new receptor
Noncompetitive Antagonist
Do not bind to receptor bound to your
endogenous ligand. Can be either chemical or
physiologic antagonist.
NON – RECEPTOR ANTAGONIST
Protamine, a protein that is positively charged at
physiologic pH, can be used clinically to counteract the
effects of heparin, an anti-coagulant that is negatively
charged. This is an example of:
a. Chemical Antagonism
-Protamine (a positively charged protein at
physiologic pH) binds heparin (a negatively
charged anticoagulant) making it unavailable for
interactions with proteins involved in the formation
of blood clots.
One drug may antagonize the action of a second
by binding to and inactivating the second drug.
a. Chemical Antagonism
Ted, 50 – year - old diabetic, was rushed to the ER due to
bronchial Asthma in acute exacerbation. He was given
Salbutamol nebulization and Hydrocortisone
(Glucocorticoid). Insulin was administered to oppose the
hyperglycemic effects of glucocorticoid. This is an example
of?
Physiologic Antagonism
-(Nonreceptor Antagonism) Hydrocortisone can increase
blood sugar. Insulin was administered to oppose the effect
of the hydrocortisone. Another example: Histamine
(bronchoconstriction) and Epinephrine (Bronchodilation).
