Pharmacodynamics Flashcards

1
Q

Definition of pharmacodynamics

A

Mechanisms of action of a drug
Therapeutic uses
Adverse or side effects

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2
Q

Definition of pharamcokinetics

A
Mechanisms by which body handles the drug
Absorption
Distribution
Metabolism
Elimination
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3
Q

Theory of drug interactions

A

Drugs do not create effects, they modify ongoing functions
Effects of the body of most drugs are a result of interactions between the drug and functional macromolecular components of the organism

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4
Q

Stages in receptor function

A

Binding (L+R LR)

Transduction (LR -> Effect)

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5
Q

Alternatives to receptor-mediated drugs

A

Enzyme inhibitors
Transport inhibitors
Ion channel inhibitors
Note all of these still tend to follow the same paradigm as receptor-mediation

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6
Q

Characteristics of receptors

A

Specificity: Receptors are targeted by specific drugs
Selectivity: Receptors target a specific subset of cell pathways
Sensitivity: Effects at receptors are amplified within the cell, therefore, only a small amount of drug is needed

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7
Q

Pharmacological Classification Schema

A

Structural features of ligands (Muscarinic, Nicotinic cholinergic receptors)

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8
Q

Biochemical Classification Schema

A

Based upon transduction mechanism (Metabotropic vs ionotropic)

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9
Q

Molecular/Structural Classification Schema

A

Families of similar gene products

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10
Q

Definition of Kd

A

Dissociation constant at equilibrium
Kd = [L][R]/[LR] = k2/k1
Inverse of affinity
Units of M

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11
Q

Equation of [LR]

A

[LR] = Rt*[L]/(Kd + [L])

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12
Q

Characteristics of Ionic Bonds

A

Receptors have charged amino acids
Ligands are weak acids or bases and are charged at physiological pH
Major determinant of k1

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13
Q

Characteristics of Hydrogen Bonds

A

Hydrogen bound to an electronegative atom will have a partial positive charge
Weaker than ionic bonds, and require close proximity

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14
Q

Characteristics of Van der Waals interactions

A

Hydrophobic interactions
Act only at very close distances
Greatly strengthen the binding interaction and are the major determinant of k2

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15
Q

Occupancy theory

A
Effect is directly proportional to [LR]
E/Emax is proportional to [LR]/Rt
E = (Emax * C)/(Kact + C)
C = [Drug]
EC50 = Kact
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16
Q

Efficacy in occupancy theory

A

Idea of intrinsic activity for a ligand (0 < α < 1)
E/Emax = α[LR]/Rt
Full agonist: α = 1
Antagonist: α = 0

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17
Q

Spare receptors

A

Effector units are limiting factor, not receptors
Results in EC50 not being equal to KD
Increases a cell’s sensitivity to low ligand concentration and low activation time

18
Q

Classes of antagonists

A

Chemical: Combines with agonist to disallow interaction
Physiological: Activates an oppposing physiological target (ACh vs Norepi)
Pharmacological: Blocks effects of agonist at site of action

19
Q

Competitive Antagonist

A

Blocks target site of the drug
If reversible then it can be surmounted by agonist
Apparent affinity loss

20
Q

Equation for EC50’

A

EC50’ = EC50(1 + [I]/Ki)

21
Q

Implications of competitive therapeutic use

A

Dependence upon both its concentration and the agonist concentration
Antagonist with highest affinity for the receptor will produce the greatest inhibition

22
Q

Irreversible Competitive

A

Covalent binding to site or in an effectively irreversible rate
Reduces receptor pool
Assuming no spare receptors, no change in affinity (EC50), but efficacy decreases (Emax)

23
Q

Implications of irreversible therapeutic use

A

New receptor synthesis is the only way to overcome the effects of the antagonist
Degree of inhibition produced is not influenced very much by the concentration of agonist present

24
Q

Noncompetitive Antagonist

A

Binds to receptor at different target site

Decreases efficacy, completely irrespective of affinity even with spare receptors

25
Implications of noncompetitive therapeutic use
Independent of agonist concentration of receptor Can be used to inhibit the effects of multiple agonists that use the same signal transduction cascade (inhibition of voltage operated calcium channels)
26
Partial agonist
Partial agonist decreases effect of agonist
27
Tonic Activity
Equilibrium between active and inactive receptor states True antagonist does not have effect so it does not alter basal equilibrium Agonist and partial agonists shift equilibrium towards active state Inverse agonist shift equilibrium toward inactive state
28
Dose Response Theory
Ideally follows pharmacodynamical models in vitro | Issues from pharmacokinetics causes non-idealized behaviors (absorption, distribution, metabolism, excretion)
29
Definition of potency
Drug response equivalent of affinity (EC50 => ED50) | Result from site affinity, delivery to site
30
Definition of efficacy
Drug response equivalent of Ema Determinants: intrinsic activity, characteristics of effector, limits on amount that can be actually given in dose (risks of adverse effects)
31
Deviations from sigmoid response curve
Additive effects of the drug Threshold effects Antagonist effects Need to be considered for therapeutic purposes
32
Population dose response curves
Response frequency: Log-normal Culmulative response: Log-sigmoid You didn't see that coming, did you?
33
Causes for dose response variations
Pharmacokinetic differences Variations in the amount of endogenous agonist present Changes in the number of functioning of the drug target Differences in a component distal to the drug target
34
Definition of idiosyncratic drug responses
Unexpected based upon the mechanism of actions of the drug
35
Definition of hyporeactive and hyperreactive
Tails of frequency distribution
36
Definition of hypersensitivity
Allergic or inflammatory response to the drug
37
Definition of tolerance
Slowly developing resistance to the drug
38
Definition of tachyphylaxis
Rapidly developing resistance to the drug
39
Quantal dose response curves
Culmulative frequency relationships between drug dose and population response Shape of curve reflects the variability in response the population
40
Parameters from quantal dose response curves
``` ED50 - Median effective dose TD50 - Median toxic dose LD50 - Median lethal dose Therapeutic index (Ti) = TD50/ED50 ```