Lecture 5A: Dose Response Flashcards
What is an Agent?
Any chemical, biological, or physical material capable of eliciting a biological response
What is a dose?
the amount of that agent that comes into contact with a living organism or some part of a living organism
What is a response?
The biological reaction to an agent./Change in structure or function, morbidity, or mortality.
What is exposure?
Any condition which provides an opportunity for an external environmental agent to enter the body
Exposure is “____” the body while Dose is “____” the body
Exposure is “outside” the body while Dose is “inside” the body
What is a dose-response relationship?
the relationship between the effect of a substance on a single organism or population in relation to a specific dose.
What is another word for the does-response relationship?
It is also call dose-exposure relationship
Correlative relationship between exposure and the spectrum of effects
refer to as dose–response relationship
Whatever response is selected for measurement, the relationship between the ____________ of the biological system and the __________administered.
degree of response & amount of toxicant
Features of a Dose-Response Graph
- Shows the response data to each experimentally derived dosage
- Shows the dosage or exposure concentration of the chemical of interest.
- Usually in mg/kg (ppm)
- The values are usually in log format
D/R place pharmacology on a mathematical footing while on a practical level they are essential for making estimates of:
- Potency
- Efficacy
Uses of Dose Response (D/R) curves
- Therapeutic ratios of ED50
- Can be used as tool for investigating mechanisms of drug action and structure activity relationships
In a D/R relationship the response is due to
the chemical administered.
the data that is presented in D/R relationship is similarly to the presentation
of “dose response” in pharmacology and toxicology
The dose–response relationship is based on
the knowledge that the effect is a result of a known toxic agent or agents.
In a D/R relationship , the magnitude of the response is
in fact related to the dose.
What 3 other assumptions that recur frequently in D/R relationship?
- There is a molecular target site (or sites) with which the chemical interacts to initiate the response.
- The production of a response and the degree of response are related to the concentration of the agent at the target site.
- The concentration at the site is, in turn, related to the dose administered
The existence D/R relations means there is
A quantifiable method of measuring and a precise means of expressing the toxicity
For any given dose–response relationship, a great variety of
criteria or endpoints of toxicity could be used.
The ideal criterion for a D/R relationship would be
one closely associated with the molecular events resulting from exposure to the toxicant.
Changes in enzyme levels in blood can be indicative of
tissue damage.
Types of Dose-Response Relationships
- Individual (Graded)
- Quantal (Population)
Individual Dose-Response Relationships
Shows the response of one organism to the administered dosages of a chemical.
Individual Dose-Response Relationships is characterized by
characterized by a dose-related increase in the severity of the response.
Quantal Dose-Response Relationships
Shows the response of a population to the administered dosages
of a chemical
When a dose is increased in quantal dose response
The proportion of animals which exhibit a given response is greater.
In a quantal response it is either ____ or ___.
A quantal dose response is all-or-nothing: there either is or is not a
response.
In quantal dose response an organisms are either
Organisms are either “a responder” or “non responder”.
Quantal Dose-Response is used to calculate
Quantal Dose-Response is used to calculate LD50.
What is the first experiment performed with a new chemical?
Determination of the median lethal dose (LD50) is usually the first experiment performed with a new chemical.
The LD50 is the statistically derived from
A single dose of a substance that can be expected to cause death in 50 percent of the animals tested.
Hypersusceptable
Refers to organisms that respond as the dosage decreases.
Resistant
Refers to organisms that respond as the dosage increases.
The Sigmoid Curve
This curve is derived from cumulative experimental responses of animals to various dosages.
The minimum Effective Dose or threshold is
The minimum dose that causes a response.
ED = Effective (Therapeutic) Dose is
Dose that cause a therapeutic effect
TD = Toxic Dose
Dose that cause a toxic effect on organism
LD = Lethal Dose
Dose that cause lethality to organism
Median Dose
Dosage that affects 50% of the population
Therapeutic Index (TI)
The ratio of the dose required to produce a toxic effect to the dose needed to elicit the desired therapeutic response.
Therapeutic Index (TI) for humnas
TI = TD50/ED50 (humans)
Therapeutic Index (TI) for rodents
TI = LD50/ED50 (rodents)
The larger the ratio, for the TI
the greater the relative safety.
The steeper of the slope means it is, the more risk
The steeper it is, the more risk
Potency of a drug refers to
Potency of a drug refers to the quantity of drug that generates a response over a certain range.
* Strength of medicine
Factors to look at for potency
Factors to look at therefore are:
1. Range
2. First to elicit a response (if slope is similar)
Maximal efficacy reflects the
the limit of the dose–response relationship on the response axis to a certain chemical. `
Maximal Efficiency refers to
Maximal Efficiency refers to the intensity of the response for a specific chemical.
