Pharmacology: Dose-Concentration-Effect Relationship

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Questions and Answers

What are the changes that occur directly in relatively simple systems like cells, tissues, and organs, and are of a fundamental nature?

Effect

What term is used to describe changes that occur in an organ or the whole organism depending on the drug and can be directly seen or monitored?

Influence

What do undesirable changes that occur in the patient during drug treatment called?

Side effects

What is the relationship where drugs must be above a certain minimum concentration at their site of action to have an effect?

Dose-Concentration Relationship Signup and view all the answers

In the Dose-Concentration Relationship, if the dose of the drug is increased, the effect increases proportionally.

False Signup and view all the answers

What term refers to the curve showing the concentration profile of a drug, which varies according to dosage, route of administration, and dose?

Plasma Concentration-Time Curve Signup and view all the answers

The time taken to reach steady-state in intravenous infusion is based on the infusion rate.

False Signup and view all the answers

What is the percentage decrease in effect observed with each half-life?

15% Signup and view all the answers

At what concentration of the drug does the effect become almost proportional to the concentration?

Less than 1/4 of EC50 Signup and view all the answers

What is the primary factor that influences the time-dependent variation of the effect at concentrations below EC50?

Exponential decrease in concentration Signup and view all the answers

What is the characteristic of delayed effects of drugs?

Depend on the dispersion time of the drug Signup and view all the answers

What is the purpose of intermittent administration of aminoglycoside?

To preclude cumulative effects Signup and view all the answers

What is the characteristic of cumulative effects of drugs?

Depend on the accumulation of effects Signup and view all the answers

What is the half-life required for the effect to decrease from 80% to 20% of Emax?

4 Signup and view all the answers

What is the term used to describe the time taken for the drug to reach the site of action?

Dispersion time Signup and view all the answers

What is the primary reason for the delayed effects of warfarin?

Slow synthesis rate of physiological substances Signup and view all the answers

What is the characteristic of the effect of drugs used in cancer treatment?

Cumulative effects over time Signup and view all the answers

Study Notes

DOSE-CONCENTRATION-EFFECT RELATIONSHIP

Effect: Changes caused by the drug in relatively simple systems, such as cells, tissues, and organs.
Influence: Changes in organs or the whole organism that can be directly observed or measured.
Result: Combination of effect and influence.

DOSE-CONCENTRATION RELATIONSHIP

A minimum concentration of the drug is required at the site of action for it to have an effect.
The effect increases in a dose-dependent manner, but plateaus when the maximum effect is reached.
Increasing the dose beyond this point can increase side effects.

PLASMA CONCENTRATION-TIME CURVE

Measures the concentration of the drug in plasma over time.
The curve varies depending on the dose, route of administration, and other factors.
Key points on the curve include the peak concentration (Cmax), time to reach peak concentration (tmax), and area under the curve (AUC).

ADMINISTRATION OF SINGLE DOSE

Complete absorption of the drug leads to 100% bioavailability.
Fractional absorption equals systemic bioavailability (F).

ADMINISTRATION OF REPEATED DOSES

Drugs are administered in repeated doses to maintain a continuous effect.
The plasma concentration fluctuates around the average steady-state concentration (Css).
Factors affecting the fluctuation include the dose interval (T) and the elimination half-life (t1/2).

TARGET CONCENTRATION APPROACH IN RATIONAL DOSING

Loading dose: given to quickly reach the desired concentration in patients with a long elimination half-life.
Maintenance dose: continued to maintain the desired concentration.

ADMINISTRATION OF THE DRUG BY INTRAVENOUS INFUSION

The drug enters the body at a constant rate, and its elimination follows first-order kinetics.
The concentration of the drug in plasma at steady-state is directly proportional to the infusion rate.

DOSE-EFFECT AND CONCENTRATION-EFFECT RELATIONSHIPS

Gradual dose-effect curve: shows the effect of increasing doses of the drug.
Concentration-effect curve: shows the effect of increasing concentrations of the drug.
Important parameters include Emax (maximum effect), EC50 (concentration producing 50% of Emax), and IC50 (concentration inhibiting 50% of Emax).

POTENCY AND EFFICACY

Potency: the dose or concentration of the drug required to produce a certain effect.
Efficacy: the maximum effect that the drug can produce.

QUANTAL DOSE-EFFECT RELATIONSHIP

Used to study the effect of the drug on a large population.
The dose that produces the desired effect in 50% of individuals (ED50) is an important parameter.

THERAPEUTIC INDEX

Compares the dose required to produce the desired effect with the dose that produces an undesirable effect.
A higher therapeutic index indicates a safer drug.

RELATIONSHIP BETWEEN DURATION OF ACTION AND DOSE

The duration of action depends on the dose, with higher doses leading to longer durations.
This relationship can be influenced by the drug's pharmacokinetics and pharmacodynamics.

TIME-DEPENDENT VARIATION OF DRUG EFFECT

Immediate effects: the effect of the drug changes over time, depending on the concentration and pharmacokinetics.
Delayed effects: the effect of the drug is delayed due to factors such as slow synthesis of physiological substances.
Cumulative effects: the effect of the drug accumulates over time, leading to a delayed but prolonged effect.

Area Under the Curve (AUC)

AUC is a measure of the total exposure of a drug to the body
It is calculated by plotting the concentration of the drug against time
Peak concentration (tmax) reflects the absorption rate of the drug

Single Dose Administration

When a drug is given orally or intramuscularly, complete absorption results in AUCs equal to 100% bioavailability
Fractional absorption is equal to systemic bioavailability (F)

Repeated Dose Administration

Drugs are administered in certain doses and at intervals to achieve a continuous effect
The interval (T) is determined so that the doses after the first dose are given long before the plasma level provided by the previous one approaches zero
The newly added drug is added to the remaining drug concentration
The plasma concentration at steady-state does not follow a constant course, but fluctuates around the average steady-state concentration (Css)
Cssmax is the peak concentration, and Cssmin is the bottom concentration
The amplitude of the fluctuation varies with the ratio between the dose interval (T) and the half-life of the drug (t1/2)

Accumulation of the Drug

The rate of attainment of steady-state is not dose-interval-dependent, but depends on the elimination rate constant and thus on the half-life of the drug (t1/2)
The drug is considered to have reached steady-state in plasma at 4 elimination half-times, at which point it has reached 94% of the plateau level

Target Concentration Approach

A loading dose is given to patients with a long elimination half-life, followed by a maintenance dose
Examples of drugs that require a loading dose include digoxin and theophylline

Administration of the Drug by Intravenous Infusion

The drug enters the body at a constant rate (zero-order kinetics)
Its elimination is according to first-order kinetics
The concentration of the drug in the plasma at steady-state is directly proportional to the infusion rate
The time taken to reach steady-state depends on the half-life of the drug (t1/2)

Dose-Effect and Concentration-Effect Relationships

Gradual dose: the effect increases with the increasing dose
Quantal dose: the effect is all or nothing (e.g. relieving headaches, preventing convulsions)
Emaks: the maximum effect that the drug can create
EC50: the molar drug concentration that creates an effect equal to 50% of the Emax
IC50: the concentration that inhibits an inhibition equal to 50% of Emax

Potency and Efficacy

Potency: the ability of a drug to produce a certain effect at a smaller dose or concentration
Efficacy: the maximum effect value of the drug
A drug with a low EC50 value is stronger

Therapeutic Index

The therapeutic index is the ratio of the LD50 (median lethal dose) to the ED50 (median effective dose)
It is a measure of the safety of a drug

Relationship Between Duration of Action and Dose

The effect of the drug begins when it reaches the minimum effective concentration (MEC) and continues as long as it remains above this level
The dose is not increased to prolong the duration of action; instead, the drug is re-dosed at certain intervals or slow-release modified-release tablets are used

Time-Dependent Variation of Drug Effect

Immediate effects: the effect is directly proportional to the concentration, and the time-dependent variation of the effect depends on the exponential decrease in concentration
Delayed effects: the effect is delayed due to the dispersion time it takes for the drug to reach the site of action or the slow synthesis rate of physiological substances responsible for the emergence of the drug effect
Cumulative effects: the effect depends on the accumulation of effects, as opposed to their rapidly rotating effects

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Description

Understand the relationship between drug dose, concentration, and effect on the body, including the minimum required concentration and dose-dependent increase in effect.