Two-compartment model and zero-order kinetics Flashcards
Kinetics of may drug is more accurately fit using ?
A two-compartment
Assumes two compartments:
Central (plasma) and peripheral (tissues, fat etc.)
Why does Cp initially drop quickly ?
Due to distribution into tissues
This is followed by a slower decrease in Cp due ?
Due to elimination
What does the two-compartment model assume?
That after administered into the central compartment, drug distributes between the central and the peripheral compartment
At a time interval a distribution equilibrium ?
Is achieved and elimination of the drug occurs from the central compartment
Central compartment =
Highly perfused (high blood flow) tissues, e.g. heart, lungs, kidney, liver and brain
Peripheral compartment =
Poor blood flow tissues, e.g. muscle, fat and skin
Decrease in Cp occurs in two phases:
- Fast phase (α) - distribution to peripheral compartment
2. Slow phase (β) - elimination by excretion and metabolism
Some drugs, such as ethanol and phenytoin, do not show?
Exponential decrease in Cp
Decrease in Cp is ? what is this called ?
Linear. Called zero order or saturating kinetics
How is alcohol mainly eliminated by ?
Metabolism
What is the first step ?
Oxidation to aldehyde by alcohol dehydrogenase (ADH)
Ethanol + NAD+ ⇌
Acetaldehyde + NADH + H+
ADH enzyme has ?
A very low Km
Why do we need to understand dose-response relationships ?
- Deduce mechanism of drug actions:
- Dose response curves can help us deduce whether a drug acts on a particular receptor and whether it is competitive or non-competitive antagonist or neither - Determination of dosage:
- Help to determine the appropriate dose of a given that produces the desired therapeutic effect while limiting harmful side effects - Facilitate therapeutic choices:
- Understanding of efficacy and potency enable better choices of therapeutic agents
What is potency ?
This is a measure of the amount or concentration of a drug required to produce a response and can be determined by a drug’s EC50
What makes a drug more potent ?
Drugs that are able to produce responses at lower doses than others are said to be more potent
What is Efficacy ?
This is a measure of the maximum effect a drug can produce, it can thus be determined by a drug’s Emax
A drug with a higher Emax is thus said to ?
Be more efficacious
Explain Quantal dose-response relationships ?
- All or none dose response
- Commonly used for assessing safety (therapeutic index)
- E.g. Effectiveness of an oral contraceptive, percentage of rodent death at a given dose of phenorbarbitone
What is meant by ED50 ?
The dose of a drug that produces an effect in 50% of the test population
What are some examples of drugs with narrow therapeutic index ?
- Digoxin (1.0-2.0μg/L)
- Theophylline (10-20mg/L)
- Phenytoin (10-20mg/L)
- Lithium (0.4-1.0mmol/L)
- Aminoglycosides such as Gentamicin
- Warfarin
- Etc…
