Flashcards in Time course of delayed drug effects Deck (12):
Why are all drug effects delayed in some way to the plasma concentrations?
- there needs to be time for the drug to distribute to the receptor site
- it takes time for the drug to bind and unbind from receptors
- it takes time for the physiological mediator produced to take effect. (for the binding of the drug to actually result in a product that causes a cellular change)
Which of the above drug effect delays are pharmakokinetic and which are physiokenetic?
Pharmacokinetic = distribution to receptor site (usually a delay of minutes - very short)
Physiokinetic = the time taken for the drug to change a cellular response for the effect to be observed (usually a delay of hours or more - long)
Why is there a time delay from peak concentration of thiopentone in the blood to peak effect of the drug which is recorded on an EEG?
There is a delay of a few minutes as it takes time for the drug to diffuse/travel from the blood plasma into the brain where thiopentone acts as a rapid anaesthetic.
How can we measure/describe the drug concentration at the site of action?
It is difficult or impossible to directly measure the conc of a drug at the site of action but if drug concentrations in the plasma are constant then the rate of input to the effect compartment will be constant and so the time to steady state in the effect compartment will simply be determined by the equilibrium half life. (also called the effect compartment half life)
This is determined by the same factors used to calculate the elimination half life. (volume of effect compartment and clearance of effect compartment)
Is it the volume of distribution of thipentone in the brain or the clearance of thiopentone from the brain that gives it its very short equilibrium half life?
Clearance - the high blood flow to the brain results in a rapid washout of Thiopentone from the brain which gives it an equilibrium half life of a few minutes
What is the main cause of the delay in drug effect of the drug digoxin?
It dissosciates very slowly from the receptor it binds to (binds to Na/K/ATPase). (it is very potent due to its slow dissosciation).
Na/K/ATPase is found in almost all tissues of the body but the effect compartment (the heart) reaches peak before the average tissue conc reaches peak and this is in part due to the rapid perfusion of the heart compared with other tissues such as fat.
What does warfarin do? (in terms of Vit K)
It inhibits Vit K reductase and Vit K epoxide reductase which are two important enzymes that convert Vit K epoxide back to the active form of Vit K. (warfarin inhibits Vit K recyling).
Vit K is as essential cofactor for the production of clotting factors and so it inhibits blood clotting.
The delayed response is a prolonged coagulation time.The action of warfarin in rapid - it is absorbed quickly from the gut and reaches the liver where it acts on the formation of Vit K in the liver cells.
Why should you wait at least a week to make a judgement on whether you have given the correct dosing of Warfarin?
The prothrombin complex of clotting factors has a half life of about 14 hours. This means that is take about 2-3 days for a new steady state to be reached once warfarin is introduced. Therefore wait at least 3 days to make any dose changes.
What is another drug that shouldnt be judge for dose changes until a week or so?
It takes a week for sodium turnover to reach a new steady state.
What is the time course of the drug frusemide? (after a large oral dose)
Maximum effect (excretion of sodium) is larger than the maximum conc on sodium in the plasma. The effect remains at a high plateau but then drops off below the level of drug in the plasma.
(steep hill coefficient)
What is schedule dependance and which drug illustrates this?
Schedule dependance is where the effect of the drug dosent just depend on the total conc given over 24 hours, it also depends on the dosing schedule.
Frusemide shows schedule dependence. It is more effective for the drug to be given in smaller doses 4 hourly than one big dose.