Flashcards in 16. Pharmacokinetics Deck (52)
What process looks at the drug getting into the patient?
What process looks at the drug getting to the site of action?
What process looks at the drug producing the desired effect?
What process looks at the therapeutic effect of a drug?
The therapeutic process.
How can the pharmaceutical process be altered?
Formulation of the drug: tablets vs liquid, compliance: take once a day vs three times a day.
What does the rate of action of a drug initially depend on?
What are the advantages of administering the drug at the site of action?
Less sympathetic absorption, less off-target effects (side effects).
Name the possible routes of administration of a drug.
Intravenous, intramuscular, subcutaneously, orally, transdermal patch, rectal, topical, and sublingual.
What is the oral bioavailability of a drug?
The proportion of a drug given orally, or any other route other than IV, that reaches the circulation unchanged?
What is the oral bioavailability of a drug?
Amount of drug, rate of absorption.
How is oral bioavailability calculated?
(Area under curve oral concentration / area under curve injected concentration) x 100.
What is the therapeutic ratio?
Maximum tolerated dose 50/ Minimum effective dose 50.
Why is a small therapeutic ratio more dangerous than a large one?
Because with small therapeutic windows, a small mistake in prescribing is likely to take it into toxic levels, whereas with a large window it is more likely to still be within the safe level.
How can drug composition affect whether the drug is within the therapeutic window?
Changing to a slow release composition can mean the drug always stays below toxic concentrations so you only experience the therapeutic effects, not toxic effects.
What is first pass metabolism?
When a drug is administered orally and is first exposed to the liver so may be extensively metabolised before reaching the body and therefore has a smaller effect.
How can first pass metabolism be overcome?
The drug is not administered orally, but instead parenterally (IV, IM, or SC), rectally, or sublingually.
What is the therapeutic volume?
The volume into which drug is distributed if this occurred instantaneously.
How can C0 (the hypothetical drug concentration predicted if the distribution had been achieved instantly) been worked out from a graph?
Extrapolate the line of the elimination phase back to zero time.
What is protein binding drug interactions caused by?
Displacement of drugs from binding sites.
What happens when a bound drug dissociates from the protein?
Goes to the target receptor or is eliminated by the renal or liver systems.
In which three cases are protein binding interactions important?
Is highly bound to albumin (>90%), has a small volume of distribution, or has a low therapeutic ratio.
What are the two types classes of drugs binding to proteins?
Class I drug (object drug) is used at dose lower than number of albumin binding sites.
Class II drug (precipitant drug) is used at doses greater than number of binding sites, and thus displaces the class I drug.
How is steady rate restored when free drug levels rise?
The elimination rate will also rise.
What is the effect of taking a precipitant drug on the object drug?
The precipitant drug will raise the effects of the object drug, making its effects more potent.
Give an example of a precipitant drug for the object drug Warfarin.
Sulfonamides, aspirin, or phenytoin.
Give an example of a precipitant drug for the object drug Tolbutamide.
Sulfonamides, or aspirin.
Where are drugs predominantly metabolised?
In the liver.
Where are drugs predominantly excreted?
Renally, in the kidneys.
What is 1st order kinetics?
When the rate of elimination is proportional to drug level. A constant fraction of drug is eliminated in unit time, and the half life can be defined.
What is zero order kinetics?
The rate of elimination is constant, irrespective of the amount of drug.
What shape would the graph of linear scale plasma concentration vs time be for 1st order kinetics?
What shape would the graph of log scale plasma concentration vs time be for 1st order kinetics?
A straight line.
What shape would the graph of linear scale plasma concentration vs time be for zero order kinetics?
A straight line.
How quickly, after drug administration, is a new steady state reached?
After 5 half lives of that drug.
What can be done in an emergency where the drug needed has a long half life but needs a rapid effect?
A loading dose can be given and maintenance doses after that.
What determines the loading dose?
The volume of distribution.
What are the two phases of drug metabolism in the liver?
Phase I - drug is mostly inactivated, oxidised, reduces and/or hydrolysed.
Phase II - drug made more insoluble, conjugation products.
What two properties make the enzyme susceptible to some important drug interactions?
Inducible and inhibitable.
In what three circumstances are drug interactions in metabolism likely to matter clinically?
Drugs with low therapeutic ratio, drugs being used at minimum effective concentration, and when drug metabolism follows zero order kinetics.
How do enzyme inducers affect drug interactions?
They induce enzymes in the liver so increase rate of metabolism, this means the effect of the drug is shorter lived.
How do enzyme inhibitors affect drug interactions?
They inhibit liver enzyme so decrease rate of reaction, thus increasing the effect and life of the drug.
What enzyme inducer affects warfarin and phenytoin?
Which drug does the enzyme inducer, rifampicin affect?
The oral contraceptive pill.
Which drug does the enzyme inducer - cigarette smoke, affect?
What enzyme inhibitor affects warfarin?
What are the three key stages of renal excretion of a drug?
Free drug enters the glomerular filtrate, there is active secretion along the proximal tubule, loop of Henle, distal tubule, and the collecting duct, also passive reabsorption of lipid-soluble, un-ionised drugs along this route too.
What is passive reabsorption of the drug in the kidneys dependent on?
The drug being lipid soluble and also the pH.
How does pH affect the passive reabsorption of the drug in the kidneys?
pK of the drug is the pH at which half of it is ionised, and half is non-ionised. Only the non-ionised moiety is lipid soluble to cross the membranes.
How can absorption along the kidneys of weak acids be affected by the pH?
Urine made more acidic increases absorption, made more alkaline decreases absorption.
How can absorption along the kidneys of weak bases be affected by the pH?
Urine made more acidic decreases absorption, more more alkaline increases absorption.
How can pH be altered to increase elimination of aspirin?
Forced alkaline diuresis in aspirin overdose to increase elimination and reduce absorption as aspirin is a weak acid.