Pharmacokinetics Flashcards
Where are most drugs metabolised?
The liver
What is the purpose of metabolism?
To increase water solubility and aid excretion
What is the name given to the group of drugs that are activated follow metabolism?
Prodrugs
Give 2 examples of prodrugs
Codeine
Enalapril
What kind of metabolism can involve hydrolysis, oxidation or reduction?
Phase 1
How does phase 1 metabolism provide an active site for phase 2?
Increasing the polarity
Name the super family of metabolising enzymes?
Cytochrome P-450 enzymes
What does the isoform of the cytochrome P-450 determine?
Drug specificity
Name the three families of cytochrome P-450 that are important in oxidative drug metabolism
CYP1, CYP2, CYP3
Name the major constitutive enzyme in the human liver
CYP3A4
What can induce the enzyme CYP1A2?
Smoking
What does increased water solubility mean in phase 2 metabolism?
Enhanced excretion of the metabolised compound
What conjugation usually result in?
Inactivation
What happens to the drug’s effect when the the drug metabolising enzyme is induced?
Decreased drug effect
What are the most common enzyme inducers?
Alcohol and smoking
What does increased synthesis lead to in terms of enzymes?
Increased activity
What can drugs such as clarithromycin do?
Inhibit drug metabolising enzymes
Lack/decreased activity of an enzyme often results in what?
Increased drug toxicity
What can deficieny in renal function in young children lead to?
Metabolites rapidly building up to toxic levels
By what ages can children metabolise many drugs more rapidly than adults?
Two
Name the important process involved in eliminating drugs from the body?
Metabolism
What is the therapeutic process?
Producing the correct therapeutic effect
Name the four basic factors that determine drug pharmacokinetics?
Absorption
Distribution
Metabolism
Elimination
What is Tmax?
Time to peak concentration
What is Cmax?
The peak concentration
What is the range of when the drug is active?
Therapeutic range
What is the therapeutic index a measure of?
The range at which a drug is safe and active
What bioavailability does a drug given intravenously have?
100%
Most drugs are what kinds of acids?
Weak Acids
Small changes in pH will do what to the ionisation of a drug?
Will significantly influence it
Why should aspirin be absorbed more easily from the stomach?
It is a weak acid
What must a drug be to pass across a lipid layer?
Must be in solution and be lipid soluble
What is the name given to the ability of a drug to diffuse across a lipid barrier
Lipid-water partition coefficient
Where does the bulk flow of liquid occur?
Through inter-cellular pores
Why is bulk flow important?
It is the major mechanism which drugs cross through capillary walls
What must drugs resemble to undergo active transport?
Naturally occurring compounds
What is first pass metabolism?
Metabolism of drug prior to reaching systemic circulation
What does subcutaneous route depend on?
Blood flow to site
Drugs given via rectum bypass what?
First pass metabolism
What do drugs generally need to reach to reach target tissues?
Systemic circulation
How are most drugs given?
Orally
Once a drug has been absorbed, what must it be ready for?
Biological action and distribution to tissues
What, in theory, should volume of distribution be?
40L
What does volume of distribution show?
Where drugs go
How can side effects of a drug be cleared?
Metabolism or Renal excretion
What is the name given to the theoretical volume of fluid from which a drug is completely removed over a period of time?
Clearance
What is the name given to the time taken for the drug concentration in the blood to decline to half of the current value?
Half-life
What does a long half-life indicate?
Plasma levels will stay long for higher
What will the knowledge of the half-life of a drug help us to work out?
How often a drug needs to be administered
What will increase the toxicity of a drug in terms of half-life?
Prolongation of the half life
Why do most drugs need to be given chronically?
To have a therapeutic effect
How many half-lives does it take to reach stable plasma levels?
5-6
What are the primary organs for drug excretion?
The kidneys
What is the main mechanism used for drug excretion?
Glomerular filtration
If a patient is dehydrated, what happens to the clearance of a drug?
It reduces
How much bile a day does the liver secrete?
1 litre
What determines where a drug will reach?
Chemical properties of the drug
What is the definition of drug interaction?
Modification of a drug’s effect by prior or administration of a drug at the same time
What does a narrow therapeutic index indicate?
A small change in blood levels can induce profound toxicity from a drug
What can increase the probability of a drug-drug interaction?
Increase of number of medicaments
What spectrum of antibiotics can destory normal gut flora?
Broad Spectrum
Where are most oral medicines absorbed?
The small intestine
Following absorption, where are drugs distributed to?
The site of action
Name the main inducer of cytochrome P450 enzymes?
Smoking
Why can drugs that work on the brain not be taken alongside alcohol?
As they can produce a synergistic effect that leads to toxicity
Where does elimination of drugs occur?
In the kidney
What side effect does isionazid produce?
Peripheral neuropathy
What is the definition of first pass metabolism?
When drug is metabolised before reaching systemic circulation
What are the examples of sub-acute onset of adverse drug reactions?
Rash
Serum Sickness
How long does the onset of a latent adverse drug reaction?
Over 2 days
Which type of adverse drug reaction does not require a change of therapy?
Acute
What are type A adverse drug reactions linked to>
Too high a dose
How are type A adverse drug reactions stopped?
When drug is reduced or stopped
Chronic adverse drug reactions are related to what?
Duration of treatment
Give an example of an ADR that cannot be avoided
Nausea in chemotherapy treatment
