Pharmacokinetics Flashcards
(40 cards)
True or false, if you can predict the pharmacokinetic effect, you can often predict the pharmacodynamic effect of a drug.
True
Pharmacokinetics will reveal the quantitative characterization of the time course of a drug concentration in the body
What are the three main components of the pharmacokinetic response of an individual?
Absorption
- Eg. drug administration route and measuring blood concentration
Distribution
- Target site vs. tissue and other extravascular sites
- Reversible movement of drugs from site of administration (eg. blood)
Elimination
- Removal of drug from blood and body (most variation!)
What are three routes for drug administration?
Systemic
- Enteral (digestive tract, includes rectal)
- Parenteral (non-digestive tract, ie. injection)
Local
- Topical (applied directly to area)
The oral administration method is not suitable for drugs which are ____ (3)
- Rapidly metabolized (first pass effect)
- Acid labile
- Known to cause GI irritation
What is the most rapid means of drug delivery?
Intravenous injection (a parenteral method of drug administration)
There is also a 100% bioavailability
Give 6 administration methods for topical drugs
- Epicutaneous (apply to skin)
- Inhalational
- Eye drops
- Ear drops
- Intranasal
- Vaginal
True or false? Most drugs are absorbed through active transport.
FALSE
Most drugs are absorbed through passive diffusion across lipid bilayer of enterocytes (intestinal cells)
Give four physiochemical factors that affect oral drug absorption
Concentration differences across membrane
- Primary driving force for passive diffusion
- Usually very large for most drugs
Size
- Larger drugs are less efficiently absorbed
- Relatively constant for most drugs
Polarity
- Highly polar drugs are less efficiently absorbed
Ionization
- Highly ionized (charged) drugs are less efficiently absorbed
List three physiological factors that affect oral drug absorption
Gastrointestinal motility
- How fast things move through tract
Metabolism
- First pass effect (esp in liver)
pH changes in GI tract
- Ionization
What is ‘volume of distribution (Vd)?’ How is it determined?
- The apparent volume of fluid into which an administered drug is dispersed
- Determined from measurements of initial plasma drug level (after IV bolus/rapid injection)
Why is volume of distribution (Vd) apparent?
If these assumptions were true, what would Vd be for every drug?
It assumes equal partitioning throughout the body (ie. plasma concentration is equal to that of all other volumes)
It is assumed that the drug distributes equivocally through all the body’s water. assuming the concentration is the same in all constituents of body water. But you are only measuring plasma volume.
If true, Vd of every drug would be 42 (total body water volume for 70 kg person)
What are the three components of total body water?
List in order from least to most
- Plasma
- Interstitial volume
- Intracellular volume
What does a large or small Vd inger about a drug?
Why is this important?
Small Vd: Infers retention within the plasma volume
Large Vd: Infers retention in volumes outside of plasma
Vd must be factored into dose calculations. As Vd increases, the dose (Q) of the drug required to achieve a particular initial plasma concentration (Co) also increases.
Lipophilic drugs commonly bind to the plasma protein albumin, what is the consequence of this?
These drugs are inactively retained, reservoirs of the drug can form in the blood.
The free (active) drug can be increased by displacement by another drug or reduction of serum albumin (as seen in some diseases).
What element of pharmacokinetics accounts for the greatest variability among individuals?
Elimination
Drugs have a finite duration of effect on the body as determined by its rate of elimination from the body
Why do most drugs require metabolism before they can be excreted?
Because they are lipophilic and only partially ionized at physiological pH (optimized for oral absorption)
They can also be partitioned into lipid-rich tissue, which is undesirable.
What are the major methods of drug elimination (2) and the minor methods (5)?
Major
- Urine
- Bile (poop)
Minor
- Saliva
- Sweat
- Milk
- Other body fluids
- Exhalation
Why are lipophilic drugs poorly excreted by the kidney and liver?
They are resistant to glomerular filtration. They will easily reabsorb at renal tubules and biliary epithelium.
What four things does metabolism mainly do to drugs?
Increases:
- Polarity
- Ionization
- Water solubility
- Deactivation
Where is the main site for the metabolism of drugs?
The liver and the intestine (to a lesser extent)
What are prodrugs?
Drugs that have more active or toxic metabolites (bioactivation) after metabolism.
Why must the administration method for drug delivery by accounted for in dose calculations?
The amount of administered drug that reaches the system circulation following administration differs.
IV > oral > other routes
The oral route always exhibits less than 100% bioavailability due to the first pass effect
Compare and contrast phase I and phase II metabolism
Phase I: Creation or unmasking of small polar or reactive functional groups (eg. thiols, amines, hydroxyls). Often the rate limiting step in drug metabolism. P450 CYP genes involved.
Phase II: Addition (conjugation) of large polar groups to small reactive functional groups. This generates a more polar molecule, which facilitates efficient elimination.
What is most often the rate limiting step in drug metabolism?
Phase I
