lecture 4 part 2 Flashcards
define distribution
the process by which a drug leaves the site of administration and is DISTRIBUTED throughout the tissues
when a drug enters the blood, how is it distributed throughout the body? where exactly is it transported to?
by systemic circulation
transported to the the TARGET SITE of drug action and to other tissues/organs
the pharmacological action of a drug is related to what?
the concentration of the drug at the site of action – the relative rates of drug access to the receptor and the rate of removal of the drug from its site of action
true or false
basic drugs bind albumin
false - acidic
once the drug reaches systemic circulation (through absorption) what happens
it will pass to other areas of the body (distribution)
the passage (uptake and distribution) of the drug depends on what 4 factors?
-its movement across the membranes
-blood flow
-the physiochemical properties of the drug
-drug may be bound to plasma proteins
what is typically the relationship between drugs that are bound and unbound to plasma proteins?
typically they are in equilibrium
what do basic drugs typically bind to (plasma protein)
alpha 1-acid glycoprotein
true or false
ONLY unbound drug can diffuse through the tissues
true
true or false
a change in the amount of bound drug cannot alter the activity of a given dose
false - it can
what factor can alter drug-plasma protein binding?
the disease state of the patient
at most drug concentrations, what is the fraction bound to plasma proteins?
constant
besides binding to plasma proteins, what else can a drug bind to in the body?
in the tissues.
if they bind in the tissues, they may serve as a “depot”
true or false
many drugs accumulate in the TISSUES at higher concentrations than in the extracellular fluids and blood
TRUE - such is the case with quinacrine (anti malerial)
the concentration of quinacrine in the liver may be SEVERAL THOUSAND times that in the blood
what is quinacrine
an anti-malerial drug
it is characteristic to have a concentration in the liver that is several thousand times that in the blood
when drugs bind to tissues, where exactly does it usually occur
WITHIN cellular constituents – such as protein, phospholipids, or nuclear proteins
true or false
drug-tissue binding is generally irreversible
false - generally reversible, but the amount of time it is bound can vary
true or false
tissue binding and accumulation can cause harmful effects
true
it can cause local toxicity
gentamicin is an aminoglycoside antibiotic can accumulate in the kidney
what is gentamicin
an aminoglycoside antibiotic that is known to accumulate in the kidney and cause local toxicity
many ________ soluble drugs are stored in physical solution in ______
lipid soluble drugs in neutral fats
in obese persons, the fat content of the body may be as high as ____%
what is the significance of this
50%
many lipid soluble drugs are stored in physical solution in the neutral fats.
fats can serve as a reservoir.
true or false
both fat and bone can be sites of accumulation for drugs
true
basically any tissue
fat - mainly for lipid soluble drugs
bone - the tetracycline antibiotics (and other divalent metal-ion chelating agents) and heavy metals may accumulate in bone by ADSORPTION ONTO BONE CRYSTAL SURFACES
-EVENTUALLY INCORPORATE INTO CRYSTAL LATTICE
bone can also be reservoir for toxic agents such as leads or radium
bone can be a reservoir for what drugs
-tetracycline antibiotics
-other divalent metal-ion chelating agents
-heavy metals
-reservoir for slow release of toxic agents such as lead or radium into the blood
WHAT BASIC PHARMACOKINETIC PARAMETERS ARE MODIFIED BY FACTORS SUCH AS AGE AND DISEASE STATE
Vd and CL
(volume of distribution and clearance)
volume of distribution measures…..
the apparent space in the body that is able to contain the drug
clearance measures…..
the ability of the body to eliminate the drug
what does a high Vd indicate?
there is more drug in the tissues of the body
low Vd indicates…
there is more drug in the blood/plasma
is it better to have a low or high Vd value?
high. this means that the blood is properly distributing the drug to the tissues
the only case you want Vd to be low (more drug in blood) is in the case of a blood infection or blood cancer – where the site of action is the blood itself
name 3 drug factors that affect the volume of distribution and 4 PATIENT factors that affect the volume of distribution
drug pka
drug-plasma protein binding
partition coefficient of the drug (lipid solubility)
patients…
gender
age
disease state
body composition
a poorly lipid soluble agent will have a Vd of about what?
about equal to the extracellular water volume
