Dr. E Exam 1 Flashcards
What is drug distribution?
The movement of drug after absorption from one location in the body to another
Why cant we use one compartment models for drug distribution?
One compartment models assume that drug distribution occurs instantaneously at time = 0
Use multicompartment models
What are the two parts of drug distribution?
Rate and extent
What is distributional clearance?
The rate of drug transfer between compartments
How long distribution phase lasts
What are the other names for distributional clearance?
Intercompartmental clearance
Rate of perfusion
What is the extent of drug distribution determined by?
Determined by volume of distribution
What does the rate of distribution tell?
How fast the drug distribution takes place
What are the two phases of drug distribution?
Presentation of drug to tissues by blood
Diffusion or uptake of drug from the blood to the tissue
Rate is limited by the slower of the two steps
What is the rate of tissue perfusion?
Rate of drug presentation (mL/min)
What happens during perfusion-controlled drug distribution?
Some drugs tend to distribute less to tissues because of lower perfusion rate
What can cause perfusion controlled drug distribution?
Congestive heart failure
What does hydrostatic pressure do?
Creates the pressure gradient between artierial end entering tissue and venous end leaving tissue
What is hydrostatic pressure responsible for?
Penetration of water soluble drugs into spaces between endothelial cells and into the lymph
What happens during diffusion controlled drug distribution?
Drug arrives to the tissue site, diffuses into interstitial fluid of capillaries and across tissue membrane into tissues through passive diffusion and is controlled by slow diffusion
What can cause diffusion controlled drug distribution?
Inflammation
What is the equation for distribution half life?
0.693/alpha
What happens at tss?
Distribution equals redistribution
What is extent of drug distribution?
Relative distribution of drug molecules between plasma and the rest of the body
What is the volume of plasma?
3L
What is the volume of blood?
5L
What is the volume of interstitual H2O?
12 L
What is the volume of intracellular H20?
27L
What is the volume of extracellular fluid?
15 L
What is the volume of total body fluid?
42 L
How do you calculate the volume in plasma?
0.04L/kg
How do drugs get into plasma?
Drug molecules are in systemic circulation and distribute throughout plasma
What factors affect the drug distribution in plasma?
Lipid solubility (increase causes more drug out of plasma)
Molecular size (decrease causes more drug out of plasma)
Plasma protein binding (more means more in plasma)
Permeability of membrane
How do you calculate drug in EC fluid?
0.2L/kg
Why are most drugs distributed to the EC fluid?
Epithelial membrane of capillary cells is very loose and allows passage of even polar and protein molecules
How do you calculate drug in total body fluid?
0.6L/kg
How do drugs get into total body fluid?
Drug exposed to individual cells by entering into intracellular fluid of tissues
What does the drug’s ability to get past total body fluid depend on?
Lipophilicity
Tissue structure binding
What is volume of distribution?
Hypothetical volume of fluid required to contain the total dose of a drug in the body at the same concentration as that measured in plasma
What does Vd relate?
Amount in the body to concentration in plasma
What is Vd affected by?
Pathological conditions
Weight
Otherwise it is the same for the same drug
Why is Vd at steady state clinically important/
Has physiological relevance reflecting the extent of the drug distribution from the plasma pool into tissues
Why can Vd exceed physiological total body volume?
Because of drug binding to peripheral tissue structures
What are the plasma proteins?
Albumin (55% and synthesized in liver)
Globulins
Alpha 1 acid glycoprotein
lipoproteins
What are the tissue structures?
Nucleic acids
Ligands
Calcified tissues
ATPhosphotases
What happens to volume of distribution when plasma protein binding increases?
It decreases
What happens to Vd when tissue binding increases?
Vd increases
How do you find Abody?
Aplasma+Atissue
VdxCplasma
How do you find fplasma?
Aplasma/Abody
Vplasma/Vd
How do you find ftissue?
1-fplasma
How do you find Aplasma?
Vplasma x Cplasma
What form of drug undergoes passive diffusion?
Unbound drug concentrations in plasma
How do you find fuplasma during Steady state?
same as futissue
How do you find Cuplasma?
Cplasma x fuplasma
How do you find Cutissue?
Ctissue x futissue
What happens if the concentration of drug unbound decreases?
Drug dissociated from bound
What does Cu,plasma do?
Diffuses across membranes to the drug’s site of action
Interacts with receptors to cause pharmacological and toxicological activities and is available for distribution and elimination
What is k1/k2?
Affinity between the drug and plasma protein
Magnitude association constant
What happens when K1 is much greater than K2?
affinity increases and drug binding is favored
What happens to plasma protein amount when concentration of drug increases?
Increases
What causes a decrease in albumin?
liver disease
age
pregnancy
burns
trauma
What causes an increase in albumin?
Thyroid hormone
Corticosteroids
Growth hormone
Insulin
What causes an increase in AAG?
Stress caused by MI
Cancer
Surgery
What causes a decrease in lipoprotein?
dieting
statins
What causes an increase in lipoprotein?
alcoholism
diabetes
What does renal disease cause?
decrease in albumin
decrease in drug binding
increase in accumulation
What does liver disease cause?
Decrease in plasma protien binding
decrease in albumin and AAG
What is concetration dependent displacement?
Binding of one drug might displace a second drug from binding site
Competition for a limited number of binding sites on the protien
What can decrease the consequences of toxicity due to decreased binding?
Increase in elimination
Changes in drug concetration outside the plasma (plasma is very low in concentration while the outside is large)
How do you calculate loading dose?
Vss x Target Cp
What is Vd affected by?
Weight
Age
Concentration of plasma protein
