Pharmacokinetics Flashcards
(24 cards)
What is pharmacokinetics?
how drugs move through your body
What is pharmacodynamics?
how drugs affect its target to produce the desired physiological effects
What is the life of a drug molecule in the human body?
Absorption- how does the drugs get into the body
Distribution (to target) - how does the drug get to the target site
Metabolism- how is the molecule chemically altered in the body
Clearance- how it is removed from the body
What is the first step of absorption?
Drugs must pass through epithelial and endothelial cell layers, likely several
What charged state must drugs be in to pass through the plasma membrane?
The drugs must be hydrophobic (which is NEUTRALLY charged) to pass through the cell since the plasma membrane very hydrophobic
What is simple diffusion and what type of cells are able to undergo it?
molecules moving down their gradient without additional help.
Hydrophobic drugs are able to do this
Which forms of drug absorption are saturable and non-saturable?
Simple diffusion is not saturable- meaning it is not dependent on presence of any other transport protein
-only on concentration of drug
Facilitated diffusion and active transport are SATURABLE
What types of drug absorption are faster at lower concentrations?
Facilitated diffusion and active transport
What is pKA and what does it tell you?
pKA is the pH at which a molecule is 50% split between hydrophilic and hydrophobic forms.
How does a weak base behave in high and low ph environments? A weak acid?
For weak acids
at low pH: hydrophobic and charged
high pH: hydrophobillic and uncharged
For weak bases
At low pH: hydrophilic and charged
At high pH: hydrophobic and uncharged
How does a weak base behave in high and low ph environments? A weak acid?
For weak acids
at low pH: hydrophobic and uncharged (H+ attached)
high pH: hydrophilic and charged (H+ leaves)
For weak bases
At low pH: hydrophilic and charged (H+ binds to base, forming positive ion)
At high pH: hydrophobic and uncharged (no H+ present, neutral state)
What is the Henderson- Hasselbach equation for weak acids?
What is it for weak bases?
For acids-
[A-]/[AH]= 10^ (pH-pKa)]
[B]/[BH+]= 10^(pH-pKA)
What does the Henderson- Hasselbach equation solve for for weak acids?
What is it for weak bases?
For acids-
[A-]/[AH]= 10^ (pH-pKa)]
-AH is absorbable
[B]/[BH+]= 10^(pH-pKA)
-B is absorbable
How does pH compare to pka for weak acids and weak bases
For weak acids, when is less than pKA it is more neutral molecule
For weak bases, when pH is greater than pKa, molecule is more neutral
Define pH trapping?
Ex) Aspirin molecules in stomach (pH) are 99% in their hydrophobic (AH) absorbable form:
They can the diffuse into the plasma
Because plasma has a much higher pH, it will drive aspirin into its hydrophilic for (A-, in a huge proportion)
A- cannot cross back over into the stomach area again so it is trapped
Explain the reasons for the high levels of weak base drugs in lysosomes:
As drugs are converted from their charged to uncharged form, they are capable of entering cellular and lysosomal compartments, but not exiting (the inside of the cell is more acidic than the outside)
What is bioavailability?
What fraction of drug makes it into circulatory system ( after the drugs have completed the first pass (through liver and through cytochome p45)
(IV administration will be 100%)
What is the equation for bioavailability and what how do you calculate it?
Bioavailability= AUC (oral)/AUC (IV)= 1 mg-hour/L divided by 3 mg hour/L= % by the oral route of administration
What does Area Under Curve represent?
a measure of total drug exposure
What is the equation to calculate for Volume of Distribution?
Vd= Q/Cp
Q=mg of drug
Cp= Plasma coc
Name 3 things that a high Vd indicates about a drug:
- It is actively moved out of the plasma
- tissue binding
- ph trapped
What type of drugs typically have a Vd greater than the total?
Lipophilic drugs
Where in the body will lipophilic drugs, like propophol, is moved out of the plasma?
Propophol is an extremely hydrophobic and redistributes quickly to other hydrophobic tissue
Brain, skeletal muscle, finally ends up in adipose tissue
How two physical bodily aspects need to me taken into account with drug administration?
Body fat content and age
