Week 3 Pharmacokinetics Flashcards
How can pH of the medium affect the absorption and excretion of a drug?
Acidic drugs are better absorbed in acidic mediums and better excreted in basic medium.
Basic drugs are better absorbed in basic medium and better excreted in acidic medium.
On a basic level, which drugs are more easily absorbed?
Non-ionized (protonated and non-polar) are more easily absorbed because they can pass through the plasma membrane
The pH of a drug is 3.4, what would you expect this drug’s absorption in the stomach (pH 1.4) and plasma (pH 7.4)?
In the stomach most of the drug will be protonated and absorbed.
In the plasma most of the drug will ionized and not absorbed.
What are the two main paths of drug metabolism and excretion?
Metabolism: Liver
Excretion: Kidneys
Describe Phase I of drug metabolism in the liver
P450 enzyme converts parent drug to more polar daughter drug by two ways:
- Unmasking polar group on molecule, or
- Inserting polar group into molecule
The isoenzymes Include: CPY2D6, CPY2C9, CPY3A4
Describe Phase II of drug metabolism in the liver
Conjugation of subgroups to drugs at the -OH, -SH, and -NH2 sites
What is p-glycoprotein (AKA MDR-1)?
P-glycoprotein is a transport protein that transfers drugs to the bile or lumen.
Describe drug-to-drug interaction through absorption.
- Direct interaction between two drugs
- One drug may alter the gastric pH
- One drug may decrease p-glycoprotein
Describe drug-to-drug interaction through excretion.
- Change in renal flow
- Inhibited tubular secretion
- Altered tubular absorption
What is enzyme induction?
The increased expression (transcription or translation) and decreased degradation of P450. Usually as a result of another molecule triggering the event.
What is enzyme inhibition?
The increased degradation and decreased expression (transcription or translation) of P450. Usually as a result of another molecule triggering the event.
Inhibition of p-glycoprotein (AKA MDR-1) causes what?
Inhibiting p-glycoprotein causes toxic leves of a drug in the system
Explain the zero-order of drug elimination
Zero-order drug elimination:
- Elimination is constant
- Elimination process is saturated
- Half-life is INDEPENDENT of drug concentration
Explain the first-order of drug elimination
First-order drug elimination:
- Elimination is proportional to drug plasma concentration
- Half-life is DEPENDENT of drug concentration
- Most drugs are eliminated via first-order
What is the area under the curve?
A plot of concentration of drug in blood plasma against time
What does the volume of distribution mean?
The amount of drug in the body as measured by plasma.
What does clearance mean?
The ratio of the rate of elimination of a drug to the concentration of the drug in the plasma or blood.
What does Cp mean?
Plasma drug concentration
What is the equation for half-life?
t1/2 = (0.693 x Vd) / CL
Where Vd is volume of distribution
CL is clearance
What is the equation for dosing rate?
dosing rate = CL x Cp
What is the equation for loading dose?
loading dose = Vd x Cp
What does bioavailability mean?
A measure of the drug available to the systemic circulation over time after administration
What does steady state mean?
Steady state refers to the condition where the averaged plasma drug concentration does not change.
The dosing rate equals the rate of elmination
How would renal disease affect a drug?
- Reduces clearance of the drug
2. Has greater potential for re-absorption
