One Compartment Model and Elimination

Question 1

What is zero order elimination?

Answer 1

There is a constant amount of drug per unit of time metabolized
The rate does not increase as drug concentration increases
(concentration vs time = linear)

Question 2

What is first order elimination?

Answer 2

There is a constant fraction of drug per unit of time metabolized.
Rate increases as drug concentration increases
(concentration vs time = logarithmic)

Question 3

How is the rate of elimination determined for an oral dose?

Answer 3

The negative slope (delta Y/delta X)*2.303

Question 4

Describe the renal elimination of drugs

Answer 4

Low molecular weight drugs (and unbound drugs) enter the kidney (Bowman’s capsule)
Lipid soluble drugs move back into the bloodstream
Non-lipid soluble, polar and ionized drugs remain in the urine

Question 5

How is renal impairment assessed?

Answer 5

Via creatinine clearance

Question 6

How does renal impairment affect pharmacology?

Answer 6

If someone has kidney disease, it’s likely that the drug will stay in the body longer (affects the rate of excretion). This leads to increased duration of time of the drug in the body and possibly an increase in the intensity of the drug

Question 7

What are OATs and OATPs? Where can we find them?

Answer 7

Organic anion transport proteins and organic anion transporting polypeptides
They can be found in the gut walls, the kidneys and the liver

Question 8

What are OCTs?

Answer 8

Organic cation transport proteins aka Solute Carrier transporters (SLC)

Question 9

What is P-gp?

Answer 9

P-glycoprotein aka multidrug resistant protein (MDR)

Question 10

There’s a variety of OCTs and OATs. Why is this important?

Answer 10

Specific transporters take up certain drugs (specificity). Different drugs use different transporters. Since transports are proteins, there is genetic variability which affects how drugs are metabolized

Question 11

What is enterohepatic cycling?

Answer 11

Basically, what can happen is there are some cases where drugs can get reabsorbed and they go back into the blood stream. This reduces elimination and prolongs the half life

Question 12

Summary on drug excretion:

Answer 12

Renal excretion is a major route for drug elimination (i.e., for most drugs)
Drug excretion has 3 steps (glomerular filtration, tubular reabsorption, tubular secretion)
Bile excretion favours compounds with higher molecular weight
Creatinine clearance can be used to assess renal impairment (i.e., does the drug dose need to be reduced?)