First/Zero Order & Volume of Distribution, Renal Clearance

In zero order, the rate of change is _____ with respect to time. This means the amount eliminated is _______ of drug concentration.The percentage lost _______ as time goes on.

• constant

• independent

• increases

Which order forms a straight line?

zero order

In first order, what does it do to half-life?

half life is constant

In first order, the amount of drug eliminated is ______ on how much drug is present in the body. A constant _______ of drug is eliminated per unit time.

• dependent

• percentage

What is the formula for Cl?

Cl = K x Vd

what is the formula for Vd?

Vd = dose/Co

What are the 5 factors that governs a drug’s distribution throughout the body?

• Log P of the drug: the higher the LogP, the more lipophilic

• Molecular Weight: larger MW drugs can’t leave the plasma

• Ionization: ionized cells can only leave paracellularly but unionized cells can more transcellularly & paracellularly

• Binding to Plasma Proteins: the higher the plasma protein binding, the less likely to leave the plasma

• Binding to tissue proteins

When a drug is administered, where does it go first?

goes to the plasma then to the tissues

What can you assume about one compartment model & what happens in this model?

• instantaneously & uniform (equal distribution)

• elimination of drug occur in this compartment

How does drug flow in the body?

plasma to interstitial fluid

• Ionized drug: goes paracellularly only

• Unionized drug: goes paracellularly & transcellularly

Interstitial fluid to Intracellular fluid

• only unionized drug goes transcellularly into interacellular fluid (cell)

What happens in two compartment models?

• Central: dose administered & rapidly distributed (elimination occurs)

• Peripheral: drug accumulates & distributes more slowly

drugs that have a very high ________ has a large _______ and small __________.

• tissue binding

• Vd

• Co

No Vd______ than the patient’s _______ volume.

less; plasma

True or false. The more you weigh, the larger your plasma volume is going to be & the larger the intestinal volume.

true

characteristics of a low Vd (3-5) drug

• drug is confined to the plasma

• either high MW or high protein binding

• hydrophilic

characteristics of Moderate Vd (10-20) drug

• mostly in the extracellular water (plasma+intestinal fluid)

• small MW

• hydrophilic

Characteristics of High Vd (>30) drug

• evenly distributed throughout the body

• lipophilic

• small MW

• low protein binding

Drug Characteristics of Albumin:

• acidic (ionized)

• lipophilic

Characteristics of Alpha 1 Acid Glycoproteins drugs

• basic

• lipophilic

4 Things that alter (decrease) plasma albumin levels:

• Liver disease

• kidney disease

• malnutrition

• burn/trauma

5 things that alter (increase) plasma alpha1-AGP

• trauma

• burns

• surgery

• inflammatory disease

• cancer

What happens in drug interactions involving plasma protein binding displacement, when taking two drugs that have high binding to albumin?

• Increased fraction unbound & the patient can experience toxicity due to more free drug

• If you have lower affinity to the plasma, your Vd is increased & decreased Concentration

• If you have higher affinity to plasma, your Vd is decreased

What is the relation between fraction unbound and hepatic clearance ?

As fraction unbound increases, clearance increases

What does the red & green lines represent?

• green: distribution phase (alpha)

• read: elimination phase (beta)

two compartment model

What goes on in a two compartment model?

• drug is administered into the central compartment

• drug leaves the central compartment via elimination & moves to the peripheral compartment

• Unbound drug reaches distributional equilibrium between the two compartments

• As drug is eliminated from the central compartment, unbound drug shifts from peripheral to central compartment to maintain equilibrium