7. Excretion

Question 1

Excretion

Answer 1

Removal of drug and/or metabolites from the body

Kidney is primary organ responsible for excretion of drug and metabolites

Question 2

Nephron

Answer 2

Basically structural unit of the kidney

4 main processes

1. Glomerular filtration
2. Reabsorption
3. Secretion
4. Excretion

Question 3

Glomerular Filtration

Answer 3

Depends on plasma protein binding and renal blood flow

Polar and nonpolar can be filtered here : no cell membrane crossing

Glomerular capillaries are fenestrated with bigger pores so drug is filtered into Bowmans capsule

Drug bound to albumin cannot be excreted

Question 4

Cl (clearance)

Answer 4

Volume of plasma that is cleared per unit of time

Volume/time (mL/min)

Question 5

Glomerular Filtration Rate (GFR)

Answer 5

Measure of clearance through the kidney. Used to make clinical decisions regarding does and choice

Dose according to kidney function

Estimated by calculating patients creatinine clearance

Normal adult about 120mL/min that decreased with age

Question 6

Creatinine Clearance

Answer 6

Creatinine: breakdown of creative phosphate in muscle cells, produced constantly and eliminated through glomerular filtration in kidneys

So when we look are creative clearance we can estimate GFR and look at how well the kidneys are working

Question 7

Renal dosing

Answer 7

Many drugs require dose adjustment for decreased kidney function

GFR declines progressively with age and in chronic kidney disease

May need to decrease dose or spread out drug dose interval

Question 8

Tubular reabsorption

Answer 8

Depends on drugs lipid solubility and urine pH. Drug could be excreted or reabsorbed into peri tubular capillaries

If drug is lipophilic, unionized it is reabsorbed

Hydrophilic, ionized excreted in urine

Question 9

Weak Acids

Answer 9

RCOO- + H+. —- RCOOH

Excreted faster in ALKALINE urine, less ions around, drives equilibrium to left

Ionized form is more hydrophilic and excreted more readily

Question 10

Weak bases

Answer 10

RNH2 + H+ ——- RNH3+

Excreted faster in ACIDIC urine

Greater concentration of H+ ion drives equilibrium to the right, more hydrophillic and excreted more readily

Question 11

Clinical example of Urine pH: Patient overdoses on asprin

Answer 11

Aspirin is a weak acid

To facilitate more excretion of aspirin we want to alkalinize the urine pH

Give sodium bicarbonate = urine more basic pH so aspirin in ionized form and excreted

Question 12

Secretion and excretion

Answer 12

Drugs can cross into peritubular capillaries and then back into urine tubule

Excretion=filtration - reabsorption + secretion

Question 13

T 1/2 elimination half life

Answer 13

Time required for plasma concentration of drug to decrease by 50%

Units = time (hours)

If clearance is low then the elimination half life is high

Useful in determining dosing interval

Question 14

Css Steady-State Plasma Concentration

Answer 14

Steady state= attained after approximately 4 half times

When rate of entry of drug to plasma = rate of exit of drug

If emergent give loading dose: use Vd to immediately get to therapeutic level, then give lower maintenance dose for Css

Question 15

Therapeutic Drug Monitoring

Answer 15

Aims to optimize drug treatment by maintaining plasma drug concentration within the therapeutic range

Take a sample of patients blood after drug reaches steady state and measure concentration of drug in the blood to make sure you are in therapeutic range