Pharmacology and the Kidney and Excretion

Question 1

Define excretion:

What is pharmacokinetics?

Answer 1

• the processes that remove the drug, or its metabolites, from the body, principally the kidneys, but other routes may be important for specific agents
• Pharmacokinetics is the mathematical analysis of all drug disposition factors (absorption, distribution, metabolism and excretion)

Question 2

What does the fllowing stand for?

• V_d
• K_abs
• K_el

If drug is added rapidly by IV injection, what happens?

Answer 2

• V_d: consider human body as a single, well-stirred compartment of volume
• K_abs: rate drug is added to compartment by absorption
• K_el: rate of elimination of drug

Absorption is by-passed:

• the initial concentration (C₀) = D/V_d (mass/volume)
• the concentration at a later time (C_t) will depend upon K_el

Question 3

Define clearance:

Answer 3

Clearance: the volume of plasma cleared of drug in unit time

• a constant relating the rate of elimination to plasma concentration
• determines the maintenance dose rate (dose per unit time required to maintain a given plasma concentration)
• applies oly to drugs that exhibit first order kinetics

Question 4

What is volume of distribution?

Answer 4

• the volume into which a drug appears to be distributed with a concentration equal to that of plasma
• a proportionality constant relating the plasma concentration (C_p) to the amount of drug in the body (Ab)

Ab = V_d x C_p

Question 5

Define half-life:

What is half-life dependent upon?

Answer 5

Half-life is the time taken for the concentration of drug in plasma (or amount of drug in body) to halve

• Dependent upon V_d and Cl, whicha re both independent variables

Question 6

Explain zero order kinetics:

Answer 6

• initially eliminated at a constant rate rather than a rate proportional to concentration
• elimination is initially zero order, converting to first order at low concentration

Question 7

What is renal excretion?

In general, what happens during metabolism?

What happens if drugs are lipid soluble?

How are drugs eliminated?

What happens to drugs which are not sufficiently polar?

Answer 7

• renal excretion is responsible for the elimination of most drugs
• drugs are metabolised to more hydrophilic compounds, accelerating excretion by the kidneys as less lipid soluble
• if drugs are lipid soluble they are readily reabsorbed in the renal tubules by passive diffusion
• drugs are eliminated in the urine by glomerular filtration
• drugs and metabolites which are not sufficiently polar are made more hydrophilic by conjugation with endogenous compounds in the liver

Question 8

What is glomerular filtration rate (GFR)?

What are glomeruli?

State the range for:

• Normal GFR
• Mild stage 2 renal failure
• Moderate stage 3
• Severe stage 4
• Established renal failure, stage 5

How is normal renal function measured?

Answer 8

• a test to show how well the kidneys are working, estimating how much blood passes through the glomeruli every minute
• glomeruli are tiny filters in the kidney which filter waste from blood
• Normal GFR: 90mls/min or higher
• Mild stage 2 renal failure: 60-89
• Moderate stage 3: 30-59
• Severe stage 4: 15-29
• Established renal failure, stage 5: <15
• measured in terms of estimated GFR (eGFR) calculated from a formula or expressed as creatine clearance

Question 9

Use of drugs in patients with reduced renal function can cause problems due to;

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How can this be avoided?

Answer 9

• reduced renal excretion of a drug or its metabolites, causing toxicity
• sensitivity to dome drugs is increasedm even if elimination is impaired
• many side effects are poorly tolerated by patients with renal impairment
• some drugs are not effective when renal impairment is reduced

Many of these problems can be avoided by reducing the dose or using alternative drugs