Lecture 4

Question 1

What are the key parts of clinical pharmacology?

Answer 1

The effect - what is the fact you re trying to achieve.

The dose - what is the dose to a chive the right effect.

Question 2

What is the reason why e get drug effects?

Answer 2

Concentration. This is the concentration at the receptor. What is the concentration? What dose causes the concentration. Can measure drug concentration in blood, but you cannot see it, touch it or smell it.

Question 3

Describe pharmacokinetics?

Answer 3

This is the way in which dose and concentration is linked. Thinking about the movement of molecules.

Question 4

Describe pharmacodynamics?

Answer 4

This is the way in which concentration and effect is linked. Thinking about the effect and the forces involved.

Question 5

What are the properties for pharmacokinetics?

Answer 5

CL - clearance.

V - volume distribution.

Question 6

What are the properties for pharmacodynamics?

Answer 6

EMAX - the maximum effect we can expect from a drug molecule.
EC50 - the concentration of the drug that produces 50% of the maximum effect.

Question 7

What is clearance?

Answer 7

The relationship between drug concentration and the rate of elimination of drug from the body.
[Rate out = CL x concentration].

Thus if the rate of elimination of the drug from the body decreases then so will the clearance.

Question 8

Describe the theophylline target concentration?

Answer 8

One of the medications used to treat severe asthma is theophylline. The target concentration to treat asthma is 10mg/L. If we use a higher concentration, it was found that there were adverse side affects (vomiting). This tells us that the target concentration is used as it is a balance for minimal adverse effects as well as helping treat the disease to it’s maximum ability.

Question 9

Describe maintenance dose rate?

Answer 9

When you are infusing a drug, it is at steady state. So this is where the rate out (eliminated) = rate in. This concentration is constant. Thus the infusion rate of a drug is (CL x concentration).

Question 10

Describe the bathtub model?

Answer 10

The rate out = rate in (where if the plug was pulled out and water was running continuously) -> thus it would reach steady state (so the height of the water in the bathtub would remain constant - this is the concentration).

Question 11

What determines the rate out (in terms of the bathtub model)?

Answer 11

How big the plug hole is. The water pressure. The height of the water above the plug hole.

Question 12

What is the clearance in the bathtub model?

Answer 12

How big the hole is.

Question 13

What is the concentration in the bathtub model?

Answer 13

The height of the water.

Question 14

What are the main routes of elimination of drugs in the body?

Answer 14

1) Urine - this is via the kidney. Glomerulus (bunch of holes), nephron, collecting duct and bladder. This represents the plug hole in the bathtub model.
2) Liver - organ of metabolism, once they get metabolised they transfer into a metabolite. So the drug molecule itself has been eliminated.

Question 15

Describe the physiological basis of clearance?

Answer 15

1) Kidney blood flow: the upper limit for renal elimination is 70L/h. Glomerular filtration accounts for 6L/h of all drugs. Tubular secretion does the rest.
2) Liver blood flow: the upper limit of clearance from the liver is 90L/h.

Question 16

Describe very rapid drugs in terms of clearance?

Answer 16

Glyceryl trinitrate is the drug with the highest clearance. It’s clearance is 150L/h. It is a drug used to treat angina (it is an vasodilator). It is an unstable molecule (it is an explosive). It breaks down in many tissues of the body and its clearance is not limited by blood flow to a single organ.

Question 17

Describe rapid drugs in terms of clearance?

Answer 17

Morphine has a clearance rate of 60L/h - metabolised nearly all in the liver. It will be extensively extracted from the blood as it passes through the liver.

Question 18

Describe medium drugs in terms of clearance?

Answer 18

1) Gentamicin - this drug is eliminated via the kidneys. CL = 6L/h. Highly ionised, so it doesn’t cross cell membranes. Cannot get from the urine back into the tubules to be reabsorbed. It must be cleared via glomerular filtration.
2) Digoxin (drug used to help treat heart failure) - it is eliminated bia the kidneys and the liver. CL - 9L/h (Liver is 3L/h and Kidney 6L/h).

Question 19

Describe slow drugs in terms of clearance?

Answer 19

Theophylline CL is at 3L/h. All metabolised in the liver. Then there are drugs like warfarin which re very slow and have a CL of3L/day.

Question 20

What are the ways in which clearance can be classified?

Answer 20

1) Constant - 99% of cases. Doesn’t change with concentration.
2) Concentration dependent.
3) Flow dependent.

Question 21

Describe constant classification of clearance?

Answer 21

Also known as first order elimination or linear. Most metabolic processes are first order.

Question 22

Describe concentration dependent classification of clearance?

Answer 22

Known as mixed order. It’s non-linear and is the Michaelis-Menten elimination. Phenytoin is where we get close to saturating metabolism. The clearance is dependent on the concentration.

Question 23

Describe flow dependent classification of clearance?

Answer 23

Usually elimination of a drug via the liver i.e. morphine.