Maintenance dose and loading dose

Question 1

What is the formula for dose rate.

what is the relevance of dose rate

Answer 1

Dose rate (mg/hr) = Dose (mg) / dosing interval (hr)

It is relevant when considering the definition of steady state.

Steady state occurs when dose rate = elimination rate

Importantly as drug concentration gets higher it is eliminated from the body faster (1st order kinetics)

Question 2

What is the formula fo loading dose (LD)

Answer 2

LD = Vd x Desired concentration

for non-IV drugs, this needs to be divided by the bioavailability

Question 3

What is the formula for maintenance dose rate

Answer 3

MD = Desired peak [Drug] x Clearance

for non-IV drugs, this needs to be divided by the bioavailability

Question 4

What is the practical problem with the using loading dose

Answer 4

If a drug has very high Vd then the loading dose to achieve steady state concentration may be impractically large

E.g. phenobarbitone LD would be lethal 1.5 g

Question 5

How does oral dosing effect the appearance of the concentration - half lives curves for intervaled drug administration

Answer 5

soothes the sharp peaks due to slower intestinal absorption

Question 6

What is a general rule for working out the dosing interval for drugs

Answer 6

Generally speaking, for most drugs, the dosing interval is approximately one half life

Question 7

What are the major factors that influence the dosing interval?

Answer 7

1. Elimination half life
2. Therapeutic index
3. Convenience (compliance)

Question 8

Give an example of a drug with a vast volume of distribution in which a loading dose would be lethal

Answer 8

Phenobarbitone 1.5 g loading dose

Question 9

Give an example of a drug in the ICU that would be have poor oral bioavailability

Answer 9

Morphine

Question 10

Give an example of a drug which is highly protein bound which is highly affected by low plasma albumin in the ICU

Answer 10

Phenytoin
Narrow therapeutic index
Metabolic enzymes are near saturation

–> Easily becomes toxic

Question 11

Give an example of a drug who in the critically ill should maintain unchanged loading and maintenance dosing but whose dosing interval should be extended

Answer 11

In the presence of kidney injury –> Gentamicin dosing interval should be increased without changing dose