McKenna's Pharmacology, 2e

25

C H A P T E R 2  Drugs and the body

4

O r a l

Critical concentration

2

1

I n t r a v e n o u s

0

1

2

3

4

5

6

(Drug half-life) Serum drug concentration (Units/mL) Serum drug concentration A

FIGURE 2.4  Influence of biological half-life, route of administration, and dosing regimen on serum drug levels. A. Influence of route of administration on the time course of drug levels after administration of a single dose of a drug. The dashed lines indicate how the biological half-life of the drug may be determined from the curve of drug concentration after an intravenous dose. At time 0, immediately after the injection, there were 4 units of the drug in each millilitre of serum. The drug concentration fell to half of this amount, 2 units/mL, after 1 hour, the drug’s biological half-life. B. Influence of dosing regimen on serum drug levels (drug given four times daily, at 10 am and at 2, 6, and 10 pm ). The drug accumulates as successive doses are given throughout each day; the drug is being given at a rate greater than the person’s body can eliminate it. This dosing regimen has been chosen so that the person will have a therapeutic level of the drug for a significant portion of the day yet never have a toxic level of the drug.

Time in hours

Toxic level

Critical concentration

10 AM

2 PM 6 PM 10 PM

10 AM

2 PM 6 PM 10 PM

Day 1

Day 2

B

Time of day

KEY POINTS

KEY POINTS

Weight The recommended dose of a drug is based on drug evaluation studies and is targeted at a 70 kg person. People who are much heavier may require larger doses to get a therapeutic effect from a drug because they have increased tissues to perfuse and increased receptor sites Weight Age Gender Physiological factors—diurnal rhythm, electrolyte balance, acid–base balance, hydration Pathological factors—disease, hepatic dysfunction, renal dysfunction, gastrointestinal dysfunction, vascular disorders, low blood pressure Genetic factors Immunological factors—allergy Psychological factors—placebo effect, health beliefs, compliance Environmental factors—temperature, light, noise Drug tolerance Cumulation effects Interactions ■■ BOX 2.2  Factors affecting the body’s response to a drug

■■ Pharmacokinetics is the study of how the body deals with a drug.

■■ The concentration of a drug in the body is determined by the balance of absorption,

distribution, metabolism and excretion of the drug. ■■ In determining the amount, route and appropriate timing of a drug dose, the pharmacokinetics of that drug has to be considered. FACTORS INFLUENCING DRUG EFFECTS When administering a drug to a person, the professional must be aware that the human factor has a tremendous influence on what actually happens to a drug when it enters the body. No two people react in exactly the same way to any given drug. Even though textbooks and drug guides explain the pharmacodynamics and pharmacokinetics of a drug, it must be remembered that such information is usually based on studies of healthy adult males. Things may be very different in the clinical setting. Consequently, before administering any drug, it is vital to consider a number of factors. These are discussed in detail in the following sections and summa­ rised in Box 2.2.