Chapter 8

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Chapter 8

Individual Variation in Drug Responses

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.


Key factors that cause one patient to respond to drugs differently than another patient

Important for nurses to know to be better prepared to reduce individual variation in drug responses



Body weight and composition Body surface area (BSA) versus weight

Age Significant variability with age Infants and elderly patients especially sensitive to

drugs• Infants: organ immaturity• Elderly patients: organ degeneration

Due to increased severity of illness, multiple pathologies, treatment with multiple drugs



Pathophysiology Kidney disease

• Reduced excretion and increased toxicity Liver disease

• Reduced metabolism and increased toxicity Acid-base imbalance

• pH changes that alter absorption, distribution, metabolism, and excretion of drugs

Altered electrolyte status• Rare for electrolyte changes to have a significant impact

on drug responses


Fig. 8-1. Effect of renal failure on kanamycin half-life. Kanamycin was administered at time “0” to two patients: one with healthy kidneys and one with renal failure. Note that drug levels declined very rapidly in the patient with healthy kidneys and extremely slowly in the patient with renal failure, indicating that renal failure greatly reduced the capacity to remove this drug from the body. (T1/2 = half-life.)


Fig. 8-2. Altered drug distribution in response to altered plasma pH. Lower curve, Plasma (extracellular) pH. Note the decline in pH in response to inhalation of CO2. Upper curve, Plasma levels of phenobarbital. Note the decline in plasma drug levels during the period of extracellular acidosis. This decline results from the redistribution of phenobarbital into cells. (See text for details.)



Tolerance Decreased responsiveness to a drug as a

result of repeated drug administration Higher doses required Three categories of drug tolerance

Pharmacodynamic tolerance Metabolic tolerance Tachyphylaxis


Three Types of Drug Tolerance

Pharmacodynamic tolerance Associated with long-term administration of drugs

such as morphine or heroin Metabolic tolerance

Resulting from accelerated drug metabolism Tachyphylaxis

Reduction in drug responsiveness brought on by repeated dosing over a short time


Placebo Effect

Any response a patient has to a placebo is based solely on his or her psychologic reaction to the idea of taking a medication, and not to any direct physiologic or biochemical action of the placebo itself.

Nurses need to present a positive but realistic assessment of the effects of therapy.

Primary use is control group for clinical trials.


Variability in Absorption

Bioavailability Ability of the drug to reach the systemic circulation

from its site of administration Occurs primarily with oral preparations, not with

parenteral administration Tablet disintegration time, enteric coatings,

sustained-release formulations Other causes of variable absorption

Changes in gastric pH, diarrhea, constipation, food in the stomach


Genetics and Pharmacogenomics

Pharmacogenomics: study of how genes affect individual drug responses

Altered drug metabolism May accelerate or retard the metabolism Warfarin, succinylcholine, isoniazid, cytochrome

P450


Variations

Altered drug targets Genetic variations alter the structure of drug

receptors. Other ways genetics can influence drug

responses Some genetically determined drug responses are

based on factors other than changes in drug metabolism or drug targets.


Variations

Gender Alcohol is metabolized more slowly by women

than by men. Certain opioid analgesics are much more effective

in women than in men. Quinidine causes greater QT interval prolongation

in women than in men. Race

Genetic variations Psychosocial factors


Variations

Failure to take medicine as prescribed Issues include manual dexterity, visual acuity,

intellectual capacity, psychologic state, attitude toward drugs, and ability to pay for medication.

Drug interactions One drug alters the effects of another.

Diet Starvation reduces protein binding of drugs, which

increases levels of free drugs.

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