Tài liệu Color Atlas of Pharmacology (Part 8): Adverse Drug Effects pptx

Adverse Drug Effects

The desired (or intended) principal ef￾fect of any drug is to modify body func￾tion in such a manner as to alleviate

symptoms caused by the patient’s ill￾ness. In addition, a drug may also cause

unwanted effects that can be grouped

into minor or “side” effects and major or

adverse effects. These, in turn, may give

rise to complaints or illness, or may

even cause death.

Causes of adverse effects: over￾dosage (A). The drug is administered in

a higher dose than is required for the

principal effect; this directly or indirect￾ly affects other body functions. For in￾stances, morphine (p. 210), given in the

appropriate dose, affords excellent pain

relief by influencing nociceptive path￾ways in the CNS. In excessive doses, it

inhibits the respiratory center and

makes apnea imminent. The dose de￾pendence of both effects can be graphed

in the form of dose-response curves

(DRC). The distance between both DRCs

indicates the difference between the

therapeutic and toxic doses. This margin

of safety indicates the risk of toxicity

when standard doses are exceeded.

“The dose alone makes the poison”

(Paracelsus). This holds true for both

medicines and environmental poisons.

No substance as such is toxic! In order to

assess the risk of toxicity, knowledge is

required of: 1) the effective dose during

exposure; 2) the dose level at which

damage is likely to occur; 3) the dura￾tion of exposure.

Increased Sensitivity (B). If certain

body functions develop hyperreactivity,

unwanted effects can occur even at nor￾mal dose levels. Increased sensitivity of

the respiratory center to morphine is

found in patients with chronic lung dis￾ease, in neonates, or during concurrent

exposure to other respiratory depress￾ant agents. The DRC is shifted to the left

and a smaller dose of morphine is suffi￾cient to paralyze respiration. Genetic

anomalies of metabolism may also lead

to hypersensitivity. Thus, several drugs

(aspirin, antimalarials, etc.) can provoke

premature breakdown of red blood cells

(hemolysis) in subjects with a glucose￾6-phosphate dehydrogenase deficiency.

The discipline of pharmacogenetics deals

with the importance of the genotype for

reactions to drugs.

The above forms of hypersensitivity

must be distinguished from allergies in￾volving the immune system (p. 72).

Lack of selectivity (C). Despite ap￾propriate dosing and normal sensitivity,

undesired effects can occur because the

drug does not specifically act on the tar￾geted (diseased) tissue or organ. For in￾stance, the anticholinergic, atropine, is

bound only to acetylcholine receptors of

the muscarinic type; however, these are

present in many different organs.

Moreover, the neuroleptic, chlor￾promazine, formerly used as a neuro￾leptic, is able to interact with several

different receptor types. Thus, its action

is neither organ-specific nor receptor￾specific.

The consequences of lack of selec￾tivity can often be avoided if the drug

does not require the blood route to

reach the target organ, but is, instead,

applied locally, as in the administration

of parasympatholytics in the form of eye

drops or in an aerosol for inhalation.

With every drug use, unwanted ef￾fects must be taken into account. Before

prescribing a drug, the physician should

therefore assess the risk: benefit ratio.

In this, knowledge of principal and ad￾verse effects is a prerequisite.

70 Adverse Drug Effects

Lüllmann, Color Atlas of Pharmacology © 2000 Thieme

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