RAMB - Fevereiro 2017

eixeira

102

ssoc

ras

2017; 63(2):100-108

scribed, in recent medical literature, the occurrence of

secondary and opposite reactions of the organism after

the primary actions of different drugs, confirming the

homeopathic postulate. As mentioned previously, this

secondary action or organism’s reaction, which manifests

itself automatically and instinctively in order to maintain

the homeostasis of the system, is described by contem-

porary pharmacology and physiology as the rebound

effect of the drugs, or paradoxical reaction of the organ-

ism, respectively. Analogously, the primary action of the

drugs cited by Hahnemann corresponds to the therapeu-

tic, adverse and collateral effects of modern drugs.

According to evidence from experimental and clinical

pharmacology,

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the rebound effect of modern drugs

presents similar characteristics to the secondary action or

the reaction of the organism described by the homeo-

pathic model (

Organon of medicine,

§ 59, 64, 69):

(i) it

causes an opposite reaction of the organism with greater

intensity than the primary action of the drug; (ii) it occurs

after the primary action of the drug as an automatic man-

ifestation of the organism; (iii) it is independent of the

drug, dose, duration of treatment or the type of symptom

(illness); (iv) its magnitude is proportional to the primary

action of the drug; and (v) it only manifests in susceptible

individuals (idiosyncratic character).

According to the extensive literature,

2-13

several studies

illustrate the universality of the rebound phenomenon in

relation to the distinct classes of palliative drugs (antiangi-

nal, antihypertensive, antiarrhythmic, antithrombotic, and

antihyperlipidemic agents, anxiolytics, sedative-hypnotics,

neurostimulants, antidepressants, antipsychotics, anti-

-inflammatory drugs, analgesics, diuretics, bronchodilators,

anti-dyspeptics, bone antiresorptive agents, and immuno-

modulators, among others), showing aggravation of the

signs and symptoms initially suppressed by the primary

and direct action of the drug, after its discontinuation.

By definition, the rebound effect presents an inten-

sity and/or frequency a few times higher than the corre-

sponding baseline symptoms suppressed by the primary

action of the antipathic drug, a characteristic that distin-

guishes the rebound phenomenon from the natural reap-

pearance of chronic symptoms after the end of treatment.

Epidemiological studies show that this magnitude can

cause severe and fatal events after the suspension of cer-

tain classes of drugs (antithrombotics, antidepressants,

bronchodilators, anti-dyspeptics and immunomodulators,

among others).

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The rebound effect manifests itself at different intervals

(hours to weeks) after the exhaustion of the biological effect

(half-life) of the drug, and its duration is also variable. De-

spite the suspension or discontinuation of the drug being

a prerequisite for the manifestation of the rebound effect,

given that the primary action of the drug persists while the

receptors are being stimulated (biological half-life), studies

show that the rebound effect may also occur in the course

of treatment due to therapeutic failure or the development

of tolerance, tachyphylaxis or desensitization. On the

other hand, a slow and gradual reduction of doses (taper-

ing) to prevent abrupt discontinuation can minimize the

occurrence of the rebound effect.

2-13

In analogy to the proposal to be detailed below, reports

in the literature describe the use of conventional drugs

according to therapeutic similarity. Among these, we can

cite the use of biphasic oral contraceptives to promote

ovulation and rebound pregnancy in women with func-

tional sterility and the use of central nervous system

stimulants (methylphenidate) to treat attention deficit

hyperactivity disorder (ADHD).

39,40

aradoxical

pharmacology

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A strategy suggested by Richard A. Bond in 2001,

para-

doxical pharmacology proposes the therapeutic use of the

paradoxical effects of drugs (secondary reactions of the

organism with the opposite nature to the primary effects

of the drugs). Universal in nature, such paradoxical, bidi-

rectional or compensatory effects appear in several class-

es of drugs, regardless of the dose, and affect various per-

centages of individuals. Although not fully elucidated, this

paradoxical effect is manifested at different levels of the

biological self-regulation systems, increasing the func-

tional complexity of the entire organism, from subcellular

components (channels, enzymes, receptors, transporters,

organelles, etc.) to cells, tissues and organs.

15-19

Present in any physiological system, these paradoxical

and bidirectional effects occur due to varying mechanisms:

different actions on the same receptor, due to temporal

effects (for example, beta-blockers with intrinsic sympa-

thomimetic activity); stereochemical effects (for example,

salbutamol); multiple receptor targets, with or without

associated temporal effects (for example, procainamide);

antibody-mediated reactions (for example, heparin-in-

duced thromboembolism); pharmacokinetic effects of

competing compartments (for example, bicarbonate);

interruption and non-linear effects on systems (for ex-

ample, dopaminergic agents); systemic overcompensation

(for example, antiretroviral therapy and immune recon-

stitution inflammatory syndrome); other higher level

feedback mechanisms (for example, digoxin) and multi-

level feedback cycles (for example, isotretinoin-associated

acne fulminant), and more.