RAMB - Fevereiro 2017

herapeutic

use

the

rebound

effect

modern

drugs

: “N

homeopathic

medicines

”

ssoc

ras

2017; 63(2):100-108

103

As described for the rebound effect,

2-13

the authors cite

several examples of paradoxical and bidirectional effects

of drugs in different pharmaceutical classes and physio-

logical systems: immunomodulators (systemic corticoids

and TNF-

inhibitors), anticancer drugs (chemotherapy,

radiotherapy and arsenic), antiarrhythmics (procainamide

and isoproterenol), antihypertensives (methyldopa, cloni-

dine, guanabenz, moxonidine and thiazides), vasodilators

(nitrates), drugs for heart failure (beta-blockers, ACE in-

hibitors, angiotensin II receptor blockers and hydralazine),

lipid modifying drugs (fibrates and ezetimibe), inotropic

and chronotropic drugs (isoproterenol, epinephrine, beta-

-blockers and calcium channel blockers), vasoconstrictors

(ergot alkaloids and vasopressin), anesthetics (sevoflurane,

ketamine and propofol), antiepileptic drugs (benzodiaze-

pines, barbiturates and hydantoin), sedative-hypnotics

(anticholinergics, antihistamines, antispasmodics, barbi-

turates, benzodiazepines, bromides, chloral hydrate, etha-

nol and opioids), psychotropic drugs (antidepressants and

antipsychotics), peripheral nervous system drugs (acetyl-

cholinesterase and capsaicin inhibitors), antidyskinetic

drugs (dopaminergic agents), acid-base agents (sodium

lactate and bicarbonate), bone metabolism agents (para-

thyroid hormone and bisphosphonates), electrolytes (hy-

pertonic saline and magnesiumhydroxide), glycemic agents

(insulin and hypoglycemic agents), steroid hormones (dexa-

methasone), thyroid agents (iodine and lithium), antihy-

peruricemic agents (xanthine oxidase and urate oxidase

inhibitors), gastrointestinal agents (opiates, cholecystoki-

nin and ceruletide), hematological agents (erythropoietin,

vitamin K antagonists and adenosine diphosphate receptor

inhibitors), bronchodilators (short- and long-acting beta-

adrenergic bronchodilators), dermatological agents (his-

tamine receptor inhibitors, high-intensity long-wave ultra-

violet light and 8-methoxypsoralen), and more.

For Bond,

a possible hypothesis to explain the func-

tioning of paradoxical pharmacology is the “difference

between acute and chronic effects of drugs.” Reiterating

that the acute and chronic responses to drugs may differ

substantially, often being of opposite natures, he pro-

poses that “the exacerbation of a disease can make the

compensatory and redundant mechanisms of the organ-

ism achieve a beneficial long-term response.” This is par-

ticularly evident in events mediated by receptors: acute

exposure to inhibitors can produce receptor activation

and increased signaling, while chronic exposure can pro-

duce receptor desensitization and decreased signaling.

The same phenomenon occurs with receptor inhibitors.

Similar to the homeopathic method of treatment,

which uses ultra-diluted doses of medicines with the aim

of avoiding possible aggravation of the illness after ap-

plication of therapeutic similarity, as a general rule, pro-

ponents of paradoxical pharmacology suggest starting

with “very small doses, increasing them gradually over

the following weeks.”

Exemplifying the therapeutic use of the paradoxical

reactions of the organism, the authors describe clinical

conditions which can be treated using this proposal. Con-

gestive heart failure (CHF) is a disease related to impaired

cardiac contractility, in which the acute use of beta-adren-

ergic receptor inhibitors increases cardiac contractility,

improves hemodynamics and reduces related symptoms.

However, chronic use results in increased mortality. On

the other hand, while the short-term use of beta-adrener-

gic antagonists (beta-blockers: carvedilol, metoprolol,

bisoprolol, among others) decreases contractility and

exacerbates the CHF, causing the worsening of the illness,

long-term use results in increased cardiac contractility and

decreased mortality.

14,18-20

The same is observed with cal-

cium channel blockers.

Similarly, beta-adrenergic agonists are the most potent

bronchodilators and play an important role in all stages

of asthma management. However, as mentioned in the

study of the rebound effect, chronic use is associated with

irreversible and fatal paradoxical bronchospasms. On the

other hand, while short-term use of beta-adrenergic an-

tagonists leads to bronchoconstriction and worsening of

asthma, long-term use leads to bronchodilation and in-

creased asthma management.

14,18,22,23

Additional examples include the use of methylphe-

nidate (a central nervous system stimulant) in the treat-

ment of ADHD and the use of 5-HT1A serotonin receptor

agonists (mediators of hyperalgesia) to produce analgesia.

Of ancient knowledge, the use of thiazide class diuretics

provides a paradoxical antidiuretic benefit in the treat-

ment of diabetes insipidus, reducing polyuria and increas-

ing urine osmolality.

Arsenic trioxide (As

), an important carcinogen,

has been used by homeopathy for more than two centuries

as an adjuvant drug in the treatment of several types of

cancer, and is being used by paradoxical pharmacology

as a promising anticancer drug,

25,26

mainly in the relapse

of acute promyelocytic leukemia,

41,42

including in Bra-

zil,

43,44

among other applications.

herapeutic

use

the

rebound

effect

of modern

drugs

: “

new

homeopathic

medicines

”

27-33

Reiterating that homeopathic treatment has the pre-

rogative of using drugs that cause pathogenetic manifes-