El papel de la medicina herbal ayurvédica en el descubrimiento de las propiedades neurolepticas de la reserpina: a propósito de la Rauwolfia serpentina y los orígenes de la era antipsicótica / The role of the ayurvedic herbal medicine in the discovering of neuroleptic properties of reserpine: Rauwolfia serpentina and the origins of antipsychotic era

En el presente trabajo se revisa el papel de la planta Rauwolfia serpentina en el origen de la denominada "era psicofarmacológica". Para ello, se ha sumarizado su empleo en la tradicional medicina ayurvédica, fundamentalmente en los trastornos mentales. En el clásico tratado hindú Charaka Samhita ya se hablaba de una forma de psicosis denominada Ounmaad, uno de cuyos remedios terapéuticos era la "planta de raíz de serpiente". La medicina científica se ocupó del estudio, durante la primera mitad del siglo XX, de las actividades farmacológicas de esta planta, destacando las propiedades sedantes e hipotensivas. Finalmente, se analiza el proceso de aislamiento de los alcaloides de la raíz de Rauwolfia, iniciado en la India, y que concluyó con el descubrimiento de la reserpina en los laboratorios suizos de Ciba. Con la reserpina, el arsenal farmacológico para el tratamiento de la esquizofrenia, sustentado únicamente en la clorpromazina, se vio sustancialmente implementado; permitiendo un gran avance en el manejo de los trastornos psiquiátricos (AU)

Treatment of mild hypertension: results of a ten-year intervention trial.

Three hundred and eighty-nine subjects, ages 21-55, with diastolic blood pressures between 90 and 115 mm Hg were studied prospectively for 7-10 years in a controlled intervention trial to determine whether pressure lowering reduces the incidence of cardiovascular complications and death. The assignment to therapy, either a combination of a diuretic and rauwolfia serpentina, or an identical placebo, was random. Adverse effects required termination in only 23 (5.9%) cases. Diastolic blood pressure (DBP) was reduced an average of 10 mm Hg (systolic equals 16 mm Hg) in the active treatment group with no change in the placebo group. The major end points of death, myocardial infarction, and stroke totaled 17 and were nearly equally divided between treatment and placebo. Other manifestations of coronary disease were also equally distributed. Complications such as electrocardiographic hypervoltage, left ventricular hypertrophy, radiogrpahic cardiomegaly, and retinopathy occurred in the placebo group at a rate of 53.1 per 100 subjects compared to 23.8 per 100 in those on active drugs. Treatment failure occurred in 24 placebo-treated cases and none of the active group. The overall effectiveness of pressure lowering in reducing these complications and treatment failure was 60%. It is concluded that given the lower level of excess risk in mild uncomplicated hypertension, and the failure of active drug therapy to protect against coronary disease, systematic follow-up without drugs while attempting hygienic intervention and control of other risk factors may be a reasonable alternative for this large group.

Breast cancer and use of rauwolfia and other antihypertensive agents in hypertensive patients: a nationwide case-control study in Finland.

Two nationwide registers, the Finnish Cancer Registry and a register of persons entitled to free drugs for hypertension, were linked in a case-control study of the association of breast cancer and use of rauwolfia. Cases were all hypertensive patients in whom breast cancer was diagnosed in 1973. To test the association specifically with rauwolfia, controls were hypertensive women matched with the cases for age and geographic area and approximately matched for duration of treatment for hypertension. There were 109 case-control pairs. Use of any physician-prescribed drugs during the year prior to diagnosis of breast cancer was ascertained from original prescriptions. In the first set of analyses the patients were classified according to the drug used during most days of the year ("main antihypertensive agent"). In the second set a person qualified as a user of the respective drug regardless of the amount taken. The relative risks in the use of rauwolfia, methyldopa, another synthetic antihypertensive or a diuretic as main antihypertensive agent all ranged between 0.90 and 1.11. The results based on use of a drug in any amount were similar. Next, pairs in which duration of treatment for hypertension was different for cases and controls were excluded. The relative risk associated with use of rauwolfia as main antihypertensive agent then increased from 1.00 to 1.30 and the risk associated with use of any amount of rauwolfia from 1.16 to 2.14. Simultaneously, the relative risk in the use of digitalis was raised from 1.33 to 2.67 and of nitroglycerin from 1.00 to 1.71. Cases also used more types of antihypertensive agents simultaneously than controls. There was no association between rauwolfia-use and breast cancer in analyses limited to pairs in which neither case nor control used digitalis. Thus, there was not a consistent drug-specific association between rauwolfia-use and breast cancer in hypertensive patients. An underlying association of hypertension, heart disease or its treatment (digitalis) and breast cancer may have confounded some of the results of this and earlier studies. In conclusion, it is unlikely that use of rauwolfia increases the risk of breast cancer.

Serum dopamine-beta-hydroxylase activity in essential hypertension and in chronic renal failure with hypertension.

Elevated serum DBH (dopamine-beta-hydroxylase) activity was found in essential hypertension. The elevated level was not reduced when blood pressure was brought to normotensive level by administration of thiazide or rauwolfia. In contrast, serum DBH activity was low in both normotensive and hypertensive patients treated on prolonged hemodialysis. However, there was no correlation between serum DBH activity and blood pressure level. It was suggested that the pathogenesis of high blood pressure might be different between essential hypertension and hypertension with chronic renal failure, and that measurement of serum DBH activity might help for clinical differentiation of essential hypertension from certain forms of secondary hypertension.

Observations on the psychopharmacology of the aged.

Psychotropic drugs are discussed under the descriptive categories of antipsychotic, antidepressive, antimanic, anti-anxiety, and cognitive acting. In the antipsychotic classification, special attention is given to side effects (extrapyramidal motor signs, tardive dyskinesias, akathisis) and to dosage for the elderly. The section on congenitive acting drugs includes some pertinent observations on cognitive ability in the aging, the importance of correct diagnosis, and therapeutic strategy. The aged are a population at risk for not only disease, but iatrongenic illness due to direct and indirect drug action. Rational therapy involves understanding the underlying dynamics of the disease and thus the selection of the most effective treatment. Psychotropic drugs in an appropriate program are valuable therapeutic assets.