RESUMO
Dopamine is a biogenic amine synthesized in the hypothalamus, in the arcuate nucleus, the caudad, and various areas of the central and peripheral nervous system. It has been widely established that dopamine and its agonists play an important role in cardiovascular, renal, hormonal, and central nervous system regulation through stimulation of alpha and beta adrenergic and dopaminergic receptors. There are several agonists of dopamine-2 (DA 2 ) dopaminergic receptors, such as bromocriptine, pergolide, lisuride, quinpirole, and carmoxirole, which inhibit norepinephrine release and produce a decrease in arterial blood pressure; in some cases, bromocriptine and pergolide also reduce heart rate. From a therapeutic point of view, the above-mentioned agonists are used for treating Parkinson's disease, acting over DA 2 dopaminergic receptors of the nigrostriatal system. Bromocriptine and the other dopaminergic agonists mentioned act over DA 2 receptors of the tuberoinfundibular system, inhibiting prolactin release and decreasing hyperprolactinemia and tumor size. Among DA 1 receptor agonists, we can mention fenoldopam, piribedil, ibopamine, SKF 3893, and apomorphine (nonspecific). Activation of these receptors decreases peripheral resistance, inducing lowering of arterial blood pressure and increases in heart rate, sympathetic tone, and activity of the renin aldosterone system. Among DA 2 receptor antagonists, we can mention metoclopramide, domperidone, sulpiride, and haloperidol. From a therapeutic point of view, metoclopramide and domperidone are used in gastric motility disorders, and haloperidol is used in psychotic alterations. Antagonists of DA 1 receptors are SCH23390 and clozapine. Clozapine is used for treating schizophrenia.
Assuntos
Dopamina/farmacologia , Dopamina/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Sistema Cardiovascular/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Agonistas de Dopamina/uso terapêutico , Antagonistas de Dopamina/farmacologia , Antagonistas de Dopamina/uso terapêutico , Epilepsia/tratamento farmacológico , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Hipertensão/tratamento farmacológico , Rim/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/uso terapêuticoRESUMO
This study was conducted in normotensive and hypertensive subjects at the Vargas Hospital of Caracas. Normotensive subjects received, in a cross-over fashion, placebo, metoclopramide (MTC), or domperidone (DOMP), 40 mg of each drug, daily for 1 week. The first group of patients under placebo for 1 week received a single 2.5-mg oral dose of bromocriptine (Br). The second group of patients received 30 mg MTC daily (divided into three doses) for 1 week. At the end of the period a single dose of 2.5 mg Br was administered to each patient. The third group of eight hypertensive patients received DOMP for 1 week at 30 mg/d and then a single 2.5-mg Br dose. Cardiovascular and biochemical parameters including arterial pressure, heart rate, plasma renin activity, and plasma aldosterone were evaluated during the 6-hour period before and after the administration of Br. Neither DOMP nor MTC significantly modified blood pressure and heart rate in normotensive patients. Br reduced both systolic and diastolic arterial pressure in hypertensive subjects. The peak of the antihypertensive effect appeared 3 hours after drug administration, but reduction of arterial pressure lasted approximately 6 hours. At the same time, Br reduced plasma aldosterone levels and plasma renin activity. MTC and DOMP reversed the antihypertensive effect of Br and its effect on aldosterone levels and plasma renin activity. We conclude from these findings that Br acts as an antihypertensive agent at peripheral and central levels by stimulating dopamine-2 receptors, which are involved in the aldosterone and renin secretion.
Assuntos
Anti-Hipertensivos/farmacologia , Bromocriptina/antagonistas & inibidores , Bromocriptina/farmacologia , Domperidona/farmacologia , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Hipertensão/tratamento farmacológico , Metoclopramida/farmacologia , Receptores de Dopamina D2/agonistas , Adulto , Aldosterona/sangue , Pressão Sanguínea/efeitos dos fármacos , Estudos de Casos e Controles , Estudos Cross-Over , Antagonismo de Drogas , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Renina/sangue , Renina/efeitos dos fármacosRESUMO
Two groups of patients with essential hypertension were studied at the Vargas Hospital of Caracas. The first group of 9 patients under placebo treatment for 1 week received a single 2.5 mg oral dose of bromocriptine. Cardiovascular and biochemical parameters including arterial pressure, heart rate, plasma renin activity, and plasma aldosterone levels were evaluated during the 6-hour period before and after the administration of drugs. The second experimental design was as follows: 9 patients received 30 mg metoclopramide daily (divided in 3 doses) for 1 week. At the end of the period a single oral dose of 2.5 mg of bromocriptine was given to each patient. The cardiovascular and biochemical parameters were also determined. Bromocriptine reduced both systolic and diastolic arterial pressure. The peak antihypertensive effect was shown 3 hours after administration of the drug, but the reduction of arterial pressure lasted approximately 6 hours. At the same time bromocriptine reduced plasma aldosterone levels and plasma renin activity. This reduction persisted 6 hours after its administration. Metoclopramide reversed the antihypertensive effect of bromocriptine and its effect on aldosterone secretion and plasma renin activity. We conclude from these findings that bromocriptine acts as an antihypertensive agent by stimulating DA2 dopaminergic receptor, the dopaminergic receptor involved in aldosterone and renin secretion is possibly DA2.
Assuntos
Anti-Hipertensivos/antagonistas & inibidores , Bromocriptina/antagonistas & inibidores , Antagonistas de Dopamina/farmacologia , Hipertensão/fisiopatologia , Metoclopramida/farmacologia , Aldosterona/sangue , Pressão Sanguínea/efeitos dos fármacos , Bromocriptina/uso terapêutico , Antagonistas dos Receptores de Dopamina D2 , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Renina/sangueRESUMO
Fourteen subjects (normotensive, hypertensive) were studied at the Vargas Hospital of Caracas. They were treated with placebo (2 periods), domperidone, a peripheral dopaminergic blocker, at the daily oral dose of 40 mg, and metoclopramide, a central and peripheral dopaminergic blocker, at the daily oral dose of 40 mg. All placebo and active drug periods lasted 1 week. Cardiovascular hemodynamic parameters (blood pressure, heart rate) were measured before, during and after submitting subjects to treadmill exercise according to the Bruce's protocol. Metoclopramide decreased significantly heart rate before and during exercise stress and systolic blood pressure during stage 1 exercise in normotensive subjects. Domperidone decreased significantly heart rate before and during exercise stress, and systolic blood pressure during stage 3 exercise in hypertensive subjects. Neither heart rate nor blood pressure were changed significantly after 8 minutes resting period post exercise. Our results suggest the existence of an excitatory modulatory influence of dopaminergic influence during exercise over the sympathetic activity.
Assuntos
Dopamina/fisiologia , Exercício Físico/fisiologia , Hemodinâmica/fisiologia , Hipertensão/fisiopatologia , Adulto , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Estudos Cross-Over , Domperidona/farmacologia , Antagonistas de Dopamina/farmacologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Masculino , Metoclopramida/farmacologiaRESUMO
Eleven patients with moderate to severe hypertension were studied at the Vargas Hospital of Caracas. The patients were pretreated with labetalol, 800 to 1200 mg/day, orally, over a period of 1 week, after which an intravenous infusion of dopamine, .5 to 3 micrograms/kg/minute, was given. Two intravenous dopamine infusions (30 minutes each) were performed before and after the injection of metoclopramide (30 mg, intravenous bolus). Two washout periods were also included before and after metoclopramide administration. Dopamine induced a decrease of blood pressure from 171.9 + 6.35/103.6 +/- 3.12 to 152.7 +/- 7.55/93.8 +/- 2.97 mm Hg (P < .001) without altering heart rate, and it increased plasma insulin levels from 8.29 +/- .70 microU/mL to 12.09 +/- 1.83 microU/mL (P < .01). Metoclopramide caused no changes of blood pressure or plasma insulin levels. Hypotensive responses and plasma insulin increases due to dopamine were blocked by metoclopramide, however. The authors conclude that a dopaminergic receptor may be involved in some cardiovascular responses and in modulating insulin secretion in humans.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Antagonistas de Dopamina , Hipertensão/tratamento farmacológico , Insulina/sangue , Labetalol/uso terapêutico , Metoclopramida/farmacologia , Glicemia/análise , Dopamina/administração & dosagem , Dopamina/farmacologia , Feminino , Humanos , Infusões Intravenosas , Masculino , Metoclopramida/administração & dosagem , Pessoa de Meia-Idade , Pré-MedicaçãoRESUMO
A comparative study between two dopaminergic antagonists: metoclopramide and domperidone, was undertaken in nineteen (19) hypertensive patients at the Vargas Hospital, Caracas. The patients were pretreated with labetalol, 800-1,200 mg/day, orally, over a period of one week, after which they were divided into two groups: group A, a total of eleven patients were intravenously infused with dopamine hydrochloride 0.5-3 micrograms/kg/min, before and after treatment with metoclopramide (10 mg, i.v. as a bolus); group B (n = 8), was pretreated with domperidone, 20 mg b.i.d., p.o. over a period of one week and intravenously infused with dopamine hydrochloride, 0.5-3 micrograms/kg/min. In group A, dopamine induced a decrease of blood pressure from 171.9 +/- 6.35/103.6 +/- 3.12 to 152.7 +/- 7.55/93.8 +/- 2.97 mmHg (p < 0.001) without altering heart rate, and it increased plasma insulin levels from 8.29 +/- 0.70 microunits/ml to 12.09 +/- 1.83 microunits/ml (p < 0.01). Metoclopramide caused no changes of blood pressure or plasma insulin levels. However, hypotensive responses and plasma insulin rises due to dopamine were blocked by metoclopramide. In group B, domperidone also blocked dopamine-induced antihypertensive effect (from 170.0 +/- 9.23/102.8 +/- 3.80 to 160.2 +/- 9.84/95.5 +/- 2.50 mmHg) although it was less effective than metoclopramide. Domperidone also blocked dopamine-induced increase of plasma insulin levels from 9.65 +/- 4.50 microunits/ml to 11.78 microunits/ml. We conclude that a dopaminergic receptor may be involved in some cardiovascular responses and in modulating insulin secretion in man.
Assuntos
Domperidona/farmacologia , Dopamina/farmacologia , Hipertensão/fisiopatologia , Insulina/sangue , Metoclopramida/farmacologia , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Antagonistas de Dopamina , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/metabolismo , Infusões Intravenosas , Pessoa de Meia-Idade , Radioimunoensaio , Receptores Dopaminérgicos/metabolismoRESUMO
Eleven patients with moderate to severe hypertension were pre-treated with oral labetalol 800-1200 mg/day for one week, prior to receiving two i.v. infusions of dopamine 1-3 micrograms/kg/min each of 30 min each, before and after the i.v. bolus injection of metoclopramide 30 mg. There were washout periods before and after the metoclopramide administration. Dopamine induced a significant decrease of blood pressure from 172/104 to 153/94 mm Hg without altering heart rate, and it increased the plasma insulin level from 8.3 to 12.1 microU.ml-1. Metoclopramide did not itself affect blood pressure or plasma insulin, but it did block the hypotensive response and rise in plasma insulin due to dopamine. We conclude that the pharmacological actions of intravenous dopamine on the cardiovascular system and on insulin secretion may be mediated by dopaminergic receptor stimulation.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Dopamina/farmacologia , Hipertensão/fisiopatologia , Insulina/sangue , Glicemia/metabolismo , Dopamina/administração & dosagem , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Infusões Intravenosas , Labetalol/uso terapêutico , Masculino , Metoclopramida/farmacologia , Pessoa de Meia-IdadeRESUMO
A case of hepatic cell adenoma associated with peliosis hepatis is reported. Both these conditions developed in a 41 year-old woman after the patient was under oral contraceptive therapy for 13 years. The relation between the use of oral contraceptives and these hepatic conditions are briefly discussed.
Assuntos
Carcinoma Hepatocelular/induzido quimicamente , Doença Hepática Induzida por Substâncias e Drogas , Anticoncepcionais Orais/efeitos adversos , Neoplasias Hepáticas/induzido quimicamente , Peliose Hepática/induzido quimicamente , Adenoma/patologia , Adulto , Feminino , Humanos , Neoplasias Hepáticas/patologia , Peliose Hepática/patologiaRESUMO
E descrito um caso de adenoma de celulas hepaticas associado a peliose hepatica.Essas duas condicoes desenvolveram-se em uma mulher de 41 anos de idade, apos uso continuado de contraceptivos orais por 13 anos. A relacao entre o uso de contraceptivos orais e essas duas patologias hepaticas e brevemente discutido