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PubMedDate not supplied

[Intracavernous injections of etilefrin: its efficacy in the treatment of priapism in sickle cell patients].

OBJECTIVE: To date, the treatment of priapism in sickle-cell patients has relied on measures aimed at lowering blood viscosity and acidosis and reducing the level of circulating hemoglobin S (hyperhydration, alkalinization, or exsanguinotransfusion...) Surgical cavernous-venous shunt may be proposed if conservative treatment fails. We examined the efficacy of intracavernous etilefrin injections. PATIENTS AND METHODS: From January 1996 through October 1997 (20 months) we performed 35 consecutive intracavernous injections of an alphastimulant, etilefrin in 7 sickle-cell patients (6 SS, 1 AS) who had experienced one or several episodes of low-flow priapism lasting 2 to 28 hours. RESULTS: Involution of the tumefaction was rapidly achieved in all cases. Tolerance was satisfactory, although some post-injection undesirable effects were reported by certain patients: moderate transient pain (2-5 min) in the retrosternal area, or intense pain in the penis (more intense than the priapism) which lasted 10 to 30 minutes. This work confirmed the earlier reported efficacy of intracavernous injections of etilefrin and suggests that the autonomous nervous system plays an important role in the genesis of this condition in sickle-cell patients. Patients should be informed about the observed undesirable effects which have not been reported previously in the literature. CONCLUSION: Etilefrin can be proposed as first line treatment for priapism in sickle-cell patients (at least in cases lasting less than 24 h). The pathogenic mechanism could involve neuromuscular dysfunction.

Administration, Topical↗
PubMed1986

[Intracavernous injection of etilefrine hydrochloride in iatrogenic priapism].

Intracavernous injection of etilefrine hydrochloride (1 or 2 mg) was performed on four patients with fully erected penis after intracavernous injection of 40 mg of papaverine hydrochloride. One case needed three injections of etilefrine hydrochloride (1 mg), but the erection disappeared in the other three cases within 10 minutes after a single injection of 2 mg of etilefrine hydrochloride. The injection resulted in complete detumescence and relief of the erection in all cases. These observations strongly suggest that the intracavernous injection of etilefrine hydrochloride is effective in treating not only iatrogenic priapism but also priapism due to other etiologies. Also, it might be useful to control erection time after intracavernous injection therapy for impotence.

Adult↗
PubMed1987

The action of relaxin, fenoterol and etilefrine on uterine motility of the rat.

In uterine motility tests in virgin rats, the inhibitory action of the peptide hormone relaxin has been compared with the actions of fenoterol and etilefrine. At molecular levels, relaxin and fenoterol showed similar uterine inhibitory activity. Etilefrine was markedly less effective in inducing uterine relaxation. By pretreatment with propranolol, the inhibitory action of both fenoterol and etilefrine could be prevented but not the tocolytic effect of relaxin. Etilefrine, in higher doses, developed alpha-receptor activity as demonstrated by resumed uterine contractions. The doses required to induce beta 2- and alpha-activities differed by a factor of approximately 4,000.

Animals↗
PubMed1996

Etilefrine in the prevention of prolonged erection after diagnostic pharmacological stimulation.

The aim of this study was to verify the efficacy and safety of intracavernous injection of etilefrine hydrochloride in the prevention of pharmacologically induced prolonged erection. Two hundred rigid erections due to diagnostic pharmacological stimulation were treated with immediate intracavernous injection of 5 to 10 mg etilefrine hydrochloride. Penile response and general side effects after the injection were recorded. Patients were interviewed after 1-2 weeks about possible side effects. Detumescence occurred within 10 minutes in 194 (97%) cases. In the remaining six (3%), detumescence occurred after cavernous aspiration and additional injection of 5 mg etilefrine. Thirteen patients (6.5%) had transitory palpitations. None of the patients had hypertensive crisis, cardiac arrythmia or ischaemic events. Intracavernous injection of etilefrine is effective and safe in preventing prolonged erection after diagnostic pharmacological stimulation.

Adult↗
PubMed1989

Etilefrine and amezinium reduce uterine blood flow of pregnant guinea pigs.

Etilefrine and Amezinium are used during pregnancy to prevent hypotension and fetal growth retardation. The effect of these drugs on uterine blood flow (UBF), uterine vascular resistance (UVR) and fetal growth are, however, unknown. 31 guinea pigs were injected daily with Etilefrine (3 X 0.14 mg/kg) and Amezinium (0.14 mg/kg) from day 30 to day 60. Uterine blood flow was measured with radioactive-labeled microspheres. Uterine vascular resistance was calculated from arterial blood pressure and uterine blood flow. 10 guinea pigs treated with 0.9% sodium chloride served as controls. As a response to Etilefrine and Amezinium, UBF fell by 68 and 48%, respectively, accompanied by an increase in UVR. The fetal weight decreased only slightly. It is concluded that long-term application of anti-hypotensive drugs may be hazardous to uterine blood flow and fetal growth.

Animals↗
PubMed1979

Vascular effects of etilefrine. Further studies to substantiate the predominant indirect sympathomimetic action of this agent.

The suggested use of etilefrine in the treatment of patients with orthostatic hypotension is based on the premise that it has an action similar to that of noradrenaline (Miller, Wiener and Bloomfield, 1973). However, earlier work from this laboratory (Frost, Frewin and Gerke, 1977; Frost, Frewin, Gerke and Downey, 1978; Frost, Halloran, Frewin, Gerke and Downey, 1978) on blood vessels in the rat tail has suggested that the drug acts predominantly as an indirect sympathomimetic agent. The present study examined the action of etilefrine on the central artery of the rabbit ear. This vessel is known to have a rich sympathetic innervation (de la Lande, Frewin and Waterson, 1967) and has the added advantage that it can be surgically denervated. It therefore became possible to examine the effects of etilefrine on both normal and denervated arteries and to quantitate the extent to which the drug relied on the symphathetic nerves for its vasoconstrictor effects.

Animals↗
PubMed1977

The effects of etilefrine on blood vessels in the rat tail.

Etilefrine was found to constrict blood vessels in the rat tail through a mechanism which was partly dependent on the sympathetic nerves present in these vessels. The response to the drug was enhanced by pretreagment with noradrenaline and cocaine, and totally abolished by the alpha-receptor antagonist phentolamine. When compared with several other sympathomimetic agents which were tested on the vessel, etilefrine appeared to have a low order of vasoconstrictor activity. These findings would seem to have considerable relevance to the clinical situation where an attempt has been made to use etilefrine in the treatment of patients with orthostatic hypotension.

Animals↗
PubMed2001

Management of sickle cell priapism with etilefrine.

Intracavernous injections of etilefrine were effective in seven children with acute sickle cell priapism, and stuttering priapism resolved in five children after one to seven months of oral etilefrine. Compared with our previous reports in adults, etilefrine appears to be more effective in childhood.

Administration, Oral↗
PubMed2000

Effect of midodrine on chlorpromazine-induced orthostatic hypotension in rabbits: comparison with amezinium, etilefrine and droxidopa.

Orthostatic hypotension was produced in urethane-anesthetized rabbit by a combination of chlorpromazine (0.1 mg/kg, i.v.) and 45 degrees head-up tilt. The effect of midodrine (1 and 3 mg/kg, i.d.) was investigated in comparison with amezinium (10 and 30 mg/kg, i.d.), etilefrine (10 and 30 mg/kg, i.d.) and droxidopa (30 and 100 mg/kg, i.d.). The higher doses of each drug significantly mitigated the chlorpromazine-induced orthostatic hypotension, while none of the lower doses caused a significant effect. The effect of midodrine developed most rapidly; a significant effect was observed 25 min after administration. The order of onset time was midodrine < etilefrine < amezinium < droxidopa. The effect of droxidopa was significant only at 130 to 160 min after administration. The amplitude of effect was in the following order; midodrine = droxidopa > or = etilefrine > amezinium. Midodrine (3 mg/kg, i.d.) mitigated orthostatic hypotension induced by prazosin (0.1 mg/kg, i.v.), but not by pentolinium (0.6 mg/kg, i.v.). It is suggested that midodrine competes with chlorpromazine at alpha1-adrenoceptors and subsequently recovers reflex vasoconstriction. Midodrine may be useful to protect patients with impaired baroreflex activity from accidental orthostatic hypotension during treatment with neuroleptics.

Adrenergic alpha-Agonists↗
PubMed1989

Formation of a direct mutagen, diazo-N-nitrosoetilefrin, by interaction of etilefrin with nitrite.

Reaction of an antihypotensive drug, etilefrin [alpha-[(ethylamino)methyl]-m-hydroxybenzyl alcohol], with nitrite under mildly acidic conditions produced N-nitrosoetilefrin [alpha-[(N-nitrosoethylamino)methyl]-m-hydroxybenzyl alcohol] (a mixture of syn and anti forms) (Iab) and diazo-N-nitrosoetilefrin [1-(4-diazo-3-oxo-1,5-cyclohexadienyl-2-(N-nitrosoethylamino )ethanol] (a mixture of syn and anti forms) (IIab). Treatment of etilefrin with an equivalent amount of nitrite at pH 3 and 37 degrees C for 4 h gave Iab (yield, 30%) and IIab (yield, 5%). Treatment of etilefrin with 4 eq of nitrite under the same conditions gave Iab (23%) and IIab (53%). Compounds Iab and IIab were each composed of two isomers due to the configuration of the N-nitroso group. While compound Iab was not mutagenic, compound IIab showed mutagenicity to Salmonella typhimurium TA98 and TA100 strains without metabolic activation. Specific mutagenic activity of IIab was 300 his+ revertant colonies for both TA98 and TA100 strains with a dose of 0.1 mumol. Addition of a microsomal activation system little affected the activity. It is noteworthy that this orally administered drug can produce a direct-acting mutagen by reaction with nitrite, which is present in the digestive tract.

Chromatography, Thin Layer↗
PubMed1977

[On the action of antihypotensive agents in sympathicotonic orthostatic hypotension in geriartric patients: comparison between placebo and etilefrin (author's transl)].

The action of etilefrin (Effortil Depot Perlongets) was compared with placebo in a double-blind study in 24 female geriatric patients with sympathicotonic orthostatic hypotension. After determining the basic values, all patients were treated with the active substance in a titration phase lasting one week (dosage 2-3 Perlongets/day). The decrease in systolic blood pressure and the increase in pulse rate while standing were then statistically significant lower (p less than (p less than 0.001) when compared with the basic values. In 17 out of 21 cases of collapse which occured while standing before therapy was commenced no further collapse occurred (p less than 0.005). Following the titration phase treatment with etilefrin was continued in 12 patients in a double-blind study while the remaining 12 patients were changed over to placebo as a withdrawal study. The effect continued in those patients treated with the active ingredient and the average values and incidence of effects improved further. On the other hand, in the placebo group there was one again a marked decrease in systolic blood pressure and increase in pulse rate as observed in the basic values. The symptomatology, particulary episodes of collapse increased again. There was a statistically significant difference between the action of etilefrin and placebo for all criteria (both objective and subjective parameters). Side-effects were not observed.

Age Factors↗
PubMed1978

[The hypertensive effect of adyston and etilefrin. Comparative animal experimental studies].

According to the results obtained under the described conditions it can be stated that after i.v. administration Adyston induces a dose-dependent rise in systolic and diastolic blood pressure, in comparison with etilefrin the new product Adyston shows a greater potency in rising the systolic and diastolic blood pressure; Adyston induced rise of blood pressure is in general of longer duration in comparison with that induced by etilefrin, it is interesting that in the dose of 0.01 mg/kg Adyston increases the arterial blood pressure but at the same time slightly decreases the heart rate; this is not the case after administration of etilefrin which at the same dose increases both arterial blood pressure and heart rate.

2-Hydroxyphenethylamine↗
PubMed1997

[Prevention of prolonged drug-induced erection by intracavernous injection of etilefrine].

Here in we report the results of intracavernous injection of etilefrine hydrochloride in a group of 12 patients who developed rigid erection after a diagnostic test with intracavernous PGE1 injection or cavernosometry. Etilefrine reversed erection in all cases. No side-effects or significant changes in blood pressure were noted. Etilefrine is believed to be a safe and low cost alternative to other alpha-adrenergic agents in the prevention of drug-induced priapism.

Adrenergic alpha-Agonists↗
PubMed2004

Sequential injection spectrophotometric determination of etilefrine hydrochloride.

A simple, fast, economical and automated sequential injection spectrophotometric method for the determination of etilefrine hydrochloride is developed. The method is based on the condensation reaction of etilefrine hydrochloride with 4-aminoantipyrine in the presence of alkaline potassium hexacyanoferrate and the absorbance of the colored product measured at 503 nm. Aspiration order, flow rate, reaction coil diameter, reaction coil length, concentration of 4-aminoantipyrine and potassium ferricyanide, as well as aspiration volume of reagents and sample has been optimized. Using these optimized parameters, a linear relationship between the relative peak height and concentration was obtained in the range 1-20 mg l(-1). The detection limit (as 3sigma value) was 0.1 mg l(-1) and precision was 2.7% and 1.5% at 1 and 2 mg l(-1), respectively. This method is superior over previously reported ones in terms of linear range, short analysis time, high sample throughput, excellent reagent economy and minimum waste generation.

Etilefrine↗
PubMed2002

Etilefrine for the prevention of priapism in adult sickle cell disease.

Priapism is a common complication of sickle cell disease (SCD) that could lead to erectile dysfunction and psychosocial problems. Treatment of established fulminant priapism is usually not satisfactory. It is therefore important to prevent this complication of SCD. The alpha-adrenergic agonist etilefrine (50-100 mg/d) produced a good clinical response in 13 of 18 (72%) adults who have recurrent priapism; 17 had SCD and one sickle cell trait. After a follow-up of 1-48 months, none of the 18 people on etilefrine developed hypertension or sexual dysfunction. Similar efficacy and safety profiles of the drug have been reported previously.

Adrenergic alpha-Agonists↗
PubMed1979

The effect of etilefrine (Effortil) on central hemodynamics and aorto-coronary bypass blood flow. A pre-operative study.

In an attempt to elucidate the function of an aorto-coronary bypass in patients with coronary artery obliterative disease, intravenous injection of etilefrine was used to bring about variations of central hemodynamics. Etilefrine proved to cause a significant increase of cardiac output (QPA), mean systemic blood pressure and aorto-coronary bypass flow. Calculations of peripheral myocardial resistance showed a rather pronounced decrease in all vascular regions studied. There was no change of central venous pressure. The decrease of the myocardial vascular resistance, as shown by the increase of aorto-coronary bypass flow, is indicative of the myocardial vascular capacity. Hence, it may be of value as a prognostic test.

Adult↗
PubMed1978

[The effect of etilefrine and dihydroergotamine on sympathetic nervous system activity when standing up (author's transl)].

Systolic blood pressure, heart rate and concentrations of adrenaline, noradrenaline and dopamine as well as plasma dopamine-beta-hydroxylase (DBH) were measured in 22 subjects in recumbency and on standing up. Six subjects each had previously been given intravenously dihydroergotamine (0.5 mg) or etilefrine (0.25 mg/min) or a placebo. It was demonstrated that orthostasis leads to an increased activity of the sympathetic nervous system and the adrenal system. After administration of dihydroergotamine there was a diminished reaction of the sympathetic nervous system with an increase of venous tone which counteracted the decrease in cardiac output. Etilefrine, on the other hand, inhibited the sympatho-adrenal reaction on orthostasis and decreased the liberation of adrenaline. It acts directly via stimulation of alpha-and beta-receptors and is thus predominantly indicated if there is insufficient response of the baroreceptor reflex at its efferent limb.

Adult↗
PubMed1981

[Abnormalities of hypotonic orthostatic regulation: cardiovascular effects of dihydroergotamine, etilefrine and their combination (author's transl)].

In a double-blind inter-individual study of 51 patients with abnormal hypotonic orthostatic regulation, the effect of dihydroergotamine (2 mg), etilefrine (20 mg) or their combination (2 mg and 20 mg, respectively) was studied. Blood pressure, heart rate, dicrotic ratio as well as number and severity of symptoms during standardised orthostasis were studied before and after a week on placebo and after one and two weeks of drug administration. Resting blood pressure after treatment with the two drugs combined rose from 111/73 to 120/77 mm Hg, after etilefrine from 114/74 to 122/79 mm Hg, remaining essentially unchanged after dihydroergotamine. Fall in dicrotic ratio, as a measure of change in mean blood pressure, was 10% during the first minute of standing with the combined drugs, 30-35% with each drug separately. Treatment with the combined drugs was also superior when considering systolic blood pressure, pressure amplitude and heart rate. Similarly, the drugs in combination caused the least number and lowest severity of symptoms: side-effects were less common with the combination than with each drug alone.

Adolescent↗