LA CONSULTA SEMANAL

DICIEMBRE 2000

CONSULTA

Crit Care Med 2000 Nov;28(11):3679-83 
Inhibition of nitric oxide synthase enhances the myocardial toxicity of phenylpropanolamine.
Zaloga GP, Clark JD, Roberts PR
Department of Medicine, Washington Hospital Center, DC, USA. 
OBJECTIVE: To investigate the direct and indirect effects of the anorexic agent phenylpropanolamine (PPA) on the heart and to determine whether nitric oxide deficiency exacerbates the myocardial toxicity of PPA. DESIGN: Dose response effects using sequential drug administration. SETTING: Animal research laboratory of a large tertiary academic medical center. SUBJECTS: Isolated hearts (n = 8) from male Sprague-Dawley rats weighing 300-400 g. INTERVENTIONS: Measurement of heart rate, maximal change in pressure over time (dP/dtmax), -dP/dtmax, and coronary blood flow in isolated hearts perfused on a Langendorff apparatus. PPA was infused through the aortic cannula at 0.05, 0.125, 0.25, 0.5, and 1.25 mmol/L before and after inhibition of nitric oxide synthesis with N-nitro-L-arginine methyl ester (L-NAME). RESULTS: PPA had little effect on myocardial contractility of normal hearts until the highest dose of PPA (1.25 mmol/L). However, after L-NAME, PPA significantly depressed contractility at a dose of 0.25 mmol/L. PPA had no significant effects on coronary blood flow. PPA failed to induce arrhythmias in normal hearts. However, after L-NAME, PPA induced ventricular fibrillation in 50% of the hearts. CONCLUSION: PPA causes myocardial contractile depression without altering global coronary artery blood flow. Inhibition of nitric oxide synthesis sensitizes the heart to the 
myocardial depressant effects of PPA and increases the risk for ventricular 
fibrillation. 



BMJ 2000 Oct 28;321(7268):1037A [Texto completo]
Phenylpropanolamine in drugs could be a risk for stroke.
Charatan F
Florida. 


Pharmacol Biochem Behav 2000 Jul;66(3):489-94 
Stimulus effects of phenylpropanolamine optical isomers in (+)amphetamine-trained rats.
Young R, Glennon RA
Department of Medicinal Chemistry, School of Pharmacy, Box 980540, Virginia Commonwealth University, Richmond, VA 23298, USA. 
There are eight phenylpropanolamine optical isomers related in structure to the central stimulants methamphetamine and amphetamine. Some of these are quite well known, such as (-)ephedrine, whereas others are relatively obscure, such as (-)cathine. Although certain of these phenylpropanolamines, such as (-)ephedrine and (+)cathine, retain central stimulant activity and are about 10- to 25-fold less potent than (+)amphetamine, the eight phenylpropanolamines have been compared only once before in drug discrimination studies. This latter study employed (-)ephedrine as the training drug. Because there are striking similarities between (-)ephedrine and (+)amphetamine as training drugs, it was of interest to determine and compare the effect of all eight phenylpropanolamines in (+)amphetamine trained animals. Using rats trained to discriminate 1 mg/kg of (+)amphetamine from saline vehicle under a variable interval 15-s (VI 15-s) schedule of reinforcement, the (+)amphetamine stimulus generalized only to (-)ephedrine (ED(50) = 4. 5 mg/kg) and (+)cathine (ED(50) = 8.0 mg/kg), and both agents were at least 10 times less potent that (+)amphetamine (ED(50) = 0.37 mg/kg). These results stand in contrast to those obtained with the (-)ephedrine-trained animals where the ephedrine stimulus generalized to all of the phenylpropanolamines except for (-)pseudoephedrine and (-)cathine. It is concluded that although there might be some similarity between the (-)ephedrine and (+)amphetamine stimuli, there are clear differences between them as determined in tests of stimulus generalization under the conditions employed. 

Am J Psychiatry 2000 Jun;157(6):1021-2 
Exacerbation of psychosis by phenylpropanolamine.
Goodhue A, Bartel RL, Smith NB
Publication Types:
Letter 

Am J Emerg Med 2000 May;18(3):343-5 
Phenylpropanolamine-associated intracranial hemorrhage in an infant.
Hamilton RS, Sharieff G
Publication Types:
Letter 

Br J Dermatol 2000 Apr;142(4):845-7 
Fixed drug eruption due to phenylpropanolamine hydrochloride.
Heikkila H, Kariniemi AL, Stubb S
Publication Types:
Letter 

Acta Otolaryngol 1999;119(7):837-42 
Effects of sustained-release oral phenylpropanolamine on the nasal mucosa of healthy subjects.
Graf P, Toll K, Palm J, Hallen H
Department of Otorhinolaryngology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden. 
Phenylpropanolamine (PPA) is widely used as a nasal decongestant administered orally in sustained release preparations and, in Sweden, the recommended dose nowadays is 50 mg twice daily for adults. The aim of this placebo-controlled, cross-over study was to determine the onset and duration of the decongestive effect of 50 and 100 mg PPA in 15 healthy subjects. All subjects arrived at the laboratory at 07.30 h. After an acclimatisation, the nasal mucosal baseline was established with rhinostereometry and the minimal cross-sectional area was measured using acoustic rhinometry. The systolic and diastolic blood pressures were also determined. Then all subjects were given their study drugs for the day and the measurements were repeated every hour for 8 h. This procedure was repeated for 3 days at 48 h intervals between the days. For purposes of comparison, the decongestive effect of oxymetazoline nasal spray was studied on a separate day. The decongestive effect of 100 mg PPA was similar to that of topical oxymetazoline. It develops after 1 h and lasts for approximately 6 h. The decongestive effect of oxymetazoline was significantly greater than that of 50 mg PPA and that of 100 mg PPA was significantly greater than that of 50 mg PPA using rhinostereometry, but not when using acoustic rhinometry. However, 50 mg PPA had no significant decongestive effect, compared with placebo, with rhinostereometry or acoustic rhinometry. In the first 3 h after administration of PPA, there was a dose-response increase in the systolic and diastolic blood pressures, which then returned to baseline. In conclusion, this study shows that PPA in double the recommended dose, i.e. 100 mg, has a significant decongestive effect on the nasal mucosa in healthy subjects. However, when the dose of PPA is increased the systolic and diastolic blood pressures also increase. 

Publication Types:
Clinical trial 


J Emerg Med 2000 Jan;18(1):55-9 
Myocardial infarction associated with phenylpropanolamine.
Oosterbaan R, Burns MJ
Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. 
Phenylpropanolamine is a sympathomimetic agent widely used in over-the-counter and prescription decongestant medications. We describe a young woman without cardiac risk factors who sustained myocardial infarction after unintentional overuse of a nasal decongestant containing phenylpropanolamine. The pathophysiology of myocardial injury and current management strategies as related to this agent are discussed. Although serious adverse reactions to phenylpropanolamine are uncommon, potentially serious harm may be caused by this widely available drug in healthy individuals. 

Am J Med 1999 Jan;106(1):118-9 
Hypertensive crisis secondary to phenylpropanolamine interacting with triple-drug therapy for HIV prophylaxis.
Khurana V, de la Fuente M, Bradley TP
Department of Medicine, State University of New York, Health Science Center at 
Brooklyn, 11203, USA. 

Rev Med Chil 1996 Dec;124(12):1499-503 
[Cerebral hemorrhage associated with the use of phenylpropanolamine. Clinical cases].
Tapia J
Departamento de Neurologia, Escuela de Medicina, Universidad Catolica de Chile. 
We report three women aged 33, 63 and 43 years old receiving an anorexigenic medication that contained phenylpropanolamine who, 30 min to 3 h after the ingestion of this medication, presented a frontal hematoma, a left putaminal hematoma and a subaracnoidal hemorrhage, respectively. Cerebral angiography, performed in all of them, did not show any vascular abnormality. This complication of phenylpropanolamine use, has been reported previously abroad and the mechanism of production, could be related to an elevation of blood pressure and the production of a vasculitis by the drug. The risk of this complication must be taken into account when prescribing phenylpropanolamine. 

Ann Emerg Med 1996 Sep;28(3):359-62 
Phenylpropanolamine and associated myocardial injury.
Leo PJ, Hollander JE, Shih RD, Marcus SM
Department of Emergency Medicine, New York Methodist Hospital, Brooklyn, USA. 
We report the cases of two patients without significant past medical history in whom developed myocardial injury attributed to the use of anorectic agents containing phenylpropanolamine. The pharmacologic properties of phenylpropanolamine and the current management of common adverse reactions to phenylpropanolamine are briefly reviewed. 

Gen Hosp Psychiatry 1995 Nov;17(6):457-8 
Psychotic episode related to phenylpropanolamine and amantadine in a healthy female.
Stroe AE, Hall J, Amin F
Publication Types:
Comment 
Letter 
Comments:
Comment on: Gen Hosp Psychiatry 1994 Sep;16(5):358-60 

Rev Esp Cardiol 1995 Nov;48(11):762-4 
[Ventricular tachycardia secondary to phenylpropanolamine poisoning: apropos a case].
Barriales Villa R, Batalla Celorio A, Lopez de la Iglesia J, Barriales Alvarez V, Iglesias Cubero G, Rodriguez Blanco VM, Cortina Llosa A
Servicio de Cardiologia, Hospital Central de Asturias, Oviedo. 
We report a case of a 17-years-old patient with an accidental ingestion of high doses of phenylpropanolamine. Nine hours after the ingestion she presented ventricular bigeminy and an episode of non sustained ventricular tachycardia. No cardiovascular disease was demonstrated. 

J Formos Med Assoc 1995 Jan-Feb;94(1-2):53-5 
Cerebral arteritis associated with oral use of phenylpropanolamine: report of a case.
Ryu SJ, Lin SK
Department of Neurology, Chang Gung Memorial Hospital, Taipei, Taiwan R.O.C. 
Phenylpropanolamine (PPA) is the major ingredient of many over-the-counter cold remedies and diet pills. Use or abuse of PPA may cause hemorrhagic stroke or cerebral vasculitis similar to the clinical and angiographic picture associated with amphetamine use or abuse. We report a 32-year-old Taiwanese women who developed sudden onset of severe headache, nausea and vomiting on the seventh day of oral ingestion of 75 mg PPA per day. Cerebral angiograms showed multiple areas of alternating focal constriction and dilatation ("beading" appearance) in the anterior and posterior cerebral arteries consistent with cerebral arteritis. This case should alert medical practitioners to the potential hazards of over-the-counter drugs like PPA. 

Gen Hosp Psychiatry 1994 Sep;16(5):358-60 
Phenylpropanolamine-induced psychosis. Potential predisposing factors.
Marshall RD, Douglas CJ
New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, NY 10032. 
Phenylpropanolamine (PPA) is a sympathomimetic drug contained in numerous over-the-counter and prescription decongestants and appetite suppressants. A range of adverse effects have been reported, including neuropsychiatric reactions in patients known to be taking recommended doses. Given that psychiatric symptoms are not included in the manufacturer's lists of adverse drug reactions, the incidence may be significantly higher. We report a cae of paranoid psychosis following use of a decongestant containing PPA and summarize the case report literature of psychiatric adverse effects to PPA in which doses were known and stated to be within recommended guidelines. A pattern of possible risk factors emerges from these reports. These may include 1) symptoms or history of mood spectrum disorder, 2) history of psychosis, 3) female sex, 4) family history of psychiatric disorder. The possibility that a higher incidence of adverse events occurs in a vulnerable population has not been systematically addressed, and seems called for. We recommend that physicians specifically inquire about patients' use of decongestants and diet aids. In half of the above cases, symptoms resolved without the use of antipsychotics. Comments:
Comment in: Gen Hosp Psychiatry 1995 Nov;17(6):457-8