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Abstract

B. Brosig¹, J. Kupfer², V. Niemeier¹ and U. Gieler¹

¹Clinic for Psychosomatics and Psychotherapy, and ²Department of Medical Psychology, Center for Psychosomatic Medicine, Justus Liebig University, Gießen, Germany
The psychic-dynamic factors underlying the hypochondriac disorder involving an obsessive preoccupation with physical attractiveness (dysmorphophobia) and the treatment possibilities for some manifestations of this syndrome have been examined. This psychosomatic illness frequently leads to the taking of finasteride, a medication that halts the balding process in cases of androgenetic alopecia or even stimulates renewed hair growth. The nosological demarcation of the disorder requires the differential diagnosis of depressive, hypochondriac and delusionary disorders. The psychodynamics involved, as deduced from 2 case studies, takes the form of an expansion of the patients’ reductionist perspective, characterized by an emphasis on external types extending to a psychogenetic attitude with regression into narcissistic fixation. The authors seek eternal youth which is a “leitmotif” of the disorder, and they apply the term “Dorian Gray Syndrome” after Oscar Wilde’s novel. The treatment recommended is a course of intensive psychotherapy; often the topic of “life-style medication” must be introduced before the specific narcissistic conflicts behind the current symptoms can be treated.Correspondence to:
Dr. B. Brosig; Center for Psychosomatic Medicine, Clinic for Psychosomatics and Psychotherapy, Justus Liebig University, Gießen, Ludwigstraße 76, D-35394 Gießen, Germany
Email: Burkhard.Brosig@psycho.med.uni-giessen.de

Abstract

W. Harth and R. Linse

Clinic for Skin Diseases, Erfurt, Germany
The body dysmorphic disorder is the repeated preoccupation with a minimal or non-evident defect and includes a wide spectrum of imagined defects in appearance. These patients present themselves in every clinical practice and are extraordinarily difficult to treat. The focus of the preoccupation concerns head, face, chest and the genital area. Following the introduction of the new “life-style” drug, finasteride, we observed a dramatic increase in the number of patients suffering from body dysmorphic disorder attending our clinic for skin diseases in Erfurt. These patients frequently contact their doctor demanding specifically for prescription of a particular life-style drug. However, there is no indication for using life-style drugs for the treatment of a body dysmorphic disorder. The appropriate treatment includes psychotherapy and psychopharmacological treatment.Correspondence to:
Dr. W. Harth; Hautklinik, Klinikum Erfurt, Arnstädterstraße 34, D-99096 Erfurt, Germany

Abstract

E. Jazwinska-Tarnawska¹, K. Orzechowska-Juzwenko¹, P. Niewinski¹, Z. Rzemislawska¹, K. Loboz-Grudzien², M. Dmochowska-Perz² and J. Slawin²

Chair and Department of Clinical Pharmacology, Wroclaw Medical University and ²Department of Cardiology, Marciniak T. Hospital, Wroclaw, Poland
Objective: Propafenone (PPF) is an antiarrhythmic, Class Ic agent. Its metabolism is genetically controlled by a cytochrome P450 isoenzyme named CYP2D6, which shows polymorphism in human population. The aim of this paper was to determine the correlation between the antiarrhythmic efficacy of PPF and the oxidation phenotype. Subjects and material: The study group consisted of 42 patients, aged 36 to 75 years, suffering from paroxysmal atrial fibrillation (AF). The oxidation phenotype was described by the metabolic ratio (MR) of sparteine. The MR value separated the group of poor metabolizers (MR > 20) from the group of extensive metabolizers (MR < 20) with the subgroup of very extensive metabolizers (MR < 1). Method: The study was conducted during a 3-month PPF therapy for the prophylaxis of paroxysmal atrial fibrillation. PPF was given orally, 300 – 450 mg/day. The oxidation phenotype was checked prior to the administration of PPF. Serum concentration of PPF at 7, 11 days and the end of PPF therapy were determined. Statistical analysis of data was performed with the c2 test and the Pearson’s correlation methods. Results: In the group of 42 patients, PPF therapy was 100% effective in poor metabolizers (PM). In extensive metabolizers (EM), 61% efficacy was observed with efficacy 0% in very extensive metabolizers (VEM). The correlation between oxidation phenotype and the ability to maintain sinus rhythm (SR) was statistically significant (r = 0.414, p < 0.05). Conclusions: The antiarrhythmic efficacy of propafenone depends on the oxidation phenotype; 100% efficacy occurred in the group of poor metabolizers whereas PPF, at the dose tested, was ineffective in very extensive metabolizers.Correspondence to:
Dr. E. Jazwinska-Tarnawska; Chair and Department of Clinical Pharmacology, Wroclaw Medical University, Bujwida St. 44, 50-345 Poland

Abstract

S.L. Eeckhoudt¹, J.P. Desager², A.R. Robert³, I. Leclercq², R.K. Verbeeck¹ and Y. Horsmans²

¹Unité de Pharmacocinétique, Métabolisme, Nutrition et Toxicologie, ²Département de Gastroentérologie, and ³Unité d’Epidémiologie, Ecole de Santé Publique, Université catholique de Louvain, Brussels, Belgium
Introduction: CYP3A is responsible for the metabolism of numerous endogenous and exogenous compounds. Several substrates of CYP3A have been investigated to assess the CYP3A-metabolizing capacity of an individual in an attempt to predict the rate of metabolism of other CYP3A substrates. Two such tests of CYP3A activity are the midazolam plasma clearance after its intravenous administration and the 6b-OH cortisol urinary ratio. Possible correlations between these 2 tests were investigated before and after treatment with rifampin in a group of healthy volunteers. Methods: Pharmacokinetic parameters of midazolam and 6b-OH cortisol urinary ratio were evaluated in 8 volunteers before and after 6 days treatment with rifampin, a potent inducer of CYP3A, and after cessation of rifampin treatment. Results: Midazolam systemic clearance and the 6b-OH cortisol urinary ratio were significantly higher at Days 7 and 10 than at Day 0. There was a strong positive correlation between these 2 parameters (r = 0.70, p < 0.001). In contrast, no correlation was observed between the ratio of the AUCs of 1'-OH midazolam vs. midazolam/) or the ratio of plasma concentration of 1'-OH midazolam vs. midazolam and the 6b-OH cortisol urinary ratio (r = 0.05, p = 0.82; r = 0.04, p = 0.88, respectively). Considering only data obtained before or after treatment with rifampin, however, no correlation was observed between midazolam systemic clearance and the 6b-OH cortisol urinary ratio. Conclusions: These data demonstrate that there is a strong positive correlation between systemic midazolam clearance and 6b-OH cortisol urinary ratio before and after induction. This suggests that the 6b-OH cortisol urinary ratio test is a non-invasive alternative to the use of systemic midazolam clearance for monitoring the time-course of CYP3A induction.Correspondence to:
Dr. Y. Horsmans; Université catholique de Louvain, Département de Gastroentérologie, Avenue Mounier 7369, B-1200 Brussels, Belgium
Email: horsmans@gaen.ucl.ac.be

Abstract

F.P. Meyer

Institute of Clinical Pharmacology, Otto-von-Guericke University, Magdeburg, Germany
There are many well-known factors and variables which play a role in the evaluation of pharmacokinetic and pharmacodynamic results gained from healthy volunteers. The genetic constitution is influenced by age, sex, circadian and seasonal variations, dietary factors, immunological function, alcohol intake, smoking, etc. Vesell repeatedly pointed out these facts some time ago [Vesell 1982, Vesell and Passananti 1977]. Since Janke [1964], we have suspected that personality traits can also influence the drug response. The following overview is dedicated to this field designated as differential psychopharmacology which, from the point of view of the author, has been given too little attention by pharmacologists and clinical pharmacologists. It has been demonstrated that the effect of psychotropic drugs, including placebo, can be differentially influenced by personality traits, e.g. introversion/extroversion, high level neuroticism/ low level neuroticism and success motivation/failure motivation. For example, relatively high doses of diazepam (0.3 mg/kg), when compared to placebo, only impaired the psychophysical performance of extroverted volunteers whereas introverted volunteers remained unaffected. Pharmacokinetic parameters, e.g. absorption, biotransformation, can also be affected by the level of neuroticism or by anxiety, as demonstrated for diazepam, caffeine, paracetamol and theophylline. The absorption kinetics of diazepam and caffeine clearly differ between volunteers with high neuroticism scores and those with low neuroticism scores. Emotionally unstable volunteers absorbed the substances more quickly and more completely than emotionally stable volunteers. There were surprising differences in various immunological indices between dominant and submissive subjects. In dominant volunteers the immune system was more activated than in submissive volunteers. In the future, it will become increasingly necessary to obtain results for such target groups and to avoid generalized data, which may conceal the actual events. Differential clinical psycho-neuro-immunopharmacology may be an approach which is helpful in the development of “volunteer models” for clinical research in Phase I.Correspondence to:
Prof. Dr. F.P. Meyer; Institute of Clinical Pharmacology, Otto-von-Guericke
University Magdeburg, Leipziger Straße 44, D-39120 Magdeburg, Germany
Email: Frank-Peter.Meyer@medizin.uni-magdeburg.de

Abstract

O. Kirimli¹, S. Kalkan², S. Guneri¹, Y. Tuncok², B. Akdeniz¹, M. Ozdamar¹ and H. Guven²

¹Department of Cardiology, and ²Department of Pharmacology, Dokuz Eylul University School of Medicine, Izmir, Turkey
The effects of captopril on serum digoxin concentrations were studied in 8 patients with severe (NYHA Class IV) congestive heart failure. Serum digoxin concentrations were determined before and after the administration of captopril for 1 week in patients on chronic digoxin therapy. Each patient who was taking 0.25 mg of digoxin PO q.d., was administered 12.5 mg of captopril PO t.i.d. for 7 days. The peak serum concentration of digoxin (Cmax) before and after (on Days 0 and 7) captopril administration was 1.7 ± 0.2 ng/ml and 2.7 ± 0.2 ng/ml, the time to peak (tmax) was 2.4 ± 0.5 h and 1.3 ± 0.2 h, and the area under the 24-hour digoxin concentration-time curve (AUC0-24h) was 30.0 ± 1.5 ng×h/ml and 41.7 ± 3.4 ng×h/ml, respectively. While captopril caused a significant increase in peak serum concentration and the area under the digoxin concentration-time curve, it decreased the time to digoxin peak (p = 0.01, p = 0.04, p = 0.01, respectively). No patient developed evidence of digoxin toxicity. Concomitant administration of captopril with digoxin increases serum digoxin concentration in patients with severe congestive heart failure.Correspondence to:
Dr. H. Guven; Department of Pharmacology, Dokuz Eylul University School of Medicine, Balcova TR-35340 Izmir, Turkey
Email: hulya.guven@deu.edu.tr

Abstract

K. Haseroth¹, P. Löffler¹, C.P. Janson¹, S. Kropff², B.M.W. Schmidt¹, M. Feuring¹, M. Christ¹ and M. Wehling¹

¹Institute of Clinical Pharmacology, Faculty of Clinical Medicine Mannheim, University of Heidelberg, and ²SmithKline Beecham Pharma, Munich, Germany
Abstract. Modulation of autonomic activity is considered to be a prognostic marker in patients with cardiovascular disease. The aim of the present study was to evaluate the modulation of sympathovagal balance after single-dose administration of carvedilol using various autonomic tests as challenges of sympathovagal balance. We conducted a randomized double-blind, placebo-controlled study in 18 male volunteers and applied a crossover design. While heart rate variability (HRV) remained unchanged in 24-hour measurements, modulatory effects on sympathovagal balance were demonstrated in controlled autonomic maneuvers at expected maximal drug levels of carvedilol: time-dependent HRV parameters indicative of vagal tone were increased during controlled breathing (15 cycles/min) in the supine body position by carvedilol. The percentage of successive normal RR intervals > 50 ms (pNN50) was increased to 39.8 ± 5.1 vs. 32.7 ± 4.7% in the placebo group (p < 0.05), root mean square successive differences (rMSSD) to 81.5 ± 10.8 vs. 69.3 ± 9.1 ms (p < 0.05 vs. placebo). In contrast, carvedilol versus placebo significantly reduced time- and frequency-domain parameters after an active standing-up procedure. This included rMSSD (26.5 ± 2.8 ms vs. 34.9 ± 3.8 ms), pNN50 (6.9 ± 2.2% vs. 12.4 ± 2.5%), total power (4329 ± 592 ms2 vs. 6428 ± 1158 ms2), low frequency (1472 ± 179 ms2 vs. 2093 ± 284 ms2) and high frequency power (251 ± 42 ms2 vs. 353 ± 92 ms2) of heart rate variability. Apparently, the effects of even small doses of carvedilol, too low to induce effects detectable in the 24-hour analysis of HRV testing, can be detected on controlled maneuvers of autonomic because of their ability to modulate autonomic balance. Under conditions of vagal stimulation, a potentially beneficial augmentation of HRV parameters indicative for this component is induced by carvedilol, while under conditions of sympathetic activation, carvedilol effects seem opposite. Interpretation of the latter results, in particular, requires further investigation.Correspondence to:
Prof. Dr. M. Wehling; Institute of Clinical Pharmacology, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
Email: martin.wehling@kpha. ma.uni-heidelberg.de

Abstract

F.I. Mohammed and Y.A. Shafagoj

Department of Physiology and Biochemistry, Faculty of Medicine, University of Jordan, Amman, Jordan
Objective: The purpose of this study was to evaluate the effect of alum on human platelet aggregation. Methods: Platelet-rich plasma fractions were prepared from fresh blood drawn from a group of healthy male volunteers. Platelet aggregation was induced by various inducers. The percent aggregation was recorded in the absence and presence of various concentrations of alum. Results: Alum at concentrations less than 1.5 mg/ml inhibited platelet aggregation induced by collagen, epinephrine, ADP and thrombin in a dose-dependent manner. The IC50s were 0.668, 0.324, 0.250 and 0.191 mg/ml of alum, for collagen-, epinephrine-, ADP- and thrombin-induced platelet aggregation, respectively. In contrast, alum at concentrations up to 1.5 mg/ml did not inhibit ristocetin-induced platelet aggregation. Conclusion: Alum has an anti-platelet action and should be used cautiously in the treatment of intractable intravesical hemorrhage. Alum is a cheap anti-platelet drug that needs further investigation.Correspondence to:
Dr. F.I. Mohammed; Department of Physiology and Biochemistry, Faculty of Medicine, University of Jordan, Amman 11942, Jordan
Email: fmmed@ju.edu.jo

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Volume 39, No. 7/2001(July)