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Biomedical subjects

W Hetzel

Publications and source records attributed to W Hetzel.

At least 19 recordsLinked to original sources
PubMed1997

[Anticonvulsant treatment in old age--principles and differential indications].

When administering anticonvulsive drugs to the elderly, a number of peculiarities should be taken into consideration. Age-related changes in pharmacokinetics and drug interactions can make such treatment a complicated issue. Some of the side effects which hardly play a role among younger patients can lead to fatal consequences among the elderly. Both phenytoin (PHT), if submitted intravenously (but not in oral form), and carbamazepine (CBZ) may cause life-threatening cardiac arrhythmias. Valproate (VPA), otherwise well tolerated, seems to be less effective than CBZ and PHT in partial seizures. Cognitive dysfunction is a known side effect of barbiturates, but also seems to occur among the other drugs of first choice. In contrast to a widely held opinion, VPA, CBZ and PHT hardly differ in their effect on cognitive function if administered correctly.

Aged↗
PubMed1995

Co-induction of anaesthesia: the rationale.

Combination therapy with two or more different drugs, with the intention of reaching the same therapeutic goal, was heavily criticized for a long time. However, it is accepted today, especially when advantages over monotherapy can be shown. For the induction of anaesthesia or for long-term sedation in the intensive care unit, combination therapy may offer an improved effect profile, a more balanced ratio of desired versus adverse effects, an improved time-course of effect, simpler treatment requirements or lower costs. Midazolam and propofol have been investigated as potential partners for those two indications. The mechanism of action, pharmacokinetic properties, pharmacological effect, the way in which they interact at the receptor site, the differences in pharmaceutical formulations, the side-effect profiles and economic considerations were compared. Animal experiments and clinical pharmacology studies have shown that midazolam and propofol have synergy with other centrally active drugs. It could be expected that the relationship between desired effects and adverse effects could be improved by skilful use of the synergism between midazolam and propofol. Co-induction of anaesthesia and co-administration in long-term sedation can offer improvements in therapeutic situations compared with monotherapy. These improvements are in terms of a more suitable effect profile, a more favourable ratio of desirable effects to side-effects, optimization of the time-course of effects and reduced costs.

Anesthesia↗
PubMed1993

RIMA--a new concept in the treatment of depression with moclobemide.

Moclobemide, a specific reversible inhibitor of monoamine oxidase that shows a preference for the A isoenzyme, has been developed as a new antidepressive agent. Unlike earlier generation monoamine oxidase inhibitors, moclobemide is devoid of any clinically significant tyramine interaction, thus making dietary restrictions during therapy unnecessary. In comparative trials, moclobemide has been found to be superior to placebo and similar to imipramine, clomipramine, and amitriptyline in clinical efficacy. Long-term trials involving moclobemide therapy for up to one year have indicated that antidepressant efficacy can be maintained for this period. Tolerance is good and is significantly better than for tricyclic antidepressants. In addition, unlike the tricyclic antidepressants, overdoses of moclobemide do not appear to be life-threatening.

Benzamides↗
PubMed1992

Patients at risk of suicide and overdose.

Suicide is a complex and confusing subject. Although social factors may be important a clear relationship has been established between suicide and some medical conditions, notably depression, schizophrenia and alcohol dependence. Primary care physicians are in the "front line" as far as the recognition of suicidal risk is concerned. There is good evidence that many individuals who commit suicide have had recent contact with medical services. Those who have attempted suicide are at a much greater risk of subsequently completing the act than the general population. Poisoning by solids or liquids is a common method of committing suicide. Prescribed medication is often used. Antidepressants vary considerably in their toxicity in overdosage. Newer compounds, including moclobemide appear to be safer than older ones. There is some evidence that suicide rates can be influenced by changing the availability of lethal substances and methods. It is suggested the prescription of toxic antidepressants should be restricted or avoided in patients in whom the risk of suicide is high.

Adult↗
PubMed1992

Safety of moclobemide taken in overdose for attempted suicide.

Moclobemide is a reversible inhibitor of the monoamine oxidase type A. In clinical studies, more than 3900 patients have been treated with moclobemide for depression. Eighteen of these patients attempted suicide by overdosing moclobemide with or without other drugs. All patients recovered fully without leaving signs of cardio- or hepatotoxicity. Moclobemide can safely be prescribed for in- and out-patient treatment of depression.

Adult↗
PubMed1992

Serum angiotensin-converting enzyme activity and active renin plasma concentrations in insulin-dependent diabetes mellitus.

We report here the alterations of serum angiotensin-converting enzyme activity (S-ACE) and of active renin plasma concentrations (ARPC) in 41 insulin-dependent diabetes mellitus (IDDM) patients compared with those of 26 control subjects. The IDDM patients had S-ACE activity (54 +/- 16 I.E.) in the upper normal range (controls, 39 +/- 7). When the patients were subclassified according to their diabetic complications, a significant increase of S-ACE within the IDDM group compared to the controls was observed in patients with nephropathy (68 +/- 13, P less than 0.001) with persistent proteinuria and with retinopathy (63 +/- 14, P less than 0.001). A significant correlation was found between proteinuria and S-ACE (r = 0.98, P less than 0.001) and between retinopathy and S-ACE levels (r = 64, P less than 0.001). No correlation between blood pressure and S-ACE or between blood glucose and S-ACE was observed. The ARPC were within the normal range in the IDDM (21 +/- 9 ng/l) and in control (19 +/- 3) groups. No correlations between ARPC and blood pressure or blood glucose or the degree of diabetic complications were registered. These data show that S-ACE activity is elevated in IDDM patients with nephropathy-proteinuria and/or with retinopathy and the circulating renin may not represent the renal renin-angiotensin vascular system.

Adult↗
PubMed1992

RIMA: a safe concept in the treatment of depression with moclobemide.

Moclobemide--a new, safer antidepressant drug--is described and clinical studies are reviewed. Moclobemide represents a new class of drug, the so-called RIMA compounds--reversible inhibitors of MAO-A. Unlike classical monoamine oxidase (MAO) inhibitors, moclobemide is devoid of hepatotoxicity and has only a slight potentiating effect on the hypertensive action of tyramine; treatment does not require a tyramine-restricted diet. Studies comparing moclobemide with tricyclic antidepressants (TCAs) indicate that moclobemide is significantly better tolerated than TCAs and slightly less well tolerated than placebo.

Antidepressive Agents, Tricyclic↗
PubMed1991

[Polyneuropathy and fasciitis in eosinophilia-myalgia syndrome].

Eosinophilia-Myalgia-Syndrome (EMS), a newly recognized illness, was described first in October 1989, when it formed an epidemic in the USA and later also in Europe. In the meantime, ingestion of L-tryptophan containing products has been recognized to trigger this syndrome, but the pathophysiological basics are still subject to speculation. Often starting with a flu-like period, the disease is dominated by dermatologic (fasciitis) and neurologic (neuropathy, myopathy) symptoms in the subsequent stages. Reporting on an own case and reviewing the literature, clinicopathological aspects and the problems of treatment are discussed. In contrast with the majority of published cases, which showed predominance of axonal damage, our patient displayed the clinical and electro-physiologic characteristics of demyelinating neuropathy.

Depressive Disorder↗
PubMed1990

Moclobemide (Ro 11-1163) safety in depressed patients.

Safety aspects were compared in 2203 patients given moclobemide and 1214 who received other antidepressants or placebo. A total of 2294 adverse events were reported by patients on moclobemide, mainly subjective symptoms (28.6%). Adverse events such as dry mouth, tremor, sweating, dizziness and constipation occurred much more frequently among 681 patients treated with various tricyclic antidepressants than in the 694 moclobemide patients with whom they were compared. Among 271 placebo-treated patients there were 287 adverse events, compared with 386 events in the 285 moclobemide patients in the same studies. Hypertensive episodes or food-drug interactions were reported by 19 patients on moclobemide and 5 on other antidepressants, but in only 2 of the former was ingestion of cheese a possible cause of headache. The assessment of tolerance on moclobemide was essentially the same as for placebo. Of the 1401 moclobemide patients in the electronic database, only 3.2% stopped treatment prematurely because of poor tolerance; the rates were higher for tranylcypromine, nomifensine, desipramine, clomipramine, amitriptyline and imipramine. During treatment, 6 patients attempted suicide with moclobemide alone (950-2000 mg) or together with imipramine (300 mg and 1200 mg). None of the intoxications was life-threatening.

Antidepressive Agents↗
PubMed1990

Pharmacology of Dormicum (midazolam) and Anexate (flumazenil).

Midazolam and flumazenil have some characteristics in common which make them suitable partners as benzodiazepine (BZD) agonist and antagonist. After intravenous (i.v.) administration, both drugs are rapidly distributed into similar distribution volumes, from which they are cleared with a comparable short elimination half-life (t1/2 beta) in the range of 1 h (flumazenil) to 3 h (midazolam). Both drugs undergo hepatic metabolisation with a relatively high hepatic extraction ratio of around 0.3 for midazolam and 0.6 for flumazenil. The metabolisation of midazolam and flumazenil may equally be affected by considerable loss of active liver cells or by temporarily reduced hepatic blood flow. In such a case, elimination of both drugs may be prolonged in the same way. Flumazenil has only an inactive metabolite. The main active alpha-hydroxy-metabolite of midazolam does not contribute much to the activity of midazolam after parenteral administration. Its potency is lower than that of midazolam and its shorter elimination half-life (0.8 h) does not prolong the activity of the parent drug. As indicated by the therapeutic index, both drugs have a very high safety margin, which is considerably higher than that of thiopentone or propofol. Only low doses of both drugs are necessary to produce initial effects. Increasing doses intensify the drug activity and a ceiling effect is observed after maximal doses of midazolam and flumazenil. The onset of effect immediately follows the diffusion of the substances into the CNS and can be observed within the first minutes following flumazenil or midazolam administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Clinical pharmacology of flumazenil.

(1) Flumazenil is a highly specific benzodiazepine (BZ) antagonist. It exerts its effect by competitive interaction at the BZ receptor site. (ii) Flumazenil antagonizes all central BZ effects irrespective of its contiguity to the BZ administration. (iii) The pharmacological effect of flumazenil depends upon the number of BZ receptors that can be occupied by flumazenil according to the mass-action law. Receptor occupancy is determined by the affinity of the BZ for the receptor and the free BZ concentration near the receptor. (iv) The minimal effective dose of flumazenil is 0.2 mg. After extreme BZ overdose 1 mg may be needed. (v) The optimal dosing strategy starts with an initial dose of flumazenil 0.2 mg i.v. The administration of further low doses of 0.1 mg at 1-min intervals allows the interruption of the injection of flumazenil exactly at the stage of vigilance that is most convenient for the patient. (vi) The duration of effect depends upon the type and dose of the administered BZ, the dose of flumazenil, and the time interval between flumazenil and the BZ administration. (vii) The therapeutic or safety index is above 3000, which means that a 3000 times overdose is still tolerated.

Animals↗
PubMed1987

[Better acceptance of measures for induction of anesthesia after rectal premedication with midazolam in children. Comparison of results of an open and placebo-controlled study].

The rectal administration of midazolam for premedication of children before induction of anesthesia by mask was investigated in two clinical studies. In 62 children aged between 2 and 10 years, midazolam was given by open design at various dosages (0.15 mg.kg-1, 0.25 mg.kg-1, 0.30 mg.kg-1, 0.35 mg.kg-1, 0.40 mg.kg-1) to evaluate the most effective dose for optimal acceptance of the mask and gas mixture. An additional 40 children between 3 and 9 years received 0.2 mg midazolam.kg-1 body weight or placebo in a double-blind design to estimate the lower limit of efficacy of midazolam. All children were classified as ASA I and had to undergo a surgical procedure. Within the two studies the children were not different with respect to their general data, age, weight, and sex. In both studies more boys than girls were included. Parameters of efficacy were the degree of sedation before and at 10, 20, and 30 min after midazolam as well as acceptance of the mask and the gas mixture at induction of anesthesia. In all groups, including placebo, a sedative and tranquilizing effect of the premedication was found. The rectal administration of 0.35-0.4 mg midazolam.kg-1 is most suitable for the preoperative medication of children between 2 and 10 years. Due to the degree of sedation and the relief of anxiety toward the surroundings and the operation, the induction of anesthesia is optimally accepted by the child. In contrast, the effect of a dose around 0.2 mg midazolam.kg-1 body weight is not much different from that of placebo and is not sufficient for effective premedication.

Administration, Rectal↗
PubMed1980

Post-mortem modifications of the ependyma of the lateral ventricular wall.

The ependymal lining of the lateral ventricles of the brain of rats, rabbits, and man was investigated at several times after death. In contrast to control material that was fixed by the aldehyde perfusing method, the following post-mortem (p.m.) changes were found: (1) Cytoplasmic protrusions of ependymal cells appear 15 min p.m. They are present up to several hours after death. (2) The formation of these protrusions causes the tufts of cilia to clump together and later to become integrated within the ependymal cell. This may simulate an unciliated surface. (3) Small porelike holes, which are present 15 min p.m. in the ependymal cell membrane, enlarge and in later stages produce a meshwork of fibers instead of a closed ependymal lining. (4) TEM observation shows that ependymal cells are separated from each other very soon after death by intercellular gaps. Cell junctions between ependymal cells resist separation over a longer p.m. period. In animal or human material that is fixed at any time after death, such modifications have to be considered very critically. In human p.m. autopsy material they are mostly the expression of a p.m. alteration.

Animals↗
PubMed1978

Ependyma and ependymal protrusions of the lateral ventricles of the rabbit brain.

The ependymal lining of the lateral ventricles of the rabbit brain was studied by means of scanning (SEM) and transmission electron microscopy (TEM). There exist cells devoid of cilia in the anterior horn over the region of the caudate nucleus, in the inferior horn over the hippocampus and on the opposite side over cortical regions. On the surface of some of these ependymal cells, accumulations of cytoplasmic folds and globules can be found. They bulge at different height over the ependymal cells. Clots of these cell particles are tied off from the cell, coming to lie as globules either on or between the cilia of the ependyma. TEM reveals that these protrusions are cell debris consisting of different sized vesicles, cell organelles, tubuli and cell filaments. They originate from the ependymal layer but may reach down to subependymal cells. Multivesicular protrusions into the ventricular lumen are also observed. Possible causes of these protrusions are discussed; they are likely to be related to the age of the animals. On the ependyma of the caudate nucleus cilia, microvilli, microblebs and supraependymal neuronal cell processes are distributed unevenly over the surface. Within regions where cilia predominate there are cells which are tightly covered with microvilli. A certain direction of the course of the supraependymal neuronal fibers could not be found.

Animals↗