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Biomedical subjects

M Heeringa

Publications and source records attributed to M Heeringa.

16 recordsLinked to original sources

[Severe parkinsonism due to metoclopramide in a patient with polypharmacy].

A 73-year-old woman, with tuberculosis of the large intestine, developed nausea as a side effect of the antituberculosis drugs. The nausea was treated with metoclopramide. Subsequently she developed severe medication-induced parkinsonism. As her symptoms initially mimicked a depressive disorder, drug-induced parkinsonism was only considered at a later stage. Due to drug-induced impaired function of the liver and kidney the patient had received a toxic dose of metoclopramide. Treatment with biperiden and withdrawal of the metoclopramide resulted in a reduction of the complaints within 3 months, after which the anti-tuberculosis medication could be reintroduced. Adjusting the dose of metoclopramide could possibly have prevented this severe side effect.

Aged↗

[Side effects of sildenafil: findings from two years practical experience].

Sildenafil has been registered for the treatment of erectile dysfunction since 1998. World wide a large number of patients were reported, dying of acute heart disease after using sildenafil. Therefore the patient instruction text was adapted. Simultaneous use of sildenafil and nitrates is contraindicated because of serious decrease of the blood pressure. The use of sildenafil can lead to physical stress in patients with a history of heart disease and a treadmill test assessment is advisable. In two years 38 adverse reactions were seen in 25 Dutch patients. The Dutch reports (three cardiovascular deaths since the introduction) also show the dilemmas in the assessment of the safety of sildenafil: is it the underlying disease or is it the drug that causes death? Further research into the adverse reactions has to be done, therefore reporting suspected side effects of sildenafil is important.

Adverse Drug Reaction Reporting Systems↗

[Delirium due to increase in clozapine level during an inflammatory reaction].

Between January 1999 and May 2000, the Netherlands Pharmacovigilance Foundation LAREB received five reports of patients with clozapine intoxication attributed to inflammation. The reports all concerned men with schizophrenia, aged 63, 54, 41, 45 en 42 years. The occurrence of increased clozapine levels during inflammation, and normalisation after recovery, strongly suggest a causal relationship. No other possible explanations were found. A three to five-fold increase occurred in most instances, but one patient experienced a ten-fold increase compared with the basal levels of clozapine. Three of the patients developed a delirium as an intoxication symptom, probably due to anticholinergic effects on the central nervous system. In case of an inflammatory reaction in patients on clozapine treatment, the physician should be aware of the possibility of clozapine intoxication and delirium. Measuring clozapine levels during infection and dosing based on these levels can minimise the adverse effects of clozapine intoxication.

Adult↗

Agranulocytosis and granulocytopenia associated with quetiapine.

OBJECTIVE: Quetiapine is a recently introduced atypical antipsychotic. Although adverse effects are mainly mild, more serious infrequent adverse effects including leucopenia are mentioned. METHOD: We describe three case-reports concerning haematological adverse effects of quetiapine. RESULTS: Quetiapine was associated with leucopenia in two patients and clinically apparent agranulocytosis in one patient. CONCLUSION: Although a definite association has not been proven, clinicians should be aware of the possibility of agranulocytosis while using quetiapine. Further post-marketing surveys are required.

Adult↗

Combined 5-HT2/D2 receptor blockade inhibits the firing rate of SNR neurons in the rat brain.

1. The aim of the present study was to evaluate the contribution of serotonin (5-HT) and dopamine (DA) receptor antagonism to the distinct inhibitory effects of the atypical antipsychotics clozapine and risperidone on SNR neurons, we have shown previously. 2. Utilizing extracellular recordings in the SNR in chloral hydrate anaesthetized rats, raclopride, a selective DA D2/D3 receptor antagonist and LY 53857, a 5-HT2A:2c receptor antagonist were studied separately and in combination for their effects on the firing rate of the SNR neurons. 3. Both raclopride and LY 53857 induced a slight but significant increase in the firing rate of the SNR neurons in a limited dose range. 4. Upon pretreatment with a single dose of raclopride, LY 53857 induced a dose-dependent inhibitory effect on the firing rate of the SNR neurons. 5. Concurrent 5-HT2 and moderate DA D2 receptor antagonism can mimic the in vivo effects of the atypical antipsychotics clozapine and risperidone on the firing rate of SNR neurons.

Animals↗

[Lengthening of the QT-interval in a newborn treated with cisapride].

In a 7-week-old female infant a prolonged QTc interval, up to 485 ms, was measured and attributed to the use of the prokinetic agent cisapride. The girl was born at 32 1/7 weeks of gestational age, started to use cisapride (0.8 mg/kg/day) at the age of 7 weeks because of gastro-oesophageal reflux. After cessation of cisapride therapy, the QTc interval returned to normal. A normal QTc interval had also been observed before the use of cisapride. Because of the risk of QTc prolongation and possibly cardiac arrhythmias during the use of cisapride by newborn infants, electrocardiography should be performed before and during cisapride therapy; they should also be checked for possible risk factors like electrolyte disturbances and congenital QTc prolongation. Prudence is called for in case of patients with pre-existing disorders which could result in QT prolongation like electrolyte disturbances, congenital QT prolongation, and the concomitant use of medication associated with QT prolongation.

Cisapride↗

Elevated plasma levels of clozapine after concomitant use of fluvoxamine.

Selective serotonin reuptake inhibitors can be added to clozapine therapy in order to treat remaining negative symptoms and obsessive compulsive symptoms. The present case report describes a 44-year-old man exhibiting extremely elevated plasma levels of clozapine after the addition of fluvoxamine, up to 4160 mcg/l. The elevated plasma levels of clozapine, which were discovered 6 months after the SSRI was added, is likely to be caused by a drug-drug interaction. Clozapine is a substrate of CYP 1A2 and is predominantly metabolised in the liver. Of the SSRIs, fluvoxamine is one of the most potent inhibitors of the isoenzyme CYP 1A2. This case serves to emphasise the need for continuous attention to drug-drug interactions, especially when they might be easily overlooked due to the lack of clear symptoms.

Adult↗

[Convulsions during prophylactic use of mefloquine].

In 1996 and 1997 the Dutch Pharmacovigilance Foundation LAREB received 6 reports of patients with convulsions that were attributed to prophylactic use of mefloquine. Five patients had no neurological history; one patient had a history of epilepsy but had not had any convulsion during the preceding 5-year period. The convulsions took place 1 to 23 days after start of the treatment with mefloquine. Because of the convulsions, the treatment was discontinued. The 4 patients with known follow-up showed full recovery with regard to the convulsions. The practising physician should be aware of the possible occurrence of rare neuropsychiatric adverse events like convulsions during the prophylactic use of mefloquine.

Adult↗

[Major psychiatric side effects of interferon alpha-2b].

The Netherlands Pharmacovigilance Foundation Lareb and the Drug Safety Unit of the Inspectorate for Health Care in 1997 received 6 reports of serious psychiatric symptoms during the use of interferon alpha-2b. Of these patients, three men aged 42, 49 and 62 years and three women aged 31, 40 and 33 years, two had had psychic symptoms before. Depression or psychosis developed 12-24 weeks after the start of the use of interferon alpha-2b with 3-10 million IU per week subcutaneously because of chronic hepatitis B or C. After cessation of the medication, four patients recovered after a few days or weeks; the course of one patient was unknown, one patient had committed suicide. Knowledge of these psychiatric adverse drug reactions to interferon alpha-2b can contribute to early recognition by the physician and timely treatment of the symptoms.

Adult↗

[Severe tardive dyskinesia during treatment with risperidone and fluoxetine].

A 26-year-old man with schizophrenia, disorganised type, and depression, developed severe tardive dyskinesia during treatment with risperidone and fluoxetine. In view of the course of the symptoms and the findings in the neurological analysis a causal relation with the use of the these second-generation psychopharmaca was probable. These new-generation psychopharmaca are supposed to have fewer adverse events. Nevertheless, as is illustrated in this case, prescription is not without risk. Especially when using a combination of psychopharmaca, side effects must be monitored carefully.

Adult↗

Differential effect of systemic administration of bromocriptine and L-dopa on the release of acetylcholine from striatum of intact and 6-OHDA-treated rats.

A presumed balance between striatal dopaminergic and cholinergic systems forms a major theoretical framework for the development of new agents for the treatment of Parkinson's disease. We therefore studied the effect of two drugs currently used as anti-parkinsonian agents, bromocriptine (BROMO) and L-beta-3,4-dihydroxyphenylalanine (L-DOPA), on the release of striatal acetylcholine (ACh) in intact and 6-hydroxy-dopamine-treated rats using in vivo microdialysis. Lesioned rats with a > 90% tissue depletion of striatal dopamine (DA) had a significantly higher output of striatal ACh than unlesioned rats (88 fmol/min vs. 52 fmol/min; 0.3 mumol/l neostigmine in perfusate). BROMO (4 mg/kg) inhibited the output of striatal ACh in both groups. Whereas the lowest dose of L-DOPA (50 mg/kg) potently stimulated ACh output in lesioned rats, unlesioned rats were significantly less responsive. A higher dose of L-DOPA (100 mg/kg) stimulated ACh output to the same extent in both groups. At the highest dose tested, L-DOPA (200 mg/kg) given to intact rats did not further increase striatal ACh output. Thus, BROMO decreases whereas L-DOPA increases striatal ACh release after systemic application. Therapeutic as well as side effects of L-DOPA may therefore be mediated by neurochemical alterations that are more complex than previously thought.

Acetylcholine↗

Behavioral and biochemical effects of early postnatal cholinergic lesion in the hippocampus.

The effects of early postnatal (PD 8) intracerebroventricular injection of ethylcholine mustard aziridinium ion (AF64A) on development of open-field and cognitive behaviors and cholinergic markers in several brain areas were examined in the rat. The cholinotoxin was bilaterally administered in a dose range of 0.25 to 2.0 nmol. In the open-field tests, the cholinergic lesion caused a dose-dependent increase in activity at 20 days of age, while it resulted in lengthened latency to initiate exploration and decreased rearing activity at adulthood. Hole-board spatial learning was severely inhibited in adult age. The biochemical activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the hippocampus was markedly decreased in a dose-dependent manner, but was unchanged in the neocortex and striatum. Histochemical staining of AChE-positive fibers revealed a severe cholinergic denervation of the granular and pyramidal cell layers of the hippocampus. The results showed that a selective cholinergic deafferentation of the hippocampus at a critical stage of development leads to long-lasting abnormal open-field and spatial learning behaviors.

Acetylcholinesterase↗