P-MD021. Drug induced extrapyramidal syndrome in a young girl diagnosed to be SLE

SummaryTwo patients developed an extrapyramidal syndrome after therapy with lithium carbonate. Although the clinical features of this syndrome were indistinguishable from those of drug-induced parkinsonism, it was made worse by the anti-parkinsonian drug, orphenadrine. These findings were reproduced later under laboratory conditions when extrapyramidal symptoms and physiological tremor were recorded before and after challenge doses of orphenadrine. This unwanted effect of lithium carbonate may be explained by selective blockade of dopamine receptors.

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Cigarette smoking: Effects on treatment efficacy and drug induced extrapyramidal syndrome in schizophrenic patients

Biological Psychiatry ◽

10.1016/s0006-3223(97)87591-9 ◽

1997 ◽

Vol 42 (1) ◽

pp. 170S

Author(s):

M. Krsmanović ◽

Č.D. Miljević ◽

S. Kecojević ◽

C. Cmobarić ◽

M. Jašović-Gašić

Keyword(s):

Cigarette Smoking ◽

Treatment Efficacy ◽

Drug Induced ◽

Extrapyramidal Syndrome ◽

Schizophrenic Patients

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Pharmacogenetics of chlorpromazine and its role in the development of antipsychotic-induced parkinsonism

Personalized Psychiatry and Neurology ◽

10.52667/2712-9179-2021-1-1-11-17 ◽

2021 ◽

Vol 1 (1) ◽

pp. 11-17

Author(s):

E. E. Vaiman ◽

M. A. Novitsky ◽

R. F. Nasyrova

Keyword(s):

Basal Ganglia ◽

Psychotic Disorders ◽

Motor Disorders ◽

Dopaminergic Receptors ◽

Drug Reactions ◽

Single Nucleotide Variants ◽

Drug Induced ◽

Single Nucleotide ◽

Extrapyramidal Syndrome ◽

Neurological System

Antipsychotics (AP) is a group of psychotropic drugs for the treatment of mental disorders, in particular schizophrenia. In the mid-1950s, the first AP was synthesized (known as chlorpromazine (CPZ)). This drug has revolutionized the treatment of psychotic disorders. This drug, in addition to the antipsychotic effect, caused severe adverse drug reactions in patients, in particular from the neurological system, such as AP-induced extrapyramidal syndrome (EPS) — chlorpromazine-in-duced parkinsonism (CPZ-IP). CPZ-IP characterized by the occurrence of motor disorders. CPZ-IP is as a result of damage to the basal ganglia and subcortical-thalamic connections. Drug-induced EPS is subdivided into primary and secondary. Among the primary EPS, drug-IP is the most common (the leading form of secondary parkinsonism). Pharmacogenetic markers of CPZ safety are being actively studied. Some pharmacogenetic markers of therapy safety have been established: single nucleotide variants/polymorphisms of candidate genes for dopaminergic receptors D2 and D3 (DRD2 (rs1799732 (-141C Ins/Del)), DRD3 (rs6280 (Ser9Gly)), laforine phosphatase (EPM2A (rs1415744 (C/T)).

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One patient with schizophrenia showed reduced drug-induced extrapyramidal symptoms as a result of an alternative regimen of treatment with paliperidone 3 and 6 mg every other day

SAGE Open Medical Case Reports ◽

10.1177/2050313x17742836 ◽

2017 ◽

Vol 5 ◽

pp. 2050313X1774283 ◽

Cited By ~ 1

Author(s):

Hidenobu Suzuki ◽

Hiroyuki Hibino ◽

Yuichi Inoue ◽

Hideo Matsumoto ◽

Katsunaka Mikami

Keyword(s):

Adverse Effects ◽

Scale Score ◽

Clinical Symptoms ◽

Involuntary Movement ◽

Maintenance Phase ◽

Extrapyramidal Symptoms ◽

Drug Induced ◽

Extrapyramidal Syndrome ◽

Abnormal Involuntary Movement Scale ◽

Alternative Regimen

Background: Schizophrenia is a chronic disease that requires long-term management with antipsychotics. Antipsychotic drugs are given by tapering their dose, extending the dosing interval, and so on, as part of a treatment strategy to minimize the adverse effects while at the same time maintaining efficacy. Methods: We report the case of one patient with schizophrenia in whom the clinical symptoms were alleviated after treatment with 6 mg paliperidone. However, the patient developed extrapyramidal syndrome, for which 3 and 6 mg paliperidone were administered alternately every other day. Extrapyramidal syndrome was assessed using the Drug-Induced Extrapyramidal Symptoms Scale, Abnormal Involuntary Movement Scale, or Barnes Akathisia Scale. Results: There was improvement in Drug-Induced Extrapyramidal Symptoms Scale score and Abnormal Involuntary Movement Scale score. However, there was almost no change in the Positive and Negative Syndrome Scale total score, positive score, negative score, or general score. Conclusion: The results indicate the possibility of lessened adverse effects as a result of an alternative regimen of treatment with paliperidone 3 and 6 mg every other day in the maintenance phase.

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Beneficial effects of metformin on haloperidol-induced motor deficits in rats. A behavioral assessment

Acta Marisiensis - Seria Medica ◽

10.2478/amma-2021-0017 ◽

2021 ◽

Vol 67 (2) ◽

pp. 115-121

Author(s):

George Jîtcă ◽

Zsolt Gáll ◽

Camil E Vari ◽

Bianca E Ősz ◽

Amelia Tero-Vescan ◽

...

Keyword(s):

Open Field ◽

Motor Coordination ◽

Behavioral Assessment ◽

Motor Deficit ◽

Motor Deficits ◽

Drug Induced ◽

Reduced Haloperidol ◽

Extrapyramidal Syndrome ◽

Beneficial Effects ◽

Anxiety Behavior

Abstract Objective: One of the most common side effects of haloperidol is the extrapyramidal syndrome, resulting from inhibition of nigrostriatal dopaminergic circuits and mitochondrial dysfunction due to structural similarities to pyridinium derivative, MPP+ that induce oxidative stress. In exchange, the use of metformin appears to enhance neurogenesis, energy metabolism, and oxidative status, so these properties can be speculated in the context of drug-induced pseudoparkinsonism by haloperidol. Methods: To assess motor coordination and activity, rodents were divided into four groups: CTR (n = 10) - animals that received distilled water, METF (n = 10) - animals that received metformin 500 mg / kgbw, HAL (n = 10) - animals that received haloperidol 2mg / kgbw, HALMETF (n = 10) - haloperidol 2mg / kgbw and metformin 500 mg / kgbw. The treatment was administered for 34 days at the same time by gastric gavage, during which time behavioral tests, rotarod (days 7, 14, 21, 28), catalepsy (day 30), open field (day 32) and novel object recognition (day 34) were performed. Results: The monitored parameters, showed significant differences between the groups of interest (HAL and HALMETF respectively), so that the administration of metformin at the beginning of treatment reduces the cataleptic behavior. The HALMETF group shows an attenuation of the motor deficit during the rotarod test and the freezing period from the Open Field test, is diminished. Conclusions: Metformin treatment has a beneficial effect in haloperidol-treated rats, demonstrated by decreased cataleptic behavior, improved motor performance and reduced haloperidol-induced anxiety behavior.

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The factor structure of extrapyramidal symptoms evaluated using the DIEPSS in patients with schizophrenia: results from the 2016 REAP AP-4 study

10.21203/rs.3.rs-266833/v1 ◽

2021 ◽

Author(s):

Chika Kubota ◽

Toshiya Inada ◽

Shih-Ku Lin ◽

Ajit Avasthi ◽

Kok Yoon Chee ◽

...

Keyword(s):

Factor Analysis ◽

Confirmatory Factor Analysis ◽

Factor Structure ◽

Clinical Psychiatry ◽

Extrapyramidal Symptoms ◽

Muscle Rigidity ◽

Drug Induced ◽

Extrapyramidal Syndrome ◽

Confirmatory Factor ◽

Dopaminergic Mechanisms

Abstract Drug-induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug-induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The participants were 1,478 patients with a diagnosis of schizophrenia whose EPS was assessed using the DIEPSS in India, Indonesia, Japan, Malaysia, and Taiwan in the 2016 REAP AP-4 study. The records of the participants were randomly divided into two subgroups: the first for exploratory factor analysis of the eight DIEPSS items and the second for confirmatory factor analysis. The factor analysis identified three factors: F1 (sialorrhea, akathisia, dystonia, and dyskinesia), F2 (gait and bradykinesia), and F3 (muscle rigidity and tremor). The present results suggest that the eight individual items of the DIEPSS could be composed of three different mechanisms: central dopaminergic mechanisms with the pathophysiology other than acute parkinsonism (F1), acute parkinsonism observed during action (F2), and acute parkinsonism observed at rest (F3).

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Early Development of Drug-Induced Hepatic Necrosis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066942 ◽

1971 ◽

Vol 29 ◽

pp. 576-577

Author(s):

F. G. Zaki ◽

E. Detzi ◽

C. H. Keysser

Keyword(s):

Early Development ◽

Hepatic Necrosis ◽

Screening Tests ◽

Dense Matrix ◽

Sprague Dawley ◽

Electron Microscopic ◽

Drug Induced ◽

Hepatocellular Damage ◽

Sprague Dawley Rats ◽

Microscopic Studies

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.

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Effect of piperacillin on morphology and viability of gram-negative bacteria

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100111203 ◽

1984 ◽

Vol 42 ◽

pp. 218-219

Author(s):

R. H. Liss

Keyword(s):

Inhibitory Concentration ◽

Cytoplasmic Membrane ◽

Drug Binding ◽

Gram Negative Bacteria ◽

Bacterial Cells ◽

Drug Induced ◽

Penicillin Binding Proteins ◽

Lactam Antibiotic ◽

Drug Free ◽

Tube Dilution

Piperacillip (PIP) is b-[D(-)-α-(4-ethy1-2,3-dioxo-l-piperzinylcar-bonylamino)-α-phenylacetamido]-penicillanate. The broad spectrum semisynthetic β-lactam antibiotic is believed to effect bactericidal activity through its affinity for penicillin-binding proteins (PBPs), enzymes on the bacterial cytoplasmic membrane that control elongation and septation during cell growth and division. The purpose of this study was to correlate penetration and binding of 14C-PIP in bacterial cells with drug-induced lethal changes assessed by microscopic, microbiologic and biochemical methods.The bacteria used were clinical isolates of Escherichia coli and Pseudomonas aeruginosa (Figure 1). Sensitivity to the drug was determined by serial tube dilution in Trypticase Soy Broth (BBL) at an inoculum of 104 organisms/ml; the minimum inhibitory concentration of piperacillin for both bacteria was 1 μg/ml. To assess drug binding to PBPs, the bacteria were incubated with 14C-PIP (5 μg/0.09 μCi/ml); controls, in drug-free medium.

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Drug Induced Changes in Cell Organelles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100299 ◽

1968 ◽

Vol 26 ◽

pp. 110-111

Author(s):

Sarah A. Luse

Keyword(s):

Clinical Medicine ◽

Cell Organelles ◽

Riboflavin Deficiency ◽

Drug Induced ◽

New Era ◽

Health And Disease ◽

In The Beginning ◽

Cellular Pathology ◽

Induced Changes ◽

The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

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Acetaminophen: Macula densa hypersecretory activity by induced hepatotoxicity

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010012895x ◽

1987 ◽

Vol 45 ◽

pp. 934-935

Author(s):

S.S. Poolsawat ◽

C.A. Huerta ◽

S.TY. Lae ◽

G.A. Miranda

Keyword(s):

Cell Proliferation ◽

Liver Function ◽

Chronic Inflammation ◽

Foam Cell ◽

Term Effect ◽

Short Term ◽

Drug Induced ◽

Experimental Induction ◽

Tissue Alterations ◽

Toxic Responses

Introduction. Experimental induction of altered histology by chemical toxins is of particular importance if its outcome resembles histopathological phenomena. Hepatotoxic drugs and chemicals are agents that can be converted by the liver into various metabolites which consequently evoke toxic responses. Very often, these drugs are intentionally administered to resolve an illness unrelated to liver function. Because of hepatic detoxification, the resulting metabolites are suggested to be integrated into the macromolecular processes of liver function and cause an array of cellular and tissue alterations, such as increased cytoplasmic lysis, centrilobular and localized necroses, chronic inflammation and “foam cell” proliferation of the hepatic sinusoids (1-4).Most experimentally drug-induced toxicity studies have concentrated primarily on the hepatic response, frequently overlooking other physiological phenomena which are directly related to liver function. Categorically, many studies have been short-term effect investigations which seldom have followed up the complications to other tissues and organs when the liver has failed to function normally.

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