Pshycotropic Drugs: A Persuader for Metabolic Syndromes

 

Parvathi K J, Ramalingam Kameswaran R*, Sambathkumar R

Department of Pharmacy Practice, J.K.K. Nattraja College of Pharmacy,

Kumarapalayam-638183 Tamil Nadu, India.

 

ABSTRACT:

 

 

INTRODUCTION:

Schizophrenia is a dominant civil health issue that customarily affects in the interim or during adolescence. Antipsychotic medications is an imperative integral of the treatment of this disarray and research theorize that these drugs may be even spare constructive if given during the pioneer phase of illness.¹ Patients with schizophrenia and bipolar disorders who are taking second generation antipsychotics they are customarily contemplated allied meticulously with heightened peril of metabolic syndrome, an inaugural peril factor for cardiovascular disease.^1-5

 

Heightened statistics of reports incidence to diabetes, ketoacidosis, hyperglycemia and dysregulation in patients employ with second generation antipsychotics have lifted mega crop about a possible guild between these medications.^5-6 Second generation antipsychotics (SGA) have testify to scanty leverage over first generation antipsychotics (FGA) in terms of positive, negative, cognitive and affective symptoms and a lower proclivity if extrapyramidal symptoms. In contempt of these under in admissible leverage, SGA have been associated with causing and exacerbating metabolic syndromes such as obesity, diabetes, and hyperlipidemia.⁷

 

Substantial evidence from a variety of human populations, including some recent confirmatory evidence in treated psychiatric patients, indicates that increased adiposity is associated with a variety of psychotropic drugs.

 

Methods:

A total of 100 PubMed indexed articles were collected which established a clear-cut idea about psychotropic drugs and metabolic syndromes. From that by analysed excluded 20 articles which did not provide enough information for the work. On total data analysis and by checking the criteria for the study finally 80 articles were taken. The datas from all the 80 articles were read out and gathered and finally structured into my study form.

 

Metabolic syndrome:

Metabolic syndrome is a prevalent and serious disease that has been recognized recently. The term metabolic syndrome refers to a syndrome consisting of central obesity as indicated by excessive visceral fat, plasma lipid abnormalities, glucose dysregulation and high blood pressure.

 

National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) ATP III/WHO defines metabolic syndrome as:

·       Obesity: High waist circumference

·       BMI > 30

·       Dyslipidemia

·       Hypertension

·       High fasting glucose (> 110mg/dL)

 

Schizophrenics- the peril population:

Schizophrenics are those sensitive clusters for metabolic syndrome because of the following factors:

·       Smoking

·       Obesity

·       Diet higher in fat lower in fiber

·       Sedentary lifestyle

·       Increased prevalence of diabetes

·       Proneness to central obesity⁴

 

Atypical antipsychotics and metabolic syndrome accord:

Major causes of atypical antipsychotics are:

·       Most of the antipsychotics can induce weight gain

·       Insulin resistance-diabetes

·       Worsening lipid profile which predispose to metabolic syndrome.^8-9

Table No:1: American Diabetologists Association (ADA) unanimity on Antipsychotic Drugs and Obesity and Diabetes

 

Dims mechanisms and pharmacogenomics:

The evolution of anitipsychotic DIMS is portray by two phases. In the first phase, susceptible patients experience significant weight gain during a short period of time, usually within 6 to 8 weeks. Development of an independent hyperglycemia along with weight gain can be found in patients at the same time.¹⁰In most of the cases hyperglycemia can be reversed after the drug withdrawal. It is interesting that a high proportion of HIV infected patients receiving protease inhibitors, as part of the highly active antiretroviral therapy (HAART) regimen, also develop DIMS.¹¹

 

Using a complement DNA (cDNA) as a neuroarray, composed of genes which are related to brain function, especially used to examine tissue from the cerebellum and the prefrontal cortex of patients and of matched controls (drug-naive and drug-treated subjects with schizophrenia vs. healthy subjects). The genes for drug-treated patients included cytochrome coxidase, subunit 4, β1-noncatalytic subunit of adenosine monophosphate (AMP)-activated protein kinase, ionotropic glutamate receptor AMPA2, ubiquitin thiolesterase, P-450 oxidoreductase, and guanine nucleotide binding protein-like 1, among others.¹²

 

The clone faction, using microarray shielding of lymphoctyes for gene expression discrepancy in a populous schizophrenia pedigree, found possible contributions to AAP-induced weight gain and metabolic syndrome by neuropeptide Y receptor, corticotropin-releasing hormone, phospholipase A2, protein kinase C, and cytosolic malate nicotinamide adenine dinucleotide (NAD) dehydrogenase.¹²

 

 

Table No: 2: American Diabetologists Association (ADA) unanimity on Antipsychotic Drugs and Obesity and Diabetes: Monitoring Protocol

 

 

Olanzapine and weight gain:

Olanzapine induced weight gain can be elucidated by the ensuing mechanisms:

I.      Improved functioning-less self-neglect, improved eating habits.

II.    Increase in appetite-carbohydrate craving, sedation and decreased motor activity.

III. Altered adipose tissue-metabolism, fat composition and distribution.

IV. Effect on neurotransmitters - 5HT, H1, DA, Alpha 1 blockade.

V.   Increase in leptin and prolactin levels.

 

The investiture of leptin secretion also has significant bounce on bodyweight gain in patients treated with atypical antipsychotics.¹³ The molecular mechanisms responsible for antipsychotic drug-induced weight gain have been hypothesized to be due to interactions of antipsychotic drugs with several neurotransmitter receptors, including 5-HT (2A) and 5-HT (2C) serotonin receptors, H(1)-histamine receptors, alpha (1)- and alpha (2)-adrenergic receptors, and m3-muscarinic receptors.

 

Antipsychotics and Glucose Abnormalities:

Glucose transporter functions are affected by antipsychotics drugs. The drugs which are structurally and functionally similar accomplish comparably higher intracellular concentrations may bind to, and hamper with the function of, the glucose transporter proteins. Ardizzona et al studies suggest that the drugs may block glucose accumulation directly at the level of the glucose transporter (GLUT) protein in cells derived from both peripheral and brain tissue.¹⁴ Margaret et al study on Hyperglycaemic Clamp Assessment of Insulin secretory response found that olanzapine or risperidone directly not impair pancreatic beta cell function. ¹⁵However, Bettinger et al,¹⁶ hypothesized that serotonin (5-HT1A) antagonism may decrease the responsiveness of the pancreatic beta-cells.

 

The dysregulated blood glucose could be due to central blood glucose regulation by the hypothalamus and the hypothalamic dopamine antagonism by some antipsychotics.¹⁷

 

According to the studies the changes in the levels of FBS by various antipsychotics at base line after 6 weeks can be illustrated as:

 

Table No:3: Antidepressants And Weight Gain

 

Figure No: 1: Antipsychotics drugs and FBS levels at baseline and after 12 weeks

 

Monitoring Parameters of Antipsychotics:

The monitoring parameters of antipsychotics include:

I.      Personal and family history of diabetes and cardiovascular disease (obesity, dyslipidemia, hypertesion)

II.    BMI (weight and height)

III. Waist circumference

IV. Blood pressure

V.   FBS

VI. Lipid Profile

 

Endocrine Dysregulation in Depression:

The central drivers of the stress hormone system are corticotrophin-releasing hormone and arginine vasopressin they extort corticotrophin into the periphery and thereby activate the corticosteroid release from the adrenal cortex. Persistent hyper secretion of stress hormones can arouse severe clinical conditions and pannier an adequate adaptation to stress. These hormones also act as neuromodulators in the brain, affecting higher mental functions including emotion, cognition, and behaviour.¹⁸

 

Depression is a stress-related disorder, the extorted chronic stress corticosteroids impair corticosteroid-receptor signaling, which is an important risk factor in interpretation of an individual supine to stress-related disorders.¹⁹ Glucocorticoid activated glucocorticoid receptors can be opposed by mineralocorticoid receptors which are rapidly activated and terminated by humoral responses.²⁰ Open label and double-blind studies by several groups have indicated that corticosteroid synthesis inhibitors may be efficacious or of adjunctive value in some patients with depression, including those refractory to other agents; however, there is a need for more controlled studies.²¹

 

The prevalence of depressive symptoms in hypothyroidism is near to 50% whereas in hyperthyroidism it reaches up to 28% of the cases.^22-23 Clinical depression occurs in more than 40% of people suffering from hypothyroidism.^24-25 Absolutely, low TSH levels in healthy individuals might be connected to an elevated peril of depression.²⁶ Vice versa, patients suffering from depression display higher than expected rates of subclinical hypothyroidism.

 

Depression and cardiovascular disease:

A close linked relationship exist between depression and cardiovascular disease,²⁷ the cardiac disease that interconnects depression includes myocardial infraction, congestive heart failure, and isolated systolic hypertension leading to increased mortality and morbidity in patients.

 

Altered blood pressure levels, increased heart rate, altered autonomic baseline function have observed in dysphoric patients. Due to the elevation in systemic arterial pressure, higher circulatory levels of norepinephrine, higher sympathetic tone, increased systemic vascular resistance.²⁷

 

CONCLUSION:

High mental distress persons have a high prevalence of health risk behaviours. Optimal care for medical conditions are not satisfactory in mental distress patients. The burden of their medical conditions must curb their full recovery from their psychiatric illness. Health Outcomes are not part of recovery goals or mental health system design.

 

Metabolic side effects can be caused by atypical antipsychotics. Proper monitoring of metabolic parameters should be strictly followed. Life style management, drugs for controlling weight gain can be considered. There is a need for double blind studies, of long duration, with oral glucose tolerance test, other advanced tests and also to include children as group as there are reports to have a high liability for children to experience antipsychotic induced weight gain and associated metabolic disturbances.²⁷

 

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Accepted on 15.12.2019           © RJPT All right reserved

Research J. Pharm. and Tech 2020; 13(6): 2695-2698.