الفهرس 
Introduction History and Basic ChemistryOnly 14 pages are availabe for public view
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Abstract
Early intervention with antipsychotic medications in treatment of psychotic disorders increases the likelihood of favorable long-term course, however the pharmacologic management is complicated by high rate of adverse effects including sexual and metabolic, atypical antipsychotics have demonstrated efficacy in the treatment of psychotic disorders with fewer extra pyramidal side effects than typical antipsychotics. However, other side effects have been described,their use has been associated with weight gain, exacerbation of previously well controlled diabetes, and onset type II diabetes mellitus, although a recent report failed to demonstrate an association between weight gain and development of hyperglycemia.
The therapeutic actions of conventional antipsychotic drugs are due to blockade of D2 receptors specifically in the mesolimbic dopamine pathway. This has the effect of reducing the hyperactivity in this pathway that is postulated to cause the positive symptoms of psychosis. All conventional antipsychotics reduced positive psychotic symptoms about equally in schizophrenic patients who were studied in large multicenter trials. That is not to say that one individual patient might not occasionally respond better to one conventional antipsychotic agent than to another, but there is no consistent difference in antipsychotic efficacy among the conventional antipsychotic agents.
Unfortunately, it is not possible to block just these D2 receptors in the mesolimbic dopamine (DA) pathway with conventional antipsychotics because these drugs are delivered throughout the entire brain after oral ingestion. Thus, conventional antipsychotics will seek out every D2 receptor throughout the brain and block them all. This leads to a high ”cost of doing business” in order to get the mesolimbic D2 receptors blocked.
The development of the second-generation antipsychoticsadded a profound effect on antipsychotic prescribing.In a few short years, they became not onlythe agents of choice but also greatly expanded the useof antipsychotics. Off-label use in mood, anxiety, sleep, personality, and impulse control disorders raced aheadof approved new indications by regulators. Across thelifespan, more people today are prescribed antipsychoticsthan at any time in the past. Giventhis, it comes as no surprise that, in 2008, antipsychoticsbecame the leading revenue generators fortheir manufacturers, more so than lipid regulators, proton pump inhibitors, and antidepressants.
Over time, as clinical and research experience withthe second-generation antipsychotics accumulated,their negative effects on metabolic and cardiovascularindicators became increasingly obvious. This is particularlyunsettling considering that patients for whomantipsychotics are primarily indicated tend to be atmuch higher risk for obesity, dyslipidemia, hypertension,hyperglycemia, diabetes, and major adverse cardiovascularevents such as myocardial infarction,stroke, and sudden cardiac death, and have a markedlyreduced expected lifespan, all independent of drugtherapy.
A positive effect of these new concerns is the enhancedattention and interest given to the overall health of peoplewith chronic psychiatric disorders and to the qualityof their healthcare. Quality of care has generallybeen found to be below that of the general population,especially for people with schizophrenia and substanceuse disorders. This is a result of several factors related tomental illness, such as greater reluctance to seek oraccept medical care and advice, and to service access and delivery.
Before second-generation antipsychotics were developed,monitoring patients taking antipsychotics requiredthe skills of a neurologist more so than an internist. Thefocus ofmonitoringwas in the detection of parkinsonism,akathisia, dystonia, and tardive dyskinesia.Several scaleswere developed to help clinicians reliably detect andmeasure these drug-induced movement disorders andwere standards in the training of psychiatrists and care ofpatients (e.g. the Simpson Angus Scale for extrapyramidalsymptoms, the Abnormal Involuntary MovementsScale [AIMS] for tardive dyskinesia, and the comprehensiveExtraPyramidal Symptom Rating Scale). Otheradverse effect measurement instruments, such as theUKU side-effect rating scale, were developed to assessmore comprehensively the side effects of older antipsychotics.
This study was designedto answer the following questions:
10. Is there difference in occurrence and severity of metabolic disturbance between first and second generation antipsychotics?
11. Is there difference among each brand in each group in occurrence and severity of metabolic disturbance?
12. Is there difference between in the occurrence and severity of sexual performance disturbance?
13. Is there any difference among any individual drug within each group in the occurrence and severity of sexual performance disturbance?
14. Do antipsychotics sexual adverse events differ in the affection of sexual cycle?
15. Does the presence of family history of diabetes mellitus affect the metabolic adverse events of antipsychotics?
16. Does gender affect the occurrence or severity of metabolic adverse effects?
17. Does age affect the occurrence or severity of adverse effects?
18. What is the relation between change in the BMI and occurrence and severity of metabolic adverse effects?
The current study investigates the prevalence of metabolic and sexual side effects, 80 patients are suffering from psychotic disorders and treated with antipsychotic medications in two groups according to the family of the antipsychotics:
Group I: Patient receiving first generation antipsychotics; three brands used (Haloperidol, Trifluoperazine and Flupenthixol).
Group II: Patients receiving second generation antipsychotics; three brands used (Olanzapine, Risperidone and Quetiapine).
Assessment of the metabolic profile High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Cholesterol and Triglycerides (TG), and fasting blood sugar will be done initially before introduction of antipsychotics, after six seeks and after twelve weeks from the initial assessment. Beside the assessment of body weight and Body Mass Index (BMI).
The disturbance in sexual functioning will be assessed with the Changes in Sexual Functioning Questionnaire (CSFQ).
The tools were carefully selected to serve for the purpose of the study, this included:
• Clinical Psychiatric assessment tools including General Health Questionnaire,Structured Clinical Interview for DSM-IV (SCID I).
• The Changes in Sexual Functioning Questionnaire (CSFQ) was developed with specific versions for females and males to assess sexual functioning in all the domains of the sexual response cycle.
• Weight and height were taken for the calculation of the body mass index.
• The laboratory assessment was done on a twelve hours fasting blood sample, five millilitre of blood was collected by vacuum aspirator introduced to the antecubital vein, blood was analysed for High density lipoprotein (HDL), Low density lipoprotein (LDL), Cholesterol and Triglycerides (TG), and fasting blood sugar. These levels were determined by enzymatic analysis procedures applying the BoehringerMannheirn standard analytical packs, Hitachi 714 automated chemistry analyser.
All data gathered were recorded, tabulated and transferred on Statistical Package for Social Sciences (SPSS) Version 19, using personal computer and the suitable statistical parameters were used.
The demographic distribution of the 2 groups of the study was matching with no statistical difference of age and gender or the presence of family history of diabetes mellitus.
In the head to head comparison between the 6 individual antipsychotic drugs used in the study concerning the metabolic indicators:
• LDL: all drugs showed significant changes from visit to visit.
• HDL:Changes were statistically significant from visit to visit for the haloperidol and flupenthixol and non-significant for Trifluoperazine, in group two changes were significant for risperidone and quetiapine and non-significant for olanzapine
• Cholesterol: Changes were statistically significant for haloperidol from the initial visit to visit 2 but non-significant from visit 2 to visit 3, and were statistically significant for the rest of the drugs from visit to visit.
• TG: Changes were statistically significant for all the drugs used from visit to visit.
• Body Weight: Changes were statistically significant for all the drugs used from visit to visit.
• BMI: Changes were statistically significant except for Flupenthixol they were non-significant.
In the comparison between both groups regarding metabolic side effect profile: no statistical significance could be found between both groups except:
1. For visit 3 in the comparison regarding total serum cholesterol level where the second generation antipsychotics had a significant higher level.
2. The comparison regarding FBS comparison was significant through the 3 visits.
3. The comparison regarding Body Weight comparison was significant through the 3 visits.
4. The comparison regarding BMI comparison was significant through the 3 visits.
In the comparison within each group regarding gender for the metabolic side effect profile: no statistical significance could be found between both genders except for the weight gain, where males gained higher weight in the first generation antipsychotics group, while female gained higher weight in the second generation antipsychotics group, but weight gain did not anyway affect the BMI.
In the comparison within each group regarding age where each group divide into 2 age groups below and above 30 years old for the metabolic side effect profile: no statistical significance could be found between both age subgroup in both first and second antipsychotics.
We got the same results when we divided the groups according to the presence or absence of family history of DM.
The CSFQ we used formed of 14 questions specified for males and females each question has five answers with one score for the least answer and five for the highest.
The CSFQ is divides into 5 dimensions each of them testing different phases of sexual cycle as follows:
Pleasure: item 1
Desire/Frequency: items 2 + 3
Desire/Interest: items 4 + 5 + 6
Arousal/Erection: items 7 + 8 + 9
Orgasm/Ejaculation: items 11 + 12 + 13
Worsening in the sexual function on the head to head comparison between first and second generation antipsychotics in regard to total score of CSFQ was significant from visit to visit to all the studied drugs.
For the dimension of pleasure worsening in the sexual function as well and changes were significant from visit to visit for all drugs except for Flupenthixol it was non-significant after 6 weeks but significant after 12 weeks from the initial visit.
For the dimension of Desire/Frequency significant changes were seen from visit to visit for the drugs used in the study.
For the dimension of Desire/Interest significant changes were seen from visit to visit for the drugs used in the study.
For the dimension of Arousal/Erectionsignificant changes were seen from visit to visit for the drugs used in the study.
For the dimension of Orgasm/Ejaculation significant changes were seen from visit to visit for the drugs used in the study.