The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

The roles of histamine and its receptor ligands in central nervous system disorders: An update

Revisiting the role of neurotransmitters in epilepsy: An updated review

Cardiovascular disease (CVD) is a growing burden across the world. In Asia and the Middle East, in particular, CVD is among the most prevalent and debilitating diseases. Dyslipidemia is an important factor in the development of atherosclerosis and associated cardiovascular events, and so effective management strategies are critical to reducing overall cardiovascular risk. Multiple dyslipidemia guidelines have been developed by international bodies such as the European Society of Cardiology/European Atherosclerosis Society and the American College of Cardiology/American Heart Association, which all have similarities in practice recommendations for the optimal management of dyslipidemia. However, they differ in certain aspects including pharmacological treatment, lifestyle modification and the target levels used for low-density lipoprotein cholesterol. The evidence behind these guidelines is generally based on data from Western populations, and their applicability to people in Asia and the Middle East is largely untested. As a result, practitioners within Asia and the Middle East continue to rely on international evidence despite population differences in lipid phenotypes and CVD risk factors. An expert panel was convened to review the international guidelines commonly used in Asia and the Middle East and determine their applicability to clinical practice in the region, with specific recommendations, or considerations, provided where current guideline recommendations differ from local practice. Herein, we describe the heterogeneous approaches and application of current guidelines used to manage dyslipidemia in Asia and the Middle East. We provide consensus management recommendations to cover different patient scenarios, including primary prevention, elderly, chronic kidney disease, type 2 diabetes, documented CVD, acute coronary syndromes and family history of ischemic heart disease. Moreover, we advocate for countries within the Asian and Middle East regions to continue to develop guidelines that are appropriate for the local population.

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Expert opinion on the applicability of dyslipidemia guidelines in Asia and the Middle East

Recent developments on target tracking problems: A review

Cardiovascular disease (CVD) constitutes one of the major causes of deaths and disabilities, globally claiming 17.3 million lives a year. Incidence of CVD is expected to rise to 25 million by 2030, and Saudi Arabia, already witnessing a rapid rise in CVDs, is no exception. Statins are the drugs of choice in established CVDs. In the recent past, evidence was increasingly suggesting benefits in primary prevention. But over the last decade Saudi Arabia has a witnessed significant rise in CVD-related deaths. Smoking, high-fat, low-fiber dietary intake, lack of exercise, sedentary life, high blood cholesterol and glucose levels were reported as frequent CVD-risk factors among Saudis, who may therefore be considered for primary prevention with statin. The prevalence of dyslipidemia, in particular, indicates that treatment should be directed at reducing the disorder with lipid-modifying agents and therapeutic lifestyle changes.

The recent American College of Cardiology (ACC)/American Heart Association (AHA) guidelines has reported lowering the low-density lipoprotein cholesterol (LDL-C) target levels, prescribed by the 2011 European Society of Cardiology (ESC)/the European Atherosclerosis Society (EAS). The new ACC/AHA guidelines have overemphasized the use of statin while ignoring lipid targets, and have recommended primary prevention with moderate-intensity statin to individuals with diabetes aged 40–75 years and with LDL-C 70–189 mg/dL. Treatment with statin was based on estimated 10-year atherosclerotic-CVD (ASCVD) risk in individuals aged 40–75 years with LDL-C 70 to 189 mg/dL and without clinical ASCVD or diabetes. Adoption of the recent ACC/AHA guidelines will lead to inclusion of a large population for primary prevention with statins, and would cause over treatment to some who actually would not need statin therapy but instead should have been recommended lifestyle modifications. Furthermore, adoption of this guideline may potentially increase the incidences of statin intolerance and side-effects. On the other hand, the most widely used lipid management guideline, the 2011 ESC/EAC guidelines, targets lipid levels at different stages of disease activity before recommending statins. Hence, the 2011 ESC/EAC still offers a holistic and pragmatic approach to treating lipid abnormalities in CVD. Therefore, it is the 2011 ESC/EAC guidelines, and not the recent ACC/AHA guidelines, that should be adopted to draw guidance on primary prevention of CVD in Saudi Arabia.

Primary prevention with statins in cardiovascular diseases: A Saudi Arabian perspective.

Introduction: Methanol ingestion is an uncommon form of poisoning that can cause severe metabolic disturbances, blindness, permanent neurologic dysfunction and death. While methanol itself may be harmless, it converts, in vivo, to highly toxic formic acid. Methanol intoxication clinically manifests as ocular toxicity. The present study investigated the cardiovascular effects of methanol. Materials and Methods: On the day of the experiment, Wistar rats were anesthetized with urethane. The femoral artery on one side was exposed, and a polyethylene catheter was inserted into the artery for recording arterial blood pressure (ABP). The catheter was attached to a pressure transducer (Statham - P23D). Systolic blood pressure (BP), mean ABP, and heart rate were recorded on a power-lab data acquisition system with a computerized analysis program. Rats were administered with different dilutions (9.5%, 19.0%, 28.5%, 38.0%, 47.5%, 57.0%, 66.5%, 76%) of methanol (95% v/v, i.v.). Results: Of all dilutions of methanol, 66.5% dilution showed maximum decrease of diastolic BP from 124.64 ± 5.39 to 62.30 ± 11.90 mmHg; 76.0% dilution showed maximum decrease of systolic BP from 165.70 ± 5.57 to 112.11 ± 12.0 mmHg, and mean ABP from 160.61 ± 12.45 to 86.14 ± 4.11 mmHg. The heart rate increased (from 250 beats/s to near about 275 beats/s) following administration of methanol dilution from 19.0% till 76.0%. Conclusion: The present study is consistent with previous studies suggesting that methanol ingestion leads to severe hypotension as observed from decrease in diastolic BP, systolic BP, and mean ABP. However, severe increase of heart rate suggests activation of a compensatory mechanism to offset hypotension that eventually leads to death in methanol poisoning. Hence, this study emphasizes the need to monitor all the hemodynamic parameters in accidental methanol poisoning.

Effects of methanol in blood pressure and heart rate in the rat.

Background Animal models based on N-methyl-d-aspartate receptor blockade have been extensively used for schizophrenia. Ketamine and MK-801 produce behaviors related to schizophrenia and exacerbated symptoms in patients with schizophrenia, which led to the use of PCP (phencyclidine)- and MK-801 (dizocilpine)-treated animals as models for schizophrenia. Methods The study investigated the effect of subchronic dosing (once daily, 7 days) of histamine H3 receptor (H3R) antagonists, ciproxifan (CPX) (3 mg/kg, i.p.), and clobenpropit (CBP) (15 mg/kg, i.p.) on MK-801 (0.2 mg/kg, i.p.)-induced locomotor activity and also measured dopamine and histamine levels in rat's brain homogenates. The study also included clozapine (CLZ) (3.0 mg/kg, i.p.) and chlorpromazine (CPZ) (3.0 mg/kg, i.p.), the atypical and typical antipsychotic, respectively. Results Atypical and typical antipsychotic was used to serve as clinically relevant reference agents to compare the effects of the H3R antagonists. MK-801 significantly increased horizontal locomotor activity, which was reduced with CPX and CBP. MK-801-induced locomotor hyperactivity attenuated by CPX and CBP was comparable to CLZ and CPZ. MK-801 raised striatal dopamine level, which was reduced in rats pretreated with CPX and CBP. CPZ also significantly lowered striatal dopamine levels, although the decrease was less robust compared to CLZ, CPX, and CBP. MK-801 increased histamine content although to a lesser degree. Subchronic treatment with CPX and CBP exhibited further increased histamine levels in the hypothalamus compared to MK-801 treatment alone. Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.), counteracted the effect of CPX and CBP. Conclusions The present study shows the positive effects of CPX and CBP on MK-801-induced schizophrenia-like behaviors in rodents.

Histamine H3 receptor antagonists display antischizophrenic activities in rats treated with MK-801.

Implementation Of underwater target tracking techniques for Gaussian and non-Gaussian environments

The present study was designed to investigate the role of serotonin and other neurotransmitters namely dopamine (DA), histamine, nor-epinephrine (NE), glutamate, and γ-aminobutyric acid (GABA) in the 6-Hz-induced psychomotor seizures in Swiss albino mice. Parachlorophenylalanine (PCPA, 300 mg/kg/day, i.p for 3 days)-treated mice were given 6-Hz stimulation. Sodium valproate (SVP) (200 mg/kg/day, p.o for 3 days) was used as a reference antiepileptic drug. The behavioral changes induced by 6 Hz including increased rearing and grooming, Straub's tail, behavioral arrest, stun position were amplified by PCPA. The 6-Hz-induced seizures were accompanied by reduced brain 5-HT, DA, NE, histamine, GABA, and enhanced glutamate levels. PCPA facilitated further reduction of endogenous 5-HT and DA levels but not NE, histamine, GABA, and glutamate levels. Pre- and post-treatment with SVP protected the mice from 6-Hz seizures and attenuated PCPA-induced changes in the levels of 5-HT and DA in the mice brain suggesting the protective effect of SVP in the pharmacoresistant model of epilepsy involving mainly serotonergic mechanism. However, the study also suggests modulation of other neurotransmitters both in 6-Hz psychomotor seizures and in the action of SVP against such seizures.

Kausar Jahan

Papers

Primary prevention with statins in cardiovascular diseases: A Saudi Arabian perspective.

Effects of methanol in blood pressure and heart rate in the rat.

Histamine H3 receptor antagonists display antischizophrenic activities in rats treated with MK-801.

Implementation Of underwater target tracking techniques for Gaussian and non-Gaussian environments

Parachlorophenylalanine-induced 5-HT depletion alters behavioral and brain neurotransmitters levels in 6-Hz psychomotor seizure model in mice.