تعتبر قرحة المعدة والإثنى عشر من أكثر أمراض الجهاز الهضمي شيوعاً. ورغم معرفة معظم العوامل المسببة للقرحة مثل الادوية المضادة للالتهابات الغيرستيرويدية وبكتيريا مثل helicobacter pylori والكحول والتدخين وغيرها ورغم توفر الأدوية المختلفة لعلاجها الاأن هناك الكثير من الحالات التي لاتستجيب بفعالية لهذه الأدوية وذلك لعدم المعرفة التامة ببعض العوامل المؤثرة على حدوثها. من المعروف أن ايونات الكالسيوم تلعب دوراً مهما في تنظيم إفراز الحامض المعدي، وتعتبر هذه الايونات مسؤلة عن تطور حدوث الأنواع المختلفة للقرحة، كما يلعب تدفق الكالسيوم دوراً مهما في إفراز وتحفيز الخلايا mammalian oxyntic cells , التأثير الذي يمكن منعه من قبل حاصرات الكالسيوم calcium channel blockers وعلاوة على ذلك تمارس حاصرات الكالسيوم تأثيرا مانعا لتحفيز إفراز الحامض المعدي عن طريق الهستامين , والجاسترين لذا يمكن أن يكون لحاصرات قناة الكالسيوم تأثير وقائي ضد القرح المعوية وذلك بتخفيض تدفق الكالسيوم مما يؤثر على إفراز الحامض في المعدة. ولهذا هدفت هذه الدراسة لتقييم تأثيرات احد أنواع حاصرات قنوات الكالسيوم الفيرباميل عند إعطاءه مع مضاد الهيستامين الرانتيدين على قرحة المعدة المستحدثة في الفئران بواسطة الكحول الإيثيلي (الايتانول). وقد أظهرت نتائجنا أن مضاد الكالسيوم، الفيراباميل، الذي يستخدم عادة لعلاج أمراض القلب والأوعية الدموية بما في ذلك ارتفاع ضغط الدم والذبحة الصدرية، وعدم انتظام ضربات القلب يملك خصائص مضادة للقرحه حيث أشارت النتائج إلى انخفاض في قرح المعدة وإفراز الحامض المعدي و ذلك عندما يعطى بمفرده أو جنبا إلى جنب مع مضادات الهيستامين الرانتيدين، وبالتالي فأنه من الممكن أن يلعب الفيراباميل دور مفيد في المرضى الذين يعانون من أعراض القلب والأوعية الدموية، وكذلك يتناولون الكحول. ويمكن الجمع بين استخدام الفيراباميل و الرانيتيدين بشكل فعال في القرحة المعوية الحادة ومتلازمة زولينجر إليسون، وربما يكون مفيداً للغاية في المرضى الذين يعانون من القرحة الهضمية، وامراض القلب والأوعية الدموية، قد تكون هناك الحاجه إلي إضافة جرعة صغيره من الرانتيدين لأن الفيراباميل وحده لن يكون كافياً للسيطرة على القرحه المعديه. وهناك حاجة إلى مزيد من الدراسات لتحديد الآلية الدقيقة للتأثير الواقي من القرحه للفيراباميل بما في ذلك تقييم تأثيره على إطلاق مخاطية المعدة للبروستاجلاندين، وتدفق الدم في مخاطية المعده، وعلى اطلاق وسائط الالتهاب الأخرى وبالإضافة إلى ذلك هناك الحاجة إلى المزيد من الدراسات السريرية على الإنسان لتأكيد هذه الفعالية.
زينب رمضان الشريف (2012)

Paracetamol is one of the most widely used drug as antipyretic and analgesic for mild to moderate pain. Currently, paracetamol is the first-line choice for pain management and antipyresis. Ion channels are pore-forming proteins that allow the flow of ions across membranes and involved in many cellular processes; drugs acting on ion channels have long been used for the treatment of many diseases. Objective: To estimate the effect of voltage gated ion channel blockers on analgesic activity of Paracetamol and explore the interaction between ion channel blockers and paracetamol on pain behaviour. Materials and Methods: Male albino mice were used. The central antinociceptive activity was determined by hot plate test and formalin test (Phase I; neuropathic pain). Antiinflammatory activity was determined by formalin test (Phase II). Intraperitoneal injection was adopted. Five groups of mice were used. Group 1; control group (1% T80), group 2; treated with (200mg/kg) paracetamol, group 3; treated with different drugs of ion channel blockers, group 4; received standard drugs, Aspirin (200mg/kg) for formalin test (phase II) or tramadol (5mg/kg) for hot plate test and formalin test (phase I), group 5; received combined treatment of ion channel blockers and paracetamol. Results: Pain produced by noxious stimuli (heat and formalin) was significantly reduced by acute administration of paracetamol. Inflammation pain produced by formalin injection was significantly decreased by acute administration of paracetamol. Acute administration of nifedipine showed significant decrease in nociception and inflammation pain. Combined treatment of nifedipine and paracetamol produced antinociceptive and anti-inflammatory activity but less than the additive effect. Verapamil has no analgesic effect in the two models, and did not change the affect of paracetamol analgesic activity when administered together. Phenytoin produces significant decrease in nociceptive pain using hot plate but not in formalin test (Phase I), and produce significant decrease in inflammatory pain (Phase II). The combined treatment of phenytoin and paracetamol showed analgesic activity less than the additive effect. 4-Aminopyridine produces significant antinociceptive and anti-inflammatory activity. The combined administration of 4-aminopyridine and paracetamol showed analgesic activity, which is less than the additive effect using formalin test, while paracetamol analgesic activity is potentiated by 4-aminopyridine using hot plate test. Conclusion: Paracetamol has antinociception and anti-inflammatory activity on pain model used (Hot plate test and Formalin test). Ion channel blockers produce antinociception and anti-inflammatory activity. Verapamil has no effect on nociception or inflammation pain and no effect on paracetamol analgesic activity. Nifedipine, phenytoin and 4-aminopyridine interact with paracetamol producing less additive analgesic effect, except 4-aminopyridine in thermal stimuli (Hot plate) is more sensitive compared to chemical stimuli (formalin test – phase I), where potentiates paracetamol action.
هناء مدحت الزقلعي (2014)

Abstract Benzodiazepines are frequently prescribed as anxiolytics, sedatives hypnotics, and muscle relaxants as well as anticonvulsants. Non-steroidal anti-inflammatory drugs (NSAIDs) are also the most widely used for their anti-inflammatory, analgesic and antipyretic activities. Because of the chronic nature of epilepsy, NSAIDs may be used with benzodiazepines in patients with epilepsy. Therefore, there’s a probability of an interaction of NSAIDs and benzodiazepines in clinical practice. In order to study such interactions experimentally, an animal model was used. Thus, this thesis was aimed to explore pharmacological interactions between selective and non selective NSAIDs and diazepam anticonvulsant effect. Convulsion was induced in male albino mice by picrotoxin in two different doses (6 and 8 mg/kg), NSAIDs were used according to selectivity to cyclooxygenase enzyme (COX): Aspirin at 10 mg/kg (COX-1 selective inhibitor) and Aspirin at 100 and 200 mg/kg, diclofenac 10 and 20 mg/kg (non selective COX inhibitors) and celecoxib 20 mg/kg (COX-2 selective inhibitor). Diazepam at 1 and 2 mg/kg were chosen as low doses and parameters of convulsive behavior of picrotoxin deviation. psy, NSAIDs may be used with benzodiazepines in patients with epilepsy. Therefore, there’s a probability of an interaction of NSAIDs and benzodiazepines in clinical practice. In order to study such interactions experimentally, an animal model was used. Thus, this thesis was aimed to explore pharmacological interactions between selective and non selective NSAIDs and diazepam anticonvulsant effect. Convulsion was induced in male albino mice by picrotoxin in two different doses (6 and 8 mg/kg), NSAIDs were used according to selectivity to cyclooxygenase enzyme (COX): Aspirin at 10 mg/kg (COX-1 selective inhibitor) and Aspirin at 100 and 200 mg/kg, diclofenac 10 and 20 mg/kg (non selective COX inhibitors) and celecoxib 20 mg/kg (COX-2 selective inhibitor). Diazepam at 1 and 2 mg/kg were chosen as low doses and parameters of convulsive behavior of picrotoxin were observed in this thesis: onset time, episode frequency and death occurrence within post-injection of picrotoxin for 24 hrs. Aspirin in low dose (10 mg/kg) showed protection against death to about 50%. This protection which seems to be partially effective as anticonvulsant agent, however, higher dose of Aspirin (100 mg/kg) did not produce any significant change against convulsing in mice, Aspirin 200 mg/kg showed highly significant reduction of episode frequency (P < 0.001) and decreased percent of death. Furthermore, Aspirin 200 mg/kg in combination with diazepam has potentiated the effect of diazepam to complete protection against convulsion induced by picrotoxin. With respect to diclofenac, diclofenac pretreated-mice did not show any significant effect at 10 and 20 mg/kg with picrotoxin but in combination with diazepam showed significant potentiated effect of diazepam. Moreover, COX-2 inhibitor (celecoxib) alone delayed onset of convulsion without significant influence against the control but significantly decreased episodes and percent of death. Also in combination of celecoxib and diazepam, a highly potentiation of the effect and almost complete protection against convulsion behavior were noted (P < 0.001). Thus, it can be concluded that the studied NSAIDs have anticonvulsant behavior-like activity alone and in combination with diazepam. The most profound effect of anticonvulsant activity was showed in low episodes and mortality rate. In combination with diazepam, NSAIDs have more positive potential role in diazepam anticonvulsant effect. The present findings may also suggest that NSAIDs most likely COX-2 selective inhibitor is more potentiated diazepam’s anticonvulsant activity than COX-1 selective and non-selective inhibitors and such interaction could be more likely to be pharmacodynmic type.
نجمية محمد الزواوي (2014)