ABSTRACT
The authors discuss the results of application of melatonin in patients with hypertensive disease. Treatment with melatonin facilitated normalization of arterial pressure and cerebral hemodynamics at night time.
Subject(s)
Blood Pressure/drug effects , Cerebrovascular Circulation/drug effects , Hypertension , Melatonin , Blood Pressure Monitoring, Ambulatory/methods , Central Nervous System Depressants/administration & dosage , Central Nervous System Depressants/adverse effects , Circadian Rhythm/drug effects , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/metabolism , Hypertension/physiopathology , Male , Melatonin/administration & dosage , Melatonin/adverse effects , Middle Aged , Treatment OutcomeABSTRACT
During the sleep person is in the state of antiorthostasis, this state provokes vascular cerebral abnormalities (night cerebral hypervolemia). The nature of encephalon blood supply is changing in this horizontal state, in the result there is lowering of hydrostatic blood pressure, rise of the encephalon blood supply and more difficult venous outflow. 60 patients with essential hypertension (1-2 phases) at the age of 64.2 +/- 1.8 years which were in the state of slightly raised upper segment of the head and body during night sleep were examined. By the method of the cerebral venous hemocirculation defined. Conclusion. Cerebral arterial blood flow of examined patients has increased by 25-30% during the sleep, the changes of arterial and cerebral venous hemocirculation have attended hypervolemia. Being in the state of upper (by 10-15 degrees) head of the bed decreases blood redistribution and decreases the extension of cerebral blood circulation's acute abnormalities.
Subject(s)
Brain/blood supply , Cerebral Arteries/physiopathology , Cerebrovascular Circulation , Hypertension/therapy , Hypokinesia/therapy , Sleep , Aged , Blood Flow Velocity , Brain/physiopathology , Female , Humans , Hypertension/physiopathology , Hypokinesia/physiopathology , Male , Middle AgedABSTRACT
The marked analgesic efficacy of ketorolac in humans, relative to other nonsteroidal anti-inflammatory drugs (NSAIDs), has lead to speculation as to whether additional non-NSAID mechanism(s) contribute to its analgesic actions. To evaluate this possibility, we characterized (R,S)-ketorolac's pharmacological properties in vivo and in vitro using the nonselective cyclooxygenase (COX) inhibitors [indomethacin (INDO) and diclofenac sodium (DS)] as well as the selective COX-2 inhibitor, celecoxib, as references. The potency of racemic (R,S)-ketorolac was similar in tests of acetic acid-induced writhing, carrageenan-induced paw hyperalgesia, and carrageenan-induced edema formation in rats; ID50 values = 0.24, 0. 29, and 0.08 mg/kg, respectively. (R,S)-ketorolac's actions were stereospecific, with (S)-ketorolac possessing the biological activity of the racemate in the above tests. The analgesic potencies for (R,S)-, (S)-, and (R)-ketorolac, INDO, and DS were highly correlated with their anti-inflammatory potencies, suggesting a common mechanism. (R,S)-ketorolac was significantly more potent than INDO or DS in vivo. Neither difference in relative potency of COX inhibition for (R,S)-ketorolac over INDO and DS nor activity of (S)-ketorolac at a number of other enzymes, channels, or receptors could account for the differences in observed potency. The distribution coefficient for (R,S)-ketorolac was approximately 30-fold less than for DS or INDO, indicating that (R,S)-ketorolac is much less lipophilic than these NSAIDs. Therefore, the physicochemical and pharmacokinetics properties of (R,S)-ketorolac may optimize the concentrations of (S)-ketorolac at its biological target(s), resulting in greater efficacy and potency in vivo.
Subject(s)
Analgesics/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Tolmetin/analogs & derivatives , Acetic Acid , Animals , Brain/metabolism , Carrageenan , Cyclooxygenase 1 , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/pharmacology , Disease Models, Animal , Epoprostenol/analogs & derivatives , Isoenzymes/metabolism , Ketorolac , Male , Membrane Proteins , Prostaglandin-Endoperoxide Synthases/metabolism , Rats , Rats, Sprague-Dawley , Stereoisomerism , Tolmetin/administration & dosage , Tolmetin/metabolism , Tolmetin/pharmacologyABSTRACT
The authors give a concise characteristics of different types of the cochleovestibular syndromes. On the basis of a study concerning the effect of injectable Seduxen in 54 patients with vascular brain disorders (transient disorders of cerebral circulation, ischemic strokes, chronic vertebro-basillar insufficiency) and 3 patients with cochleo-vestibular syndromes of a non-vascular genesis the conclusion is made of the effectiveness of this preparation for arresting acute vestibular disorders of vascular etiology. The preparation exerts a normalizing multidirected action on the different links of the CNS and the vegetative nervous system.
