Comparison of onset of action of Intrathecal Clonidine vs Intrathecal Fentanyl as an adjuvant with hyperbaric Bupivacaine and Bupivacaine alone under spinal anesthesia for lower limb orthopedic surgeries

Background: Adjuvants are added to a local anesthetic solution to prolong the duration of analgesia. There is a paucity of studies comparing the onset of action of adjuvants like Clonidine and Fentanyl. In this study, the time of onset of action of intrathecal clonidine and intrathecal fentanyl as adjuvants to bupivacaine and bupivacaine alone were compared in the subarachnoid block for lower limb orthopedic surgeries. Materials and Methods: 90 adult patients posted for orthopedic surgery of the lower limb were divided into three equal groups of 30 each. Group A being the control group was given hyperbaric Bupivacaine(3ml) +0.5ml of Normal saline, Group B was given Intrathecal hyperbaric Bupivacaine (3 ml) +30 ?g Clonidine and Group C was given Intrathecal hyperbaric Bupivacaine (3 ml) + Fentanyl 25 ?g. The primary objective was to compare the time of onset of block and duration of analgesia. The secondary outcomes were the duration of sensory and motor block, duration of analgesia, hemodynamic parameters, and side effects. Results: The time of onset of the sensory blockade was 4.83 ± 0.64, 1.72 ± 1.47, and 3.4 ± 1.43 mins in groups A, B, and C respectively. The time of onset of the motor blockade as estimated by the time to reach level 2 on the Bromage scale, was 6.07 ± 0.55, 2.38 ± 1.32, and 5.06 ± 1.28 mins in groups A, B, and C respectively. The duration of postoperative analgesia was prolonged in the Clonidine group compared to the Fentanyl group. Conclusion: The study reveals that the time of onset of action of sensory and motor block was faster and the duration of analgesia was prolonged with adjuvants like Clonidine when compared to Fentanyl when added to Bupivacaine.

Preparation and physicochemical characterization of meloxicam orally fast disintegration tablet using its solid dispersion

ABSTRACT Meloxicam (MLX) is a non-steroidal, anti-inflammatory drug that is prescribed in the treatment of rheumatoid arthritis and osteoarthritis. MLX is practically insoluble in water and exhibits a slow onset of action. In this study, MLX solid dispersions (MLX SDs) were prepared to improve the water solubility of this poorly water-soluble drug. Then orally disintegrating tablets (ODT) of MLX were developed using MLX SD to decrease the onset of action of this drug. MLX, poloxamer 188, and crospovidone of different ratios were melted in molten poloxamer 188 as a hydrophilic carrier. The optimum SD with the highest saturation solubility in water (13.09±0.34 microgram/mL) consisting of MLX: poloxamer 188: crospovidone in the ratio of 1:2:0 was used for the preparation of MLX ODTs. MLX ODTs were prepared by the direct compression method and optimized by the 23 factorial design. The effect of the superdisintegrant concentration, the mannitol-avicel ratio, and the level of compression force on the disintegration time, hardness, and percent of dissolved MLX from MLX ODTs after 30 min was evaluated. DSC and XRD analysis approved an amorphous form of MLX in SDs. The optimized ODT formulation containing 10% of superdisintegrant, and mannitol and avicel in the ratio of 4:1 respectively was compressed using a high level of compression force. The optimized ODT showed hardness (34.37±2.1 N) and friability (1.26±0.04%). This formulation showed a rapid disintegration in 12.66±2.5 seconds, which 82.66±5.1% of the MLX released within 30 min. MLX ODTs, prepared from MLX SD, could be introduced as a suitable dosage form of MLX with improved solubility and the onset of action.

Influence of onset and duration of action on addiction potential of abused drugs / 中国药理学通报

The addiction potential of abused drugs can be different although their pharmacodynamics characteristics are quite similar.In this article, the influence of pharmacokinetics characteristics of a drug on its addiction potential was discussed. A more rapid rate of onset had been shown to result in greater propensity to addiction. Although prolonging the duration of action could reduce the responding rate in animal self-administration experiments, it might not influence the strength of a drug. Understanding the relationship between the pharmacokinetics characteristics and addiction potential may contribute to the rational use and development of these kinds of drugs.

Progress in the development of early-onset antidepressants / 中国药理学通报

Existing antidepressants exhibit delayed onset of action,which can decrease the compliance of the patients and enhance the risk of suicide.How to produce early-onset antidepressants with higher efficacy and lower adverse reactions has become a crucial point in the research of antidepressants.It has been demonstrated that selective 5-HT1Aantagonist,?2 antagonist and 5-HT2Aantagonist can accelerate the response of classic antidepressants.Furthermore,5-HT/NE dual reuptake inhibitor and 5-HT/NE/DA triple reuptake inhibitor can also produce early onset of action.Here,several reasons for the delayed onset of action and the progress in the development of early-onset antidepressants are reviewed.