Richard N. Herrier

Convulsions as the etiology of lactic acidosis in acute isoniazid toxicity in dogs

Abstract The mechanism by which acute isoniazid (INH) overdose causes lactic acidosis is unknown. This study examines the role of convulsion in the development of lactic acidosis in dogs given po lethal doses of INH (75 mg/kg). Following INH, dogs did not develop acidosis until after they had experienced clonic-tonic convulsions. Acidosis, which became more pronounced with successive convulsions, was associated with marked increase of serum lactate (immediate postconvulsive level, 12.3 meq/liter, compared to control of 1.83 meq/liter). Diazepam, 0.5 mg/kg, plus pyridoxine HCl, 150 mg/kg, injected iv immediately following po INH, prevented both convulsions and changes in pH and lactate. When the antidotes were administered after the second convulsion of INH toxicity no further convulsions occurred and blood pH and lactate returned to control levels in 2 hr. “Curarization” of INH-treated dogs prevented both motor seizures and marked increase of lactate. In animals treated with INH and allowed to convulse two times to develop severe acidosis, correction of the acidosis with NaHCO 3 failed to prevent further convulsions and death. Diazepam and pyridoxine combinations, in doses that were ineffective for terminating INH-induced convulsions, became effective when given after correction of acidosis with NaHCO 3 . It is concluded that convulsion is the main cause of lactic acidosis in acute INH toxicity and that correction of acidosis does not terminate acute INH toxicity. Although correction of acidosis increases the antidotal effectiveness of diazepam plus pyridoxine, increasing the dose of either or both of these two drugs achieves the same antidotal advantage without the potential problems of metabolic alkalosis which may result from NaHCO 3 administration.

Evaluation of diazepam and pyridoxine as antidotes to isoniazid intoxication in rats and dogs.

Abstract Because information regarding efficacious treatment of acute isoniazid (INH) toxicity is incomplete and controversial, diazepam and pyridoxine were investigated as iv antidotes in rats and dogs following administration of po lethal doses of INH. There is a marked species variation in the lethality of INH; the lowest consistently lethal dose is 1500 mg/kg for rats and 75 mg/kg for dogs. Of the two species, the dog more closely approximates mans sensitivity to the lethal effect of INH overdose (80–150 mg/kg). Species variation was also observed in the effects of the antidotes. Diazepam exerted dose-related protection against convulsions in rats; paradoxically, survival was increased by the lowest dose (1 mg/kg) but not by higher doses. In dogs, however, diazepam failed to prevent convulsions but provided dose-related protection against death. Pyridoxine, in rats, did not protect against INH toxicity, but in dogs it showed dose-related effectiveness against convulsions, and all doses (75–300 mg/kg) prevented lethality. Significantly, the highest dose of pyridoxine tested in rats (750 mg/kg) was substantially below the optimal pyridoxine-to-INH antidotal ratio recommended for man (a dose that at least equals the amount of INH ingested), but that dose of pyridoxine would be larger than its LD50 for rats. Combined administration of diazepam with pyridoxine protected against convulsions and death in rats and dogs. Used concurrently, the two antidotes are clearly synergistic for controlling the manifestations of experimental INH overdose. These results have important implications for the management of acute INH intoxication in man.

Advances in the treatment of moderate-to-severe plaque psoriasis

PURPOSE Advances in the treatment of moderate-to-severe plaque psoriasis, including new biological agents and related drugs, are reviewed. SUMMARY Most patients with psoriasis have mild disease that can be treated with topical agents alone; however, over one third of patients have more-extensive disease, called moderate-to-severe plaque psoriasis. Although effective, traditional therapies, including methotrexate, cyclosporine, acitretin, and phototherapy, have serious adverse effects that limit both the initiation and duration of treatment, necessitating sequential treatment regimens. With the increasing knowledge of the immune nature of the disease, biological agents that target T lymphocytes, tumor necrosis factor (TNF)-α, interleukin (IL)-12, and IL-23 have been used successfully in moderate-to-severe psoriasis. Etanercept, adalimumab, and infliximab are also highly effective in the treatment of moderate-to-severe plaque psoriasis. Ustekinumab, a new agent that targets IL-12 and IL-23, was approved for marketing in 2009 and offers similar efficacy and safety profiles to the anti-TNF agents. While the rapid onset and apparent lack of long-term toxicity of biological agents make them major advances in the treatment of more severe forms of psoriasis, the lack of extensive experience with these agents in patients with psoriasis leaves several unresolved issues that must be addressed before their exact place in therapy can be determined. CONCLUSION With the development of biological therapies over the past 10 years, health care providers have a much broader choice of highly effective agents with which to treat patients suffering from moderate-to-severe plaque psoriasis. Though costly to use, biological agents offer considerable advantages over previously available systemic therapies.

Potentiation of pyridoxine by depressants and anticonvulsants in the treatment of acute isoniazid intoxication in dogs

Abstract Treatments for acute isoniazid (INH) intoxication have included, singly and in various combinations, a great variety of drugs. As a consequence it is difficult to evaluate the efficacy of these antidotes, except for pyridoxine, the most commonly recommended one. In some cases of INH poisoning evaluation is further complicated because of concurrent alcohol ingestion. The objectives of this investigation were to determine whether ethanol enhances the toxic effects of acute INH overdose, as suggested by some clinical reports, and to evaluate the antidotal efficacy of phenobarbital, pentobarbital, phenytoin, ethanol, or diazepam when each is administered in combination with pyridoxine. Male dogs were either pretreated with iv ethanol and challenged 1 hr later with po INH, 50 or 75 mg/kg, or they were given INH, 75 mg/kg, and injected iv 30 min later with the test drugs, alone or in combination with pyridoxine. Ethanol pretreatment not only did not enhance the toxicity of INH but, in fact, it reduced the severity of convulsions, although it did not change the mortality rate. In the antidotal study, none of the five CNS depressants or anticonvulsants protected against clonic-tonic seizures or death. Pyridoxine, however, reduced the severity of the seizures and prevented death, although it did not completely block convulsions. The combination antidotal treatments (pyridoxine plus each of the CNS drugs) were the most effective; they prevented both convulsions and lethality. It is suggested that pyridoxine is the basic antidote for treatment of acute INH poisoning, and that the addition of an anticonvulsant or a CNS depressant to the therapy enhances effectiveness.

Case Study Using Descriptive Analysis to Estimate Hidden Costs in Processing Third Party Prescriptions

OBJECTIVE To identify and quantify additional hidden costs associated with processing third party prescriptions. DESIGN/SETTING Using time and motion techniques, the frequency of rejected third party prescriptions and the time involved to resolve those rejections were measured in one supermarket chain pharmacy and one independent pharmacy. From this information, additional costs attributed to processing third party prescriptions were calculated. RESULTS In a market where almost 95% of all prescriptions are third party reimbursed, payers rejected 18.7% and 22.3% of the prescriptions submitted by the supermarket chain and independent pharmacies, respectively. Additional or hidden costs for rejected prescriptions averaged

Development of a Pharmacy Capstone Course From Focus Groups to Advanced Patient Care

1.10 at the supermarket chain pharmacy and

The role of rapid-acting insulin analogues and inhaled insulin in type 2 diabetes mellitus

1.54 at the independent pharmacy, with the difference attributable to the higher level of pharmacy staff involvement in resolving rejections at the independent pharmacy. When additional costs for all third party prescriptions were calculated, the average additional cost per third party prescription dropped to

Responses to "Is it time to start teaching basic diagnostics?".

0.44 for the supermarket chain pharmacy and

US Pharmacists' Effect as Team Members on Patient Care Systematic Review and Meta-Analyses

0.61 for the independent pharmacy. CONCLUSION Increasing pharmacist availability for pharmaceutical care requires decreasing time spent in the dispensing process, especially resolving third party problems. Systems analysis and time and motion techniques were effectively used to more accurately measure the time and costs associated with processing third party prescriptions. Actual costs found in this study were considerable, but significantly less than those reported previously in studies using estimates and surveys.

Economic Effects of Pharmacists on Health Outcomes in the United States: A Systematic Review

Objective. To describe the development of a capstone course using qualitative results of focus groups and to determine the impact of the course using a pre- and postcourse surveys. Design. A course titled Advanced Patient Care was developed using themes emerged from 3 stakeholder focus groups and implemented with case-based sessions, interactive exercises, and Objective Structured Clinical Examinations (OSCEs). Pre- and postcourse surveys were conducted to assess the students’ confidence and knowledge in managing 8 commonly-encountered conditions. Assessment. During the 2-year course implementation, a total of 169 students participated in the pre- and postcourse surveys (87.6% response rate). The mean total confidence score increased significantly from 54.3 (±9.2) to 69.0 (±8.6, p<0.001), and the total mean knowledge score increased significantly from 6.3 to 6.9 (p<0.001). Conclusion. The capstone course, fueled by focus group findings and implemented using interactive sessions and simulations, positively impacted students’ confidence and knowledge for clinical practice experiences and professional practice.