Linked electronic medication systems in community pharmacies for preventing pseudoephedrine diversion: A review of international practice and analysis of results in Australia

Introduction and Aims. Pseudoephedrine is a precursor often diverted into the illegal manufacture of amphetamine type substances (ATS). The aim of this study was to evaluate the effectiveness of a linked electronic medication recording system (LEMS) established in Australian pharmacies in 2005 for preventing the diversion of pseudoephedrine. Design and Methods. The number of illegal ATS laboratories detected in each jurisdiction of Australia from 1996–1997 to 2004–2005 were analysed by linear regression nationally and by each jurisdiction. The statistical significance of seizures in 2005–2006 was based on the comparison of the observed value to the 95% prediction confidence intervals calculated from the historical data for each jurisdiction and nationally. Results. Pharmacies in Queensland commenced an LEMS in late 2005 to minimise retail pseudoephedrine diversion. The number of ATS laboratories seized in 2005–2006 in Queensland was significantly lower (P < 0.05) than predicted by historical data. For all other jurisdictions and nationally the totals of laboratories seized in 2005–2006 were not significantly different from predicted values. Discussion and Conclusions. The significant decline in ATS illegal laboratories seized in Queensland in 2005–2006 suggests the effective use of LEMS in pharmacies to minimise pseudoephedrine diversion. In order to evaluate a national LEMS, more frequent data on numbers of linked pharmacies, ATS laboratories seized and indicators of pseudoephedrine sales and misuse are required. Testing the use of LEMS by pharmacies for preventing the diversion of other medicines seems appropriate.[Berbatis CG, Sunderland VB, Dhaliwal SS. Linked electronic medication systems in community pharmacies for preventing pseudoephedrine diversion: A review of international practice and analysis of results in Australia. Drug Alcohol Rev 2009]     

The Role of Concomitant Arrhythmia Surgery in Patients Undergoing Repair of Congenital Heart Disease

Long-term survival after repair of complex congenital heart lesions is associated with the late development of arrhythmias as well as residual hemodynamic abnormalities. Understanding arrhythmias as electromechanical problems provides the basis for surgical intervention to correct the arrhythmia as well as anatomical disturbances. Operative techniques are highly effective in treating atrial reentry tachycardia and atrial fibrillation. Surgery for ventricular tachycardia is less effective: the arrhythmia may be reduced by improving hemodynamics, but a defibrillator may be required. Integration of device therapy into surgery may improve outcomes by preventing bradycardia as a precursor to tachycardia, and optimizing ventricular synchrony.     

Synthesis of a potent agonist of substance P by modifying the methionyl and glutaminyl residues of the C-terminal hexapeptide of substance P

Analogues of [Orn⁶]-SP_6-11 have been synthesized in which the Met¹¹ residue is replaced by glutamate γ-alkylesters. These analogues were tested in three in vitro preparations representative of NK-1, NK-2, and NK-3 receptor types. Substitution of the SCH₃ group of the Met¹¹ side chain by a COOR (R = methyl, ethyl, n-propyl, n-butyl, cyclohexyl) group results in analogues which are full agonsists in NK-1 and NK-2 preparations but show little agonist activity in the NK-3 preparation. When the SCH₃ group is replaced by a t-butyl ester group and the resulting analogue is a full agonist in all the above preparations and more active than the parent hexapeptide and SP-OCH₃ at NK-1 receptors. It is concluded that for activity at NK-1 receptors methionine can be replaced by γ-t-butyl glutamate without loss of activity, whilst at NK-2 and NK-3 receptors the above substitution increases the activity of [Orn₆]-SP_6-11. Other γ-alkyl esters of the glutamic acid reduce its biological activity.     

Nifedipine as a second line antihypertensive drug in pregnancy

Summary. Slow-release nifedipine has been used in the treatment of severe hypertension in 23 pregnant women. In 22 this was in combination with other drugs, in 18 including atenolol. Good control of blood pressure was achieved in 20 women. The perinatal mortality of the group was 130/1000, with a high caesarean section rate (71% of live-births), a high rate of abnormal CTGs, a high rate of premature delivery, and a high rate of infants who were small-for-dates. Whether this is due to the disease process or the medication is uncertain. For the present time these combinations should only be used in severe hypertensives or in the context of a controlled trial.     

Synthesis and biological activity of locust AKH-I and its analogues with modifications at the threonine residues

A convenient method of synthesis, using a combination of solid and liquid phase methodology, for locust Adipokinetic Hormone-I (AKH-I) and its analogues with modifications at the threonine residues are reported. The N-terminal nonapeptide acid of AKH-I is synthesized in the solid phase using the 2-chlorotrityl chloride resin and the Fmoc/t-Bu strategy. Quantitative cleavage of the nonapeptide acid from the resin, with the tert-butyl type side-chain protection intact, is achieved with a mixture of acetic acid/trifluoroethanol/ dichloromethane. The nonapeptide acid is then coupled in solution to the threonine derivatives, H-Thr-NH₂ or H-Thr(Bz1)-NH₂, with the DCC/HOBt method. The efficiency of this approach in the synthesis of AKH-I is demonstrated by the high yields and purity of the synthesized peptides. All the synthesized peptides were tested in two ways: first, in a lipid mobilization assay in locusts in vivo; and second, in a novel assay in vitro concerned with the uptake of radiolabelled acetate into locust tissue. Replacement of the hydroxyl hydrogen in Thr⁵ of locust AKH-I by the bulky and highly lipophilic tert-butyl group reduced the potency markedly, whereas efficacy is unaffected, but when the hydroxyl hydrogen of Thr¹⁰ in AKH-I is replaced by a benzyl group, the activity of the resulting analogue is identical to that of the natural peptide. Structure-activity relationships are discussed. © Munksgaard 1994.     

Morbidity of prophylactic inguinal lymphadenectomy with saphenous vein preservation for squamous cell penile carcinoma

BACKGROUND: Inguinal lymphadenectomy has an essential role in the cure of patients with inguinal metastasis from penile cancer; however, this procedure is associated with a significant morbidity. In recent years, modified lymphadenectomy with saphenous vein preservation has been postulated to reduce morbidity. Herein, we present our recent experience with prophylactic inguinal lymhadenectomy and saphenous vein preservation in patients with invasive penile carcinoma and non-palpable inguinal lymph nodes. METHODS: Seven patients with invasive squamous cell penile carcinoma, who underwent bilateral prophylactic inguinal lymphadenectomy with saphenous vein preservation between 1995 and 2001, were reviewed retrospectively. Mean age was 67.7 years. The pathological stage of the primary tumor was pT2 in four and pT3 in three patients respectively. Postoperative complications were defined as minor--wound infection, seroma formation requiring drainage, and skin necrosis, and major-- deep venous thrombosis, persistent seroma formation, flap necrosis requiring a skin graft, as well as permanent and disabling leg lymphedema. RESULTS: Minimum follow up was 2 years. Minor complications--wound infection--occurred in one patient (one groin). No major complications occurred. All patients are alive without evidence of disease recurrence. CONCLUSIONS: Prophylactic inguinal lymphadenectomy seems to offer reduced morbidity in high risk penile cancer patients without compromising survival outcome.     

Synthesis and biological activity of analogues of the C-terminal hexapeptide of substance P with modifications at glutaminyl and methioninyl residues

Analogues of [Orn⁶]-SP_6-11 have been synthesized in which the methionyl residue is replaced by glutamine γ-carboxamide substituted derivatives. These analogues where tested in three in vitro preparations representative of NK-1, NK-2 and NK-3 receptor types. Substitution of the SCH₃ group of the Met¹¹ side chain by CONHCH₃, CON(CH₃)₂, CONHPh and CONCH₃Ph groups results in analogues which are full agonists in NK-1 and NK-2 preparations with the exception of the Glu[N(CH₃)₂]¹¹ and the Glu(NHCH₃)¹¹ analogues, which are partial agonists at NK-1 and NK-2 receptors respectively. The Glu(NHCH₃)¹¹ analogue shows selectivity for the NK-1 receptor type and is equipotent to the Glu(NCH₃Ph)¹¹ analogue in the same receptor type. The latter analogue is 2.84 times more potent than the parent hexapeptide in the NK-2 preparation. The Glu(NHPh)¹¹ analogue is a full agonist in the NK-3 preparation and equipotent to the parent hexapeptide, in contrast to the other analogues in which Met has been replaced by glutamine γ-carboxamide substituted residues. It is concluded that for NK-1 receptor type the lipophilic character of Met¹¹ side chain is not a determining factor for activity but it is an important factor for activity in the NK-2 receptor type and has a stronger effect when a phenyl group is present, thus leading to analogues which are full agonists and more potent than the parent hexapeptide.