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At least 19 recordsLinked to original sources
PubMed2026

Cardiovascular Drug Access in Australia and New Zealand: New PBS and PHARMAC Listings, 2023-2025.

BACKGROUND: Cardiovascular disease is a leading cause of death in Australia and New Zealand. Publicly subsidised access to new cardiovascular medications is governed by the PBS (Pharmaceutical Benefits Scheme) in Australia and PHARMAC (Pharmaceutical Management Agency) in New Zealand, yet no consolidated resource catalogues recent listings across both jurisdictions. METHODS: We reviewed all new cardiovascular drug listings and indications on the PBS and PHARMAC schedules from 1 January 2023 to 31 December 2025. PBS data were obtained from the PBS Pricing and Policy Branch through the Cardiac Society for Australia and New Zealand. PHARMAC data were obtained via direct communication with PHARMAC and cross-referenced with public schedule information. Pivotal trial evidence, restriction criteria, and prescribing considerations were extracted from published literature and regulatory documents. RESULTS: Five new cardiovascular drugs were PBS-listed (inclisiran, mavacamten, tafamidis, icosapent ethyl and migalastat), two existing drugs received new cardiovascular indications (empagliflozin and dapagliflozin for heart failure with preserved ejection fraction) and prasugrel was relisted for acute coronary syndrome. One major change occurred on the PHARMAC schedule (empagliflozin for heart failure with reduced ejection fraction). CONCLUSIONS: The 2023-2025 period has seen notable additions to cardiovascular pharmacotherapy in Australia, including the first cardiac myosin inhibitor, the first transthyretin stabiliser, expanded lipid lowering therapy options, and extension of SGLT2 inhibitor coverage across the heart failure ejection fraction spectrum. A pronounced access disparity persists between Australia and New Zealand.

New Zealand↗
PubMed1979

Chloroquine resistance in malaria: accessibility of drug receptors to mefloquine.

The process of mefloquine accumulation was studied in mouse erythrocytes infected with either Plasmodium berghei CS (chloroquine susceptible) or P. berghei CR (chloroquine resistant). In both cases, mefloquine was accumulated by a saturable process with an apparent dissociation constant of 2.5 x 10(-6) M and an apparent maximal capacity of 700 mumol per kg of erythrocyte pellet; uninfected mouse erythrocytes accumulated more than half as much mefloquine as infected erythrocytes. The process of accumulation was not stimulated by providing glucose as a substrate, and it was not inhibited in infected erythrocytes by azide, iodoacetate, or incubation at 2 degrees C. Although mefloquine was accumulated more effectively than chloroquine by uninfected erythrocytes and by erythrocytes infected with P. berghei CR, competition between chloroquine and mefloquine was observed, raising the possibility that the same process of accumulation serves both drugs. Chloroquine competitively inhibits mefloquine accumulation, with an apparent inhibitor constant of 1.7 x 10(-3) M, and mefloquine competitively inhibits chloroquine accumulation, with an apparent inhibitor constant of 2 x 10(-6) M. The same process of accumulation and the same group of receptors could serve both drugs if mefloquine has greater access than chloroquine to the receptors. Regardless of whether the same process serves both drugs, undiminished accumulation by erythrocytes infected with P. berghei CR provides an explanation for the superiority of mefloquine in treating chloroquine-resistant malaria.

Animals↗
PubMed2025

Worldwide Innovative Network (WIN) Consortium in Personalized Cancer Medicine: Bringing next-generation precision oncology to patients.

The human genome project ushered in a genomic medicine era that was largely unimaginable three decades ago. Discoveries of druggable cancer drivers enabled biomarker-driven gene- and immune-targeted therapy and transformed cancer treatment. Minimizing treatment not expected to benefit, and toxicity-including financial and time-are important goals of modern oncology. The Worldwide Innovative Network (WIN) Consortium in Personalized Cancer Medicine founded by Drs. John Mendelsohn and Thomas Tursz provided a vision for innovation, collaboration and global impact in precision oncology. Through pursuit of transcriptomic signatures, artificial intelligence (AI) algorithms, global precision cancer medicine clinical trials and input from an international Molecular Tumor Board (MTB), WIN has led the way in demonstrating patient benefit from precision-therapeutics through N-of-1 molecularly-driven studies. WIN Next-Generation Precision Oncology (WINGPO) trials are being developed in the neoadjuvant, adjuvant or metastatic settings, incorporate real-world data, digital pathology, and advanced algorithms to guide MTB prioritization of therapy combinations for a diverse global population. WIN has pursued combinations that target multiple drivers/hallmarks of cancer in individual patients. WIN continues to be impactful through collaboration with industry, government, sponsors, funders, academic and community centers, patient advocates, and other stakeholders to tackle challenges including drug access, costs, regulatory barriers, and patient support. WIN's collaborative next generation of precision oncology trials will guide treatment selection for patients with advanced cancers through MTB and AI algorithms based on serial liquid and tissue biopsies and exploratory omics including transcriptomics, proteomics, metabolomics and functional precision medicine. Our vision is to accelerate the future of precision oncology care.

Humans↗
PubMed1976

Pulmonary toxicity of bleomycin.

Diffuse pulmonary fibrosis is associated with bleomycin administration to humans. The sequential reactions of lung cells to this drug have now been investigated in mice following injection of 20 mg/kg bleomycin twice per week for 4 to 8 weeks. Cytoplasmic and subendothelial edema was first observed in large vessels and by 4 weeks involved the capillaries. The reaction in many animals did not progress further than endothelial lesions with accumulation of interstitial edema. However, 30% of mice subsequently showed necrosis of type 1 epithelium with a fibrinous exudate in the alveoli. Fibroblastic organization of the fibrin resulted in the deposition of intraalveolar collagen as well as extensive septal fibrosis by 8 weeks. Epithelial repair, normally accomplished by type 2 cell proliferation and transformation to type 1 cells, is characterized in this case by division and metaplasia of type 2 cells. The metaplastic cells were, however, capable of DNA synthesis and probably of further cell division. The results indicate that the pulmonary endothelium is the initial site of injury. Extensive damage to these cells could allow the drug access to interstitial and epithelial cells. Focal necrosis of type 1 epithelium is the critical event that triggers the exudation of fibrin and the subsequent reparative processes.

Animals↗
PubMed2026

Epilepsy: Bridging Epidemiological Landscapes, Molecular Mechanisms, and Emerging Precision Therapeutics.

Epilepsy ranks among the most prevalent neurological disorders worldwide, and recent years have witnessed significant advancements in understanding its epidemiological features, pathophysiological mechanisms, diagnostic methodologies, and therapeutic approaches. This review systematically examines the epidemiology of epilepsy, highlighting pronounced regional and population-based disparities, particularly the substantial treatment gap observed in low-income countries. Regarding pathogenesis, epilepsy development involves aberrant ion channel function, neuroinflammatory processes, dysregulation of the mTOR signaling pathway, and genetic predispositions. Diagnostic innovations, including ultra-high field magnetic resonance imaging, artificial intelligence-enhanced electroencephalogram analysis, and liquid biopsy techniques, have markedly enhanced the precision of epileptogenic focus localization and etiological identification. Genetic investigations have uncovered numerous epilepsy-associated genes, thereby underpinning the advancement of targeted therapies. Therapeutically, novel antiepileptic drugs, neuromodulation modalities such as vagus nerve stimulation and deep brain stimulation, alongside gene therapy, have expanded treatment options for refractory epilepsy. Nonetheless, global epilepsy management continues to confront challenges including limited drug accessibility, social stigma, and pharmacoresistance. The future trajectory emphasizes individualized and precision medicine approaches, integrating genomics, biomarker discovery, and intelligent monitoring technologies to foster comprehensive improvements in epilepsy diagnosis and treatment.

epidemiology↗
PubMed1977

Self-administration of codeine plus acetylsalicylic acid in rhesus monkeys with unlimited access to the drugs.

The reinforcing effects of codeine (5.0 mcg/kg/infusion), acetylsalicylic acid (ASA) (2500 mcg/kg/infusion) and those of combinations of codeine (50 mcg/kg/infusion) plus (2500 or 10,000 mcg/kg/infusion) were studied in four groups of drug naive rhesus monkeys. Responding was engendered and maintained by infusions of 50 mcg/kg of codeine; maximal number of daily infusions being 500 to 1000. Infusions of 2500 mcg/kg of ASA plus 50 mcg/kg of codeine per infusion initiated responding from the 9th to the 10th day of the drug period on. The number of self-administered infusions did not exceed 200 daily. Monkeys self administered codeine without signs of intoxication. All three monkeys self-administering the combination of 50 mcg/kg of codeine plus 2500 mcg/kg of ASA died during the experiment. They exhibited signs of severe intoxication. A combination of 50 mcg/kg of codeine and 10,000 mcg/kg of ASA was not self-administered until the 12th day of the drug period. Two out of three monkeys initiated responding for the combination during the drug period. The number of self-administered infusions did not exceed 50 per day. A third monkey did not initiate self-administration during the 14 day drug period. Both monkeys which engendered self-administration died on the 14th day of the experiment as a result of general intoxication. These experiments suggest that even toxic doses of ASA will not prevent monkeys from self-administration when offered together with a positive reinforcing drug such as codeine under a schedule of continuous self-administration.

Animals↗
PubMed1976

Self-administration of psychomotor stimulant drugs: the effects of unlimited access.

Rhesus monkeys surgically prepared with intravenous catheters were given 23 hr daily access to injection of either cocaine, d-amphetamine, 1-amphetamine, d-methamphetamine or diethylpropion on a fixed ratio 1 schedule of reinforcement for a maximum of 30 days. Responding was maintained by all these drugs but showed both day-to-day and hour-to-hour variability. The two animals self-administering 0.2 mg/kg/infusion cocaine died in less than 5 days. All 6 animals given access to 0.05 mg/kg/infusion d-amphetamine or 0.025 mg/kg/infusion d-methamphetamine also died, but tended to survive more days than animals exposed to cocaine. Three of the 5 animals whose responding was maintained by 0.5 mg/kg/infusion diethylpropion and one of the two animals whose responding was maintained by 0.05 mg/kg/infusion 1-amphetamine survived the entire 30 days despite high rates of intake. Food intake was initially decreased, but often returned to predrug levels and was not related to level of drug intake.

Amphetamine↗
PubMed1977

Ouabain inhibition of gill Na-K-ATPase: relationship to active chloride transport.

Ouabain circulating in blood inhibits Na-K-ATPase in the gills of seawater eels at a concentration similar to that necessary for inhibition in vitro. By contrast, a much higher concentration is required when ouabain is applied to the exterior of the gill. Inhibition by external ouabain occurs only when the drug gains access to the circulation of the fish, as evidenced by simultaneous inhibition of Na-K-ATPase in the kidney. These results suggest that the Na-K-ATPase of gill chloride cells faces inward, lining intracytoplasmic tubular channels continuous with the extracellular fluid. Inhibition of gill Na-K-ATPase by ouabain in intact salt water eels results in almost complete inhibition of the efflux of both Na+ and Cl-. The efflux is tritiated water was much less reduced, to 60% of normal. Since chloride is actively transported outward across the gill of seawater teleosts, it is suggested that active chloride transport is coupled to Na-K-ATPase. A neutral sodium chloride carrier is postulated that is energized by the movement of sodium from extracellular fluid down its electrochemical gradient into the chloride cell.

Adenosine Triphosphatases↗
PubMed1979

Relationship of pharmacokinetics to pharmacological response for acetazolamide.

Acetazolamide concentration values derived from a nonlinear model system were related to two pharmacological responses in the rabbit. Kidney response was measured by monitoring urine flow and sodium elimination. Ocular response was followed using an applanation tonometer. Maximum urine flow and sodium elimination occurring immediately after injection correlated with log dose. Urine flow dropped below control values along with a rise in osmolality, suggesting the involvement of antidiuretic hormone. Sodium elimination was correlated with plasma levels. Urine pH is thought to be involved in reducing accessibility of drug to carbonic anhydrase in the kidney. Maximum ocular response also was correlated with log dose. Ocular response was related to a protein fraction, which is believed to be mainly carbonic anhydrase. However, the duration of ocular response was related to the red blood cell protein fraction. Thus, drug activity could conceivably be regulated by monitoring a tissue that is not the site of action and can be sampled readily.

Acetazolamide↗
PubMed1978

Synaptic delay in the heart: an ionophoretic study.

1. Neurotransmitters were applied ionophoretically to spontaneously beating clusters of ventricular muscle cells cultured from neonatal rats. 2. Acetylcholine or its analogue carbachol produced hyperpolarization and decreased the rate of spontaneous beating. These responses had minimum latencies of about 250 msec and total durations of 6-12 sec. 3. Noradrenaline, adrenaline or isoprenaline increased the rate of spontaneous beating. The minimum latency for this effect was 3-6 sec. Following a single brief pulse the rate remained elevated for 2 min or more. 4. Chronotropic responses of intact atria from adult rats to stimulation of the autonomic nerves were of similar time course to responses of the cultured muscle cells. 5. Calculations based on the theory of diffusion showed that access of drugs to their receptors could not be rate-limiting for the observed responses, unless a diffusion barrier of rather special properties was postulated. A number of other explanations for the long latencies have been ruled out; these are most likely to be due to some physical or chemical process occurring in or under the cell membrane. 6. Attempts to mimic responses to catecholamines by intracellular application of cyclic AMP were unsuccessful, perhaps because the release of nucleotide from the pipettes was insufficient. A theoretical treatment suggests that ionophoretic efflux of anions might be greatly diminished by the opposing electro-osmotic flux.

Acetylcholine↗
PubMed1978

Continuous intravenous naltrexone effects on morphine self-administration in rhesus monkeys.

Rhesus monkeys, surgically prepared with intravenous catheters, were given opportunities to self-administer morphine for 3 days, methamphetamine for 2 days and saline for 2 days in a constantly repeating cycle. Access to drugs was limited to a 15-minute period every 4 hours. After stable base-line self-administration rates, saline or various concentrations of naltrexone were infused continuously through the catheter. In the first phase of the study each concentration of naltrexone was infused for 4 weeks (separated by 3 weeks of saline) while the dose of morphine available for self-administration was held constant at 8 microgram/kg/injection. Stable naltrexone dose-related suppression of morphine self-administration occurred throughout each 4-week infusion. In the second phase of the study, various doses of morphine were made available for self-administration during 6- to 8-week continuous infusions of saline or various concentrations of naltrexone. The dose-effect curve relating self-administration rate to morphine dose per injection shifted to the right and decreased in maximum as the rate of infusion of naltrexone increased. Methamphetamine and saline self-administration rates were unaffected by naltrexone.

Animals↗
PubMed1978

On the origin and fate of external acetylcholinesterase in peripheral nerve.

1. Rabbit peroneal nerves were exposed to echothiophate, a quaternary ammonium inhibitor of acetylcholinesterase (AChE), and 217-AO, its tertiary analogue, in an attempt to characterize the localization of the enzyme. Although 217-AO readily inhibited AChE throughout the nerves, echothiophate spared significant amounts unless the tissues had first been homogenized. Notably, doses of echothiophate inhibiting 84% of the total AChE inhibited only 30% of the rapidly transported enzyme, suggesting that AChE was distributed between compartments differing greatly in their accessibility to this drug. 2. Since charged molecules penetrate cells poorly, it seemed likely that the more accessible compartment of AChE was external, perhaps consisting mainly of enzyme incorporated into the outer surface of the axolemma. If one assumes that the inhibition of the transported enzyme accurately reflected the inhibition throughout the inaccessible compartment, it can be calculated that external AChE comprised about 80% of the total. 3. The quasi-irreversible inhibition of AChE by echothiophate was used to probe the dynamics of the external enzyme. Locally exposing nerves to this drug in vivo markedly inhibited the AChE in a short region, which subsequently recovered with a half-time of about 5 days. Recovery appeared to reflect delivery of new enzyme into the inhibited region rather than spontaneous reactivation or local synthesis of AChE. Surprisingly, the zone of inhibition neither broadened nor moved noticeably for at least 8 days. This implies that external AChE is largely fixed in place and must be renewed locally, presumably by incorporation of rapidly transported enzyme from the internal compartment.

Acetylcholinesterase↗
PubMed1979

Pharmacy practice in an operating room complex.

The steps involved in establishing a comprehensive pharmaceutical service in an operating and recovery room complex is described. Objectives of the operating room pharmaceutical satellite were to: (1) improve control of distribution, storage and charging for all drugs, especially Schedule II controlled substances; (2) reduce inventory costs and loss of revenue; (3) improve compliance with the drug formulary; and (4) establish patient-oriented pharmaceutical services. The pharmacy satellite improved inventory control and patient charging, assured continual access to all drugs and appropriate security for controlled substances, and expanded the pharmacy department's clinical, drug information and research activities.

Alabama↗
PubMed1978

The reinforcing properties of procaine and d-amphetamine compared in rhesus monkeys.

Twelve rhesus monkeys were studied under a fixed-ratio (FR) schedule of intravenous procaine or d-amphetamine injection from 8 A.M. to 4 P.M. daily. Under the FR schedule, every nth lever press produced an injection. The FR value (n) and the dose per injection of procaine and d-amphetamine were varied systematically. At a FR value of 10, responding was maintained by doses of procaine ranging from 0.125 to 12 mg/kg/injection and by doses of d-amphetamine ranging from 0.01 to 0.1 mg/kg/injection. At doses of 1 mg/kg/injection of procaine and 0.1 mg/kg/injection of d-amphetamine, responding was maintained at FR values up to 100 by procaine and d-amphetamine but not by saline. Responding and drug intake were relatively constant throughout each 8-hour session with procaine, but responding tended to decrease and was more variable over the session with d-amphetamine. No toxic effects were observed in doses up to 6 mg/kg/injection with procaine. At this dose, eating and drinking ceased during the period of access to the drug. One of the four monkeys died at 8 mg/kg/injection of procaine. At 12 mg/kg/injection all three monkeys tested showed signs of toxicity.

Animals↗
PubMed1979

Temperature experiments on nerve and muscle membranes of frogs. Indications for a phase transition.

The influence of temperature changes in the range of 25 degrees C to -6 degrees C on the time constants of Na activation (tau m) and inactivation (tau h) was studied in twitch muscle fibers and the node of Ranvier under voltage-clamp conditions. Arrhenius plots of tau m and tau h exhibit a change in activation enthalpy at temperatures below 10 degrees C. Cooling and subsequent heating induce a hysteresis in the temperature dependence of tau m and tau h; Ni2+ and UO22+ increase the hysteresis width. With fast temperature changes the gating kinetics relax to their new values more slowly than the temperature change. Hence, temperature must be changed more slowly than 5 degrees C/min if an additional apparent hysteresis due simply to this relaxation is to be avoided. The data are explained by the hypothesis of a phase transition in the membrane lipids. This conception is favoured over a temperature-induced change in protein conformation, since the neutral local anaesthetic benzocaine shows use-dependent block as if low temperature restricted the access of the drug through the lipid phase to its receptor.

Animals↗
PubMed1977

Leukemic nodules in the eye in immature-cellular infantile leukoses.

Two boys, aged 5 1/4 and 10 1/4, respectively, with acute immature-cell leukosis, died of massive cerebral haemorrhage. Their eyes showed extensive leukaemic involvement of the retina with development of numerous miliary leukaemic nodules; the vitreous of case 2 was also involved. The lesions were considered to have developed because of high circulating white cell counts, a tendency of blast cells to produce nodules, an oxygen poor avascular matrix in which to grow, and a physical environment which permitted growth without haemorrhage or distortion due to tissue pressures etc. Using histological methods, an attempt is made to trace the pattern of formation of the nodule, from an initial growing focus through "colonial" form resembling a bacterial colony to lysis. Necrotic blast cells are apparently a metabolic source for viable tumour cells. Their localization in the eye makes access by cytotoxic drugs difficult; thus they should be considered as blast cell pools.

Acute Disease↗
PubMed1977

The uptake and overflow of radiolabelled beta-adrenoceptor blocking agents by the isolated vas deferens of the rat.

1. A comparison of uptake into and overflow from the isolated vas deferens of the rat has been made between [3H]-noradrenaline ([3H]-NA), [14C]-D-sorbitol and three radio-labelled beta-adrenoceptor blocking agents, [14C]-practolol, [14C]-(+/-)-propranolol and [3H]-penbutolol. 2. The accumulation of [3H]-NA after 30 min incubation was reduced by desmethylimipramine (DMI) 1 X 10(-8)M and was also reduced in vasa from rats pretreated with 6-hydroxydopamine (6-OHDA). This was not so with [14C]-D-sorbitol. 3. 6-OHDA pretreatment of the rats reduced the uptake of [3H]-penbutolol after 30 min incubation but not that of [4C]-propranolol or [14C]-practolol. DMI 1 X 10(-8)M did not alter the tissue uptake of [14C]-propranolol, [14C]-practolol or [3H]-penbutolol. 4. Electrical stimulation of vasa preloaded with [3H]-NA caused a significantly greater increase in [3H]-NA overflow than during the resting, unstimulated periods. No such increase in overflow was observed with [14C]-sorbitol or any of the three beta-adrenoceptor blocking agents use. 5. The beta-adrenoceptor blocking agent penbutolol was shown to possess adrenergic neurone blocking activity in the isolated vas deferens of the rat. 6. It is concluded that any effect that practolol or (+/-)-propranolol have on noradrenergic neurones is brought about without the need for these drugs to gain access to the interior of the neurone.

Adrenergic beta-Antagonists↗