1,721,020 research outputs found
Analysis of medicines returned to pharmacies for disposal and estimation of the cost due to medicine wasting
No full textBackground: Studies have shown that waste medicines generate a significant cost for the national health system (NHS) in many countries. No data are available on costs and therapeutic classes of unused medicines in Italy.Objective: Conduct a quantitative and qualitative analysis of unused medicines returned for disposal to selected pharmacies in Rome, Italy, as well as to estimate the related costs for the NHS. Methods: Medicines returned to 4 pharmacies were collected for 8 months. Therapeutic class, number of remaining dosage units, remaining validity, and reimbursement by the NHS were analysed. The cost of reimbursed medicines was estimated on the prices provided by the Italian regulatory agency (AIFA). Results: The study sample consisted of 3219 medicine packages containing remaining dosage units, of which 72.4% had expired while 27.6% had not. The average remaining validity of unexpired medicines was 13 months. Medicines reimbursed by the NHS accounted for 73% of the total. Cardiovascular drugs and anti-infectives were the main therapeutic classes (17.2% and 15.2% of total packages, respectively), followed by gastrointestinal drugs, central nervous system (CNS) drugs, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroids. The average of remaining dosage units found in the examined packages was 68% of the initial number of units. In terms of cost, antibiotics were the most relevant therapeutic class, followed by cardiovascular drugs, analgesics, corticosteroids, and NSAIDs. The estimated cost for the Italian NHS was € 200,656,780 per year. Conclusion: Waste medicines constitute a significant, but reducible cost for the NHS. The high prevalence of anti-infectives in the study sample appears to be a distinctive Italian characteristic and may be due to inappropriate prescribing. Policies aimed at reducing waste should improve prescriptive appropriateness and increase the variety of packaging size
Interactions between prebiotics, probiotics, polyunsaturated fatty acids and polyphenols: diet or supplementation for metabolic syndrome prevention?
No full textThe metabolic syndrome can be prevented by the Mediterranean diet, characterized by fiber, omega-3 polyunsaturated fatty acids and polyphenols. However, the composition of the Mediterranean diet, which can be viewed as a natural multiple supplement, is poorly controlled, and its beneficial effects poorly predictable. The metabolic syndrome is associated with intestinal dysbiosis and the gut microbioma seems to be the main target and player in the interactions occurring between probiotics, prebiotics, omega 3 polyunsaturated fatty acids, and polyphenols. From the reviewed evidence, it is reasonable to manage growth and metabolism of gut microflora with specific prebiotics and polyphenols. Even though the healthy properties of functional foods and nutraceuticals still need to be fully elucidated, available data suggest that well-designed supplements, containing the better ratio of omega-3 polyunsaturated fatty acids and antioxidants, specific probiotic strains, and selected polyphenols and prebiotics, could be useful in metabolic syndrome prevention and treatment..........
The importance of reporting unexpected drug failure
Full text linkUnexpected drug failure is a lack of therapeutic effect, which is not expected based on the characteristics of the drug and patient. Essentially, it may occur either for interactions (with other drugs or foods) or for biopharmaceutical issues. The risk arising from interactions is generally well characterised and physicians are well aware of it, and the importance of reporting cases of failure due to interactions is obvious. Less is known about the mechanisms and potential risk deriving from biopharmaceutical problems, and we will therefore focus on this issue. Biopharmaceutics describes the influence of the physical/chemical properties of the drug and drug product on the rate and extent of systemic drug absorption. Because after oral administration of solid pharmaceutical forms drugs must dissolve in gastrointestinal fluids before being absorbed through the intestinal epithelium, biopharmaceutical problems essentially arise from an insufficient dissolution performance. A typical situation where an insufficient dissolution may cause unexpected drug failure is when a patient is switched from one drug product to a different product. Different drug products with the same active substance may differ in manufacture and excipient composition
The administration in association of topical beta-blockers reduced intraocular pressure and increases tonographic outflow more effectively than the administration of the single drugs
No full textManifestations of acute opiate withdrawal contracture in rabbit jejunum after mu-, kappa- and delta-receptor agonist exposure.
No full text1. Following a 5 min in vitro exposure to morphine (1.3 x 10(-7) M), U-50,488H (2.5 x 10(-8) M) and deltorphin (1.6 x 10(-8)-6.5 x 10(-9) M), the rabbit isolated jejunum exhibited a precipitated contracture after the addition of naloxone (2.75 x 10(-7) M). 2. The precipitated responses to U-50,488H and deltorphin but not to morphine were reproducible in the same tissue. 3. The precipitated contractures were blocked completely by tetrodotoxin (3 x 10(-7) M), partially by atropine (1.5 x 10(-7) M) and not affected by hexamethonium (1.4 x 10(-5) M). 4. Naloxone administration (2.75 x 10(-7) M) before the agonist prevented the development of the adaptive response to morphine and U-50,488H but not to deltorphin. 5. The selective antagonists norbinaltorphimine (2.7 x 10(-8)-2.7 x 10(-9) M) and naltrindole (1.1 x 10(-7) M) prevented the adaptive response development only to the respective agonists. 6. The opioid agonists partially inhibited the spontaneous activity of the tissue. This study has shown that independent activation of mu-, kappa- and delta-opioid receptors can induce dependence in this isolated tissue. Rabbit jejunum is a suitable tissue for studying the acute effects of opioids on the adaptative processes determined by their administration
Permitted daily exposure for diisopropyl ether as a residual solvent in pharmaceuticals
Full text linkSolvents can be used in the manufacture of medicinal products provided their residual levels in the final product comply with the acceptable limits based on safety data. At worldwide level, these limits are set by the "Guideline Q3C (R6) on impurities: guideline for residual solvents" issued by the ICH. Diisopropyl ether (DIPE) is a widely used solvent but the possibility of using it in the pharmaceutical manufacture is uncertain because the ICH Q3C guideline includes it in the group of solvents for which "no adequate toxicological data on which to base a Permitted Daily Exposure (PDE) was found". We performed a risk assessment of DIPE based on available toxicological data, after carefully assessing their reliability using the Klimisch score approach. We found sufficiently reliable studies investigating subchronic, developmental, neurological toxicity and carcinogenicity in rats and genotoxicity in vitro. Recent studies also investigated a wide array of toxic effects of gasoline/DIPE mixtures as compared to gasoline alone, thus allowing identifying the effects of DIPE itself. These data allowed a comprehensive toxicological evaluation of DIPE. The main target organs of DIPE toxicity were liver and kidney. DIPE was not teratogen and had no genotoxic effects, either in vitro or in vivo. However, it appeared to increase the number of malignant tumors in rats. Therefore, DIPE could be considered as a non-genotoxic animal carcinogen and a PDE of 0.98 mg/day was calculated based on the lowest No Observed Effect Level (NOEL) value of 356 mg/m3 (corresponding to 49 mg/kg/day) for maternal toxicity in developmental rat toxicity study. In a worst-case scenario, using an exceedingly high daily dose of 10 g/day, allowed DIPE concentration in pharmaceutical substances would be 98 ppm, which is in the range of concentration limits for ICH Q3C guideline class 2 solvents. This result might be considered for regulatory decisions
Antinociceptive effects of trazodone and m-chlorophenylpiperazine (mCPP) in mice: interaction with morphine.
No full text1. The antidepressant trazodone and its main metabolite m-chlorophenylpiperazine (mCPP) were investigated for their analgesic properties and their sensitivity to a threshold dose of morphine in acetic acid abdominal constriction and hot plate tests. 2. The drugs elicited hypoalgesic effects at about the same doses in the two analgesic assays. 3. Naloxone (2 mg/kg i.p.) prevented the hypoalgesia of trazodone but not of mCPP in the hot plate test. The opiate antagonist did not affect the responses of both drugs to the writhing test. 4. Subanalgesic doses of the two drugs increased the sensitivity to morphine in both assays. The results further support the suggested role played by opioid and 5-HT systems on depression
Time-course of aspirin and salicylate in ocular tissues of rabbits.
No full textThe time courses of aspirin and salicylate in plasma and ocular tissues of rabbits were investigated after the i.v. administration of aspirin. Unhydrolyzed aspirin rapidly disappears from plasma and many ocular compartments but persists up to 4 hours in aqueous and vitreous humours. Salicylate decreases in plasma follow an exponential kinetics; in aqueous humour and in vascularized tissues the behaviour is similar but with a half-life longer than in plasma. In the cornea, lens and vitreous humour, the concentration of salicylate reaches a peak between 2 and 4 hours, then it decreases very slowly. Our results show that aspirin is protected from the hydrolytic action of plasmatic esterases in aqueous and vitreous humours but is rapidly hydrolyzed in the cornea and lens by local esterases present in these tissues. It is possible that both aspirin and salicylate leave the eye by means of an active transport. Our results also indicate that salicylate can accumulate in the cornea, lens and retina when aspirin is administered repeatedly
Effect of nonsteroidal anti-inflammatory drugs on withdrawal responses in guinea pig ileum after a brief exposure to morphine.
No full textThe inhibition mechanism of nonsteroidal anti-inflammatory drugs (NSAIDs) on withdrawal response was examined in vitro. Naloxone elicited a strong contraction in the isolated guinea pig ileum after a 5-min exposure of the tissue to morphine. The contraction was inhibited by aspirin, indomethacin and salicylic acid, administered concomitantly to morphine or 1 min before the opioid antagonist. The short contact time of NSAIDs with the isolated preparations seems to indicate that mechanisms other than inhibition of prostaglandins synthesis are implicated in this action. NSAIDs depressed the ileum contraction to naloxone after stimulation of the tissue with cholecystokinin, when injected into the bath 1 min before the peptide. The contraction to naloxone after exposure to indirect excitatory peptides was very similar to withdrawal contraction. After maximal ileum stimulation with prostaglandin E1, naloxone induced a strong contraction indicating that this substance activates the opioid system, as occurs with cholecystokinin. NSAIDs, at concentrations that inhibit naloxone-induced contractions, did not depress the maximal contracture to cholecystokinin and prostaglandin E1, but inhibited the submaximal one. These results suggest that the inhibition of withdrawal contraction by NSAIDs in acute dependence is due mainly to their ability to block the contraction caused by substances whose action is neuronally mediated, which are released to counteract the opioid action. Prostaglandin E1 may be part of this system of action and reaction
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