1,720,993 research outputs found
Detoxification from opioids with clonidine, clonidine-naloxone and clonidine-naltrexone
No full textIn this chapter the technical guidelines for detoxification from heroin addiction without substitutive drugs are described.
These treatment must be administered to selected patients and requires strict medical surveillance. They must not be considered a simple alternative to the use of methadone. Any modality of treatment approach could be suitable for a single addict at a different points along his life but it should always be tailored to his peceluiar needs
Treatment with naltrexone
No full textThe procedures of naltrexone treatment for the maintenance of a drug-free state from opioids are described.
Treatment with naltrexone (a competitive antagonist of the opioid receptors with oral activity and long duration of action) must be employed in order to establish a therapeutic relationship with the patients as a starting point for rehabilitation to maintain and strengthen a drug-free life style once the drug free condition is reache
Farmacologia e Tossicologia
No full textVolume che tratta la farmacologia generale e clinica e la tossicologia clinica destinato agli studenti dei corsi di diploma universitario in ambito sanitario.
Comprende una parte di Farmacologia generale (farmacocinetica e dinamica, principi di farmacologia clinica), di Farmacologia speciale (farmaci del sistema nervoso autonomo, dell'apparato cardiovascolare, dei reni e delle vie urinarie, del sangue, del sistema nervoso centrale, farmaci antiinfiammatori, che modificano la motilità uterina, dell'apparato digerente e vie biliari, apparato respiratorio, la farmacologia endocrinologica, farmaci chemio-antibiotici, vitamine, farmacologia oculare) e la tossicologia (sostanze d'abuso e intossicazioni acute più frequenti
Le neuropatie da farmaci
No full textLe neuropatie periferiche da farmaci sono un effetto collaterale relativamente frequente e possono avvenire a carico dei nervi motori, sensitivi o autonomi. I farmaci possono anche indurre una neuropatia a carico del nervo ottico. Clinicamente queste neuropatie sono estremamente variabili e possono essere acute, subacute e croniche; si possono manifestre solo con leggero intorpidimento alle estremità, disestesie, parestesie e con o senza soggettive modificazioni del tatto e della sensazine di dolore
Cefalea attribuita all'uso di sostanze o alla loro sospensione
No full textLe cefalee secondarie all’uso di sostanze o alla loro sospensione rientrano, in termini più generali, tra le reazioni avverse ai farmaci. Questo tema, come quello della sicurezza dei farmaci, è oggi di straordinaria importanza considerato il numero sempre crescente di persone che assumono farmaci e spesso più di uno contemporaneamente. Infatti le reazioni indesiderate ai farmaci sono un’importante causa di morbilità e mortalità soprattutto nel mondo occidentale.
I farmaci sono classificati sulla base della loro attività terapeutica principale ma nessun farmaco determina un effetto unico e specifico. I farmaci possono essere selettivi ma raramente sono specifici. I loro effetti sono di due tipi: quelli utili ai fini terapeutici e quelli inutili a questo fine e indesiderati. Questi ultimi sono definiti effetti collaterali o reazioni avverse. Per reazione avversa si intende una reazione nociva e non intenzionale che si presenta in rapporto con l’assunzione di un farmaco, usato nelle giuste indicazioni, per la diagnosi, la profilassi e la terapia, escludendo gli errori terapeutic
INFLUENCE OF PROLONGED THERAPY WITH FLUNARIZINE ON GLUCOSE, INSULIN AND C-PEPTIDE METABOLISM
No full textThe use of flunarizine in the preventive treatment of headaches and migraine is now widely done. Taking into account that the main and more frequent side effects of this treatment are weight gain and increase of appetite, with a typical carbohydrates craving, we studied the influence of a prolonged treatment of flunarizine on glucose, C- peptide and insulin metabolism in headache sufferers.
All these substances were studied before and after treatment and we did not find significant differences after the treatment. So we could conclude that this drug even if increases appetite , does not interfere with glucose metabolism and it is possible to hypothesize that the carbohydrate craving could be related to a facilitate income of glucose into the cell
Triptans: what is the clinical importance of kinetic differences?
No full textTriptans, selective antagonists of 5-HT1B/1D receptor, are effective and safe drugs for acute migraine treatment. Their marketing has greatly boosted research on migraine pathogenesis, has improved the methodologies of clinical trials, and has allowed defining which characteristics should have the ideal medications for acute treatment according to patients: pain-free response within 2 hours, no recurrence or need for other drugs, consistency of response, oral administration, good tolerability, safety, and no drug-drug interactions. However, triptans do not always correspond to these parameters. In particular, the maximum response after oral administration, measured as pain-free after 2 hours, is approximately 70% in clinical trials and up to 40% of attacks fail to respond to a particular triptan. Furthermore, less than 2/3 of patients respond to a triptan in 3/3 attacks [1].
In Italy there are available 6 triptans with similar mechanism of action, but different kinetics profiles. In alphabetical order, the first one is almotriptan. Its oral bioavailability is 70-80%, Tmax after oral administration is about 1 to 4 hours, and elimination half-life is 3 to 4 hours. Oral bioavailability of eletriptan is 50%, its elimination half-life is 4 to 5 hours, and Tmax after oral administration is about 1.3 hours. Frovatriptan presents long half-life (25 hours), but a relatively low bioavailability of 24 to 30%, and Tmax after oral administration is 2 to 4 hours. Elimination half-life of rizatriptan is 2-3 hours, bioavailability is 40-50%, and Tmax after oral administration is about 1-1.5 hours. Sumatriptan is rapidly, but incompletely absorbed following oral administration and undergoes first-pass metabolism. Bioavailability following subcutaneous administration is much higher (96%) than after oral (14 %) or intranasal (16%) administration of sumatriptan, and elimination half-life is about 2 hours. Half-life of zolmitriptan is 2.5 to 3 hours, and its oral bioavailability is approximately 40%.
The clinical importance of pharmacokinetic differences after oral administration (which we have summarized above) has not been established yet, as far as both efficacy and tolerability are concerned. There are no elements to foresee which triptan works best for any given patients [2]. However, it has been suggested that pharmacokinetics during early post-dose interval (0-2 hours) is the most important one for clinical response and that the initial rate of absorption and the height of the plasma levels reached may be closely related to headache relief [3]. A slow and reduced early absorption after oral administration could therefore explain the poor response reported by some patients.
[1] Dodick DW. Triptan nonresponder studies: implications for clinical practice. Headache 2005; 45(2):156-62
[2] Maas HJ, Danhof M, Della Pasqua OE. Prediction of headache response in migraine treatment. Cephalalgia 2006; 26(4):416-22
[3] FOX AW. Onset of effect of 5-HT1B/1D agonists: a model with pharmacokinetic validation. Headache 2004; 44(2):142-
Chronic headache and analgesic abuse
No full textThis research analyzed chronic headache patient-analgesic drug interactions, describing in particular the characteristics of analgesic drug-taking behaviour and its consequences in a sample of patients suffering from chronic headache and assuming daily analgesic drugs
Lessons from triptans in migraine treatment
No full textResearch for a new antimigraine compound started at Glaxo in 1972 and led to the discovery of the first triptan drug, sumatriptan, a 5-HT1-like receptor agonist with an indolic structure identical to neurotransmitter 5-HT.
On November 14th, 1991, SISC organised in some Italian Headache Centres the “Migraine Day”, officially starting the sumatriptan “revolution”, followed by the “age of triptans”. The availability of sumatriptan, a specific analgesic for migraine pain, had opened new prospects of migraine treatment, which up to then had only used non-specific analgesics, such as FANS, paracetamol, and ergotamine, an agonist drug of various receptors, with important side effects and contraindications. Research was immediately directed towards the synthesis of triptans with better pharmacokinetic and pharmacodynamic characteristics and less side effects. Six triptans were synthesized, 5 of which had the same indolic structure as sumatriptan and were therefore defined as “me-too”, while one had a carbazolic structure.
Like all revolutions, the triptans’ was a complete one. The congresses, courses, and conferences were practically all about the research of the triptan with the highest therapeutic index.
However, the physiopathology of migraine pain implies, besides 5-HT, noradrenaline, the formation of NO, GABA, enkephalins, and the release of neurotransmitters (SP and CGRP) and neuropeptides.
The proof that an agonist of receptor CGRP is effective in migraine pain treatment when taken by mouth opens new prospects. If there are available different types of antimigraine drugs and their associations, subtypes of patients shall be identified, according to the different treatments or associations they need.
The methodological elements which can be deduced from research on the clinical efficacy of triptans, opening new prospects of research about the physiopathology and clinical aspects of migraine, are the following:
1°) detecting premonitory symptoms that may increase the awareness of migraine;
2°) detecting the onset time of migraine aura and its signs and symptoms;
3°) deciding when the drug must be administered in clinical trials;
4°) detecting pain intensity (light, moderate, or severe) and the possible autonomic symptoms when administering the drug and afterwards, after established periods of time, and assessing the following primary end points:
- pain relief and pain free after 30 and 60 minutes
- pain free after 2 hours (not pain relief)
- sustained pain free after 24 hours
- sustained pain free and no side effects after 24 hours
and the following secondary end points:
- presence and intensity of possible other symptoms (osmophobia, phonophobia, photophobia, nausea, vomiting)
- recurrence after 24 hours
- disability time per treated attack
- consistency across multiple attacks.
The criteria of inclusion of migraine patients in clinical trials must consider the severity of migraine, assessing the progress and characteristics of the last 5-10 attacks, in order to divide into groups the subjects included in the studies. The efficacy of a drug is different in episodic migraine patients with attacks lasting 3-4 hours and in patients with attacks lasting 4-8 hours or previously treated with drugs causing pain relief for a few hours, with the reappearance of pain, for example, after 4-6 hours.
Patients’ selection contributes to the disparity between clinical trials and clinical practice; it is fundamental that patients in clinical trials are as similar as possible to the patients who are then going to take the drugs in clinical practice.
Drugs should be used as research tools and clinical records should be created on these bases, in order to know more about the mechanism of pain generation subsequent to the activation of the trigeminal vascular system and about the role played by vasodilatation and plasma protein extravasation
PHARMACOKINETICS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS
No full textPharmacokinetics of NSAIDS is relevant both for therapeutic and side effects especially with regard in "A" type of side effects and in their incidence. It is observed that NSAIDs reach high concentrations in body compartments in which cause therapeutic or unwanted effects, and therefore it is important to know pharmacokinetics of these drugs.
The four phases of pharmacokinetics are explained, and the differences within different drugs are reported. It is important to note that from there differences it should be possible avoid known side effects or minimize it by using an appropriate drug dispensation regimen. Finally the investigation of these pharmacokinetic parameters could lead to develop better drugs as well to avoid accidents with new compounds extensively employed in clinical practice
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