Cytisine is considered to be the oldest medication for smoking cessation and has been used for this purpose in some Eastern/Central European and Central Asian countries for over 50 years. Several sources points towards cytisine\'s efficacy and effectiveness; it\'s well tolerated when taken at the recommended dose, and adverse events reported in trials are typically non-serious and self-limiting gastrointestinal and sleep disturbances. We report a suspect case of urticaria during treatment for smoking cessation with cytisine in a woman of 48 years treated for smoking at the Unit of Addiction Medicine, Department of Internal Medicine, Hospital Trust of Verona, Italy.  The therapeutic protocol of cytisine that was used is of the \"inductive\" type; it consists in gradually increasing the daily capsules taken, with a parallel reduction in the number of cigarettes smoked until complete cessation between the fifth and ninth day of therapy (quit day) The number of capsules taken is then gradually reduced. She was treated for the firsts three days with betamethasone 1 mg/die, on the advice of her general practitioner, and suspended Cytisine. A week later the patient showed signs of recovery.

OBJECTIVE: The purpose of this exercise was to explore the utility of allometric scaling approach for the prediction of intravenous and oral pharmacokinetics of six dipeptidy peptidase-IV (DPP-IV) inhibitors viz. ABT-279, ABT-341, alogliptin, carmegliptin, sitagliptin and vildagliptin.
METHODS: The availability of intravenous and oral pharmacokinetic data in animals enabled the allometry scaling of 6 DPP-IV inhibitors. The relationship between the main pharmacokinetic parameters [viz. volume of distribution (Vd) and clearance (CL)] and body weight was studied across three or four mammalian species, using double logarithmic plots to predict the human pharmacokinetic parameters of CL and Vd using simple allometry.
RESULTS: A simply allometry relationship: Y = aWb was found to be adequate for the prediction of intravenous and oral human clearance/volume of distribution for DPP-IV inhibitors. The allometric equations for alogliptin, carmegliptin, sitagliptin, vildagliptin, ABT-279 and ABT-341 were 1.867W0.780, 1.170W0.756, 2.020W0.529, 1.959 W0.847, 0.672 W1.016, 1.077W 0.649, respectively, to predict intravenous clearance (CL) and the corresponding equations to predict intravenous volume of distribution (Vd) were: 3.313W0.987, 6.096W0.992, 7.140W0.805, 2.742W0.941, 1.299W0.695 and 5.370W0.803. With the exception of a few discordant values the exponent rule appeared to hold for CL (0.75) and Vd (1.0) for the predictions of various DPP-IV inhibitors. Regardless of the routes, the predicted values were within 2-3 fold of observed values and intravenous allometry was better than oral allometry.
CONCLUSIONS: Simple allometry retrospectively predicted with reasonable accuracy the human reported values of gliptins and could be used as a prospective tool for this class of drugs.

Serotonin syndrome is caused by excess serotonin in the central nervous system. It usually occurs as adverse drug-therapy (neuroleptic agents, monoamine oxidase inhibitors, serotonin reuptake inhibitors and others).
METHODS: a 50-year-old woman with a history of depression, was admitted to our hospital, due to suicidal drug poisoning (moclobemide- 4500 mg, venlafaxine 1050 mg, mianserin 300 mg and cytisine 30mg). She was also drunk. The patient was unconscious and sweaty, on the ECG tachycardia (120/min) was observed. In addition, several hours after admission, the patient developed acute respiratory failure, we observed myoclonus, lockjaw, body temperature increased to 37.3 degrees Celsius, and blood pressure was 170/80 mmHg. During the neurological examination there was a tendency to bilaterall Babinski sign and the nystagmus was present. The patient was intubated, and we started an intravenous infusion of Relanium. In laboratory studies: ethanol: 2.52 g/l, tests for benzodiazepines and tricyclic antidepressants were negative, WBC 13.1 tys/microl, CPK was elevated to 372 U/L, other parameters (electrolytes, transaminases, serum total protein, glucose, CRP, creatinine) were normal. The patient required intensive care and treatment during the next two days. The diagnosis of serotonin syndrome was based on the Hunter\'s criteria, which are more sensitive and more specific than Sternbach\'s criteria. The patient was discharged from hospital in good condition.

A 25-year-old man presented with Touraine-Solente-Golé syndrome (primary pachydermoperiostosis), with an area of inflammatory dermatosis (12-month evolution) of the scalp at the cranial vertex. The patient presented with arthropathy, clubbing of the digits, diffuse periostosis, pachydermia of the hands and feet, and periosteal hyperostosis of the knee. Facial seborrhea and sebaceous gland hyperplasia were evident (Figure 1A and 1B and Figure 2A and 2B). Examination of the scalp revealed an erythematous pruritic plaque with erosions, crusts, and pustules, on which multiple tufts of 10 to 20 normal-looking hairs emerged from single follicular openings (Figure 3A). Slight pressure on the perifollicular areas resulted in the discharge of purulent material through the dilated follicular openings. Cervical and occipital lymph nodes were not enlarged, and the patient was in generally good health. Routine laboratory findings were normal. Immunologic studies, including a screening for antinuclear antibody, complement, and immunoglobulins, were normal. Both potassium hydroxide staining and fungal culture were negative. Bacteriologic culture of purulent material taken from the affected area was positive for Staphylococcus aureus. Videodermoscopy of the lesion showed rarefied interfollicular twisted red loops centered around actively affected follicles and white dots with absence of normal vascular pattern (Figure 3B). These dermoscopy patterns are markers for folliculitis decalvans, of which tufted hair folliculitis (THF) is a clinical variant. Histologic examination showed hair plugging, a dense perifollicular infiltrate of plasma cells, lymphocytes, neutrophils, and large areas of scarring and fibrosis, which would confirm suspected THE THF was diagnosed on the grounds of clinical, microbiologic, histologic, and videodermoscopy data. The patient was treated with amoxicillin 875 mg plus clavulanic acid 125 mg twice daily and topical nadifloxacin 1% twice daily for 20 days, achieving substantial clinical improvement. One month after antimicrobial therapy, a single area of cicatricial alopecia with a few hair tufts emerging from single orifices was observed, and no new lesions or symptoms had appeared.

A 19-year-old Japanese man had been treated for ulcerative colitis for 2 years. He was admitted to our hospital with nodulocystic inflammatory papules and pustules on his face and chest, high-grade fever, arthralgia and general malaise. A biopsy specimen from a pustule showed prominent infiltration of neutrophils in the epidermis and dermis, particularly around hair follicles. We made a diagnosis of acne fulminans. The systemic administration of prednisolone at 30 mg daily for 1 week immediately improved his skin lesions and other symptoms; however, during tapering of prednisolone at 20 mg daily, skin lesions flared up. The addition of oral diaminodiphenylsulfone improved the skin lesions. Although there have been a few reports of acne fulminans associated with Crohn\'s disease, this is the first case report of acne fulminans in a patient with ulcerative colitis. It is noteworthy that the addition of diaminodiphenylsulfone was effective for treating the relapse of acne fulminans in this case.

Heart block and Q-Tc interval prolongation have been reported with several agents used in anesthesia, and the US Food and Drug Administration mandates evaluation of the Q-T interval with new drugs. Drug-induced Q-T interval prolongation may precipitate life-threatening arrhythmias, is considered a precursor for torsades de pointes, and may predict cardiovascular complications. In the patient described in this article, heart block occurred and the Q-Tc interval became prolonged after muscle relaxant reversal with neostigmine; both were considered to be related to the combination of agents used in the case, as well as to other predisposing factors such as morbid obesity. The agents used that affected cardiac conduction were neostigmine, desflurane, droperidol, dolasetron, and dexmedetomidine. Although the heart block was resolved after 2 doses of atropine, prolonged P-R and Q-Tc intervals persisted into the immediate postoperative period but returned to baseline within 4 hours. Clinical implications of this report include increasing awareness of the multitude of factors affecting Q-T interval prolongation during anesthesia.

Dolasetron (Anzemet) overdose is uncommon, and, to our knowledge, this is the only case report of an intentional overdose. Dolasetron (dolasetron mesylate) is a selective 5-hydroxytryptamine 3 antagonist derived from pseudopelletierine, and is used in the prevention and treatment of nausea and vomiting. Transient and asymptomatic ECG changes, including QRS widening and PR and QTc prolongation, have been reported in therapeutic doses. The case of a 21-year-old woman who presented after an intentional overdose of 10x200 mg dolasetron tablets resulting in prolongation of the QTc interval and severe hypotension is reported here. Management of hypotension included intravenous fluid resuscitation and norepinephrine infusion with invasive monitoring in a high dependency unit. Sodium cardiac channel block contributes to cardiotoxicity observed in dolasetron overdose. Sodium bicarbonate was used in an attempt to reduce cardiac sodium channel block, although we observed no apparent benefit. As dolasetron becomes more commonly used in the outpatient setting, both doctors and patients need to be aware of the dangers of dolasetron in toxic doses. The pharmacology and toxicology of dolasetron are discussed.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a significant cause of morbidity among patients undergoing general anaesthesia. The optimal strategy for prevention of PONV, however, remains unclear. This study compared two commonly used prophylactic strategies in high-risk, day-case, gynaecological surgery patients.
METHODS: We conducted a randomized trial comparing sevoflurane combined with dolasetron (SD), with propofol-based total intravenous anaesthesia (TIVA) in 126 high-risk patients undergoing day-case gynaecological surgery. The primary endpoints included the incidence and severity of nausea or vomiting before discharge and the incidence of nausea or vomiting between discharge and 24 h. To identify the factors most predictive of a complete response (no PONV at any time within the 24 h period), multiple logistic regression models were fitted.
RESULTS: Before discharge, there was no significant difference between the two treatment groups with respect to nausea and vomiting outcomes (P = 0.3). Post-discharge nausea and vomiting (PDNV), however, were significantly more common for patients in the TIVA group (nausea, P = 0.004 and vomiting, P = 0.03). Type of anaesthetic, adjusted for weight and anaesthesia duration was significantly associated with complete response (odds ratio = 2.7, 95% confidence interval = 1.15 to 6.4).
CONCLUSIONS: Although both TIVA and dolasetron prophylaxis reduce the predicted rate of PONV in the early postoperative period, the anti-emetic effects of propofol are short-lived. A longer-acting drug such as dolasetron may therefore be necessary to prevent PDNV.

Gynaecological surgery is of high emetogenic potential and both total intravenous anaesthesia (TIVA) and prophylactic antiemetic therapy may reduce the incidence of postoperative nausea and vomiting (PONV). We studied 144 patients scheduled for day-case gynaecological laparoscopy in a randomized trial comparing balanced inhalational anaesthesia and prophylactic dolasetron (group I+D) with propofol TIVA and dolasetron (group T+D) or TIVA alone (group T). The primary outcome of \"complete response\" (no vomiting, no treatment for PONV) was not significantly different among groups (34%, 51%, 32%; groups I+D vs T+D vs T, P=0.12). During the first hour after surgery, group I+D had nausea of greater severity (P<0.03). During hospital admission, group T had more vomiting (P<0.03). From discharge until 24 hours postoperatively, 55% of group I+D experience nausea and 38% vomited. The incidence and severity of nausea were significantly lower in the TIVA groups (P<0.04 and <0.05 respectively). There were no significant differences between groups T+D and T, although comparing all groups the complete response rate was highest and the post-discharge incidence and severity of nausea lowest in group T+D. In conclusion, propofol TIVA, with or without dolasetron, reduced postoperative nausea, but not perioperative vomiting or antiemetic requirement, when compared with inhalational anaesthesia plus dolasetron.

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