Incidence Of Acute Adverse Effects Research Articles

Prophylactic Methylxanthines for Preventing Extubation Failure in the Preterm Neonates with the Gestational Age of ≤30 Weeks: A Randomized Controlled Trial

Background: Preterm neonates are at a high risk of respiratory depression at birth. Incidence of respiratory distress is reported in 60-80% of the neonates born with the gestational age of less than 28 weeks and 15-30% of the neonates with the gestational age of less than 32-34 weeks. The present study aimed to compare the incidence and risk of failed extubation in using caffeine and aminophylline in the preterm neonates with the gestational age of ≤30 weeks in the periextubation period.Methods: This single-centered, parallel, open-label, randomized controlled trial was conducted in a tertiary care referral hospital in India during June 2014-2016. Neonates with the gestational age of ≤30 weeks who were intubated for a minimum of 24 hours were enrolled in the study. Neonates with major anomalies, heart disease, and sepsis were excluded from the study. After the random allocation of the infants to treatment with the standard dose of caffeine citrate and aminophylline methylxanthine, intubation continued for seven consecutive days with or without non-invasive ventilatory support. As the primary objective, the incidence and risk of failed extubation were assessed. Secondary objective of the research was to compare the relative incidence of acute adverse effects, persistent apnea, and the associated morbidities.Results: Neonates treated by caffeine were at a higher risk of extubation failure (1.09 times) adjusted with birth weight (31.5% versus 21.4%; RR=1.09; 95% CI: 0.81-1.46; P=0.55), which was not statistically significant. In addition, risk of apnea within seven days and after seven days of methylxanthine therapy was 1.57 (95% CI: 0.95-2.61) and 1.10 (95% CI: 0.95-2.61) times higher in the neonates with caffeine treatment. Also, rate of tachycardia was high in the neonates treated by aminophylline, which was statistically significant (RR=0.27; 95% CI: 0.13-0.56; P<0.001). Duration of non-invasive ventilator support, length of admission in the neonatal intensive care unit, O2 requirement at discharge, death before hospital discharge, and the associated morbidities were similar between the groups.Conclusion: According to the results, the incidence and risk of extubation failure were clinically high in the caffeine-treated neonates. However, aminophylline administration could continue as a prophylactic agent in developing countries under medical supervision.

Best Clinical Practice With Ziprasidone IM: Update After 2 Years of Experience

Acute agitation is a common psychiatric emergency often treated with intramuscular (i.m.) medication when rapid control is necessary or the patient refuses to take an oral agent. Conventional i.m. antipsychotics are associated with side effects, particularly movement disorders, that may alarm patients and render them unreceptive to taking these medications again. Ziprasidone (Geodon) is the first second-generation, or atypical, antipsychotic to become available in an i.m. formulation. Ziprasidone IM was approved by the Food and Drug Administration in 2002 for the treatment of agitation in patients with schizophrenia. In October 2004, a roundtable panel of physicians with extensive experience in the management of acutely agitated patients met to review the first 2 years of experience with this agent. This monograph, a product of that meeting, discusses clinical experience to date with ziprasidone IM and offers recommendations on its use in various settings. In clinical trials, patients treated with ziprasidone IM demonstrated significant and rapid (within 15-30 minutes) reduction in agitation and improvement in psychotic symptoms, agitation, and hostility to an extent greater than or equal to that attained with haloperidol i.m. Tolerability of ziprasidone IM was superior to that of haloperidol IM, with a lower burden of movement disorders. Clinical trials have also shown that ziprasidone IM can be administered with benzodiazepines without adverse consequences. Transition from i.m. to oral ziprasidone has been well tolerated, with maintenance of symptom control. The most common adverse events associated with ziprasidone IM were insomnia, headache, and dizziness in fixed-dose trials and insomnia and hypertension in flexible-dose trials. No consistent pattern of escalating incidence of adverse events with escalating ziprasidone doses has been observed. Changes in QTc interval associated with ziprasidone at peak serum concentrations are modest and comparable to those seen with haloperidol IM. Results of randomized clinical trials of ziprasidone IM have been corroborated in studies in real-world treatment settings involving patients with extreme agitation or a recent history of alcohol or substance abuse. In these circumstances, clinically significant improvement was seen within 30 minutes of ziprasidone IM administration, without regard to the suspected underlying etiology of agitation. Agents with a good safety/tolerability profile, such as ziprasidone IM, may be more cost effective long term than older agents, due to reduced incidence of acute adverse effects (eg, acute dystonia) that often require extended periods of observation. Additional trials of ziprasidone IM in agitated patients in a variety of clinical setting are warranted to generate comparative risk/benefit data with conventional agents and other second-generation antipsychotics.

Oral Prednisolone Supplement Abolishes the Acute Adverse Effects Following Initiation of Depot Bromocriptine Therapy

OBJECTIVE Although an effective treatment for hyperprolactinaemia, initiation of bromocriptine therapy may be associated with significant acute side-effects in some patients, particularly nausea, vomiting and postural hypotension. These may be minimized by initial treatment with i.m. depot bromocriptine (Parlodel-LAR, Sandoz, Basel, Switzerland), but adverse effects following the first injection may still be a significant problem. Following the observation that cortisol deficient patients were subject to an increased incidence of severe side-effects on initiation of bromocriptine therapy, we have evaluated whether concurrent administration of oral prednisolone to patients without cortisol deficiency might reduce adverse effects. DESIGN Double-blind placebo-controlled trial with prednisolone (20 mg) prior to, and 16 hours after, depot injection of i.m. bromocriptine (50 or 100 mg). PATIENTS Twenty-one consecutive patients with hyperprolactinaemia (serum prolactin >1000 mU/l on 3 separate occasions) who were due to start depot bromocriptine and who had a normal cortisol response to insulin-induced hypoglycaemia. MEASUREMENTS Symptoms at 0, 16 and 40 hours after injection were assessed using visual linear analogue scales and both inter and intra-group scores were compared by non-parametric tests. RESULTS Depot bromocriptine was associated with the significant occurrence of light-headedness and lethargy in the placebo-administered group by 16 hours, and also with nausea and nasal congestion by 40 hours. These symptoms did not occur in the prednisolone-administered group. CONCLUSIONS Concurrent oral administration of prednisolone significantly reduces the incidence of acute adverse effects following depot bromocriptine. Two 20 mg doses of prednisolone given at 12-hour intervals may be used to avoid dopamine-agonist-induced adverse effects at the initiation of treatment with depot bromocriptine, and may also be of value in the treatment of side-effects associated with other dopamine agonist drugs.

Piretanide. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy.

Piretanide is a potent 'loop' diuretic whose principal site of action is in the thick ascending limb of the loop of Henle. When administered orally or intravenously to healthy volunteers it rapidly increases diuresis and electrolyte excretion, and the effects are short-lived. In comparative studies, piretanide has generally been found to be 5 to 7 times more potent than frusemide (furosemide) but only one-tenth as potent as bumetanide, on a weight-for-weight basis. Piretanide 6 to 12 mg/day, in conventional or sustained release formulations, has been shown to significantly lower elevated blood pressure in a large proportion of patients with mild to moderate hypertension. Comparative trials of up to 3 months duration indicate that at this dosage piretanide is of comparable antihypertensive efficacy as hydrochlorothiazide 50 to 100 mg/day, but has significantly less effect on serum potassium levels. Short term studies in patients with oedema caused by renal, hepatic or cardiac failure demonstrated that piretanide 6 to 9 mg is of similar diuretic potency as frusemide 40 mg and bumetanide 1 mg. In medium term trials in patients with congestive heart failure piretanide 6 mg/day produced equivalent symptomatic improvement as frusemide 40 mg/day. When used to treat oedema caused by liver disease, piretanide 12 to 24 mg/day was successful in only about 50% of patients, but spironolactone added to the treatment regimen greatly increased the response rate. Generally, piretanide has been well-tolerated in clinical trials, although the conventional tablet formulation has caused a relatively high incidence of acute adverse effects--these were greatly reduced with the introduction of the sustained release formulation. Serum concentrations of most electrolytes have not shown any consistent adverse trends and hyperuricaemia and hypokalaemia have been encountered infrequently. Thus, piretanide appears to offer an effective alternative to other 'loop' diuretics for the treatment of oedematous diseases and to hydrochlorothiazide for the management of mild to moderate hypertension. However, its relative place in therapy remains to be clarified with wider clinical experience.