[Drug therapy of acute and chronic abdominal pain]

For drug therapy a differentiation of acute and chronic pain is essential. In emergency situations of acute abdominal pain a fast diagnosis is mandatory. Analgesia should be provided as soon as possible. The different groups of analgesics should be used according to their known effects, side effects and contraindications. Postoperative pain after abdominal surgery has to be considered as a special condition of acute abdominal pain. Main treatment options are non opioid analgesics and opioids. Opioids can be administered intravenously via patient controlled analgesia (PCA) devices. In major abdominal surgery neuroaxial analgesia, preferentially administered via an epidural catheter provides excellent pain relief with positive impact on gastrointestinal motility and patients' recovery. Because of difficulties to allocate chronic abdominal pain to a specific organ, causal treatment often turns out to be difficult. Peripheral and central sensitization, as well as an alteration of the endogenous pain modulation comes to the fore in these chronic pain conditions. Co-analgesics like anticonvulsants and antidepressants are utilized to reduce sensitization and improve the endogenous pain modulating system. Non drug approaches and alternative treatment options might be useful. In contrast, orally or transcutaneously administered opioids are the principal corner stone for the treatment of cancer pain.

[Drug therapy of type-II diabetes: tablets, insulin or a combination of these]

Optimal therapy of diabetes has to be based on the known pathophysiology of metabolic disturbances and should eventually alleviate reduced secretion of insulin as well as reduce the usually present resistance to insulin in order to normalize the average blood glucose levels. In less than 30% of patients with type-II diabetes, dietetic measures combined with increased physical activity alone, are sufficient for metabolic control, thus increasing the importance of pharmacologic treatment immensely. Biguanides are the therapeutic choice in patients with massive overweight, because they usually do not induce weight gain; however, specific contraindications (renal failure in particular) have to be taken into consideration. The effect of blood glucose lowering by biguanides is not due to increased secretion of insulin, thus neither hypoglycemias nor hyperinsulinism are induced or increased, respectively. Patients with normal or slightly increased body weight should profit best from sulfonylureas that stimulate insulin production. Combinations of sulfonylurea and biguanides or of insulin and oral antidiabetics or insulin alone have to be taken into account when monotherapy with oral antidiabetics is too inefficient; however, clear and generally accepted guidelines for correct indications of these therapeutic modalities are lacking. Particularly in long-lasting diabetes and for patients with distinct overweight an adequate therapeutic success is often not obtained with the currently available therapeutic means. Possibly, future developments will provide new therapeutic ways with drugs that increase insulin sensitivity or reduce gluconeogenesis.

Effects of anti-ischaemic drug therapy in silent myocardial ischaemia type I: the Swiss Interventional Study on Silent Ischaemia type I (SWISSI I): a randomized, controlled pilot study

AIMS: To determine the effect of anti-ischaemic drug therapy on long-term outcomes of asymptomatic patients without coronary artery disease (CAD) history but silent exercise ST-depression. METHODS AND RESULTS: In a randomized multicentre trial, 263 of 522 asymptomatic subjects without CAD but at least one CAD risk factor in whom silent ischaemia by exercise ECG was confirmed by stress imaging were asked to participate. The 54 (21%) consenting patients were randomized to anti-anginal drug therapy in addition to risk factor control (MED, n = 26) or risk factor control-only (RFC, n = 28). They were followed yearly for 11.2 +/- 2.2 years. During 483 patient-years, cardiac death, non-fatal myocardial infarction, or acute coronary syndrome requiring hospitalization or revascularization occurred in 3 (12%) of MED vs. 17 (61%) of RFC patients (P < 0.001). In addition, MED patients had consistently lower rates of exercise-induced ischaemia during follow-up, and left ventricular ejection fraction remained unchanged (-0.7%, P = 0.597) in contrast to RFC patients in whom it decreased over time (-6.0%, P = 0.006). CONCLUSION: Anti-ischaemic drug therapy and aspirin seem to reduce cardiac events in subjects with asymptomatic ischaemia type I. In such patients, exercise-induced ST-segment depression should be verified by stress imaging; if silent ischaemia is documented, anti-ischaemic drug therapy and aspirin should be considered.

Mechanisms and drug therapy of pulmonary hypertension at high altitude

Pulmonary vasoconstriction represents a physiological adaptive mechanism to high altitude. If exaggerated, however, it is associated with important morbidity and mortality. Recent mechanistic studies using short-term acute high altitude exposure have provided insight into the importance of defective vascular endothelial and respiratory epithelial nitric oxide (NO) synthesis, increased endothelin-1 bioavailability, and overactivation of the sympathetic nervous system in causing exaggerated hypoxic pulmonary hypertension in humans. Based on these studies, drugs that increase NO bioavailability, attenuate endothelin-1 induced pulmonary vasoconstriction, or prevent exaggerated sympathetic activation have been shown to be useful for the treatment/prevention of exaggerated pulmonary hypertension during acute short-term high altitude exposure. The mechanisms underpinning chronic pulmonary hypertension in high altitude dwellers are less well understood, but recent evidence suggests that they differ in some aspects from those involved in short-term adaptation to high altitude. These differences have consequences for the choice of the treatment for chronic pulmonary hypertension at high altitude. Finally, recent data indicate that fetal programming of pulmonary vascular dysfunction in offspring of preeclampsia and children generated by assisted reproductive technologies represents a novel and frequent cause of pulmonary hypertension at high altitude. In animal models of fetal programming of hypoxic pulmonary hypertension, epigenetic mechanisms play a role, and targeting of these mechanisms with drugs lowers pulmonary artery pressure. If epigenetic mechanisms also are operational in the fetal programming of pulmonary vascular dysfunction in humans, such drugs may become novel tools for the treatment of hypoxic pulmonary hypertension.

Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia

Early allogeneic hematopoietic stem cell transplantation (HSCT) has been proposed as primary treatment modality for patients with chronic myeloid leukemia (CML). This concept has been challenged by transplantation mortality and improved drug therapy. In a randomized study, primary HSCT and best available drug treatment (IFN based) were compared in newly diagnosed chronic phase CML patients. Assignment to treatment strategy was by genetic randomization according to availability of a matched related donor. Evaluation followed the intention-to-treat principle. Six hundred and twenty one patients with chronic phase CML were stratified for eligibility for HSCT. Three hundred and fifty four patients (62% male; median age, 40 years; range, 11-59 years) were eligible and randomized. One hundred and thirty five patients (38%) had a matched related donor, of whom 123 (91%) received a transplant within a median of 10 months (range, 2-106 months) from diagnosis. Two hundred and nineteen patients (62%) had no related donor and received best available drug treatment. With an observation time up to 11.2 years (median, 8.9 years), survival was superior for patients with drug treatment (P = .049), superiority being most pronounced in low-risk patients (P = .032). The general recommendation of HSCT as first-line treatment option in chronic phase CML can no longer be maintained. It should be replaced by a trial with modern drug treatment first.

Pharmacological and non-pharmacological therapy for arrhythmias in the pediatric population: EHRA and AEPC-Arrhythmia Working Group joint consensus statement

In children with structurally normal hearts, the mechanisms of arrhythmias are usually the same as in the adult patient. Some arrhythmias are particularly associated with young age and very rarely seen in adult patients. Arrhythmias in structural heart disease may be associated either with the underlying abnormality or result from surgical intervention. Chronic haemodynamic stress of congenital heart disease (CHD) might create an electrophysiological and anatomic substrate highly favourable for re-entrant arrhythmias. As a general rule, prescription of antiarrhythmic drugs requires a clear diagnosis with electrocardiographic documentation of a given arrhythmia. Risk-benefit analysis of drug therapy should be considered when facing an arrhythmia in a child. Prophylactic antiarrhythmic drug therapy is given only to protect the child from recurrent supraventricular tachycardia during this time span until the disease will eventually cease spontaneously. In the last decades, radiofrequency catheter ablation is progressively used as curative therapy for tachyarrhythmias in children and patients with or without CHD. Even in young children, procedures can be performed with high success rates and low complication rates as shown by several retrospective and prospective paediatric multi-centre studies. Three-dimensional mapping and non-fluoroscopic navigation techniques and enhanced catheter technology have further improved safety and efficacy even in CHD patients with complex arrhythmias. During last decades, cardiac devices (pacemakers and implantable cardiac defibrillator) have developed rapidly. The pacing generator size has diminished and the pacing leads have become progressively thinner. These developments have made application of cardiac pacing in children easier although no dedicated paediatric pacing systems exist.