[New drugs; exenatide and sitagliptin]. / Nieuwe geneesmiddelen; exenatide en sitagliptine.

Incretin hormones, secreted upon food intake, play an important role in the regulation of blood glucose levels. In type 2 diabetes mellitus, the incretin response is decreased. Substitution of incretin is a novel pharmacological target which restores postprandial glucose homeostasis. Exenatide is a mimetic of the incretin glucagon-like peptide-I (GLP-I). Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase 4 (DPP-4), which breaks down GLP-I. Both drugs increase the GLP-I concentration, thereby improving insulin secretion from pancreatic p cells, restoring glycaemic control, preventing beta cell destruction, delaying gastric emptying, and reducing food intake.

[New drugs; natalizumab]. / Nieuwe geneesmiddelen; natalizumab.

The drug natalizumab represents a new pharmacological approach in the treatment ofvery active relapsing-remitting multiple sclerosis (MS). It is a humanised murine monoclonal antibody and binds to an integrin on the surface oflymphocytes, thereby preventing them from transmigrating across the endothelium and causing inflammation in the nervous tissue. The drug has been shown to decrease the occurrence of relapses and progression of MS. A few severe adverse effects (such as the viral progressive multifocal leuko-encephalopathy) have been reported, and its clinical and long-term effects are not fully known at present. Therefore, further research is required to determine the role of natalizumab in clinical practice.

[New drugs; pegaptanib and ranibizumab]. / Nieuwe geneesmiddelen; pegaptanib en ranibizumab.

The neovascular ('wet') form of age-related macular degeneration (AMD) is characterized by vascular growth and leakage in the retina. Two new drugs, pegaptanib and ranibizumab, have been shown to improve vision or slow the progression of AMD. Both drugs inhibit the action of vascular endothelial growth factor--pegaptanib as an oligonucleotide and ranibizumab as a monoclonal antibody--thereby decreasing angiogenesis in the eye. Adverse effects are associated with the intravitreal administration of both drugs and include increased intraocular pressure, local bleeding, and infection.

[New drugs; rimonabant]. / Nieuwe geneesmiddelen; rimonabant.

The endocannabinoid system controls the regulation of food intake and appetite in the brain and lipogenesis in adipose tissue. Rimonabant belongs to the new drug class of cannabinoid-1 receptor antagonists. It can decrease appetite and food intake and thus stimulate weight loss. Rimonabant is indicated for severe obesity and as an adjunct to lifestyle modifications for obese patients with type 2 diabetes or hyperlipidaemia. Safety concerns limit the clinical applicability of the drug. The drug has not been approved in the US due to its neurological and psychiatric adverse effects. Rimonabant is approved in Europe but is contraindicated in patients with major depression and those taking antidepressants.

[New drugs; varenicline]. / Nieuwe geneesmiddelen; varenicline.

Nicotine acts in the brain by releasing dopamine in the mesolimbic pathway which results in a reward effect and in dependence when used chronically. The effect of nicotine is mediated via nicotinergic acetylcholine receptors of the alpha4beta2 subtype ofwhich varenicline is a partial agonist. Varenicline can be used for quitting smoking because of two mechanisms: it acts as a partial agonist and thus reduces the symptoms of craving when quitting smoking, and it has antagonistic actions by binding the receptor instead of nicotine and therefore decreases the reward effect of nicotine. The most important side effects of varenicline are nausea, vomiting and headache. After one year, 22% of the treated group continued to abstain from smoking.

[New drugs; daptomycin]. / Nieuwe geneesmiddelen; daptomycine.

Being a cyclic lipopeptide, daptomycin belongs to a new class of antibiotics. It acts by forming a pore in the bacterial membrane thus causing leakage of potassium and subsequent depolarization and arrest of cell function. Daptomycin has a bactericidal action on Gram-positive bacteria and is registered for the treatment of adults with complicated skin and soft tissue infections caused by Gram-positive microorganisms. There is limited experience with treatment of Staphylococcus aureus bacteraemia. Its main adverse effects include gastrointestinal symptoms, skin reactions at the site of infusion, and raised serum creatine kinase.

[New drugs; sunitinib and sorafenib]. / Nieuwe geneesmiddelen; sunitinib en sorafenib.

Sunitinib and sorafenib are both indicated for the treatment of advanced kidney carcinoma of the 'clear cell' type after failure of, or resistance to, other treatments. Both drugs inhibit the tyrosine-kinase activity of a number of growth factor receptors; sorafenib has an additional inhibitory effect on serine/threonine-kinase activity. This mechanism decreases signal transduction and results in an inhibition of tumour cell growth and angiogenesis. The adverse effects of the two drugs are different: sunitinib causes mainly fatigue and gastrointestinal discomfort, whereas sorafenib's most frequent adverse effects are diarrhoea, rash, the palmar-plantar erythrodysaesthesia syndrome, and hypertension.

[New drugs; nitisinone]. / Nieuwe geneesmiddelen; nitisinon.

Nitisinone is an inhibitor of 4-hydroxyphenyl-pyruvate dioxygenase (4HPPD). Its rare area of use is hereditary tyrosinaemia, a life-threatening disease in which the last step in the catabolism of tyrosine cannot be taken due to the absence of an enzyme. The inhibition of 4HPPD, an enzyme that is active early in the catabolic cascade, prevents the accumulation of toxic metabolites of tyrosine.

[New medications; erlotinib]. / Nieuwe geneesmiddelen; erlotinib.

Erlotinib inhibits the phosphorylation of the epidermal growth-factor receptor (EGFR/HERI), a tyrosinekinase protein. This results in an inhibition of signal transduction and therefore decreased cell division and increased cell death. The agent is indicated for the treatment of patients with advanced local or metastasised non-small-cell pulmonary carcinoma after other cytostatic therapy has failed.

[New medications; ziconotide]. / Nieuwe geneesmiddelen; ziconotide.

Ziconotide is a synthetic analogue of a peptide found in the poison of the marine snail Conus magus. Ziconotide blocks N-type calcium channels, which play an important role in the transmission of pain signals in the dorsal ganglia of the spinal cord. The drug is indicated for 'severe chronic pain' and is administered intrathecally.

[New medications; zonisamide]. / Nieuwe geneesmiddelen; zonisamide.

Zonisamide is an adjuvant for the treatment of patients with partial epilepsy, with or without secondary generalisation. It affects, among other things, the voltage-sensitive sodium and calcium channels, thus disrupting synchronised neuronal firing; as a result, it diminishes the spread of seizure discharges.

[New medications; bevacizumab]. / Nieuwe geneesmiddelen; bevacizumab.

Bevacizumab is a humanised monoclonal antibody that targets vascular endothelial growth factor. By blocking the growth factor, bevacizumab inhibits the development of new blood vessels, which in turn inhibits the growth oftumours and metastases. Mean disease-free survival is prolonged in patients with metastatic colorectal carcinoma who are treated with bevacizumab. Evaluation of bevacizumab in other indications is underway.

[New drugs; palifermin]. / Nieuwe geneesmiddelen; palifermine.

Palifermin is a human keratinocyte growth factor that is produced in Escherichia coli by recombinant-DNA-technology. This substance protects against oral mucositis in adults undergoing myeloablative therapy. The safety of this product--being a growth factor --in the long term has not yet been shown. Adverse effects may occur in the skin and mucous membranes.

[New drugs; omalizumab]. / Nieuwe geneesmiddelen; omalizumab.

Omalizumab is a humanised monoclonal antibody that binds to circulating IgE, inhibiting its binding to the surface of mast cells and basophilic granulocytes. This prevents the release of pro-inflammatory mediators that produce an allergic response. This targeted mechanism of action provides a novel therapeutic approach for the treatment of patients with severe persistent, therapy-resistant allergic asthma. Omalizumab is administered subcutaneously in addition to other anti-asthma therapy. Until recently, the most important side effects are skin reactions at the site of administration and headache. Prospective data on additional long-term side effects are still being collected.

[New drugs; ivabradine]. / Nieuwe geneesmiddelen; ivabradine.

Ivabradine lowers the heart rate by inhibiting the cardiac pacemaker current that is responsible for diastolic depolarisation. The most important side effect is the appearance of light flashes (phosphenes). The agent can be used in patients with angina pectoris when beta-blockers are insufficiently effective, provided that the heart rate is at least 60 beats per minute at the beginning of the treatment.

Quality of life after combined kidney-pancreas or kidney transplantation in diabetic patients with end-stage renal disease.

The quality of life after a successful combined kidney-pancreas transplantation was studied in 17 diabetic patients with end-stage renal disease (ESRD) and in 11 patients who experienced a failure of one or both grafts. The control group comprised 23 patients who received a kidney transplantation only. The aspects of quality of life chosen for study were: physical, psychological and social wellbeing, daily activities, level of functioning and global quality of life evaluation. Additionally, future expectations, the perceived burden of treatment, and main reason for undergoing organ replacement therapy were evaluated. In only one aspect of quality of life did patients with a successful combined transplantation score significantly better than patients with a kidney transplantation, i.e., mobility in daily functioning and activities (p = 0.03). Patients with a failure of one or both grafts reported significantly more fatigue (p = 0.02), less energy (p = 0.04), and more social isolation (p = 0.05) than patients who had well-functioning grafts. The mean duration of hospitalization following combined transplantation is twice that for kidney transplantation only 10 vs 5 weeks. Although the combined transplantation group found the first 3 months after transplantation more burdensome (p = 0.04) and more often wondered whether it had been worth all the trouble (p = 0.05), they indicated the same willingness as the group with a kidney transplant only to undergo another transplantation under similar circumstances. Although the recipients of a kidney transplant had not been offered the choice of a combined transplantation, their reasons for transplantation did not, in essence, differ from those of recipients of a combined transplantation. In both groups the main motivation to opt for organ replacement therapy was the burden of dialysis, to stop the progressive deterioration of their health, and to experience a better quality of life.