[Influence of drugs on urological diseases]. / Einfluss von Medikamenten auf urologische Krankheiten.

A number of drugs prescribed for the treatment of various diseases can induce urological symptoms as side effects. Antihypertensive drugs (particularly alpha blockers) can result in stress incontinence, whereas selective serotonin reuptake inhibitors (SSRI) can cause urge incontinence and estrogen promotes both forms. A wide range of drugs with anticholinergic activity, among them neuroleptics, tricyclic antidepressants and certain drugs used in airway disorders are associated with urinary retention. Only very few drugs bear a relevant risk for urolithiasis, i. e. the diuretic triamterene and protease inhibitors, such as indinavir; however, the widely used combination of calcium and vitamin D supplementation for prevention of osteoporosis may be an underdiagnosed cause of renal calculi. Drug-induced sexual dysfunction is a frequent side effect of antihypertensive treatment, particularly with beta adrenoceptor blockers and diuretics. The SSRI and some neuroleptics can also impair sexual function.

[Drug treatment of elderly patients]. / Pharmakotherapie alter Patienten.

Drug therapy in seniors needs to be adapted to the capacity of the aged organism. The dosages of a high number of drugs from several classes (e.g., antibiotics, low molecular weight heparins) have to be modified according to age or reduced renal function, which is a common feature in old age. Moreover, elderly patients due to their physiological alterations exhibit an increased response to drugs having an influence on renal function: diuretics, nonsteroidal anti-inflammatory drugs, inhibitors of the renin-angiotensin-aldosterone system, and contrast media. The choice of drugs should consider their age-specific tolerability, i.e., fall-risk increasing drugs and those with strong anticholinergic side effects should be avoided. Analgesics, sedatives, and narcotics have to be selected according to the age of the patient and dosages should be adapted. Multimorbidity is often treated with polypharmacy, whereby it is not unusual that this is the cause for acute hospital admission. The necessity of all drugs prescribed has to be scrutinized and the drug burden should be reduced as clinically required.

[Chemotherapy in patients with colorectal carcinoma: applicability of data from clinical trials for the individual patient]. / Pharmakotherapie beim kolorektalen Karzinom: Ubertragbarkeit der Ergebnisse auf den individuellen Patienten.

Randomised, controlled clinical trials provide a valid foundation for evidence-based clinical guidelines. The representativeness of the patient population studied is one major aspect of external validity. With respect to the patient population enrolled in clinical trials studying the effects of chemotherapy in patients with colorectal cancer, older patients are significantly underrepresented, i. e., they represent between 14 and 40 % of the study population, but approximately 70 % of the population concerned. The major reasons for the exclusion of older patients are comorbidities and functional status. Moreover, gender differences in pharmacokinetics and therapeutic effects of 5-fluorouracil are usually not considered. Although individualisation of therapy by means of pharmacogenetics and pharmacogenomics may offer promising options, to date these methods are still not in routine use for colorectal cancer patients. Due to a lack of information about the relevant populations from randomised controlled trials, data from registries and observational trials are necessary to complement our knowledge.

Pharmacokinetics of viral antibodies after administration of intravenous immunoglobulin in patients with chronic lymphocytic leukaemia or multiple myeloma.

OBJECTIVE: Intravenous immunoglobulin (IVIG) preparations are derived from human pooled plasma and should fulfil high standards of purity and viral safety. Introduction of additional purification steps, however, may result in modulation of the biological properties of immunoglobulins. Since cleavage of the Fab-fragment leads to a significant decrease in half-life, the latter provides information about the integrity of the immunoglobulin G (IgG) molecules. Therefore, a pharmacokinetic study of a novel preparation is required to determine safety and disposition in the target population. METHODS: Twenty-seven patients with chronic lymphocytic leukaemia (CLL) and 12 with multiple myeloma received intravenous infusions of IVIG containing antibodies against hepatitis B virus (anti-HBs; n= 15; 8960 IU), cytomegalovirus (anti-CMV; n = 9; 14,250 U) or varizella-zoster-virus (anti-VZV; n = 15; 6000 IU), respectively. Serum concentrations of viral antibodies were determined for 71 days during and after infusion. RESULTS: Maximum serum concentrations of anti-HBs, anti-CMV and anti-VZV were observed at about 4 h (median) after start of the infusion. Total body clearances came to 0.14 +/- 0.08 ml/min (anti-HBs), 0.10 +/- 0.02 ml/ min (anti-CMV) and 0.14 +/- 0.07 ml/min (anti-VZV). The terminal elimination half-lives were determined to be 25.34 +/- 8.34 days (anti-HBs), 24.66 7.28 days (anti-CMV) and 31.79 +/- 12.47 days (anti-VZV). Clinical chemistry parameters including C3- and C4-complement serum concentrations revealed no pathological changes, seroconversion for hepatitis B and C and HIV did not occur. CONCLUSIONS: The pharmacokinetic parameters of the IgG antibodies calculated after administration of the novel IVIG preparations to patients with CLL and multiple myeloma are in close agreement with data obtained from healthy volunteers and with values of native IgG, suggesting that the production process did not impair clinically relevant characteristics of the viral antibodies.

[Detection and evaluation of adverse drug effects]. / Erfassung und Bewertung unerwünschter Arzneimittelwirkungen.

Adverse drug reactions (ADRs) occur in about 5% of drug-treated patients. Hospital admissions are caused by ADRs in 5% of patients and roughly 2% of hospitalized patients will experience an ADR. The economic burden of ADRs can only be estimated. Type A reactions can be explained by the pharmacological action of the drugs, and are preventable in many cases. However, Type B reactions involving the immune system and/or idiosyncratic reactions occur rarely and most of them are not fully understood. Genotyping represents an elegant method to explain the presence of abnormal enzyme activities and allows prediction of adverse drug effects in individual cases. Typical time frames have been identified for the occurrence of hypersensitivity reactions, although definite causality assessment is often impeded due to the absence or unavailability of specific laboratory tests and the impossibility of rechallenge. Diagnosis of an ADR is often difficult due to comorbidity and polypharmacy, thus causality assessment is often divergent even between specialists. In Germany, ADRs are reported preferably to the manufacturer of the suspicious drug and then collected and evaluated at the Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM. However, total number and quality of reported ADRs could be improved.

Autoimmune thyroiditis and myelosuppression following treatment with interferon-alpha for hepatitis C.

CASE: We describe the case of a 48-year-old woman from Thailand diagnosed with chronic hepatitis C, who experienced a suppression of all blood cell counts accompanied by a newly developed clinically manifested autoimmune thyroid disorder after treatment with interferon alpha-2b (INF-alpha) 46 days after beginning of therapy a decrease of platelet, red and white blood cell counts became obvious. Concomitantly we observed an increase of FT4 and FT3 with a totally depressed TSH level 80 days after starting INF-alpha administration. Antibody assessment resulted in detection of high numbers of antithyroid-microsomal antibodies and antithyroglobulin antibodies. Thyroid hormone levels normalized under treatment with methimazole/propylthiouracil within 4.5 months. However, two months after cessation of antithyroid therapy increasing TSH levels and decreasing FT4 levels indicated a new tendency towards a hypothyroid state. CONCLUSION: We classify this case as an interferon-alpha-induced disorder of thyroid function accompanied by myelosuppression. A close monitoring for thyroid dysfunction, e.g. evaluation of TSH-levels before and after administration of INF-alpha is mandatory.

[Detection and evaluation of adverse drug reactions]. / Erfassung und Bewertung unerwünschter Arzneimittelwirkungen.

Adverse drug reactions (ADRs) occur in about 5% of drug-treated patients. Hospital admissions are caused by ADRs in 5% of patients and roughly 2% of hospitalized patients will experience an ADR. The economic burden of ADRs can only be estimated. Type A reactions can be explained by the pharmacological action of the drugs, and are preventable in many cases. However, Type B reactions involving the immune system and/or idiosyncratic reactions occur rarely and most of them are not fully understood. Genotyping represents an elegant method to explain the presence of abnormal enzyme activities and allows prediction of adverse drug effects in individual cases. Typical time frames have been identified for the occurrence of hypersensitivity reactions, although definite causality assessment is often impeded due to the absence or unavailability of specific laboratory tests and the impossibility of rechallenge. Diagnosis of an ADR is often difficult due to comorbidity and polypharmacy, thus causality assessment is often divergent even between specialists. In Germany, ADRs are reported preferably to the manufacturer of the suspicious drug and then collected and evaluated at the Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM. However, total number and quality of reported ADRs could be improved.

Influence of isradipine and spirapril on left ventricular hypertrophy and resistance arteries.

Left ventricular hypertrophy is a common clinical feature in hypertensive patients and may be associated with structural changes in vessel morphology. In an open prospective trial, we evaluated 14 patients with previously untreated hypertension (163 +/- 2/104 +/- 2 mm Hg) and an echocardiographically determined left ventricular mass index of 141.6 +/- 5.2 g/m2, indicating left ventricular hypertrophy. We obtained a gluteal skin biopsy sample before starting treatment to investigate subcutaneous small-artery (approximately 200 to 400 microns diameter) morphology and function. Patients then received antihypertensive treatment with a combination of spirapril (3 or 6 mg) and isradipine (2.5 or 5 mg). Echocardiographic recordings were made after 6 months and 1 year, and a final biopsy was taken after 1 year. After 1 year, blood pressure was significantly reduced to 142 +/- 3/ 90 +/- 1 mm Hg (P < .001), and left ventricular mass index decreased significantly to 105.3 +/- 5.8 g/m2 (P < .001). Baseline media-lumen ratio (7.64 +/- 0.48%) was not markedly reduced (7.21 +/- 0.55%), although a decrease occurred in 7 of 12 evaluable patients. Norepinephrine-induced vasoconstriction was markedly reduced after 1 year. In conclusion, a significant regression of left ventricular hypertrophy was obtained after 1 year of treatment with spirapril and isradipine, whereas a similar reduction in medial thickness relative to lumen diameter of subcutaneous small arteries could not be observed in all patients. Reversal of structural changes in resistance vessels may require a longer treatment period in patients with proven left ventricular hypertrophy.