[Adrenal cortex and steroids. Supplementary therapy in the perioperative phase]. / Nebennierenrinde und Steroide. Supplementäre Therapie in der perioperativen Phase.

Since the publication of two case reports that are considered to represent the first clinical demonstration of iatrogenic adrenal insufficiency, it has been the generally accepted practice to cover steroid-treated patients undergoing surgery with glucocorticoids in the perioperative period. Both the inclusion criteria for the patients and the extent of the substitution pattern have been selected on an empirical rather than on a rational basis. Scientific advances over the past 50 years in the knowledge of the hypothalamic-pituitary-adrenal system's physiology and the molecular mechanism of action of its biologically active components are, for the most part, not reflected in current clinical practice and instead seem to be ignored. Clinical and experimental evidence suggests, however, that even glucocorticoid-treated patients undergoing surgery do not require maximum stress doses of hydrocortisone, which should be reserved for the treatment of sepsis. With regard to the broad spectrum of efficacy of glucocorticoids and their side effects, revision and modification of the historical regimen appear prudent.

[Drug interactions and the anesthesiologist]. / Medikamenteninteraktionen für den Anästheisten.

Modern anesthesiology employs the combined administration of several drugs belonging to different pharmacological classes. Additionally, anesthesiologists are facing the challenge of polypharmacy regimens utilized by patients considered for surgical treatment When drugs are combined, the pharmacological effect may considerably differ from the individually expected properties. This may be beneficial or potentially lead to adverse drug reactions harming the patient. The incidence of drug interaction increases exponentially with the number of drugs administered. Depending on the mechanism involved, drug interactions can be classified as pharmaceutical, pharmacodynamic, or pharmacokinetic. Although there are enormous possibilities for adverse drug reactions nd the complexity is hard to identify, prediction of drug interaction is possible. Besides recognizing the general risk factors, fundamental knowledge of basic and clinical pharmacology is important to prevent serious or fatal drug interactions before they occur.

The effects of verapamil and diltiazem on N-, P- and Q-type calcium channels mediating dopamine release in rat striatum.

1. The putative inhibitory effects of verapamil and diltiazem on neuronal non-L-type Ca2+ channels were studied by investigating their effects on either K+- or veratridine-evoked [3H]-dopamine ([3H]-DA) release in rat striatal slices. Involvement of N-, P- and Q-type channels was identified by sensitivity of [3H]-DA release to omega-conotoxin GVIA (omega-CTx-GVIA), omega-agatoxin IVA (omega-Aga-IVA) and omega-conotoxin MVIIC (omega-CTx-MVIIC), respectively. 2. KCl (50 mM)-evoked [3H]-DA release was abolished in the absence of Ca2+, and was insensitive to dihydropyridines (up to 30 microM). It was significantly blocked by omega-CTx-GVIA (1 microM), omega-Aga-IVA (30 nM) and was confirmed to be abolished by omega-CTx-MVIIC (3 microM), indicating involvement of N-, P- and Q-type channel subtypes. 3. Verapamil and diltiazem inhibited K+-evoked [3H]-DA release in a concentration-dependent manner. The inhibitory effects of verapamil or diltiazem (each 30 microM) were fully additive to the effect of omega-CTx-GVIA (1 microM), whereas co-application with omega-Aga-IVA (30 nM) produced similar effects to those of omega-Aga-IVA alone. 4. As shown previously, veratridine-evoked [3H]-DA release in Ca2+ containing medium exclusively involves Q-type Ca2+ channels. Here, diltiazem (30 microM) did not inhibit veratridine-evoked [3H]-DA release, whereas verapamil (30 microM) partially inhibited it, indicating possible involvement of Q-type channels in verapamil-induced inhibition. However, verapamil (30 microM) inhibited this release even in the absence of extracellular Ca2+, suggesting that Na+ rather than Q-type Ca2+ channels are involved. 5. Taken together, our results suggest that verapamil can block P- and at higher concentrations possibly N- and Q-type Ca2+ channels linked to [3H]-DA release, whereas diltiazem appears to block P-type Ca2+ channels only.

Voltage-activated calcium channels involved in veratridine-evoked [3H]dopamine release in rat striatal slices.

The present study explored the role of different sub-types of voltage-activated Ca2+ channels (VACCs) in mediating veratridine-evoked [3H]dopamine (DA) release from rat striatal slices. The release of [3H]DA evoked by veratridine (25 microM) decreased by 50.6+/-2.9% (n=8) in the absence of calcium and was completely abolished by 1 microM tetrodotoxin. The L-type Ca2+ channel blockers nifedipine (10 microM), nitrendipine (10 microM), diltiazem (10 microM) and verapamil (10 microM) did not modulate this release. Similarly, [3H]DA release was affected neither by the N-type VACC blocker omega-conotoxin-GVIA (1 microM) nor by the selective P-type channel blockers omega-agatoxin-IVA and omega-agatoxin-TK at low nM concentrations (30 nM), indicating no involvement of N- and P-type Ca2+ channels. In contrast, higher concentrations of omega-agatoxin-IVA that would also inhibit Q-type VACCs, blocked the release of [3H]DA by 27.9+/-8.1% (n=5) and 37.5+/-13.6% (n=3) at 0.3 and 1 microM, respectively. In addition, application of the Q-type Ca2+ channel blocker omega-conotoxin-MVIIC (0.01-3 degrees M) reduced [3H]DA release in a concentration-dependent manner, with maximum inhibition of 35.3+/-4.1% at 3 microM (n=5). On the basis of these results, it is concluded that the Ca2+ channels that participate in veratridine-evoked [3H]DA release are Q-type Ca2+ channels.