Metamizole (dipyrone) is a popular analgetic, non-opioid drug, commonly used in human and veterinary medicine. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug (NSAID). Metamizole is a pro-drug, which spontaneously breaks down after oral administration to structurally related pyrazolone compounds. Apart from its analgesic effect, the medication is an antipyretic and spasmolytic agent. The mechanism responsible for the analgesic effect is a complex one, and most probably rests on the inhibition of a central cyclooxygenase-3 and activation of the opioidergic system and cannabinoid system. Metamizole can block both PG-dependent and PG-independent pathways of fever induced by LPS, which suggests that this drug has a profile of antipyretic action distinctly different from that of NSAIDs. The mechanism responsible for the spasmolytic effect of metamizole is associated with the inhibited release of intracellular Ca 2+ as a result of the reduced synthesis of inositol phosphate. Metamizole is predominantly applied in the therapy of pain of different etiology, of spastic conditions, especially affecting the digestive tract, and of fever refractory to other treatments. Co-administration of morphine and metamizole produces superadditive, antinociceptive effects. Metamizole is a relatively safe pharmaceutical preparation although it is not completely free from undesirable effects. Among these side-effects, the most serious one that raises most controversy is the myelotoxic effect. It seems that in the past the risk of metamizole-induced agranulocytosis was exaggerated. Despite the evidence showing no risk of teratogenic and embryotoxic effects, the drug must not be administered to pregnant women, although it is allowed to be given to pregnant and lactating animals. This paper seeks to describe the characteristics of metamizole in the light of current knowledge.

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In the present study influence of doxazosin on the porcine urinary bladder contractility has been examined. Immature pigs were treated for 30 days with: a) doxazosin (n = 5) per os at a dose of 0.1 mg/kg b.w. or b) placebo (n = 5; control group). Thereafter, animals were sacrificed and urinary bladder strips from the trigone were suspended in organ baths. The tension of the smooth musce was measured before and after exposition to acetylocholine (ACh; 10 -5 -10 -3 M), norepinephrine (NE; 10 -9 -10 -7 M) and 5-hydroxytryptamine (5-HT; 10 -7 -10 -5 M). Both the ACh and 5-HT at the highest doses significantly increased the contractility in each group, but this response was weaker in doxazosin-treated animals. NE caused relaxation in both groups, but the effect was weaker in doxazosine-treated group. The results of our study have shown that long-term administration of doxazosin caused a desensitization of the detrusor smooth muscle for in vitro applied mediators of the autonomic nervous systems.

The aim of the present study was to determine the efficacy of ivermectin against Cyathostominae infections and to describe the drug's pharmacokinetic parameters during two seasonal deworming treatments in horses. The study was performed on warm-blooded mares aged 3-12 years weighing 450-550 kg. A single bolus of an oral paste formulation of ivermectin was administered at a dose of 0.2 mg/kg BW in spring and autumn. Fecal samples were tested before treatment and 1, 2, 3, 4, 6, 10, 20, 30, 40, 50, 60, 75 days after treatment. Ivermectin concentrations in blood samples collected before treatment, 0.5, 1, 2, 3, 4, 6, 12, 24, 36 and 48 hours after treatment, and 3, 4, 6, 8, 10, 15, 20, 25, 30, 40, 50, 60 and 75 days after drug administration were determined by high pressure liquid chromatography. Drug absorption was significantly (p<0.05) slower (t max : 21.89±11.43 h) in autumn than in spring (t max : 9.78±8.97 h). Maximum concentrations (C max ) of ivermectin in the blood plasma of individual horses (8.40-43.08 ng/ml) were observed 2-24 h after drug administration during the spring treatment and 2-36 h (6.43-24.86 ng/ml) after administration during the autumn treatment. Significantly higher (p<0.05) ivermectin concentrations were found during the first 4 hours after administration in spring in comparison with those determined after the autumn treatment.The administration of the recommended dose of ivermectin resulted in 100% elimination of parasitic eggs from feces in spring and autumn treatment.