In vitro evaluation of quinidine sensitivity in brazilian Plasmodium falciparum isolates: comparative analysis to quinine and chloroquine

Falciparum malaria represents a serious and an increasing world public health problem due to the acquired parasite's resistance to the most available drugs. In some endemic areas, quinidine, a diastereoisomer of the antimalarial quinine, has been employed for replacing the latter. In order to evaluate the use of quinidine as an alternative to the increasing loss of quinine effectiveness in Brazilian P. falciparum strains, as has been observed in the Amazon area, we have assayed quinidine, quinine and chloroquine. The in vitro microtechnique was employed. All isolates showed to be highly resistant to chloroquine. Resistance to quinine was not noted although high MIC (minimal inhibitory concentration) values have been observed. These data corroborate the decreasing sensitivity to quinine in strains from Brazil. Quinidine showed IC50 from 0.053 to 4.577 mumol/L of blood while IC50 from 0.053 to 8.132 mumol/L of blood was estimated for quinine. Moreover, clearance of the parasitemia was observed in concentrations lower than that used for quinidine in antiarrhythmic therapy, confirming our previous data. The results were similar to African isolate

Antinociceptive effect of purine nucleotides

The antinociceptive effect of purine nucleotides administered systemically (sc) was determined using the formalin and writhing tests in adult male albino mice. The mechanisms underlying nucleotide-induced antinociception were investigated by preinjecting the animals (sc) with specific antagonists for opioid (naloxone, 1 mg/kg), purinergic P1 (caffeine, 5, 10 or 30 mg/kg); theophylline, 10 mg/kg) or purinergic P2 receptors (suramin, 100 mg/kg; Coomassie blue, 30-300 mg/kg; quinidine, 10 mg/kg). Adenosine, adenosine monophosphate (AMP), diphosphate (ADP) and triphosphate (ATP) caused a reduction in the number of writhes and in the time of licking the formalin-injected paw. Naloxone had no effect on adenosine- or adenine nucleotide-induced antinociception. Caffeine (30 mg/kg) and theophylline (10 mg/kg) reversed the antinociceptive action of adenosine and adenine nucleotide derivatives in both tests. P2 antagonists did not reverse adenine nucleotide-induced antinociception. These results suggest that the antinociceptive effect of adenine nucleotides is mediated by adenosine.

Prevention of ischaemia-induced biochemical changes by curcumin & quinidine in the cat heart.

Effect of myocardial ischaemia on the bioantioxidants levels in the cat heart was evaluated. In addition, effect of curcumin, an anti-inflammatory and anti-thrombotic drug, and quinidine, a standard antiarrhythmic drug, was also studied in the cat. Myocardial ischaemia was induced by the ligation of left descending coronary artery. Quinidine (1 mg/kg, iv) was administered 15 min prior to while curcumin (100 mg/kg, ip) was given 30 min before ligation. Hearts were removed 4 h post coronary artery ligation. Levels of glutathione (GSH), malonaldelhyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and lactate dehydrogenase (LDH) were estimated in the ischaemic and non-ischaemic zones. Both the drugs protected the animals against decrease in the heart rate and blood pressure following ischaemia. In the ischaemic zone, after 4 h of ligation, an increase in the level of MDA and activities of MPO and SOD (cytosolic fraction) were observed. Quinidine and curcumin pretreatment prevented the ischaemia-induced elevation in MDA contents and LDH release. Curcumin pretreatment did not prevent the increase in MPO activity while quinidine did. Results obtained indicate alterations in the bioantioxidants following ischaemia and both curcumin and quinidine prevented ischaemia induced changes in the cat heart.

Effect of lidocaine and quinidine on focal ventricular arrhythmias induced by subepicardial epinephrine in cats.

Subepicardial infusion of epinephrine (EP) in the dose of 3 x 10(-3) M in 2.5 x 10(-3)M CaCl2-0.9% NaCl (calcium-saline vehicle) at the rate of 10 microliters/min in the right ventricular myocardium of mongrel cats weighing between 2.7 and 3.3 kg produced uniform reversible and reproducible focal ventricular arrhythmias of varying intensity and duration. Infusion of two antiarrhythmic agents, lidocaine (LD) and quinidine (QD) in the same site of arrhythmogenesis in equimolar concentration of 3 x 10(-3) M along with EP in the same vehicle reduced incidence, duration, peak and mean frequencies of arrhythmias while the latent period of onset of arrhythmias increased significantly. In present study, quinidine, in equimolar concentration of 3 x 10(-3) M was found to be more effective than lidocaine in antagonizing EP-induced ventricular arrhythmias.

Effects of extracellular sodium, quinidine, and ryanodine on slow response excitability in rabbit atrial trabeculae

1. We investigated Na(+)-Ca2+ exchange and the involvement of the sarcoplasmic reticulum in frequency-dependent slow response excitability enhancement in rabbit atrial trabeculae. 2. Slow responses were induced in a modified Tyrode solution containing high K+ and Ba2+ and conventional electrophysiological techniques were used for stimulating and recording membrane potentials. 3. Under these conditions, the frequency-dependence of slow response excitability can be demonstrated with excitability enhancement as stimulation frequency is increased (0.25 to 1.0 Hz). 4. The frequency-dependent excitability enhancement depends on external Na+, increasing in high-[Na+]o (173.8 mM) and decreasing in low-[Na+]o (103.8 mM) media. 5. Quinidine (10 microM) and ryanodine (10 microM) decrease frequency-dependent slow response excitability enhancement. 6. These results indicate that the Na(+)-Ca2+ exchange might have an important role in frequency-dependent excitability enhancement of slow responses. Moreover, we suggest that the control of internal Ca2+ by the sarcoplasmic reticulum might have an additional role in regulating the excitability enhancement process in depolarized atrial trabeculae

Correlative effects of quinidine on ECG pattern and serum cholesterol concentration in Acridotheres tristis.

Antiarrhythmic drug quinidine, administered daily at the rate of 10 mg/kg for 7 days in A. tristis produced an increasing effect on the amplitude and duration of different waves and intervals. Heart rate was decreased from 478.40 to 444.47 beats/min. Serum cholesterol level was reduced from 86 to 54.30 mg/100 ml. The data of the effect of quinidine on the ECG pattern and serum cholesterol were analysed and the values of the correlation coefficient and their significance were computed. The values of the correlation coefficient computed between the level of serum cholesterol (Y) and P-R interval (X) comes out to be significant at 5% level of significance. A linear regression line Y on X was fitted to the above data and the line is found to be: Y = 2535.897 X -62.858. This regression line may be used to determine the level of serum cholesterol on the basis of changes in the P-R interval of the ECG tracing in the quinidine treated birds.

Effects of verapamil, diltiazem, propanolol and quinidine on RO 13-6438-induced cardiac dysrhythmia in guinea pigs

The effect of Verapamil, Diltiazem, Propranolol and Quinidine on Ro 13-6438-induced cardiac dysrhythmia in urethane-anaesthetized guinea pigs was studied. During this study, the tested drugs were given in advance to visualize if they can protect the animal from a subsequent dose of Ro 13-6438. Intravenous injection of Ro 13-6438 in a dose level of 50 mg/kg was able to produce persistent period of ventricular tachycardia ended with the development of ventricular fibrillation. Verapamil, Diltiazem, in a dose level of 5 mg/kg and Propranolol, in a dose level of 2.5 mg/kg, were found to protect animals against dysrhythmia induced by Ro 13-6438, whereas Quinidine, in a dose level of 5 mg/kg, was found to be ineffective. A possible role of electrolytes in the genesis of Ro 13-6438-induced cardiac dysrhythmia was discussed

Estudo com o sulfato de quinidina: correlaçöes clínicas com seus níveis plasmáticos / Quimidine sulfate: clinical correlation with its plasma levels

O presente estudo teve por objetivo avaliar a eficácia e a tolerância de um sal de quinidina, de açäo rápida, no tratamento de 40 pacientes portadores de diversas arritmias supraventriculares, em comparaçäo com o placebo administrado nos 10 primeiros dias dos 90 dias de observaçäo previstos no protocolo original. Após 7 dias de tratamento, a ao término do estudo, foram efetuadas as comparaçöes pelo método fluorimétrico de Udenfriend. O tratamento foi bem tolerado em todos os pacientes, apenas com discretos efeitos colaterais em 30%. Os resultados obtidos revelaram uma eficácia de cerca de 70% do sulfaro de quinidina na amostra estudada, sendo a concentraçäo plasmática média de 4,6 ñ 1,3, após 7 dias, e de 6,2 ñ 1,3, ao final do estudo, devido ao efeito cumulativo da substância. Os autores destacam a importância, na prática diária, da dosagem da quinidina plasmática, representando um método de baixo custo e de grande utilidade para evidenciar níveis elevados de droga no plasma, permitindo um manuseio fácil e mais seguro desta substância e evitando os fenômenos de intoxicaçäo dela decorrente, ao contrário dos outros antiarrítmicos comercialmente disponíveis