PubMed Health⌕ Search

Biomedical subjects

J Flórez

Publications and source records attributed to J Flórez.

At least 55 records · Page 3Linked to original sources
PubMed1989

Tolerance to respiratory actions of sufentanil: functional tolerance and route-dependent differential tolerance.

The work was aimed at 1) characterizing the development of chronic tolerance to the respiratory effects of sufentanil in anesthetized and awake rats and 2) analyzing the influence that routes of administration of opiates can exert on tolerance development and expression. Tolerance was developed by infusing sufentanil s.c. with osmotic minipumps for 7 days; it was evaluated by injecting acute sufentanil while the minipumps were still maintained. When maximal depression attained was considered, dose-response curves were displaced to the right, the tolerance indexes being 7.3 and 2.6 in awake and anesthetized rats, respectively. No displacement was observed when acute sufentanil was injected i.c.v. and i.v., indicating lack of tolerance. However, several signs of tolerance were detected when the areas under the time-course curve of the effects were considered: faster and more complete recovery of the depression and flattening of the slope of the dose-area under the curve responses, even after i.c.v. and i.v. administration. The results indicate the need for distinguishing between development and expression of tolerance. Differential tolerance can be explained by considering tolerance expression as a deferred phenomenon. In addition, functional compensation stands as a factor of tolerance and as a mechanism responsible for dose-response curve flattening in tolerant subjects.

Analgesics, Opioid↗
PubMed1989

Lack of interaction between cholecystokinin and opioid systems in the central control of breathing.

The present study investigates the interaction between CCK and opioid systems on the central control of breathing by analyzing the respiratory effects of CCK-8S (0.09 nmol) and met-enkephalin (0.7 and 1.4 mumol) applied to the ventral medullary surface of cats under the influence of the opiate antagonist naloxone and the CCK antagonist proglumide. Neither naloxone nor proglumide were able to modify the respiratory effects of CCK-8S and met-enkephalin, respectively. Therefore, the hypothesis that CCK and the opioid systems might operate as parallel and antagonic forces throughout the central nervous system, is no longer tenable.

Animals↗
PubMed1986

Mechanism of the respiratory action of pentobarbital at the medullary and pontine levels.

A functional differentiation of the respiratory action of pentobarbital was made by applying the drug in cats to the ventral surface of the medulla and to the dorso-rostral surface of the pons. The involvement of a GABAergic mechanism was assessed by studying the interaction of bicuculline with pentobarbital at both levels of the brain-stem. In the medulla, pentobarbital (4 to 16 mg) caused an immediate and dose-dependent depression of tidal volume down to apnea with a minimal or no change in frequency. In the pons, the depression affected selectively the frequency (-45%) without modification in amplitude. Medullary structures were much more sensitive to the action of pentobarbital. Doses that induced apnea in the medulla did not attain 50% depression of the minute volume in the pons. Bicuculline (300 micrograms) completely antagonized the effect of pentobarbital in both regions, suggesting that a GABAergic mechanism may be involved in the respiratory action of pentobarbital.

Animals↗
PubMed1985

Differential respiratory patterns induced by opioids applied to the ventral medullary and dorsal pontine surfaces of cats.

The purpose of the present study was to make a functional dissection of the respiratory action of opioids, by their restricted application to the ventral surface of the medulla oblongata and to the rostro-dorsal surface of the pons in cats. The effects were compared to those induced after intracerebroventricular (i.c.v.) injection. Two mu-agonists, morphine and D-Ala2-Me-Phe4-Met(O)ol5-enkephalin (FK-33824), and the delta-agonist D-Ala2-D-Leu5-enkephalin (DADLE) were used. When applied to the ventral medullary surface, the opioids selectively depressed the generating mechanisms for tidal volume and the response to CO2, whereas the frequency was increased. The application to the rostral dorsal surface of the pons was followed by a selective depression of the respiratory frequency. By intracerebroventricular administration, the opioids depressed both the tidal volume and frequency generating mechanisms. The effects were always reversed by naloxone. The pontine structures were more sensitive to the action of the opioids than were the medullary centres. These findings suggest that the opioids can interact with different populations of respiratory neurones and that the respiratory output differs depending on the group of neurones selectively affected and the function they subserve in regulating respiratory activity.

Animals↗
PubMed1984

A comparative study in rats of the respiratory depression and analgesia induced by mu- and delta-opioid agonists.

A comparison was made in awake rats between the analgesic and the respiratory depressant actions induced by the mu-opiate agonists morphine and Tyr-D-Ala-Gly-N-Me-Phe-Met-(O)-ol (FK-33824), and the delta-agonists Tyr-D-Ala-Gly-Phe-D-Leu ( DADLE ) and Tyr-D-Ser-Gly-Phe-D-Leu-Thr (D-Ser2- Thr6 ), injected into the cerebral ventricles. The four opioids caused a dose-dependent analgesia (tail-flick); FK-33824 was the most potent, followed by morphine, DADLE and D-Ser2- Thr6 , and the duration of the analgesic effect of D-Ser2- Thr6 was very short. Respiratory frequency was dose-dependently depressed by FK-33824 and DADLE ; dose-response curves with morphine and D-Ser2- Thr6 could not be obtained for technical reasons. The in vivo apparent pA2 values for naloxone against the mu-agonist FK-33824 and the delta-agonist DADLE were similar in analgesia suggesting an interaction with the same type of receptor. On the other hand, in respiration studies the pA2 value for the interaction of naloxone with DADLE was significantly higher than with FK-33824. The ratio between the ED50 required to induce respiratory depression and analgesia was 1,500 times higher for FK-33824 than for DADLE . It was concluded that agonist interaction with mu-receptors can result in antinociceptive effect in the tail-flick test, whereas respiratory depression seems to require a prominent, but non-exclusive, interaction with delta-receptors.

Analgesia↗
PubMed1984

Different mechanisms are involved in the respiratory depression and analgesia induced by neurotensin in rats.

The tridecapeptide neurotensin (NT), injected intracerebroventricularly in rats, induced a naloxone-insensitive and dose-dependent analgesia (tail-flick test), the ED50 being 3.22 nmol/animal. Higher doses induced a dose-dependent respiratory depression, mostly accounted for by a reduction of frequency; the ED50 for this action was 144.6 nmol/animal. In contrast to analgesia, the respiratory depression was antagonized by naloxone, suggesting the possibility that NT and opioid systems might interact at the level of respiration-related nuclei.

Analgesia↗
PubMed1983

Interaction of naloxone with mu- and delta-opioid agonists on the respiration of rats.

The respiratory depression induced by two mu-opiate agonists morphine and Tyr-D-Ala-Gly-N-Me-Phe-Met(O)-ol (FK-33824), and two delta-agonists Tyr-D-Ala-Gly-Phe-D-Leu (DADLE) and Tyr-D-Ser-Gly-Phe-Leu-Thr (D-Ser2-Thr6) was studied in rats by using the intracerebroventricular route. The four opioids caused a dose-dependent depression of respiratory frequency down to apnea but high doses of morphine elicited motor activation and seizure activity. FK-33824 was the most potent, followed by DADLE, D-Ser2-Thr6 and morphine. The in vivo apparent pA2 values were determined for naloxone against FK-33824, DADLE and D-Ser2-Thr6. The pA2 value of naloxone interacting with the mu-agonist FK-33824 was significantly lower than those obtained against the two delta-agonists. It is proposed that different types of opiate receptors are involved in the opiate-induced respiratory depression.

Animals↗
PubMed1983

Participation of pontine structures in the respiratory action of opioids.

The respiratory action of morphine, D-Ala2-D-Leu5-enkephalin, and D-Ala2-Me-Phe4-Met(O)ol5-enkephalin, restrictively applied to the dorso-rostral surface of the pons, was studied in anesthetized cats. Frequency was selectively and dose-dependently depressed, down to apnea, whereas tidal volume and its response to CO2 either remained unchanged or were increased. Similar effects were observed in vagotomized and decerebrate cats. From these and previous (1) results, it can be concluded that the medullary and pontine structures related to respiration are differentially affected by opioids. Pontine nuclei are more sensitive to opioid depression and account for changes in frequency, whereas medullary depression results in reduction of tidal volume and CO2 sensitivity.

Animals↗
PubMed1983

A comparative study of the respiratory depressant and analgesic effects of bremazocine, a kappa-agonist.

The respiratory depression and analgesia induced by a kappa-agonist, bremazocine, were studied by the ED50 ratios and the apparent pA2 values of the interaction with naloxone. The ratio between the ED50 in respiratory depression and analgesia (i.c.v.) was very high compared to that of other mu- and delta-agonists, indicating its small activity on the respiratory center. pA2 values were 7.33 and 7.20 for analgesia and respiratory depression, respectively, after i.c.v. administration. After s.c. injection, the pA2 value for analgesia was 6.16. The results confirm the involvement of different opiate receptors in the mediation of supraspinal and spinal analgesia. The results suggest that bremazocine may induce analgesia by interacting with different types of receptors located at different levels of the CNS. This property and the low activity on the respiratory center make drugs like bremazocine good candidates in the search for safer opiate analgesics.

Analgesia↗
PubMed1982

Cardiovascular effects of intracerebroventricular injection of dopamine after selective MAO inhibition in rats.

Intracerebroventricular injection of dopamine (30-300 micrograms) caused a dose-dependent reduction in the blood pressure and cardiac rate of anaesthetized rats. Inhibition of MAO-type A with clorgyline enhanced the vasodepressant effect while it reversed the bradycardiac effect. Deprenyl, a MAO-type B inhibitor, did not modify the cardiovascular effects of dopamine injected into the cerebral ventricles. The persistent hypotensive action of dopamine in clorgyline-pretreated rats was abolished by the central blockade of alpha-adrenoreceptors with intracerebroventricular injection of phentolamine, whereas haloperidol given by the same route did not affect the hypotensive response. The results suggest that dopamine centrally affects cardiovascular regulation, either after conversion into noradrenaline, or through a direct stimulation of central alpha-adrenoceptors.

Animals↗
PubMed1982

Minoxidil in severe and moderately severe hypertension, in association with methyldopa and chlortalidone.

Minoxidil is a potent antihypertensive drug widely used in severe arterial hypertension and in that refractory to treatment. Its effectiveness in less severe forms of hypertension was evaluated in 15 patients who had either a severe to moderate arterial hypertension not previously treated, or who did not tolerate the side effects of other antihypertensive drugs. The usefulness of methyldopa and chlortalidone to prevent a potential minoxidil-induced tachycardia and fluid retention, respectively, was also tested. The patients were initially treated with chlortalidone 100 mg/day, and methyldopa 500 mg/day. Minoxidil was then given in increasing doses until the diastolic blood pressure was equal to or inferior to 90 mmHg. This occurred consistently at doses which ranged from 5 to 50 mg/day (average, 29 mg). Treatment with minoxidil was continued for four months; tolerance to the drugs was not observed. Low doses of methyldopa and chlortalidone were effective in controlling the tachycardia and the retention of sodium and water induced by minoxidil. The three associated drugs were well tolerated and the life quality improved in most patients. Hypertrichosis was the most consistent side effect. Two patients were withdrawn from the study after the blood pressure was controlled by minoxidil, because of the appearance of angor in one, and edema and heart failure in the other.

Adult↗
PubMed1982

Morphine, pentobarbital and naloxone in the ventral medullary chemosensitive areas: differential respiratory and cardiovascular effects.

Morphine, naloxone and pentobarbital were applied to ventral chemosensitive areas (M and S) and nonchemosensitive areas (pyramids) of the medulla oblongata in anesthetized cats. The respiratory and cardiovascular responses were studied. Morphine and pentobarbital caused a rapid respiratory depression when they were applied for 10 min to the areas M and S; they were inactive in the pyramidal area. The area M was more sensitive than area S to both drugs, because a more rapid and higher depression was induced in the area M. Morphine affected preferentially the respiratory frequency, whereas pentobarbital depressed tidal volume, regardless of the area tested. On the other hand, only pentobarbital reduced the blood pressure, the area S being more sensitive than the area M. When the contact of morphine was extended to 30 min, slight respiratory depression was also observed in the pyramidal area. Naloxone applied to the areas M and S reversed the effects of morphine only partially; i.v. injection of the antagonist was required to achieve full reversion and overshoot. The data show that the described areas are sensitive to opiate and nonopiate drugs. They seem to behave either as chemosensitive structures interacting differentially with drugs, or as areas that allow a rapid access of drugs into some centers deeply located in the brain stem.

Animals↗
PubMed1980

Respiratory effects of beta-endorphin, D-Ala2-met-enkephalinamide, and Met-enkephalin injected into the lateral ventricle and the pontomedullary subarachnoid space.

The respiratory effects of Met-enkephalin (900 microgram), D-Ala2-Met-enkephalinamide (10 microgram), and beta-endorphin (10 microgram) were studied and compared in lightly anesthetized cats, after injection into the lateral ventricle and into the pontomedullary subarachnoid space. The 3 peptides injected into the lateral ventricle induced equidepressant effects on respiration, but the duration of action and the involvement of either frequency or tidal volume varied considerably. Met-enkephalin was shorter-acting (45 min) than both D-Ala2-Met-enkephalinamide and beta-endorphin (over 5 h). The depression induced by beta-endorphin was preceded by a long-lasting stimulation of frequency. The effects were antagonized by i.v. naloxone, but the antagonism was not complete in one third of the animals. In the pontomedullary subarachnoid space, beta-endorphin failed to depress respiration significantly whereas Met-enkephalin induced an immediate and short-acting depression (15 min), and D-Ala2-Met-enkephalinamide depressed respiration for 2-4 h in a biphasic pattern. It is concluded that: (1) respiration is depressed by the 3 opiate peptides; (2) the effects of beta-endorphin on respiration, at the dose used in this study, are secondary to other actions on higher brain structures; and (3) Met-enkephalin and D-Ala2-Met-enkephalinamide seem to affect pontomedullary areas located near the ventral surface, although they may also interact with respiratory structures located more deeply in the brain stem.

Animals↗