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Biomedical subjects

I Kissin

Publications and source records attributed to I Kissin.

At least 55 records · Page 3Linked to original sources
PubMed1991

Magnitude of acute tolerance to opioids is not related to their potency.

It was suggested that for a given analgesic effect, more potent opioids may produce smaller degrees of tolerance than those with lower analgesic potency. The use of opioids with high analgesic potency to reduce the rate of tolerance development would be an important therapeutic consideration. This study tested the hypothesis that the degree of acute tolerance to the analgesic effect of opioids is inversely related to their potency. In the experiments on rats, the analgesic effects of morphine, alfentanil, and sufentanil given by a continuous 8-h infusion at a constant rate, were determined by measuring the threshold of motor response to noxious pressure on the tail. The comparative degree of acute tolerance was determined on the basis of the decline in the level of analgesia at the end of the infusion period. Morphine 4 mg.kg-1.h-1, alfentanil 0.45 mg.kg-1.h-1, and sufentanil 0.0085 mg.kg-1.h-1 caused approximately similar increases in the pain threshold. The peak of analgesia could not be maintained; it declined by 74 +/- 6% (P less than 0.0001) with morphine, 86 +/- 6% (P less than 0.0001) with alfentanil, and 92 +/- 2% (P less than 0.0001) with sufentanil. The results indicate that the infusion of alfentanil and sufentanil, which differ from morphine by higher analgesic potency (by 10-fold and more than 100-fold, respectively), results in a decline in the degree of analgesia during infusion similar to that of morphine. These data reject the hypothesis that the magnitude of acute tolerance to the analgesic action of opioid drugs following their systemic administration is inversely related to their potency.

Alfentanil↗
PubMed1991

Acute tolerance to the hypnotic effect of morphine in rats.

To demonstrate the development of acute tolerance to the hypnotic effects of morphine, loss and recovery of the righting reflex with a constant-rate morphine infusion was studied in rats. In one group of animals, brain and serum concentrations of morphine were detected (radioimmunoassay) at the time of loss of the righting reflex, and in another group, at the time of the reflex recovery. The morphine infusion at a constant rate of 14 mg.kg-1.h-1 caused a loss of the righting reflex in all animals that was achieved by 2.5 h. However, this level of response could not be maintained, and at 5 h it began to decline. All animals recovered the righting reflex by the ninth hour, despite the continuing morphine infusion. The morphine brain and serum levels at the times of loss and recovery of the righting reflex were not different. The results suggest a development of acute tolerance to the hypnotic effect of morphine, which is determined primarily by pharmacodynamic mechanisms.

Animals↗
PubMed1990

Postoperative pain after inguinal herniorrhaphy with different types of anesthesia.

In a randomized, double-blind study, postoperative pain was assessed in 36 patients undergoing inguinal herniorrhaphy with three types of anesthesia: general (thiopental-nitrous oxide-halothane); general with the addition of local (infiltration of the abdominal wall with 0.25% bupivacaine along the line of the proposed incision); and spinal (0.5% bupivacaine). The severity of constant incisional pain, movement-associated incisional pain, and pain upon pressure applied to the surgical wound using an algometer was assessed with a visual analogue self-rating method at 24 h, 48 h, and 10 days after surgery. The addition of local anesthesia significantly decreased the intensity of all types of postoperative pain. This effect was especially evident with constant incisional pain that disappeared almost completely 24 h after surgery. With pain caused by pressure on the site of the surgical incision, the pain score difference between general and general plus local anesthesia was obvious even 10 days after the surgery (with 0.4-kg/cm2 pressure, the pain scores were 16 +/- 3 vs 2 +/- 1, P less than 0.01). The difference in postoperative pain scores between spinal and general anesthesia groups indicated that spinal anesthesia also decreases the pain intensity. However, this decrease is less pronounced than that seen with the addition of local anesthesia: movement-associated pain scores 24 h after surgery were 72 +/- 5 in the general anesthesia group, 40 +/- 6 in the spinal anesthesia group, and 16 +/- 3 in the general plus local anesthesia group (with P less than 0.002 between the groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Alfentanil potentiates midazolam-induced unconsciousness in subanalgesic doses.

The effects of alfentanil on the midazolam dose-response curve for hypnosis was studied with response to the verbal command as an end point in 95 patients. The analgesic effect of alfentanil was studied by measuring the threshold for pain caused by pressure on the trapezius muscle with the use of a dolorimeter in 21 patients. The study was randomized, double-blind, and performed on the unpremedicated patients with ASA physical status I or II. Alfentanil was found to reduce the midazolam ED50 value for the induction of anesthesia in a dose-dependent fashion. The smallest dose of alfentanil (3 micrograms/kg) that caused a marked shift of the midazolam dose-response curve to the left along the dose axis (from the ED50 of 270 micrograms/kg to the ED50 of 142 micrograms/kg, P less than 0.0005) represents approximately 2% of the alfentanil ED50 for induction of unconsciousness (130 micrograms/kg). Alfentanil (10 micrograms/kg) caused only a tendency for increase in the pain threshold, whereas a dose of 15 micrograms/kg significantly increased the pain threshold by 37% (P less than 0.05). The results demonstrate that alfentanil potentiates the hypnotic effect of midazolam in very small doses. The high potency of alfentanil in this respect, as compared to its analgesic potency, suggests a very specific mechanism of alfentanil-midazolam hypnotic interaction, one that most likely is based on a functional relationship between the GABA receptor-benzodiazepine receptor system and the opioid receptor system in mediation of hypnosis.

Adult↗
PubMed1990

Sedative and hypnotic midazolam-morphine interactions in rats.

The midazolam-morphine interactions in relation to the sedative effect and in relation to the hypnotic effect were studied in rats. Two series of experiments (sedative and hypnotic) were performed. In the sedative series, doses that inhibited locomotor activity to 10% or more of the control level were determined when the agents were given singly or in combination. Dose-response curves were determined with a probit procedure. The ED50 values of both agents and their combination were compared with algebraic (fractional) and isobolographic analyses in one subseries of experiments. The effect of a small fixed dose of morphine (1/10 of ED50 value for the sedative effect) on the slope of the sedative dose-response curve for midazolam was determined in the other subseries. In the hypnotic series of experiments, doses (ED50) that blocked the righting reflex with drugs given separately and in combination were determined by a probit procedure and, as in the sedative series, compared with algebraic (fractional) and isobolographic analyses. Sedative interaction between midazolam and morphine was found to have a tendency for synergism (interaction coefficient of 1.56, P greater than 0.05) with decreased individual variability in the sedative response to the combination. Hypnotic midazolam-morphine interaction was highly synergistic with the interaction coefficient of 3.70 (P less than 0.0001). A difference in the outcomes of midazolam-morphine interaction regarding sedation and hypnosis suggests that underlying mechanisms for these two effects are different; therefore, they should not be regarded as only increasing depths of the same action.

Animals↗
PubMed1990

Morphine and fentanyl anesthetic interactions with diazepam: relative antagonism in rats.

The anesthetic effects of morphine-diazepam and fentanyl-diazepam combinations as characterized by abolition of the movement response to noxious stimulation were studied in rats to test the hypothesis of antagonistic interactions between the components of these combinations. Noxious pressure on the tail was used to induce the response. Dose-effect curves were constructed for the drugs given alone and in combination. With the use of probit procedure ED50 values for single drugs and their combinations were determined, and the interactions were analyzed with algebraic (fractional) and isobolographic methods. It was found that both morphine and fentanyl have a less than additive (antagonistic) interaction with diazepam. In combination the sum of fractional doses was higher than a single-drug fractional dose, 1.67 versus 1.00 (P less than 0.05) for morphine-diazepam and 1.61 versus 1.00 (P less than 0.05) for fentanyl-diazepam. The observed antagonism is a relative one that does not increase the requirement for one agent upon the addition of another agent.

Animals↗
PubMed1989

Diazepam--morphine hypnotic synergism in rats.

The effect of diazepam-morphine combination on the righting reflex was studied in rats. Doses of the drugs given alone and in combination that block righting reflex (RR ED50) were determined with a probit procedure. Brain concentrations following equieffective doses of the drugs administered separately and in combination were determined by radioimmunoassay. Equieffective intravenous doses and corresponding brain concentrations for the agents were compared with fractional (algebraic) and isobolographic analyses. Interaction between diazepam and morphine was found to be synergistic. It is not likely to be pharmacokinetic in nature.

Animals↗
PubMed1989

Midazolam-alfentanil synergism for anesthetic induction in patients.

The effect of midazolam on the induction dose-response curve for alfentanil was studied in nonpremedicated ASA physical status I or II patients. The response to the verbal command was used as an end point of anesthesia. Dose-response curves for midazolam, alfentanil, and their combination were determined with a probit procedure, and compared with algebraic (fractional) analysis of drug interaction. Interaction between midazolam and alfentanil was found to be synergistic (supraadditive). The results suggest that the use of this combination is advantageous not only because it helps to achieve different anesthetic goals with specific drugs (a benzodiazepine for unconsciousness and an opioid for blockade of the responses to noxious stimulation), but also because its components are complementary for unconsciousness.

Adolescent↗
PubMed1989

Midazolam-morphine sedative interaction in patients.

The sedative effects of midazolam, morphine, and their combination were studied in ASA physical status I and II patients. The visual analog method was used to determine sedative effect. A self-rated score of 50 mm or more on a 100-mm line was regarded as a positive response to the treatment. The dose-response curves for midazolam, morphine, and their combination (each in a group of 30 patients) were determined by probit procedure and compared with isobolographic and algebraic (fractional) analyses. Interactions between midazolam and morphine when used to produce sedation represent summation, not synergism.

Adult↗
PubMed1988

Midazolam-thiopental anesthetic interaction in patients.

The effect of thiopental on the induction dose-response curve for midazolam was studied in nonpremedicated ASA physical status I and II patients. As an endpoint of anesthesia, ability to open eyes on command was used. Dose-response curves for thiopental, midazolam, and their combination were determined with a probit procedure and compared with an isobolographic analysis. Interaction between midazolam and thiopental was found to be synergistic (supraadditive). The degree of midazolam-thiopental anesthetic synergism in surgical patients was close to that reported previously in rats with loss of the righting reflex as an index of anesthesia.

Adult↗