Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of Althesin, diazepam, ketamine, propanidid and thiopentone on the release of acetylcholine was tested at the mouse neuromuscular junction. Althesin, diazepam and thiopentone increased the quantal content of the end-plate potential. Ketamine at low concentration (3.6 micromol litre-1) had a similar effect, but at high concentration (116.7 micromol litre-1) quantal content decreased sharply. Propanidid and cremophor EL did not affect quantal content. The increase in quantal content antagonized the effect of postsynaptic depression on the amplitude of the end-plate potential. The lack of enhancement of acetylcholine release appears to explain the in vitro interaction of propanidid with tubocurarine. The diversity of presynaptic actions of these drugs makes it unlikely that this is an important mechanism in producing anaesthesia.
 ...
PMID:Presynaptic effect of I.V. anaesthetic agents at the neuromuscular junction. 46 58

Since cardiovascular depression at induction is among the most common complications of anesthesia this comparative study was undertaken. Unpremedicated dogs (n = 16) were induced with 3 mg/kg piritramide i.v. and normoventilated (N2O/O2 = 2/1). In 8 animals 0.8 and 1.6 mg/kg Etomidate and 5.0 and 10.0 mg/kg thiopentone and in 8 further dogs 5.0 and 10.0 mg/kg Propanidid were tested. Equipotent doses of Thiopentone and Propanidid caused a marked myocardial depression, which was seen in a decrease in stroke volume and max dp/dt and in an increase of leftventricular end-diastolic pressure and pulmonary arterial pressure. The increased myocardial O2- cosumption mainly due to the rise in heart rate was covered after Thiopentone by an increase of coronary bloodflow (measured with a pitot-catheter) and an increase of arterio-coronaryvenous difference in oxygen. As the latter decreased after Propanidid, it appeared that Propanidid has coronary dilatory properties. The results demonstrated the uneconomic work of the heart under the influence of Thiopentone and Propanidid. In contrast to this the cardiovascular system after Etomidate remained nearly unaffected. The data of this study suggest the use of Etomidate rather than Thiopentone and Propanidid in cases of shock syndrome, heart and/or coronary insufficiency.
 ...
PMID:Comparison of the immediate effects of etomidate, propanidid and thiopentone on haemodynamics, coronary bloodflow and myocardial oxygen consumption. 122 40

Propanidid and methohexital were compared retrospectively to assess the possible neonatal depression following general anesthesia for caesarean section: both have rapid onset and short duration of action and their transplacental passages are similar. Anesthesia was induced with equivalent doses of the two agents in 90 women (45 in each group). For each anesthetic agent, three subgroups were defined according to the indications, depending on emergency criteria and fetal state. There was no significant statistical difference (Student test) regarding clinical and biochemical criteria except for the fetal arterial pH which was more acidic in the propanidid group. In both groups, Apgar scores, arterial and venous pH were significantly more altered when caesarean section was performed for acute fetal depression.
 ...
PMID:[Intravenous anesthesia for cesarean section. Comparison of propanidid and methohexital]. 195 66

1. The anaesthetic, cardiovascular, respiratory and adverse effects produced by the intravenous injection of CT 1341, thiopentone, methohexitone, pentobarbitone, propanidid and ketamine have been compared in unrestrained cats prepared with chronically implanted venous and arterial cannulae. Aortic blood pressure and heart rates were monitored before, during and after loss of consciousness.2. CT 1341 produced rapid induction of anaesthesia followed by moderately rapid recovery, was active over a wide range of doses and caused minimal respiratory depression and few adverse effects. It caused an initial short-lasting tachycardia and fall in aortic blood pressure succeeded by a secondary depressor response.3. The safety margin was narrower with the barbiturate drugs than with CT 1341, and large doses induced apnoea and respiratory depression. Small doses of methohexitone elicited excitatory effects and large doses caused severe respiratory and circulatory depression, and recovery from anaesthesia was protracted.4. Propanidid induced short-lasting light anaesthesia. The safety margin was narrowest with this drug and induction was associated with adverse circulatory, respiratory and other effects.5. Ketamine was active over a wide range of doses but exhibited qualitatively different properties from the other anaesthetics. Induction was slower after small doses and these produced circulatory stimulation, catatonia and bizarre behavioural effects. Large doses caused respiratory and circulatory depression and recovery was protracted.6. It is concluded that CT 1341 has a wider therapeutic latitude, produces less respiratory depression and has other advantages over the currently used intravenous anaesthetics.
 ...
PMID:Anaesthetic, cardiovascular and respiratory effects of a new steroidal agent CT 1341: a comparison with other intravenous anaesthetic drugs in the unrestrained cat. 465 69

Even though the anesthetic agents thiopental, ketamine, propanidid and etomidate all belong to very different chemical families they are all characterized by a very large degree of liposolubility. This explains their rapid penetration into the brain. The pharmacokinetic model of thiopental is a three compartment model. There is strong protein binding and only the free fraction is active. The very short action of the product after a single injection is due to the rapid redistribution of the agent into the muscle mass because its hepatic metabolization is very slow. However, when given over prolonged time the adipose compartment plays an important role in the mixture of the product, explaining the prolonged sleep produced. The central depressant actions of thiopental and consequently its action on CMRO2 depend on the initial dose and the route of administration. A single and massive injection produces a small and temporary reduction in the CMRO2 even though the plasmic concentration is high. In contrast prolonged intravenous infusion produces more severe and longer lasting depression of the CMRO2. The pharmacokinetic model of ketamine is tri-compartmental. There is weak protein binding. After IV injection ketamine rapidly enters the brain and the maximum concentration is reached one minute later. After that the cerebral concentration rapidly falls as does the plasma level. Signs of waking are seen at a concentration of 130 micrograms per gram of tissue. An increase in the dose of ketamine does not much influence the duration of analgesia but increase the waking time. This suggests that its indication in ambulatory anesthesia should be looked at with care. It is metabolized by the liver with the formation of several metabolites of which some are active. The kinetics of propanidid can be explained on the basis of a monocompartmental model. The speed of the fall in plasma level of the product is related to the speed of injection. High plasma concentrations mobilize a larger quantity of plasma pseudo-cholinesterases, increasing thus the speed of degradation. The product is rapidly hydrolized (plasma and liver cholinesterases). The duration of action is longer when used at low doses or when it is administered at a constant dose. Propanidid does not have any accumulative effect. The kinetics of etomidate follow a tri-compartmental model. It is very rapidly and largely distributed in the organism, the peak cerebral concentration being reached in less than one minute. There is strong protein binding. Repeated administration of the drug produces an increase in anesthetic sleep but also a delay in recovery. Etomidate is hydrolized by hepatic esterases.
 ...
PMID:[Pharmacokinetics of intravenous non-steroidal anesthetics]. 611

Propanidid, etomidate, and ketamine were compared for their effects on maternal acid-base balance and circulation as well as on postnatal general condition and acid-base balance of the newborn, on the basis of 44 women in advanced pregnancy to whom caesarean section was applied in general anaesthesia. The probands had not been deliberately selected beforehand. Results obtained from the three above anaesthetics were compared with one another as well as with parameters recorded from spontaneously delivered newborns without any medication. One of the anaesthetics produced sufficiently deep anaesthesia in all patients, and no signs of central depression were recordable from the newborns. The parameters of acid-base balance, following propanidid and etomidate anaesthesia, revealed respiratory acidosis in the newborns immediately after delivery by caesarean section. Their pH values were lower than those recorded in the context of ketamine anaesthesia or spontaneous delivery without any medication. Both values returned to normal within 30 minutes from delivery. The one-minute and five-minute Apgar scores were below those of spontaneous deliveries, at the beginning, but eventually reached normal levels. All the three anaesthetics were found to be suitable for introduction of general anaesthesia for caesarean section on account of high-rate enzymatic degradation and, consequently, absence of foetal depression. Resulting oxygen supply is higher, as compared to spontaneous delivery. Early indication and short-time introduction and delivery, thus possible, have often proved to be important to the newborn's condition.
 ...
PMID:[Comparison between ketamine, propanidid, and etomidate in general anaesthesia for caesarean section (author's transl)]. 723 13