Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many of the drugs used in anesthesia and intensive care may cause blockade of the central cholinergic neurotransmission. Acetylcholine is of significance in modulation of the interaction among most other central transmitters. The clinical picture of the central cholinergic blockade, known as the central anticholinergic syndrome (CAS), is identical with the central symptoms of atropine intoxication. This behaviour consists of agitation including seizures, restlessness, hallucinations, disorientation or signs of depression such as stupor, coma and respiratory depression. Such disturbances may be induced by opiates, benzodiazepines, phenothiazines, butyrophenones, ketamine, etomidate, propofol, nitrous oxide, and halogenated inhalation anesthetics as well as by H2-blocking agents such as cimetidine. There is an individual predisposition for CAS--but unpredictable from laboratory findings or other signs. Reports of postanesthetic occurrence of the CAS requiring treatment are not unanimous, varying between 1 and 40%. Differential diagnosis of the CAS includes disorders of glucose and electrolyte metabolism, severe hormonal imbalance, respiratory disorders (hypoxia, hypercarbia), hypothermia, hyperthermia and neuropsychiatric diseases (cerebral hypoxia, stroke, catatony, acute psychosis). The CAS may considerably impair the postanesthetic period especially when agitation is prevalent, which may endanger the patient or the surgical results. The diagnosis is confirmed ex iuvantibus by the sudden increase in the acetylcholine level in the brain. This is achieved with physostigmine, a cholinesterase inhibitor able to easily cross the blood-brain barrier. Its peripheral muscarinic effects are minimal. Postanesthetic CAS can be prevented by administration of physostigmine during the anesthesia procedure. During intensive care (IC), agitated forms of CAS may occur in patients undergoing mechanical ventilation, particularly during prolonged high-dose sedation. Artificial ventilation of such patients becomes very difficult and muscle relaxation may be necessary. In these cases of IC-CAS, physostigmine is of value and has proven beneficial during weaning from mechanical ventilation. Dealing with the CAS for more than a decade has improved knowledge of the central cholinergic transmission. For example, it can be said that CAS occurs alongside general anesthesia, being no more than a frequent side-effect. Furthermore, acetylcholine is involved in nociception through the endorphinergic and the serotoninergic systems. There is a close relation between the central cholinergic transmission and actions of nitrous oxide. Moreover, cholinergic transmission is involved in withdrawal from (among others) alcohol, opiates, hallucinogens and nitrous oxide. In some intoxications with psychoactive agents, physostigmine is useful for reversal of the central nervous symptoms of the acute intoxication itself. In addition it can be used for prevention of some withdrawal states. In
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PMID:Central anticholinergic syndrome (CAS) in anesthesia and intensive care. 268 49

In rabbits anesthetized with 70% N2O-30% O2, the rate of efflux of acetylcholine (ACh) from the cerebral cortex doubled during hypercapnia (increase of end-tidal CO2 from 4 to 8%), and during mild nociceptive stimulation of the tail. Under 0.7% halothane anesthesia, the control rate of ACh efflux was lower than that under N2O; the rate rose 2-fold during hypercapnia and 4-fold during tail stimulation. In the absence of systemic atropinization, increase in ACh efflux was correlated with a shift in EEG from high- to low-voltage ('activated'); after systemic atropinization EEG remained in the high-voltage state, but the changes in ACh efflux with hypercapnia and stimulation were not affected. Following transection of the midbrain, ACh efflux was markedly depressed and did not change during hypercapnia. Taken in context with the previously known facts that the cerebral hyperemia of hypercapnia is potentiated by cholinesterase inhibition and attenuated by atropine or decerebration, the present results support the concept of a cholinergic regulation of the cerebral vasculature.
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PMID:Cortical acetylcholine efflux with hypercapnia and nociceptive stimulation. 402 96

Little is known about the function of cholinesterase activity present in the walls of cerebral microvessels. It has been shown that systemically administered physostigmine, a cholinesterase inhibitor that penetrates the blood-brain barrier, causes barrier opening. This has led to suggestions that perivascular cholinesterase is involved in the maintenance of morphological blood-brain barrier function. The present study demonstrates that the physostigmine-induced barrier opening is fully attributable to the acute hypertension and hypercapnia the agent gives rise to. Thus, it is discussed whether the enzyme activity may function as an enzymatic barrier to cholinergic agents.
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PMID:Perivascular cholinesterase and morphological blood-brain barrier function. 651 93

Cerebral blood flow (CBF) was estimated from measurements of internal carotid blood flow and sagittal sinus blood flow in mechanically ventilated rabbits under 70% N2O-30% O2. Intravenously administered physostigmine, a cholinesterase inhibitor, increased CBF under normocapnia and enhanced the cerebral vasodilatation of hypercapnia, but did not alter the cerebral metabolic rate of oxygen (CMRO2). The cerebrovascular effects of physostigmine were antagonized by atropine but not by dihydro-beta-erythroidine, a nicotinic blocker. Neostigmine, a quaternary cholinesterase inhibitor that does not cross the blood-brain barrier, showed no cerebrovascular effects. It is concluded that the cholinergic cerebral vasodilatation does not depend on cerebral metabolic activation, and that the cholinergic receptors involved are muscarinic and located beyond the blood-brain barrier.
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PMID:Cholinergic cerebral vasodilatation in the rabbit: absence of concomitant metabolic activation. 680 71

Disease secondary to heroin abuse constitutes a rarity in Spain. While there had been no previous cases in earlier years four young heroin addicts were admitted to the Hospital "1st de Octubre" for severe medical complications of their addiction within the last twelve months. Two patients were admitted in deep coma due to drug overdose, being cardiac arrhythmias and pulmonary edema the main associated complications. Cardiac rhythm disturbances are due to a heightened vagal tone, either secondary to inhibition of acetylcholine hydrolysis or to hypoxia, hypercapnia, and acidosis, factors that diminish cholinesterase activity and act synergistically to increase vagal tone. Pulmonary edema secondary to heroin overdose is non-cardiogenic and probably due to hypoxia added to the local action of heroin on the alveolocapillary membrane. The goal of therapy in such cases is to obtain an appropriate alveolar ventilation, the use of continuous positive pressure ventilation being required when there is pulmonary edema. The third patient had staphylococcal pneumonia with multiple abscess formation secondary to venous septic embolization originated peripherally where the drug was injected. Finally, the fourth patient was admitted because of a clinical and biochemical picture of HBsAg negative acute viral hepatitis, having suffered a similar clinical picture three years previously.
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PMID:[Severe medical sequelae in heroin addicts]. 720 89