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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accidental ingestion and overdose of medications used in thyroidal illnesses may occur because of the frequency of these diagnoses. This review discusses acute overdosage of 4 groups of medicines. Acute ingestion of thyroid replacement medications occurs very frequently. Overdosage in children is usually asymptomatic and a benign condition; after evacuation of the stomach, propranolol may be used to treat symptomatic children. Other therapeutic regimens are rarely indicated in this age group. Ingestions of large amounts of antithyroid medications occur very rarely and limited information regarding treatment is available in the medical literature. Acute ingestion of iodine often results in corrosive injury of the gastrointestinal tract and renal damage. Cardiopulmonary collapse secondary to circulatory failure, oedema of the epiglottis and aspiration pneumonias may cause death. Administration of starch and sodium thiosulphate, maintenance of airway and stabilisation of circulation are the major components of therapy. Acute overdosage of beta-blockers is uncommon but can be lethal. Patients may appear well initially but they can suddenly develop convulsions and profound cardiovascular collapse requiring instant aggressive therapy. Potassium and glucose concentrations should be monitored. The usage of atropine, isoprenaline (isoproterenol), glucagon and prenalteral is discussed.
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PMID:Clinical features and management of overdosage with thyroid drugs. 246 Jul 21

During a one-month period, two cases of beta-adrenergic blocker overdose were treated by the emergency staff at our hospital. One case of propranolol intoxication demonstrated profound cardiovascular collapse and generalized tonic-clonic seizures. The condition failed to respond to high-dose intravenous pressor agents, but did improve significantly with IV glucagon infusion. The second overdose involved atenolol. Although the blood levels reported were very high, the patient showed no cardiovascular compromise and required only inhaled bronchodilators for an exacerbation of her asthma.
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PMID:Beta blocker overdose with propranolol and with atenolol. 285 42

A microsphere technique was used to study the effect of glucagon on blood flow to the different tissue layers of the stomach, small bowel, and colon of the dog in hypovolemic shock. In normal dogs, glucagon caused a twofold rise in flow to all layers of the stomach and colon, and a threefold increase to all layers of the small bowel. After administration of glucagon, a larger fraction of cardiac output was diverted to the gut microcirculation. In acute hypovolemic shock, intestinal perfusion was preserved relative to cardiac output inasmuch as cardiac output and gastric blood flow fell 75% and flow to the small bowel and colon fell by only about 50%. Glucagon markedly increased the fraction of cardiac output passing to the gut circulation in hypovolemic shock and, most importantly, sustained flow to the areas most prone to ischemic necrosis; gastric mucosa, colonic mucosa, and small intestinal villi. In more prolonged shock, however, glucagon precipitated fatal cardiovascular collapse unless part of the lost blood volume first was replaced. Glucagon, therefore, should not be used in patients in hypovolemic shock without prior replacement of at least part of the lost blood volume.
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PMID:Effect of glucagon on gastrointestinal blood flow of dogs in hypovolemic shock. 737 54

This paper reviews the mechanisms of anaphylactic shock in terms of the immunoglobulin and non-immunoglobulin triggering events, and the cellular events based on the rise in intracellular cyclic AMP and calcium that release preformed granule-associated mediators and the rapidly formed, newly synthesized mediators predominantly based on arachidonic acid metabolism. These primary mediators recruit other cells with the release of secondary mediators that either potentiate or ultimately curtail the anaphylactic reaction. The roles of these mediators in the various causes of cardiovascular collapse are examined. The treatment of anaphylactic shock involves oxygen, adrenaline and fluids. The importance and safety of intravenous adrenaline are discussed. Combined H1 and H2 blocking antihistamines and steroids have a limited role. Glucagon and other adrenergic drugs are occasionally used, and several new experimental drugs are being developed.
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PMID:Anaphylactic shock: mechanisms and treatment. 865 48

The prognosis of self-poisoning with beta-blockers is excellent, especially if medical management is started immediately but the wide variety of clinical symptoms and proposed treatments complicate the therapeutic strategy. Beta-blockers that are liposoluble or have marked anti-arrhythmic activity are more lethal (e.g. propranolol, sotalol). Similarly, pre-existing cardiac pathology or co-ingestion of psychotropic or cardioactive drugs increases mortality. The first-line symptomatic treatment is administration of atropine and volume-expanding fluids to treat bradycardia and hypotension, respectively. However atropine is often unsuccessful in reversing beta-blocker-induced bradycardia and repeated doses can provoke atropine poisoning. If symptomatic treatment fails, then antidotes should be administered in a precise order: first, high doses of glucagon, followed by isoproterenol, epinephrine, and the new inhibitors of phosphodiesterases. Mechanical ventilation should be started at the same time as pharmacological treatment in cases of severe collapse or prolonged QRS.
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PMID:Pathophysiology and management of self-poisoning with beta-blockers. 790 73

Circulatory collapse and obtundation occurred in a 37-year-old woman following an iatrogenic overdose of labetalol. Conventional therapy with glucagon and alpha-adrenergic receptor-stimulating agents was ineffective in raising the patient's cardiac output or improving her mental status despite increasing the arterial pressure. The administration of amrinone was temporally associated with significant increases in the cardiac output accompanied by improved mental status. This case suggests that amrinone may be effective adjunctive therapy for beta-adrenergic receptor blocker overdoses by reversing their negative inotropic effects.
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PMID:Labetalol overdose successfully treated with amrinone and alpha-adrenergic receptor agonists. 790 16

Class III (Vaughan-Williams classification) antiarrhythmic drugs prolong the cardiac action potential without affecting depolarisation. The 3 class III drugs currently in general use are amiodarone, sotalol and bretylium. The presenting features of acute toxicity are different for each agent and are, therefore, discussed separately. Several new class III antiarrhythmic agents are under development, including dofetilide and d-sotalol, but specific data on overdoses of these potent class III drugs are not yet available. Amiodarone toxicity following acute overdose is rare because poor bioavailability and a large volume of distribution limit the peak serum concentration. Toxicity is low even if high serum concentrations are reached. The major risks from acute overdose are hypotension (intravenous administration only) and arrhythmia if other factors, such as hypokalaemia or additional antiarrhythmic agents are present. Management is chiefly directed at reducing absorption with activated charcoal or cholestyramine, and monitoring for arrhythmia. Sotalol is a beta-blocker with additional class III activity. Oral bioavailability is high, and overdosed patients can present with bradycardia, hypotension and major haemodynamic collapse. The combination of bradycardia and prolongation of the QT interval is associated with malignant arrhythmias such as torsade de pointes. Management principles include observation and correction of bradycardia with endocardial pacing, intravenous adrenergic drugs and glucagon. The risk of arrhythmia can be substantially reduced by intravenous potassium and magnesium supplements. d-Sotalol is a potent class III drug devoid of beta-blocking activity and may be expected to share the proarrhythmic affects of the racemic mixture in overdose, without pronounced hypotension and bradycardia. Intravenous bretylium in overdose causes an initial hypertensive effect, followed by profound hypotension from systemic vasodilation. Management is directed at controlling hypotension with volume expansion and norepinephrine (noradrenaline).
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PMID:Class III antiarrhythmics in overdose. Presenting features and management principles. 812 65

Twenty-two dogs with superficial necrolytic dermatitis were evaluated prospectively, twenty-one of which had characteristic crusting lesions of the paw pads. Histologically, epidermal lesions included parakeratosis and laminar intracellular edema. The plasma amino acid concentrations of eight dogs were markedly depressed. Nine dogs had terminal diabetes mellitus. These clinical and morphologic findings were strikingly similar to those of necrolytic migratory erythema in human beings, the most common cause of which is hyperglucagonemia due to islet cell tumor of the pancreas. No pancreatic tumors were found in these dogs; plasma glucagon concentrations in the five dogs tested were normal. The serum alkaline phosphatase concentrations were elevated in all dogs. Severe vacuolar hepatopathy, suggesting metabolically or hormonally induced hepatic dysfunction, was found in 21 dogs at necropsy or by biopsy; one dog had ultrasonographic abnormalities of the liver. Histopathologically, severe vacuolar alteration resulted in parenchymal collapse and nodular regeneration, which grossly mimicked cirrhosis. Although the definitive metabolic stimulus was not discovered for the cutaneous and hepatic lesions, the similarity of the cutaneous and biochemical features of canine superficial necrolytic dermatitis to human necrolytic migratory erythema warrants further investigation into possible underlying pancreatic hormonal dysfunction.
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PMID:Superficial necrolytic dermatitis (necrolytic migratory erythema) in dogs. 844 31

We report the case of a 43-year-old schizophrenic who sustained, after 12 days of treatment including olanzapine (20 mg.day-1), carbamazepine, levomepromazine and alprazolan, a severe shock with bradycardia (HR: 40 b.min-1), circulatory collapse (SAP: 60 mmHg), hypothermia (T: 27 degrees C), coma and disseminated intravascular coagulation. A significant improvement was obtained with high doses of intravenous glucagon, whereas the normalization of central temperature, atropine, adrenaline and volume loading had been inefficient. Olanzapine, alone of associated with other psychotropics, could cause severe circulatory collapse with hypothermia and coma responding to a treatment including glucagon.
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PMID:[Severe intoxication probably from olanzapine (Zyprexa). Beneficial effect of glucagon]. 1046 38

The active neurotoxin of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium (MPP+), exerts its lethal effect by inhibiting Complex I of the electron transport chain (ETC). MPP+ shuts down aerobic oxidative phosphorylation and ETC-mediated ATP synthesis. The present investigation examines anaerobic survival during MPP+ toxicity in murine neuroblastoma cells Neuro 2-A (N2-A). MPP+ addition to the cells resulted in a reduction in cell viability, mitochondrial O(2) consumption (MOC) and ATP concentration in a dose-dependent manner. However, the addition of 10 mM of D-(+)-glucose prevented MPP+ toxicity, attenuated the loss of ATP, but did not reverse the complete inhibition of MOC, indicating substrate level phosphorylation and explicit anaerobic survival. Glucose addition prevented MPP+-mediated drop in DeltaPsim, endoplasmic reticulum and intracellular organelle membrane potential tantamount to an increase of cell viability. Secondly, we examined the metabolic regulation of pyruvate dehydrogenase (PDH) and carnitine palmitoyl transferase (CPT) activities during glucose rescue. These enzymes exert control over acetyl CoA reservoirs in the mitochondria during aerobic metabolism. DL-6,8-Thioctic acid (PDH prosthetic group) and insulin slightly augmented metabolic rate, resulting in enhanced vulnerability to MPP+ in a glucose-limited environment. Additional glucose prevented these effects. Amiodarone (CPT inhibitor) and glucagon did not hamper or potentiate glucose rescue against MPP+. These data support strict anaerobic glucose utilization in the presence of toxic levels of MPP+. Moreover, the findings indicate that MPP+ exerts two distinct modes of toxicity (fast and slow death). With MPP+ (<1 mM), anaerobic glycolysis is operational, and toxicity is strictly dependent upon glucose depletion. MPP+ (1-10 mM) initiated acute metabolic collapse, with failure to sustain or switch to anaerobic glycolysis. In conclusion, overcoming energy failure against MPP+ may involve targeting rate-limiting controls over anaerobic energy pathways.
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PMID:D-(+)-glucose rescue against 1-methyl-4-phenylpyridinium toxicity through anaerobic glycolysis in neuroblastoma cells. 1254 55


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