Vasopressin Epinephrine

K8. Konzett, H., Hortnagl, H., and Winkler, K., On the urinary output of vasopressin, epinephrine and norepinephrine during different stress situations. Psy-chopharmacologia 21, 247-256 (1971). 

Bocckino, SB, Blackmore, PE and Exton, JH (1985) Stimulation of 1,2-diacylglycerol accumulation in hepatocytes by vasopressin, epinephrine, and angiotensin II. Journal of Biological Chemistry, 260, 14201-14207. 

Early transcutaneous pacing I.V. vasopressin, epinephrine, and atropine... 

Placebo-controlled trial A randomised, placebo-controlled trial of vasopressin + epinephrine versus placebo + epinephrine in 268 patients xvith cardiac arrest foxmd that combined treatment improved survival to hospital discharge with favourable neurological outcomes. The rates of adverse events were similar in the two groups [100 -]. 

Figure 25-7. Metabolism of adipose tissue. Hormone-sensitive lipase is activated by ACTH, TSH, glucagon, epinephrine, norepinephrine, and vasopressin and inhibited by insulin, prostaglandin E, and nicotinic acid. Details of the formation of glycerol 3-phosphate from intermediates of glycolysis are shown in Figure 24-2. (PPP, pentose phosphate pathway TG, triacylglycerol FFA, free fatty acids VLDL, very low density lipoprotein.)...

Otfier fiormones accelerate tfie release of free fatty acids from adipose tissue and raise tfie plasma free fatty acid concentration by increasing the rate of lipolysis of the triacylglycerol stores (Figure 25—8). These include epinephrine, norepinephrine, glucagon, adrenocorticotropic hormone (ACTH), a- and P-melanocyte-stimulat-ing hormones (MSH), thyroid-stimulating hormone (TSH), growth hormone (GH), and vasopressin. Many of these activate the hormone-sensitive hpase. For an optimal effect, most of these lipolytic processes require the presence of glucocorticoids and thyroid hormones. These hormones act in a facilitatory or permissive capacity with respect to other lipolytic endocrine factors. 

Epinephrine 1 mg intravenous push (IVP), repeat every 3-5 min or Vasopressin 40 units IVP x one dose only (replace first or second dose of epinephrine)... 

Vasopressin is a peptide hormone produced by the hypothalamus and secreted by the posterior pituitary in response to stimulation. Normal stimuli for vasopressin release are hyperosmolarity and hypovolemia, with thresholds for secretion of greater than 280 mOsm/kg and greater than 20% plasma volume depletion. A number of other stimuli, such as pain, nausea, epinephrine, and numerous drugs, induce release of vasopressin. Vasopressin release is inhibited by volume expansion, ethanol, and norepinephrine. The physiological effect of vasopressin is to promote free water clearence by altering the permeability of the renal collecting duct to water. In addition, it has a direct vasoconstrictor effect. Consequently, vasopressin results in water retention and volume restoration. In patients with septic shock, vasopressin is appropriately secreted in response to hypovolemia and to elevated serum osmolarity (R14). 

Many hormones and other blood-borne substances (including drugs) also alter contractile activity of smooth muscle. Some of the more important substances include epinephrine norepinephrine angiotensin II vasopressin oxytocin and histamine. Locally produced substances that may alter contraction in the tissue in which they are synthesized include nitric oxide prostaglandins leukotrienes carbon dioxide and hydrogen ion. 

If neither IV nor IO access can be established, atropine, lidocaine, epinephrine, naloxone, and vasopressin may be administered endotracheally. The endotracheal dose should generally be two to two and one-half times larger than the IV/IO dose. 

Vasopressin is a potent vasoconstrictor that increases blood pressure and systemic vascular resistance. It may have several advantages over epinephrine. First, the metabolic acidosis that frequently accompanies cardiopulmonary arrest can blunt the vasoconstrictive effect of epinephrine this does not occur with vasopressin. Second, stimulation of P receptors by epinephrine can increase myocardial oxygen demand and complicate the postresuscitative phase of CPR. Vasopressin can also have a beneficial effect on renal blood flow in the kidney, causing vasodilation and increased water reabsorption. 

Despite these potential advantages, clinical experience with vasopressin is limited and comparative trials with epinephrine have produced mixed results. Overall, these studies suggest that vasopressin is effective as part of ACLS after cardiac arrest, but its superiority to epinephrine remains questionable. 

Vasopressin can be substituted for the first or second dose of epinephrine in patients with asystole. There is insufficient evidence to make a treatment recommendation for PEA. 

Izquierdo I, Dalmaz C, Dias R, Godoy M. 1988. Memory facilitation by posttraining and pretest acth, epinephrine, and vasopressin administration two separate effects. Behav Neurosci 102(5) 803-806. 

Epinephrine and norepinephrine secretions are directly related to emotion and stress (S5). Hockey players demonstrate increases in excretion of norepinephrine during active competition (E3), as do pilots during moderately stressful situations (V4, V6). Increased excretion of catecholamines has also been observed in subjects watching emotionally evocative motion pictures (L3). Muscle pain stimulated increased excretion of vasopressin and epinephrine, but not of noreiiinephrine (K8). 

The stress of cold produced increased urinary excretion of norepinephrine but not of epinephrine or vasopressin (K8). Cold in the form of accidental hypothermia also resulted in increased serum creatine phos-phokinase (M2). Mental stress (problem solving) resulted in increases of urinary vasopressin from 33 to 47.6 units, epinephrine from 5.5 to 11.3 mg, and norepinephrine from 17 to 21 mg (K8). 

The cornerstone of therapy for ventricular fibrillation is electrical deflbrillation. In the acute setting, defibrination is first-line therapy. Intravenous bretylium can occasionally contribute to conversion, but this is infrequent. In the management of out-of-hospital cardiac arrest, high-dose epinephrine (5 mg intravenously) improves the rate of successful resuscitation in patients with asystole, but not in those with ventricular fibrillation, when compared with the standard dose of 1 mg. Vasopressin (40 U intravenously) may more effective than 1 mg intravenous epinephrine in out-of-hospital patients with ventricular fibrillation that is resistant to electrical defibrillation. The OPTIC smdy (see Connolly et al., 2006) showed that amiodarone plus jS-blocker is superior than sotalol or jS-blocker alone for reducing ICD shocks in patients with reduced left ventricular function and history of sustained VT, VF, or cardiac arrest. 

Lindner KH, Dirks B, Strohmenger HU, Prengel AW, Lindner IM, Lurie KG. Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation. Lancet 1997 349 535-97. 

The chemical transmitters may be small molecules— notably acetylcholine, norepinephrine, epinephrine, serotonin, dopamine, or histamine. Acetylcholine and norpeinephrine are the dominant neurotransmitters in the parasympathetic and sympathetic nervous systems, respectively. Dopamine and serotonin are employed primarily in the central nervous system. Neurotransmitters may also be more complex peptides (small proteins) such as substance P, vasopressin, endorphins, and enkephalins. The latter agents are of particular importance to our considerations of opium since they represent the endogenous opiates—agents that exist within the body whose actions are mimicked by exogenous, or outside, agents such as morphine, heroin, codeine, and so on. These neurotransmitters serve to convey information between neurons across the synaptic cleft (the junction where two neurons meet) or at the neuroeffector junction (the site between neuron and an innervated organ such as muscle or secretory gland). 

Fig. 8. Known and potential interactions of the ACTH/adenylate cyclase/cyclic AMP-dependent protein kinase system in the adrenocortical cell with other hormones and intracellular messengers. Epinephrine activates adenylate cyclase in the adrenocortical cell [33]. Adrenocortical cells have receptors for several hormones which may activate G, including angiotensin II [34], acetylcholine [35], and endogenous opioid peptides [36]. Angiotensin II, acetylcholine and vasopressin [37-39] have all been demonstrated to activate the breakdown of PIP2 in adrenocortical cells and to stimulate steroidogenesis 5-hydroxytrypt-amine is also a known steroidogenic agent [40]. Probable receptor subtypes involved are indicated (/3 M (muscarinic) 5-HT, and V,). This is not a comprehensive diagramming of all stimuli or all possible interactions. Modified from Ref. 7.

Fig. 8. Effects of agonists on cytosolic Ca2+ (measured by fluorescence) in isolated rat hepatocytes loaded with Quin 2. The concentrations of agonists are Epi, 1 /uM epinephrine Phenyl, 10 fiM phenylephrine Vaso, 10 nM vasopressin Glue, 10 nM glucagon. Reproduced from Ref. 3 by permission of the authors and publisher.

Glucagon markedly potentiates the hepatic actions of other Ca2+-mobilizing hormones, e.g., vasopressin and epinephrine. This can be attributed to increased IP3 production and Ca2+ mobilization, and also to the opening of more plasma membrane Ca2+ channels. On the other hand, the actions of glucagon and other Ca2+-mobilizing hormones on liver cell Ca2+ fluxes are inhibited or abolished by tumor promoting phorbol esters. There is evidence that this inhibition is exerted at the level of Gp or on another factor involved in the control of PIP2 phospholipase C and may involve protein kinase C. 

The hydrolysis of triacylglycerol to monoacylglycerol and fatty acids by hormone-sensitive lipase can be stimulated by epinephrine, norepinephrine, adrenal steroids, glucagon, and the hypophysial hormones, luteotropin (prolactin or luteinizing hormone), )3- and a-lipotropins, somatotropin, thyrotropin, and vasopressin. 

To ensure a reasonably long-lasting local effect with minimal systemic action, a vasoconstrictor (epinephrine, less frequently norepinephrine or vasopressin derivatives) is often co-administered in an attempt to confine the drug to its site of action. As blood Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

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