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It has got a molecular weight of 183.2g/mol. A solution of adrenaline deteriorates rapidly on exposure to air or light turning pink from oxidation to adrenochrome and brown from the formation of melanin. Some of the many functions of adrenaline on the body include regulating heart rate, blood vessel and air passage diameter. Adrenaline is the transmitter released from the sympathetic nerve endings and are reactivated mainly by reuptake.
Adrenaline is a strong stimulant of the adrenergic receptors á¾³(alpha) and Î²(beta). These receptors are subdivided into á¾³1,á¾³2(which are Gq and Gi coupled receptors respectively) and Î²1, Î²2 andÎ²3 which are all linked to GS proteins. Activation of the á¾³ receptors causes vasoconstriction in the skin and viscera. Î’1 activation stimulates heart rate and force, increases blood pressure and increases blood flow to the skeletal muscles.
Adrenaline is a potent vasopressor drug, which when given rapidly by intravenous route evokes a characteristics effect on blood pressure, which rises rapidly to a peak proportional to the dose. There is a greater increase in systolic pressure than an increase in diastolic leading to an increase in pulse pressure. As the response wanes, the mean pressure may fall below normal before returning to control levels. The mechanism of the rise in blood due to adrenaline is three fold.
1. Direct myocardial stimulation that increases the strength of ventricular contraction (positive inotropic action)
2. An increased heart rate (positive chronotropic action)
3. Vasoconstriction in many vascular beds, especially in the precapillary resistance of the skin, mucosa and kidney along with marked constriction of the veins.
At the height of the rise of blood pressure, the pulse rate which was first accelerated, may slow down due to compensatory vagal discharge. Small doses of epinephrine (0.1 µg/kg) may reduce blood pressure. The depressor effect of small doses and the biphasic response to larger to larger doses are due to greater sensitivity to adrenaline of Î²2 receptor (vasodilator) than á¾³ receptor (vasoconstrictor).
When given slowly by intravenous infusion or by subcutaneous injection the effects are different. Absorption of the drug is slow due to local vasoconstriction. The effect of doses as large as 0.5- 1.5 mg can be duplicated by intravenous infusion at a rate of 10 -30 µg/min. There is a slight increase in systolic pressure due to increased cardiac contractile force and a rise in cardiac output. There is decrease in peripheral resistance due to a dominant action on Î²2 receptors of vessels in skeletal muscle, where blood flow is enhanced, thus diastolic pressure usually falls. As the mean blood pressure is not greatly elevated, compensatory baroreceptors reflexes do not antagonize the direct cardiac actions. Left ventricular work per beat, stroke volume, cardiac output and heart rate are increased as a result of direct cardiac stimulation and increased venous return to the heart, reflected by an increase in right atrial pressure. At slightly higher rate of infusion, there may be no change or a slight rise in peripheral resistance and diastolic pressure, depending on the dose and the resultant ratio of Î² to á¾³ responses in the various vascular beds.
Although veins and large arteries respond to adrenaline, it's main action is exerted on smaller arterioles and pre-capillary sphincters. Various vascular beds react differently resulting in a substantial redistribution of blood flow. Injected adrenaline constricts pre-capillary vessels and small vessels, decreasing cutaneous blood flow resulting in decreased blood flow in the hands and feet. Therapeutic doses of adrenaline in humans increases blood flow to skeletal muscles due in part to a powerful Î²2 mediated vasodilator action that is partially counterbalanced by a vasoconstrictor action on the á¾³ receptors that also are present in the vascular bed. Giving an á¾³ receptor antagonist, makes vasodilation in the muscle more pronounced with decrease in total peripheral resistance accompanied by fall in mean blood pressure(adrenaline reversal) In the presence of a non - selective Î² receptor antagonist only vasoconstriction occurs and the administration of adrenaline is associated with pressor effect.
Adrenaline effect on cerebral circulation is related to the systemic blood pressure with relatively little constrictor action on cerebral arterioles from usual therapeutic doses, which is of physiological advantage in response to the activation of the sympathetic nervous system by stressful stimuli. The presence of auto-regulatory mechanism limits increase in cerebral blood flow as a result of elevated blood pressure.
Doses of adrenaline that have little effect on mean arterial pressure constantly increase renal vascular resistance and reduce renal flow by 40%. As the glomerular filtration rate is only slightly altered the filtration fraction is constantly increased. Excretion of chloride, potassium and sodium ions is decreased, urine volume may be increased, decreased or unchanged. There is maximum tubular reabsorption, excretory capacities unchanged and increased secretion of renin as a result of direct action of adrenalin on Î²1 receptors in the juxtaglomerular apparatus.
Arterial and venous pulmonary pressures are raised. Although direct pulmonary vasoconstriction occurs, redistribution of blood from the systemic to the pulmonary circulation, due to constriction of the more powerful musculature in the systemic great vein plays an important part in the increase in the pulmonary pressure. At very high concentration of adrenaline pulmonary oedema results, which is precipitated by raised pulmonary capillary filtration pressure and possibly by leaky capillaries.
http://www.mc.uky.edu/pharmacology/instruction/pha824ar/pha824ar.html Effect of Beta Receptor Activation on Smooth Muscle
Adrenaline binds to both á¾³1andÎ²2 receptors in the vascular smooth muscle. When it binds to á¾³1[ a G-protein coupled receptor with a 7 membrane spanning regions which is complexed with GDP(guanosine diphosphate) in it's unstimulated state] it promotes exchange of GTP for GDP and the release of G"/GTP. The G-protein the activates phospholipase C leading to an increase in the intracellular second messengers, inositol triphosphate(IP3) and diacylglycerol(DAG). The IP3 binds to specific sight on the sarcoplasmic reticulum(SR) and stimulates the release of intracellular Ca2+ causing increase in actin myosin interaction to cause contraction.
Î²2 receptors follows the signalling cAMP pathway. The G"/GTP complex released when adrenaline binds activates adenylate cyclase causing an increase in intracellular cAMPand activates cAMPdependant protein kinase(PKA). The phosphorylated PKA decrease in Ca2+ influx and increase in Ca2+ efflux in the sarcolemma. In the sarcoplasmic reticulum Ca2+ reuptake is enhanced leading to reduced interaction between actin and myosin.The result of calcium inhibition leads to the relaxation of the vascular smooth muscle.
Although there are more á¾³1 receptors than Î²2 receptors in the vascular smooth muscles, adrenaline has higher affinity for Î²2 than á¾³1. Though Î²2 receptor causes relaxation(vasodilation) and á¾³1 causes constriction(vasoconstriction), at low doses of adrenaline, it causes vasodilation and at high doses it causes vasoconstriction. This is due to it's relative affinty and degree of receptor occupancy. At low doses adrenaline selectively stimulates Î²2 producing vasodilation, however once the concetration of adrenaline which binds to á¾³1 is reached vasoconstriction occurs. The two effects will oppose one another, however as the concentraion of adrenaline increases the predominant effect will be vasoconstrction.