Propranolol Adrenaline

If one set of these responses can be blocked (antagonised) by a drug that does not affect the other responses (e.g. propranolol blocks the increase in heart rate produced by adrenaline, but not the dilation of the pupil evoked by adrenaline) then this is good evidence that adrenoceptors in the pupil are not the same as those in the heart. 

An example of an antagonist medicine Is propranolol, which Is used to treat high blood pressure. It too acts by binding to adrenaline receptor sites, but It does not trigger a response. The propranolol therefore blocks the receptor sites and prevents the action of the body s natural compound. 

Many years later. Sir James Black identified fhe beta adrenergic receptor in heart muscle. Adrenaline increases heart rate by activating the beta adrenergic receptor in this organ. Within a decade. Black and his colleagues had synthesized a molecule known as propranolol, marketed as Inderal. 

This is not the end of the story about beta blockers. Subsequent research demonstrated that there are two subclasses of beta receptors, termed beta-1 and beta-2. Both are activated by adrenaline. Both are blocked by propranolol. Beta-1 receptors are found mostly in heart muscle but not much in the lungs, whereas beta-2 receptors are found mostly in the lungs but not much in the heart. These facts provided the opportunity for better drugs. Here is the argument. 

Adrenaline, which turns on both receptors, increases heart rate via the beta-1 receptor and dilates airways by the beta-2 receptors. Propranolol, which is a nonspecihc blocker of both beta-1 and beta-2 receptors, decreases heart rate and lowers blood pressure, beta-1 receptor action, but can constrict airways in the lung, beta-2 receptor action, and that is not so good. 

Ahlquist, in 1948, first proposed that noradrenaline could produce its diverse physiological effects by acting on different populations of adrenoceptors, which he termed a and ft receptors. This classification was based upon the relative selectivity of adrenaline for the a receptors and isoprenaline for the ft receptors drugs such as phentolamine were found to be specific antagonists of the a, and propranolol for the ft receptors. 

Non-aqueous titration with acetous perchloric acid is used in the pharmacopoeial assays of adrenaline, metronidazole, codeine, chlorhexidine acetate, chlorpromazine.HCl, amitriptyline.HCl, propranolol.HCl, lignocaine.HCl and quaternary amine salts such as neostigmine bromide and pancuronium bromide. 

If adrenaline is administered to an animal which has been pretreated with propranolol the pressor action is potentiated because the a-adrenergic vasoconstriction is not affected but the P vasodilator action is blocked. 

The similarity measure intuitively used by organic chemists is the number of structural features and their mutual arrangement which two compounds have in common. From this point of view adrenalin (1) and isoproterenol (2) would look rather similar and in fact both have similar biological properties as they are both agonists of P-adrenergic receptors. Both compounds are comparatively dissimilar to propranolol... 

The release of stored Ca2+ is often triggered by a adrenergic receptors.269 Like (3 adrenergic receptors, the a receptors are activated by adrenaline. Specific inhibitors distinguish them. For example, the (3 receptors are inhibited by propranolol, while the a receptors are blocked by phenoxybenzamine. The synthetic agonist phenylephrine activates only a receptors and no increases in cAMP or in protein kinase activity are observed. 

LIDOCAINE BETA-BLOCKERS 1. Risk of bradycardia (occasionally severe), l BP and heart failure with intravenous lidocaine 2. Risk of lidocaine toxicity due to T plasma concentrations of lidocaine, particularly with propranolol and nadolol 3. t plasma concentrations of propranolol and possibly some other beta-blockers 1. Additive negative inotropic and chronotropic effects 2. Uncertain, but possibly a combination of beta-blocker-induced 1 hepatic blood flow (due to 1 cardiac output) and inhibition of metabolism of lidocaine 3. Attributed to inhibition of metabolism by lidocaine 1. Monitor PR, BP and ECG closely watch for development of heart failure when intravenous lidocaine is administered to patients on beta-blockers 2. Watch for lidocaine toxicity 3. Be aware. Regional anaesthetics should be used cautiously in patients with bradycardia. Beta-blockers could cause dangerous hypertension due to stimulation of alpha-receptors if adrenaline is used with local anaesthetic... 

Accidental overdose with adrenaline occurs occasionally. It is rationally treated by propranolol to block the cardiac p effects (cardiac arrhythmia) and phentolamine or chlorpromazine to control the a effects on the peripheral circulation that will be prominent when the P effects are abolished. Labetalol (a + p block) would be an alternative. P-adrenoceptor block alone is hazardous as the then unopposed a-receptor vasoconstriction causes (severe) hypertension (see Phaeochromocytoma, p. 494). Use of antihypertensives of most other kinds is irrational and some may also potentiate the adrenaline. 

These two catecholamines act on the same adrenoceptors fi, and cx which are blocked by pheno>tybenzamine but not by propranolol.and 3, and [ij which are blocked by propranolol but not phenoxybeniamine. Noradrenaline is a 20-fold weaker agonist at p -receptors than is adrenaline. 

Small quantities of adrenaline, such as are present as an additive in local anesthetic formulations, can be dangerously potentiated by beta-adrenoceptor blockers propranolol should be discontinued at least 3 days in advance of administering such products for local anesthesia. A combined infusion of adrenaline and propranolol has been used for diagnosing insulin resistance, but it can evoke cardiac dysrhythmias, even in patients without signs of coronary disease (17). 

The effects of stress on the depression of serum/leucocyte levels of vitamin C were recently summarized (60). Included were myocardial infarction, and other conditions involving physical, infective, or traumatic insult, including cold virus infection, and intravenous tetracosactrin. Associated with the reduced ascorbate level in myocardial infarction was an increased cortisol level over a period of 56 d. The authors recommended 1 g of ascorbic acid/d for 1 month following the traumatic event, with a comment concerning the need for additional study (60). Plasma ascorbate was also depressed following iv administration of adrenalin this depression was prevented by prior administration of propranolol, a )3-blocker (61). Smoking not only reduces blood levels of vitamin C (62,63), but increases the proportion of the population in the scorbutic range of blood values fourfold (64). These effects are probably caused by increased... 

Beta-blockers, by inhibiting the effect of adrenaline and noradrenaline on the heart, prevent the normal increase in heart rate, and are very effective in preventing exercise angina. Examples of beta-blockers used for this purpose include acebutolol, atenolol, metoprolol. nadolol, oxprenolol, pindolol, propranolol, sotalol and timolol. See ADRENOCEPTOR ANTAGONISTS. 

Propranolol reduces the clearance of bupivacaine and so theoretically the toxicity of bupivacaine may be increased. There has been a single report of enhanced bupivacaine cardiotoxicity in a patient also receiving metoproioi and digoxin. The coronary vasoconstriction caused by cocaine is increased by propranolol. Beta blockers may interact with adrenaline (epinephrine)-containing local anaesthetics. 

One of the normal physiological responses to a fall in blood sugar levels is the mobilisation of glucose from the liver under the stimulation of adrenaline from the adrenals. This sugar mobilisation is blocked by non-selective beta blockers (such as propranolol) so that recovery from hypoglycaemia is delayed and may even proceed into a full-scale episode in a hypoglycaemia-prone diabetic. Normally the adrenaline would also increase the heart rate, but with the beta-receptors in the heart already blocked this fails to occur. A rise in blood pressure occurs because the stimulant effects of adrenaline on the beta-2 receptors (vasodilation) are blocked leaving the alpha (vasoconstriction) effects unopposed. 

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