This essay reports the belongingss of propranolol ( lipotropic ?1-selective blocker ) and atenolol ( hydrophilic ?1-selective blocker ) in the point of position of pharmacological medicine, pharmacokinetics, and physical chemical science. It is observed that their pharmacological and pharmacokinetic belongingss are different, but its physicochemical belongingss are comparative near.
Introduction to ?-blockers
The ?-blockers are drugs which act by barricading the consequence of go-betweens and agonists on the relevant receptors. The ?-blockers show an antihypertensive consequence, which is caused by decreased cardiac end product, decreased release of renin, cardinal lessening of sympathetic action. Besides, they exhibit an antianginal consequence, which is caused by decelerating of the bosom rate and therefore decreased metabolic demand. The chief side effects of general ?-blockers are cardiac failure, such as cardiac depression, hypotension, fistula node disfunction, auriculoventricular block. The side effects depend on the belongingss of ?-blockers. For case, non-selective ?-blockers show the unwanted effects caused by barricading ?2-receptor. These show bronchoconstriction which is potentially dangerous in wheezing patients and clinically unwanted in patients with other respiratory jobs. Lipophilic ?-blockers may do psychological symptoms, such as depression.
There are some of import factors in the choice of ?-blockers, which are ISA, MSA, ?1-selectivity, lipophilicity, solubility, and the continuance of effects. The ?2-selective blockers are non used clinically, because of doing bronchoconstriction. Some ?-blockers show the consequence of non merely barricading the receptors, but besides exciting ?-receptors. It depends on the state of affairs whether ISA positive ?-blockers stimulate or barricade ?-receptors. For illustration, these act as ?-blockers under the being of ?-agonists. On the other manus, these invigorate the receptors under the non-existence of ?-agonists. Such an consequence is termed ISA which is intrinsic adrenergic activity. The drugs which have ISA diminish the side effects caused by ?-blockers. The non-selective blocks of ?-receptors cause the addition in cardiac afterload and bronchocostriction, because of ?2-blocking. The ?1-selective drugs somewhat have the consequence of ?2-blocking, but the hazard of doing cardiac afterload and bronchoconstriction is lower than that of non-selective ?-blockers. The continuance of effects depends on the disease. Long acting ?-blockers are desirable for high blood pressure and bosom failure, because of the low frequence of disposal. In contrast, short moving ?-blockers, propranolol, are ideal drugs for angina, because of the fast oncoming of action. As I stated above, lipotropic ?-blockers have a hazard of doing depression. The ground is such drugs are absorbed easy, so can perforate BBB. MSA, membrane stabilising activity, is an activity which prevents Na ions from come ining inside of cells. Many ?-blockers, such as propranolol, have the activity, so these are utile for arrhythmia.
The belongingss of propranolol
Propranolol is a non-selective ?-blocker, which is clinically used as propranolol hydrochloride. The IUPAC name is ( 2RS ) -1- ( 1-Methylethyl ) amino-3- ( naphthalen-1-yloxy ) propan-2-ol monohydrochlorid. The molecular weight is 295.80, and the thaw point is around 165 grades. It is white crystalline pulverization, and it is easy to fade out in H2O and methyl alcohol. Besides, the methanol solution does n’t exhibit optical activity. Its structural expression is following.
Propranolol is absorbed from the GI piece of land, its plasma degree reach a extremum, 42.9ng/ml, after 1.5 hours of disposal. The half life is about 3.9 hours. The metamorphosis of propranolol is chiefly conducted by the liver, so it is metabolised to naphthoxylactic acid, glucuronic acid conjugate, and 4-Hydroxypropranolol. It is chiefly metabolised by CYP2D6, CYP1A2, and CYP2C19. As I discussed supra, propranolol can perforate BBB and passage to the encephalon, because of lipotropic. Its dose sum is largely excreted in piss within 48 hours, and the remainder is excreted in fecal matters, which is merely less than 4 per centums. Its pharmacological actions include an antihypertensive consequence, an antianginal consequence, and MSA. Propranolol does n’t demo ISA in the experiment with utilizing rats, so it is considered that propranolol does n’t demo human ISA every bit good as rats. Some side effects have been reported, such as, bronchoconstriction, decelerating of bosom rate, and allergic. These yearss, a new side consequence is going popular, which is mental symptoms, such as depression, incubus, and insomnia. There is the drug-drug interaction in propranol. For case, propranolol ca n’t utilize with Mellaril which is a psychoactive drug, particularly for integrating disfunction symptom. The ground is the side consequence of Mellaril is likely to go on, because of forestalling propranolol from being metabolised Mellaril by enzymes in the liver. In the same manner, propranolol ca n’t utilize with rizatriptan which is a drug for megrim. Combination usage with propranolol and rizatoriptan induce the extension of half life of and the addition of AUC, so increase the side effects. Besides, it is indispensable to avoid administrating rizatoriptan within 24 hours of disposal of propranolol for the same ground. Its bundle cusp approved by US Food and Drug Administration warns.
Therefore, its disposal should non be stopped all of a sudden. Above statement is one of the most of import warnings in the use of propranolol.
Properties of Tenormin
Atenolol is a ?1-selective blocker without demoing MSA and ISA, which is used for high blood pressure, angina, and cardiac dysrhythmias. It is sold as TENORMIN in the market. The IUPAC name is 2- ( 4- { ( 2RS ) -2-Hydroxy-3- [ ( 1-methylethyl ) amino ] propyloxy } phenyl ) ethanamide. The molecular weight is 266.34, and the thaw point is around 155 grades. It is white or light xanthous crystalline pulverization, and it is easy to fade out in H2O and methyl alcohol every bit good as propranolol. In add-on, the methanol solution does n’t exhibit optical activity. Its structural expression is following.
Atenolol is about half absorbed from GI piece of land, and the remainder enter systemic circulation without acquiring first base on balls consequence on the liver. Its half life is about 7 hours. Atenolol is small metabolised in the liver, but some are metabolised to glucuronic acid conjugate. The information shows that Tenormin is low distribution to encephalon compared to proranolol, because its drug is hydrophilic. Therefore, it has been reported that Tenormin barely have an influence on mental symptom unlike propranolol. The elimination of unwritten Tenormin is about 50 % in urine and fecal matters severally, but 90 % of them are non metabolised. As I stated above, atenolol is a ?1-selective blocker, so it is small to impact bronchial tubings which is controlled by ?2-receptor. However, the informations have been reported atenolol inhibit ?2-receptor at high dosage. Its side effects are about the same as propranolol. The chief difference between Tenormin and propranolol is the incidence of tracheal symptoms, such as bronchoconstriction and bronchial cramp. Propranolol blocks ?-receptors non- selectively, so causes different tracheal symptoms. In contrast, atenolol inhibits ?1-receptors selectively, so hardly makes such symptoms go on. The sudden surcease of therapy with Tenormin has a possibility of doing cardiac diseases for specific patients. Its cusp approved by FDA cautiousnesss,
The belongingss of ?-blockers in corpulent patients
These yearss, the figure of corpulent people is increasing due to high Calorie nutrients and the lessening of exercising. It is common for corpulent patients to take drug therapy in clinical pattern, because fleshiness is connected with many diseases, such as diabetes and cardiovascular disease. Therefore, it is of import to place pharmacological and pharmacokinetic belongingss in corpulent patients. Jerzy Wojcickia studied the pharmacological and pharmacodynamic belongingss between propranolol and Tenormin in corpulent patients. As a consequence, he concluded following.
Decision
In drumhead, there are some differences between propranolol and Tenormin from the point of position of pharmacological medicine, because of the difference of selectivity of ?-receptor. In the same manner, there are some pharmacokinetic differences every bit good, such as the continuance of half life and the mechanism of metamorphosis and elimination. In contrast, their physicochemical belongingss are similar. In clinical usage, there are some warnings severally, and the common cautiousnesss are to avoid sudden discontinuance of disposal. Its dose should be increasingly decreased over a few hebdomads in order to avoid such side effects. I studied the characters between these ?-blockers in corpulent patients. In the survey, it was non observed there are the obvious differences between corpulent patients and non-obese patients
