Beta Blockers Properties Of Propranolol And Atenolol Biology Essay

Beta Blockers Properties Of Propranolol And Atenolol Biology Essay Abstract This essay reports the properties of propranolol (lipophilic ÃŽ ²1-selective blocker) and atenolol (hydrophilic ÃŽ ²1-selective blocker) in the point of view of pharmacology, pharmacokinetics, and physical chemistry. It is observed that their pharmacological and pharmacokinetic properties are different, but its physicochemical properties are relative close. Introduction to ÃŽ ²-blockers The ÃŽ ²-blockers are drugs which act by blocking the effect of mediators and agonists on the relevant receptors. The ÃŽ ²-blockers show an antihypertensive effect, which is caused by reduced cardiac output, decreased release of renin, central decrease of sympathetic action. Also, they exhibit an antianginal effect, which is caused by slowing of the heart rate and thus decreased metabolic demand. The main side effects of general ÃŽ ²-blockers are cardiac failure, such as cardiac depression, hypotension, sinus node dysfunction, atrioventricular block. The side effects depend on the properties of ÃŽ ²-blockers. For instance, non-selective ÃŽ ²-blockers show the unwanted effects caused by blocking ÃŽ ²2-receptor. These show bronchoconstriction which is potentially life-threatening in asthmatic patients and clinically undesirable in patients with other respiratory problems. Lipophilic ÃŽ ²-blockers may cause psychological symptoms, such as depression. There are some important factors in the selection of ÃŽ ²-blockers, which are ISA, MSA, ÃŽ ²1-selectivity, lipophilicity, solubility, and the duration of effects. The ÃŽ ²2-selective blockers are not used clinically, because of causing bronchoconstriction. Some ÃŽ ²-blockers show the effect of not only blocking the receptors, but also stimulating ÃŽ ²-receptors. It depends on the situation whether ISA positive ÃŽ ²-blockers stimulate or block ÃŽ ²-receptors. For example, these act as ÃŽ ²-blockers under the existence of ÃŽ ²-agonists. On the other hand, these invigorate the receptors under the non-existence of ÃŽ ²-agonists. Such an effect is termed ISA which is intrinsic sympathomimetic activity. The drugs which have ISA decrease the side effects caused by ÃŽ ²-blockers. The non-selective blocks of ÃŽ ²-receptors cause the increase in cardiac afterload and bronchocostriction, because of ÃŽ ²2-blocking. The ÃŽ ²1-selective drugs slightly have the effect of ÃŽ ²2-blocking, but the ris k of causing cardiac afterload and bronchoconstriction is lower than that of non-selective ÃŽ ²-blockers. The duration of effects depends on the disease. Long acting ÃŽ ²-blockers are desirable for hypertension and heart failure, because of the low frequency of administration. In contrast, short acting ÃŽ ²-blockers, propranolol, are ideal drugs for angina, because of the fast onset of action. As I stated above, lipophilic ÃŽ ²-blockers have a risk of causing depression. The reason is such drugs are absorbed easily, so can penetrate BBB. MSA, membrane stabilising activity, is an activity which prevents sodium ions from entering inside of cells. Many ÃŽ ²-blockers, such as propranolol, have the activity, so these are useful for arrhythmia. The properties of propranolol Propranolol is a non-selective ÃŽ ²-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 melting point is around 165 degrees. It is white crystalline powder, and it is easy to dissolve in water and methanol. Also, the methanol solution doesnt exhibit optical activity. Its structural formula is following. Propranolol is absorbed from the gastrointestinal tract, its plasma level reach a peak, 42.9ng/ml, after 1.5 hours of administration. The half life is approximately 3.9 hours. The metabolism of propranolol is mainly conducted by the liver, so it is metabolised to naphthoxylactic acid, glucuronic acid conjugate, and 4-Hydroxypropranolol. It is mainly metabolised by CYP2D6, CYP1A2, and CYP2C19. As I discussed above, propranolol can penetrate BBB and transition to the brain, because of lipophilic. Its dosage amount is mostly excreted in urine within 48 hours, and the rest is excreted in faeces, which is just less than 4 percentages. Its pharmacological actions include an antihypertensive effect, an antianginal effect, and MSA. Propranolol doesnt show ISA in the experiment with using rats, so it is considered that propranolol doesnt show human ISA as well as rats. Some side effects have been reported, such as, bronchoconstriction, slowing of heart rate, and allergic. These days, a new si de effect is becoming popular, which is mental symptoms, such as depression, nightmare, and insomnia. There is the drug-drug interaction in propranol. For instance, propranolol cant use with thioridazine which is a psychotropic drug, especially for integration dysfunction symptom. The reason is the side effect of thioridazine is likely to happen, because of preventing propranolol from being metabolised thioridazine by enzymes in the liver. In the same way, propranolol cant use with rizatriptan which is a drug for migraine. Combination use with propranolol and rizatoriptan induce the extension of half life of and the increase of AUC, so increase the side effects. Also, it is essential to avoid administering rizatoriptan within 24 hours of administration of propranolol for the same reason. Its package leaflet approved by US Food and Drug Administration warns. Therefore, its administration should not be stopped suddenly. Above statement is one of the most important warnings in the usage of propranolol. Properties of atenolol Atenolol is a ÃŽ ²1-selective blocker without showing MSA and ISA, which is used for hypertension, 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) acetamide. The molecular weight is 266.34, and the melting point is around 155 degrees. It is white or light yellow crystalline powder, and it is easy to dissolve in water and methanol as well as propranolol. In addition, the methanol solution doesnt exhibit optical activity. Its structural formula is following. Atenolol is almost half absorbed from gastrointestinal tract, and the rest enter systemic circulation without getting first pass effect on the liver. Its half life is approximately 7 hours. Atenolol is little metabolised in the liver, but some are metabolised to glucuronic acid conjugate. The data shows that atenolol is low distribution to brain compared to proranolol, because its drug is hydrophilic. Therefore, it has been reported that atenolol hardly have an influence on mental symptom unlike propranolol. The excretion of oral atenolol is approximately 50% in urine and faeces respectively, but 90% of them are not metabolised. As I stated above, atenolol is a ÃŽ ²1-selective blocker, so it is little to affect bronchial tubes which is controlled by ÃŽ ²2-receptor. However, the data have been reported atenolol inhibit ÃŽ ²2-receptor at high dose. Its side effects are almost the same as propranolol. The main difference between atenolol and propranolol is the incidence of tracheal symp toms, such as bronchoconstriction and bronchial spasm. Propranolol blocks ÃŽ ²-receptors non- selectively, so causes different tracheal symptoms. In contrast, atenolol inhibits ÃŽ ²1-receptors selectively, so barely makes such symptoms happen. The sudden cessation of therapy with atenolol has a possibility of causing cardiac diseases for specific patients. Its leaflet approved by FDA cautions, The properties of ÃŽ ²-blockers in obese patients These days, the number of obese people is increasing due to high calorie foods and the decrease of exercise. It is common for obese patients to take drug therapy in clinical practice, because obesity is connected with many diseases, such as diabetes and cardiovascular disease. Therefore, it is important to identify pharmacological and pharmacokinetic properties in obese patients. Jerzy Wojcickia studied the pharmacological and pharmacodynamic properties between propranolol and atenolol in obese patients. As a result, he concluded following. Conclusion In summary, there are some differences between propranolol and atenolol from the point of view of pharmacology, because of the difference of selectivity of ÃŽ ²-receptor. In the same way, there are some pharmacokinetic differences as well, such as the duration of half life and the mechanism of metabolism and excretion. In contrast, their physicochemical properties are similar. In clinical use, there are some warnings respectively, and the common cautions are to avoid sudden discontinuation of administration. Its dosage should be progressively decreased over a few weeks in order to avoid such side effects. I studied the characters between these ÃŽ ²-blockers in obese patients. In the study, it was not observed there are the obvious differences between obese patients and non-obese patients