Propranolol, heart drug

In all cases except perhaps the second you need a quick and reliable answer. Suppose you are trying to identify the heart drug propranolol, one of the famous beta blockers used to reduce high blood pressure and prevent heart attacks. You would first want to know the molecular weight and atomic composition and this would come from a mass spectrum propranolol has a molecular weight (relative molecular mass) of 259 and the composition C16H21NO2. Next you would need the carbon skeleton-—this would come from NMR, which would reveal the three fragments shown. 

In epoxidation reactions, allyl alcohol can act as a prochiral alkene. Enantiomerically, pure glycidol isomer, the epoxide of allyl alcohol, may be used to make (S)-propranolol, a drug for heart disease and hypertension. The basic mechanism of epoxidation reaction, the transfer of an oxygen atom from t-butyl hydroperoxide to the alkene functionality, is as discussed earlier (see reaction 8.5.2.3). 

These dm are primarily used in the treatment of hypertension (see the Summary Drug Table Adrenergic Blocking Drugs also see Chap. 39) and certain cardiac arrhythmias (abnormal rhythm of the heart), such as ventricular arrhythmias or supraventricular tachycardia They are used to prevent reinfarction in patients with a recent myocardial infarction (1—4 weeks after MI). Some of these dm have additional uses, such as the use of propranolol for migraine headaches and nadolol for angina pectoris. 

The nurse should withhold the administration of a p -adrenergic drug, such as propranolol (Inderal), and contact the primary health care provider if the patient has a heart rate of less than 60 bpm or if there isany irregularity in the patient s heart rate or rhythm. 

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. 

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. 

Propranolol is a prototype of this series of drugs and is the oldest and most widely used nonselective )3-adrenoblocker. It possesses antianginal, hypotensive, and antiarrhythmic action. Propranolol is a cardiac depressant that acts on the mechanic and electrophysio-logical properties of the myocardium. It can block atrioventricular conductivity and potential automatism of sinus nodes as well as adrenergic stimulation caused by catecholamines nevertheless, it lowers myocardial contractility, heart rate, blood pressure, and the myocardial requirement of oxygen. 

Propranolol slows heart rate, increases the effective refractory period of atrioventricular ganglia, suppresses automatism of heart cells, and reduces excitability and contractibihty of the myocardium. It is used for supraventricular and ventricular arrhythmias. Synonyms of this drug are anaprilin, detensiel, inderal, novapranol, and others. 

The main drngs nsed for myocardial ischema therapy and for relieving pain in angina pectoris are nitrates and nitrites (nitroglycerin, isosorbide dinitrate, and pentaerythritol tetranitrate) snbstances that snppress adrenergic systems of the heart—j3-adrenoblockers (atenolol, methoprolol, propranolol, and nadolol), and Ca + channel blockers (verapamil, diltiazem, nifedipine, and nicardipine) as well as a few older drugs, in particular papaverine and dipyridamole. 

Propranolol is a nonselective j3-adrenoblocker that affects both the mechanical and elec-trophysiological properties of the myocardinm. It lowers myocardial contractibility, heart rate, blood pressure, and the myocardial need for oxygen. These properties make propranolol and other j3-adrenoblockers useful antianginal drugs. 

Propranolol has two separate and distinct effects. The first is a consequence of the drug s (3-blocking properties and the subsequent removal of adrenergic influences on the heart. The second is associated with its direct myocardial effects (membrane stabilization). The latter action, especially at high clinically employed doses, may account for its effectiveness against arrhythmias in which enhanced (3-receptor stimulation does not play a significant role in the genesis of the rhythm disturbance. 

The hemodynamic effects of diazoxide are similar to those of hydralazine and minoxidil. It produces direct relaxation of arteriolar smooth muscle with little effect on capacitance beds. Since it does not impair cardiovascular reflexes, orthostasis is not a problem. Its administration is, however, associated with a reflex increase in cardiac output that partially counters its antihypertensive effects. Propranolol and other -blockers potentiate the vasodilating properties of the drug. Diazoxide has no direct action on the heart. Although renal blood flow and glomerular filtration may fall transiently, they generally return to predrug levels within an hour. 

Experimental studies have documented changes in drug response caused by increases or decreases in the number of receptor sites or by alterations in the efficiency of coupling of receptors to distal effector mechanisms. In some cases, the change in receptor number is caused by other hormones for example, thyroid hormones increase both the number of 3 receptors in rat heart muscle and cardiac sensitivity to catecholamines. Similar changes probably contribute to the tachycardia of thyrotoxicosis in patients and may account for the usefulness of propranolol, a 3-adrenoceptor antagonist, in ameliorating symptoms of this disease. 

In patients with heart failure, lidocaine s volume of distribution and total body clearance may both be decreased. Thus, both loading and maintenance doses should be decreased. Since these effects counterbalance each other, the half-life may not be increased as much as predicted from clearance changes alone. In patients with liver disease, plasma clearance is markedly reduced and the volume of distribution is often increased the elimination half-life in such cases may be increased threefold or more. In liver disease, the maintenance dose should be decreased, but usual loading doses can be given. Elimination half-life determines the time to steady state. Thus, although steady-state concentrations may be achieved in 8-10 hours in normal patients and patients with heart failure, 24-36 hours may be required in those with liver disease. Drugs that decrease liver blood flow (eg, propranolol, cimetidine) reduce lidocaine clearance and so increase the risk of toxicity unless infusion rates are decreased. With infusions lasting more than 24 hours, clearance falls and plasma concentrations rise. Renal disease has no major effect on lidocaine disposition. 

Propranolol 13- Adrenoceptor blockade Direct membrane effects (sodium channel block) and prolongation of action potential duration slows SA node automaticity and AV nodal conduction velocity Atrial arrhythmias and prevention of recurrent infarction and sudden death Oral, parenteral duration 4-6 h Toxicity Asthma, AV blockade, acute heart failure Interactions With other cardiac depressants and hypotensive drugs... 

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