Pharmacodynamics beta-blockers

Bauman JL, Talbert RL. Pharmacodynamics of beta-blockers in heart failure lessons from the carvedilol or metoprolol European trial. J Cardiovasc Pharmacol Ther. 2004 9 117-128. 

An example of ethnic differences in pharmacodynamics is response to propranolol, a beta-blocker drug used to control high blood pressure, or hypertension. Studies have shown that African Americans are least responsive (blood pressure, heart rate) to propranolol, Asians are most responsive, and Causians are midway between the two other groups. 

Sigmoid Emax Model Jonkers and colleagues [80] studied the pharmacodynamics of racemic metoprolol, a cardioselective beta-blocker, and the active S-isomer in extensive metabolizers (EMs) and poor metabolizers (PMs). The drug effect studied was the antagonism by metoprolol of terbutaline-induced hypokalemia (abnormally low potassium concentration in the blood). The pharmacodynamic interaction was described by a sigmoidal function for competitive antagonism based on the earlier work of Holford and Sheiner [81] ... 

Describe the important subgroups of beta-blockers and their major pharmacokinetic and pharmacodynamic features. The Skill Keeper Answer appears at the end of the chapter. 

B. Toxicodynamics Toxicodynamics is a term used to denote the injurious effects of toxins, ie, their pharmacodynamics. A knowledge of toxicodynamics can be useful in the diagnosis and management of poisoning. For example, hypertension and tachycardia are typically seen in overdoses with amphetamines, cocaine, and antimuscarinic drugs. Hypotension with bradycardia occurs with overdoses of calcium channel blockers, beta-blockers, and sedative-hypnotics. Hypotension with tachycardia occurs with tricyclic antidepressants, phenothiazines, and theophylline. Hyperthermia is most frequently a result of overdose of drugs with antimuscarinic actions, the salicylates, or sympathomimetics. Hypothermia is more likely to occur with toxic doses of ethanol and other CNS depressants. Increased respiratory rate is often a feature of... 

Pharmacodynamic interactions are those where the effects of one drug are changed by the presence of another drug at its site of action. Sometimes the drugs directly compete for particular receptors (e.g. beta2 agonists, such as salbutamol, and beta blockers, such as propranolol) but often the reaction is more indirect and involves interference with physiological mechanisms. These interactions are much less easy to classify neatly than those of a pharmacokinetic type. 

Not fully agreed. There is some debate about whether the increased serum lidocaine levels largely occur because of the decreased cardiac output caused by the beta blockers, which decreases the flow of blood through the liver thereby reducing the metabolism of the lidocaine, or because of direct liver enzyme inhibition. There may also be a pharmacodynamic interaction, with an increased risk of myocardial depression. ... 

Beta blockers may also be involved in pharmacodynamic interactions with other drugs that are based on enhancement or antagonism of pharmacological effects (such as additive blood pressure reduction). 

Not understood. Where pharmaeokinetie ehanges are seen, a possible reason is that the metabolism of the beta bloekers is altered by changes in blood flow through the liver. The pharmacodynamic changes with nifedipine may be explained by the fact that nifedipine reduces the contractility of the heart muscle. This is counteracted by a sympathetic reflex increase in heart rate due to nifedipine-induced peripheral vasodilation, so that the ventricular output stays the same or is even improved. The presence of a beta blocker may oppose this to some extent by slowing the heart rate, which allows the negative inotropic effects of nifedipine to go unchecked. 

Finasteride 5 mg daily for 10 days caused no change in the pharmacokinetics or pharmacodynamics of a single 80-mg dose of propranolol in healthy subjects. Further, the manufacturers say that finasteride was used with beta blockers in clinical studies without any evidence of an interaction. Similarly, dutasteride , (p.l2S7) does not appear to interact with beta blockers. 

The UK manufacturers of citalopram say that no pharmacodynamic interactions have been noted in clinical studies in which citalopram was given with beta blockers. However the US manufacturers say that although the concurrent use of metoprolol and citalopram has no clinically significant effect on heart rate and blood pressure, the plasma levels of metoprolol are increased twofold, which may decrease its cardioselectivity. ... 

No adverse pharmacodynamic interaction normally occurs between beta-agonist bronchodilators and cardioselective beta blockers. This has been demonstrated in studies with ... 

Some pharmacodynamic effects, e.g. heart rate with beta-adrenoceptor blocker, provide a physiological marker as an indication of the presence of drug in the body. 

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