McKenna's Pharmacology for Nursing, 2e

470 P A R T 5  Drugs acting on the autonomic nervous system A drenergic blocking agents are also called sympatho­ lytic drugs because they lyse, or block, the effects of the sympathetic nervous system (SNS). The therapeutic and adverse effects associated with these drugs are related to their adrenergic-receptor-site specificity , that is, the ability to react with specific adrenergic receptor sites without activating them, thus preventing the typical manifestations of SNS activation. By occupying the adrenergic receptor site, they prevent noradrenaline release from the nerve terminal or from the adrenal medulla from activating the receptor, thus blocking the SNS effects. The adrenergic blockers have varying degrees of specificity for the adrenergic receptor sites. For example, some can interact with both alpha- and beta-recep- tors. Some are specific to alpha-receptors, with some being even more specific to just alpha 1 -receptors. Other adrenergic blockers interact with both beta 1 - and beta 2 -receptors, whereas others interact with just either beta 1 - or beta 2 -receptors. This specificity allows the clinician to select a drug that will have the desired thera­ peutic effects without the undesired effects that occur when the entire SNS is blocked. In general, however, the specificity of adrenergic blocking agents depends on the concentration of the drug in the body. Most specificity is lost with higher serum drug levels (see Figure 31.1). The effects of the adrenergic blocking agents vary with the age of the person (see Box 31.1). Various alter- native and herbal remedies can also affect these drugs (see Box 31.2).

NON-SELECTIVE ADRENERGIC BLOCKING AGENTS Drugs that block both alpha- and beta-adrenergic receptors are primarily used to treat cardiac-related conditions. These drugs include amiodarone ( Cordar­ one X ), carvedilol ( Dilatrend ) and labetalol ( Presolol , Trandate ) (see Table 31.1). Therapeutic actions and indications Adrenergic blocking agents competitively block the effects of noradrenaline at alpha- and beta-receptors throughout the SNS. Subsequently, this results in lower blood pressure, slower pulse rate and increased renal perfusion with decreased renin levels. Most of these drugs are indicated to treat essential hypertension, alone or in combination with diuretics. Labetalol is a newer drug that is used orally to treat hypertension. It can also be used with diuret- ics and has been used to treat hypertension associated with phaeochromocytoma (tumour of the chromaffin cells of the adrenal medulla, which periodically releases large amounts of noradrenaline and adrenaline into the system) and clonidine withdrawal. Amiodarone, which is available in oral and IV forms, is saved for serious emergencies and only used as an antiarrhythmic (see Chapter 45). Carvedilol is only available orally and is used to treat hypertension, as well as heart failure and left ventricular dysfunction after myocardial infarction

Effects of adrenergic blockade

Pharmacodynamics of adrenergic blockers

Tyramine (from diet)

Pupils do not dilate Increased GI secretions

Dopa

Dopamine

Increased GI activity Lowered blood pressure Decreased venous return related to vasodilation Loss of bronchodilation

Noradrenaline

Adrenergic receptor α 2

Norepinephrine

α 2 adrenergic blockers work here

Ca +

Ca +

Decreased glucose regulation

Adrenergic receptor α 1 , β 1 or β 2

Noradrenaline

Beta 1- , Beta 2- and Alpha 1- , adrenergic blockers work here

Relaxed sphincters to increase urine flow Relaxed sphincters to increase GI excretions

cAMP

Decreased sexual response

FIGURE 31.1  Site of action of adrenergic receptors and resultant physiological responses. These responses are blocked by adrenergic blockers.