Sympathetic drive

Hydralazine 4-8 hour Up to 30 minute 5-40 mg prn dosing Headache, tachycardia, lupus like syndrome, potential nephrotoxicity Often given with beta-blocker to counter reflex sympathetic drive, may increase ICP... 

Congestive heart failure In myocardial insufficiency, the heart depends on a tonic sympathetic drive to maintain adequate cardiac output. Sympathetic activation gives rise to an increase in heart rate and systolic muscle tension, enabling cardiac output to be restored to a level comparable to that in a healthy subject. When sympathetic drive is eliminated during p-receptor blockade, stroke volume and cardiac rate decline, a latent myocardial insufficiency is unmasked, and overt insufficiency is exacerbated (A). 

Bradycardia, A-V block Elimination of sympathetic drive can lead to a marked fall in cardiac rate as well as to disorders of impulse conduction from the atria to the ventricles. 

Counter-regulation in acute hypotension due to vasodilators (B). Increased sympathetic drive raises heart rate (reflex tachycardia) and cardiac output and thus helps to elevate blood pressure. Patients experience palpitations. Activation of the renin-angioten-sin-aidosterone (RAA) system serves to increase blood volume, hence cardiac output. Fluid retention leads to an increase in body weight and, possibly, edemas. These counter-regulatory processes are susceptible to pharmacological inhibition ( 3-blockers, ACE inhibitors, ATI-antagonists, diuretics). 

Mention should also be made of the possibility of affecting cardiac function in angina pectoris (p. 306) or congestive heart failure (p. 132) by reducing venous return, peripheral resistance, or both, with the aid of vasodilators and by reducing sympathetic drive applying 3-blockers. 

P-Blockers (C) protect the heart against the 02-wasting effect of sympathetic drive by inhibiting p-receptor-mediated increases in cardiac rate and speed of contraction. 

The choice between calcium antagonists must take into account the differential effect of nifedipine versus verapamil or diltiazem on cardiac performance (see above). When p-blockers are given, the potential consequences of reducing cardiac contractility (withdrawal of sympathetic drive) must be kept in mind. Since vasodilating P2-receptors are blocked, an increased risk of vasospasm cannot be ruled out Therefore, monotherapy with p-blockers is recommended only in angina due to coronary sclerosis, but not in variant angina. 

After a relatively short exposure to increased sympathetic drive, complex down-regulatory changes in the cardiac l -adrenoceptor-G protein-effector system take place that result in diminished stimulatory effects. Beta2 receptors are not down-regulated and may develop increased coupling to the IP3-DAG cascade. It has also been suggested that cardiac D3 receptors (which do not appear to be down-regulated... 

First, changes in body temperature must reflect a central process, because body temperature is regulated centrally. To produce hyperthermia, psychotogens must somehow enhance sympathetic drive and/or block cholinergic drive on the thermoregulatory centers of the hypothalamus. 

The toxicity following the administration of high doses of amphetamines arises as a consequence of the release of catecholamines from peripheral and central sympathetic neurons, combined with their reduced metabolism owing to the reduction in their reuptake. The cardiotoxicity is similar to that described for cocaine, in which sympathetic drive to the heart is increased. There is now evidence that high, chronic doses of the amphetamines can cause a degeneration of dopaminergic neurons, possibly because of the formation of an endogenous neurotoxin, 6-hydroxydopamine. 

Burke SL, Evans RG, Moretti JL, Head GA. Levels of renal and extrarenal sympathetic drive in angiotensin Il-induced hypertension. Hypertension. 2008 51 878-883. 

Beta-blockers are an alternative to an ACE inhibitor when an ACE inhibitor is contraindicated or not tolerated (for example, in women of childbearing age or those with an increased sympathetic drive). 

From the influence of the autonomic nervous system it follows that all sympatholytic or sympathomimetic and parasympatholytic or parasympathomimetic drugs can produce corresponding effects on cardiac performance. These possibilities are exploited therapeutically for instance, p-blockers for suppressing excessive sympathetic drive (p. 96) ipratropium for treating sinus bradycardia (p. 108). An unwanted activation of the sympathetic system can result from anxiety, pain, and other emotional stress. In these cases, the heart can be protected from harmful stimulation by psychopharmaceuticals such as benzodiazepines (diazepam and others important in myocardial infarction). 

Morphine, by a central action, impairs sympathetic vascular reflexes (causing veno- and arteriolar dilatation) and stimulates the vagal centre (bradycardia) it also releases histamine (vasodilatation). These effects are ordinarily unimportant, but they can be beneficial in acute left ventricular failure, relieving mental distress by tranquillising, cardiac distress by reduction of sympathetic drive and preload (by venodilatation), and respiratory distress by rendering the centre insensitive to afferent stimuli from the congested lungs. 

The cardiovascular effects of P-adrenoceptor block depend on the amount of sympathetic tone present. The chief cardiac effects result from reduction of sympathetic drive ... 

Incapacity for vigorous exercise due to failure of the cardiovascular system to respond to sympathetic drive. 

Adverse reactions. Adverse cardiac effects from overdosage include heart block or even cardiac arrest. Heart failure may be precipitated when a patient is dependent on sympathetic drive to maintain cardiac output (see Ch. 23 for an account of other adverse effects). 

The incidence of hypertension in patients with rheumatoid arthritis taking leflunomide 25 mg/day was 11% in a phase II trial (54). During phase III trials, there was new-onset hypertension in 2.1-3.7% (9,10). Increased sympathetic drive has been implicated in its pathogenesis, because leflunomide-induced hypertension is accompanied by an increased heart rate (55). However, this hypothesis remains to be tested. 

In this case the role of excessive sympathetic drive as a result of the difficult intubation and the lack of opioid use during induction must be considered, even if sevoflurane played a role in precipitating the dysrhythmia. 

Iwase M, Bishop SP, Uechi M, et al. Adverse effects of chronic endogenous sympathetic drive induced by cardiac Gsot overexpression. Circ Res 1996 78 517-524. 

Ramage, A.G., Wyllie, M.G., 1995. A comparison of the effects of doxazosin and terazosin on the spontaneous sympathetic drive to the bladder and related organs in anaesthetized cats. Eur. J. Pharmacol. 294, 645-650. 

In addition to the general symptoms described, the patient with cardiogenic edema also may become extremely anxious, perspire heavily, and expectorate sputum that is frothy and blood tinged. The skin is usually observed to be cold, ashen, and cyanotic as a result of a low cardiac output and increased sympathetic drive (Ingram and Braunwald, 1980). 

---