Sympathomimetic therapy

The goal of sympathomimetic therapy is to augment both coronary and cerebral perfusion pressures during the low-flow state associated with CPR. These agents increase systemic arteriolar vasoconstriction, thereby improving coronary and cerebral perfusion pressure. They also maintain vascular tone, decrease arteriolar collapse, and shunt blood to the heart and brain. 

Oral sympathomimetic therapy is occasionally useful in the treatment of stress incontinence. Ephedrine or pseudoephedrine may be tried. 

Status asthmaticus not responsive to intravenous amino-phylline and sympathomimetic therapy is an indication for hospitalization. Intravenous aminophylline should be continued, and intravenous corticosteroids may be required in doses equivalent to that described for orally administered prednisone. The intravenous steroid should be limited to five to seven days, and therapy switched to beclomethasone or an alternate-day oral... 

Although the cardiac side effects are considerably reduced, metabolic effects occur under the therapy with this /32-sympathomimetics increased plasma levels of free fatty acids, glucose and ketones. In diabetic patients a hyperglycaemic ketoacidosis can be induced. All /32-sympathomimetics reduce the potassium plasma level. 

Due to the numerous indications for these type of drugs a large number of compounds have been introduced into therapy. Differences between these drugs concern their affinity profile towards the Pi-and j82-adrenoceptors, the lipophilicity and the ability to partially activate the receptor (intrinsic sympathomimetic activity, ISA). One isomer of the racemic mixture of labetalol and carvedilol are a-blocker as well. Although this might be therapeutically useful in the treatment of conditions like hypertension and heart failure, there is no real evidence for a contribution of this property to the overall beneficial effect of these compounds. 

Pindolol, oxprenolol, acebutolol and alprenolol are /3-blocker ISA. A weak sympathomimetic effect can be seen in the heart if almost all /3-adrenoceptors are occupied by these compounds. The advantage of ISA might be that a basal /3-adrenergic stimulus is left. In some vessel beds a reduction of the vascular activity and thereby a reduction in resistance has been observed with pindolol which might be beneficial in the therapy of hypertension. The pharmacodynamic and -kinetic properties of some frequently used jS-blocker are shown in Table 2. 

Improper BP measurement Volume overload and pseudotolerance Volume retention from kidney diseaase Excess salt intake Inadequate diuretic therapy Drug induced or other causes Non-adherence to therapy Doses too low Inappropriate combinations Non-steroidal anti-inflammatory drugs Cocaine and other iflicit drugs Sympathomimetics (decongestants, anorectics)... 

Contraindications Advanced arteriosclerosis, agitated states, cardiovascular disease, concurrent use or within 14 days of discontinuation of MAOI therapy, glaucoma, history of drug abuse, hypertension (moderate-to-severe), hyperthyroidism, hypersensitivity to phentermine or sympathomimetic amines... 

One of the most important uses of sympathomimetic drugs is in the therapy of bronchial asthma. This use is discussed in Chapter 20. Nonselective drugs (epinephrine), -selective agents (isoproterenol), and B2-selective agents (albuterol, metaproterenol, terbutaline) all are available for this indication. Sympathomimetics other than the 32-selective drugs are now rarely used because they are likely to have more adverse effects than the selective drugs. 

Interactions with other drugs may complicate guanethidine therapy. Sympathomimetic agents, at doses available in over-the-counter cold preparations, can produce hypertension in patients taking guanethidine. Similarly, guanethidine can produce hypertensive crisis by... 

Dobutamine Betai-selective agonist t increases cAMP synthesis Increases cardiac contractility, output Acute decompensated heart failure intermittent therapy in chronic failure reduces symptoms IV only duration a few minutes Toxicity Arrhythmias. Interactions Additive with other sympathomimetics... 

Beta blockers without intrinsic sympathomimetic activity (eg, metoprolol, propranolol, atenolol) are effective therapeutic adjuncts in the management of thyrotoxicosis since many of these symptoms mimic those associated with sympathetic stimulation. Propranolol has been the 3 blocker most widely studied and used in the therapy of thyrotoxicosis. Beta blockers cause clinical improvement of hyperthyroid symptoms but do not typically alter thyroid hormone levels. Propranolol at doses greater than 160 mg/d may also reduce T3 levels approximately 20% by inhibiting the peripheral conversion of T4 to T3. 

Guanethidine increases sensitivity to the hypertensive effects of exogenously administered sympathomimetic amines. This results from inhibition of neuronal uptake of such amines and, after long-term therapy with guanethidine, supersensitivity of effector smooth muscle cells, in a fashion analogous to the process that follows surgical sympathectomy (see Chapter 6 Introduction to Autonomic Pharmacology). 

Approximately 25% of all patients with hypertrophic cardiomyopathy (HCM) have latent left ventricular outflow obstruction with an intraventricular gradient (I). Pathophysiologic features are asymmetric hypertrophy of the septum and a systolic anterior movement of the anterior leaflet. Medical treatment includes betablockers, and calcium antagonists of the verapamil type. Approximately 5— 10% of the patients with outflow obstruction are refractory to such negative inotropic therapy (2). Positive inotropic drugs such as digitalis or sympathomimetics are strictly contraindicated. In the presence of atrial fibrillation, anticoagulation therapy should be started. Since endocarditis is more common in patients with HCM because of turbulence in the left ventricle, prophylactic antibiotics should be administered for periods of potential bacteraemia. 

---