Tachycardias

Dorex is very toxic (see Table 2) and must be handled with extreme care. Because it may produce severe dermatitis on moist skin, it is difficult to use in hot, humid climates inhalation of the dust or spray may irritate the mucous membranes. Whereas symptoms may include a flushed face, tachycardia, headache, vertigo, and hypotension, it does not produce the typical cyanide effect. 

Combined Hj /H2 receptor stimulation by histamine is responsible for vasodilation-related symptoms, such as hypotension, flushing, and headache, as well as for tachycardia stimulated indirecdy through vasodilation and catecholamine secretion. 

Propanidid. Propanidid [1421-14-3] (Epontol), C gH2yNO, (7) a derivative of the propyl ester of homo vanillic acid, has been in clinical use in Europe for a number of years. Its main advantage is rapid onset of action and a fast recovery which, like etomidate, is because of rapid metaboHsm by esterases rather than redistribution (108). Excretion is rapid 75 to 90% of the dmg is eliminated as metaboUtes within two hours. Propanidid side effects include hypotension, tachycardia, and hyperventilation followed by apnea, as well as excitatory side effects such as tremor and involuntary muscle movement (109). 

Aerosol adniinistration of isoproterenol produces a prompt (2—5 minutes) intense bronchodilatation of relatively short (1 h) duration. The lack of P2-selectivity leads, in many cases, to tachycardia and blood pressure elevation. Also, use of isoproterenol, like all other known P-agonists, results in a down-regulation, or desensitization, of P-adrenergic receptors. This desensitization is only partial, and after time (depending on dose, patient, and agent), a stable, less responsive state is achieved in which P-agonists remain effective. Isoproterenol has been widely used for many years. 

Treatment of Manic—Depressive Illness. Siace the 1960s, lithium carbonate [10377-37-4] and other lithium salts have represented the standard treatment of mild-to-moderate manic-depressive disorders (175). It is effective ia about 60—80% of all acute manic episodes within one to three weeks of adrninistration. Lithium ions can reduce the frequency of manic or depressive episodes ia bipolar patients providing a mood-stabilising effect. Patients ate maintained on low, stabilising doses of lithium salts indefinitely as a prophylaxis. However, the therapeutic iadex is low, thus requiring monitoring of semm concentration. Adverse effects iaclude tremor, diarrhea, problems with eyes (adaptation to darkness), hypothyroidism, and cardiac problems (bradycardia—tachycardia syndrome). 

Arrhythmias Originating in the Sinus Node Sinus bradycardia Sick sinus syndrome Sinus tachycardia Disorders of Impulseformation ... 

Reentry mechanism Intranodal (AV node) reentry Extranodal reentry Reentrant tachyarrhythmia Atrial flutter Atrial fibrillation Ventricular tachycardia Ventricular fibrillation Conduction B/ocks ... 

The Class I agents have many similar side effects and toxicities. The anticholinergic side effects include dry mouth, constipation, and urinary hesitancy and retention. Common gastrointestinal (GI) side effects include nausea, vomiting, diarrhea, and anorexia. Cardiovascular adverse effects are hypotension, tachycardia, arrhythmias, and myocardial depression, especially in patients with congestive heart failure. Common central nervous system (CNS) side effects are headache, dizziness, mental confusion, hallucinations, CNS stimulation, paraesthesias, and convulsions. 

The cardiovascular adverse effects associated with quinidine therapy are hypotension and tachycardia, both of which are related to its a-adrenoceptor blocking actions. The tachycardia may be a reflex adjustment to the fall in blood pressure or may also be a direct action of the dmg on sympathetic nerve terminals leading to an increased release of NE. Quinidine also produces ringing in the ears (cinchonism) (1,2). 

Enca.inide, Encainide hydrochloride, a ben2amide derivative, is effective in the treatment of ventricular arrhythmias and refractory ventricular tachycardia (1,2). 

Indeca.inide. Indecainide hydrochloride is a po active antiarrhythmic agent that received PDA approval in 1989, but it has not been marketed as of this writing. Chemically, it is 9-[3-(isopropylamino)propyl]fiuorine-9-carboxamide [74517-78-5]. The dmg has potent activity against premature ventricular complexes (PVCs) and ventricular tachycardias. Indecainide has no effect on sinus node function, atrial or ventricular effective refractory periods (32,33). 

Propranolol. Propranolol hydrochloride, considered the prototype of the P-adrenoceptor blocking agents, has been in use since 1964. It is a nonselective, highly Hpid-soluble P-adrenoceptor blocker having no ISA. It is a mixture of (+) and (—) enantiomers, and the (—) enantiomer is the active moiety. The local anesthetic effects of propranolol are equipotent to those of Hdocaine [137-58-6] C 4H22N20, (see Anesthetics). Therapeutic effects include termination of catecholamine-induced arrhythmias, conversion of SA nodal tachycardias (including flutter and fibrillation) and AV nodal tachyarrhythmias to normal sinus rhythm, digitahs-induced arrhythmias, and ventricular arrhythmias (1,2). The dmg also has cardioprotective properties (37,39). 

Adverse effects with atropine therapy include dry mouth, myosis, loss of visual accommodations, constipation, and urinary retention. The dmg can also produce flushing, hyperthermia, delirium, tachycardia, and exacerbate glaucoma (85). 

Isoproterenol is given sublingually or by iv. It is metabolized by monoamine oxidase and catechol-0-methyltransferase in brain, Hver, and other adrenergically innervated organs. The pharmacological effects of isoproterenol are transient because of rapid inactivation and elimination. About 60% is excreted unchanged. Adverse effects using isoproterenol therapy include nervousness, hypotension, weakness, dizziness, headache, and tachycardia (86). 

Dlgltoxin. Digitoxin is a cardiac glycoside obtained from Digitalis purpurea. Digitoxin is indicated in the treatment of atrial flutter, atrial fibrillation, and supraventricular tachycardia. Its electrophysiologic and adverse effects are similar to those described for digoxin (87). 

Adenosine is not active orally, but adrninistered as an iv bolus dmg adenosine rapidly eliminates supraventricular tachycardias within 1—2 min after dosing. The dmg slows conduction through the AV node. Adenosine is rapidly removed from the circulation by uptake into red blood ceUs and vascular endothehal ceUs. Thus the plasma half-life is less than 10 s. Adenosine is rapidly metabolized to inosine or adenosine monophosphate and becomes part of the body pool for synthesis of adenosine-triphosphate. 

Other Glass III Antiarrhythmic Agents. Clofihum phosphate is a benzene-butanaminium derivative that has highly specific Class III antiarrhythmic activity. It is orahy active, has a rapid onset of action, and a reasonably long duration of antiarrhythmic activity. In preliminary clinical studies, clofihum has shown efficacy against spontaneous ventricular tachycardias (69). 

OC-Adrenoceptor Blockers. Nonselective a-adrenoceptor blockers (Table 6), such as phentolamine, which block both a - and a2 adrenoceptors, produce vasodilation by antagonizing the effects of endogenous norepinephrine. They also produce severe tachycardia and have been replaced by selective a -adrenoceptor blockers, such as prazosin, terazosin, and doxazosin, which do not usually cause severe tachycardia. 

Prazosin, a selective a -adrenoceptor antagonist, exerts its antihypertensive effect by blocking the vasoconstrictor action of adrenergic neurotransmitter, norepinephrine, at a -adrenoceptors in the vasculature (200,227,228). Prazosin lowers blood pressure without producing a marked reflex tachycardia. It causes arteriolar and venular vasodilation, but a significant side effect is fluid retention. Prazosin increases HDL cholesterol, decreases LDL cholesterol, and does not cause glucose intolerance. 

Nifedipine, verapamil, and diltiazem are all efficacious in the treatment of mild and moderate hypertension, but nifedipine is more efficacious than diltiazem and verapamil in the control of severe hypertension. Nifedipine does not cause significant reflex tachycardia or orthostatic hypotension. Nifedipine benefits the older and black patients and patients with low PRA. 

Nifedipine (Table 3) is a potent vasodilator that selectively dilates resistance vessels and has fewer effects on venous vessels. It does not cause reflex tachycardia during chronic therapy. Nifedipine is one of the first-line choices for black or elderly patients and patients having concomitant angina pectoris, diabetes, or peripheral vascular diseases. Nifedipine, sublingually, is also suitable for the treatment of hypertensive emergencies. Nifedipine does not impair sexual function or worsen blood Hpid profile. The side effects are flushing, headache, and dizziness. 

When clonidine is withdrawn abmpdy, patients may experience a rebound hypertensive phenomenon, whereia blood pressure rises rapidly to a level higher than the predmg level. These patients may experience symptoms of headache, tachycardia, agitation, and nervousness. If rebound hypertension occurs, resumption of clonidine therapy or adrninistration of phentolamine reduces the blood pressure. For clonidine withdrawal, the dose should be reduced gradually over a two-week period. The principal side effects are sedation, dry mouth, drowsiaess, di22iQess, and fatigue. 

Hydralazine. Hydrala2iae causes vasodilation ia all primary vascular beds and has more pronounced effects on capacitance than on resistance blood vessels. Despite the hypotension it produces, hydrala2iae iacreases renal blood flow and cardiac output. PRA iacreases with its use. Tachycardia, headache, di22iaess, and water and sodium retention are principal side effects of hydrala2iae therapy. 

There are at least 13 primary types of K+ channels known. In addition, within each type there are several subtypes. The best known chemical classes of potassium channel openers are nicorandil, piaacidil, and cromakalim. They are aU potent smooth muscle relaxants. PharmacologicaUy, they behave as classical vasodilators, lowering blood pressure and causiag tachycardia and fluid retention. 

Piaacidil has a short half-life and most human studies were carried out ia slow-release formulatioas. The reductioa ia blood pressure produced by piaacidil is accompanied by tachycardia and fluid retention. Plasma catecholamines and renin activity are iacreased. Other side effects are headache, di22iaess, and asthenia. 

Propranalol hydrochloride (5-l-isopropylamino-3-(l-naphthyloxy)-2-propanol HCl) [4199-10-4] M 295.8, m 192°, 193-195 , [a] +25° (c 1, EtOH) pK 9.5. See preceding entry for physical properties. The is the active isomer which blocks isoprenaline tachycardia and is a (i-adrenergic blocker. [Leclerc et al. Trends Pharmacol Sci 2 18 7987 Howe and Shanks Nature 210 1336 7966.]... 

Bradycardia Bradycardia is a slow heart rate (60 beats per minute or slower) that does not meet the body s metabolic demands. Symptoms of bradycardia include dizziness, extreme fatigue, shortness of breath, or fainting spells. This can be compared to tachycardia, which is an extremely rapid heart rate, usually signified by a pulse of over 100 beats per minute. Adults usually have a resting heart rate of 70-80 beats per minute, although well-trained athletes can have resting rates in the 50 s or 60 s. Newborn babies have a normal heart rate of 120-160 beats per minute. A slowed heart rate can lead to a variety of other problems. First aid treatment may include administration of oxygen. 

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