The Therapies

Ventricular tachyarrhythmia therapy in an ICD may be programmed for each zone of detection. For arrhythmias detected in the VF zone this occurs in the form of defibrillation. Shocks to terminate tachycardias in this zone may occur regardless of the timing in the cardiac cycle, and up to a maximum of 25-42 J stored energy in contemporary devices. Some ICD models may deliver up to eight shocks per arrhythmia episode. 

1 The timing of a defibrillation shock necessarily delivered with 

2 Depending on the ICD model, it may store upwards of for a single charge sequence. 

3 ATP attempts to terminate VT by pacing at a cycle length that of the tachycardia. 

Cardioversion is the next level of therapy brought to bear in a VT zone. Each shock is synchronized to occur with an R wave during the cardiac cycle. These shocks are always programmed to follow unsuccessful ATP therapies. As with a VF zone, multiple shocks may be administered for each episode should a tachycardia be refractory to termination. The initial shock energy is typically low (i.e. 1-5 J) and increased for each subsequent shock. 

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Magnesia and aluminum suspension is useflil for the therapy of duodenal ulcers when given at high doses at frequent intervals. It is available in both hquid and tablet formulations. 

This compound has antihistaminic activity and is usehil in the therapy of motion sickness. It may also be effective in the control of post-operative nausea and vomiting. It is classified as FDA Category B for Pregnancy, ie, no demonstrated risks shown in animal studies however, no controlled trials in pregnant women. Large doses may cause drowsiness and dry mouth owing to decreased secretion of saUva. 

Mecli2ine is often used for the therapy of motion sickness and is available without prescription in a variety of formulations. 

Blood dyscrasias are quite uncommon, but if they occur may be serious enough to cause discontinuance of the therapy. Both topical and systemic adrninistration of sulfas can cause hypersensitivity reactions, such as urticaria, exfoHative dermatitis, photosensiti2ation, erythema nodosum, and in its most severe form, erythema multiformexudativum. (Stevens-Johnson syndrome). In general, however, use of sulfonamide therapy is considered relatively safe. 

Table 1. Tetracyclines Used for the Therapy of Infectious Diseases...

Figures 2 and 3 illustrate the constant release of pilocarpiae over the seven day treatment period. An initial burst of dmg iato the eye is seen ia the first few hours. This is temporary and the system drops to the rated value ia approximately six hours. The total amount of dmg released ia this transitory period is less than that normally given ia pilocarpiae ophthalmic solutions. The ocular hypotensive effect of these devices is hiUy developed within 2 hours of placement ia the conjunctival sac, and the hypotensive response is maintained throughout the therapy. This system replaces the need for eyedrops apphed four times per day to control iatraocular pressure.

There are several methods of preparation of antibacterial quinolones, drugs widely used in the therapy of various bacterial diseases. The most general method is based on the nucleophilic cyclization of 2-halobenzoyl derivatives 402, leading to the key intermediates 403. The methodology is exemplified in Scheme 63 by the synthesis of a broad-spectrum drug ciprofloxacin... 

Dihydropyridines not only are intermediates for the synthesis of pyridines, but also are themselves an important class of N-heterocycles an example is the coenzyme NADH. Studies on the function of NADH led to increased interest in the synthesis of dihydropyridines as model compounds. Aryl-substituted dihy-dropyridines have been shown to be physiologically active as calcium antagonists. Some derivatives have found application in the therapy of high blood pressure and angina pectoris. For that reason the synthesis of 1,4-dihydropyridines has been the subject of intensive research and industrial use. The Hantzsch synthesis has thus become an important reaction. 

Leukotrienes are rapidly produced and released during a Type I reaction (Fig. 3). They are responsible for a massive bronchoconstriction in allergic bronchial asthma and attract leukocytes, thus being proinflamma-tory. Consequently, antagonists of the LTC recqDtor have been proven useful in the therapy of bronchial asthma, often in combination with bronchodilators (example montelukast). 

Amyloid precursor protein (APP) is the precursor of (3-amyloid, the main component of senile plaques found in the brain of Alzheimer patients. The production of (3-amyloid from APP to the cells from abnormal proteolytic cleavage of the amyloid precursor protein. Enzymes involved in this cleavage may be suitable targets for the therapy of Alzheimer s disease. 

Amphotericin B, is a polyene antibiotic, used in the therapy of systemic fungal infections. Its mode of action exploits differences in membrane composition between the pathogen and the human host. Ergosterol, the predominant sterol of fungi, plants, and some protozoan parasites, interacts with Amphotericin B, resulting in an increased ion permeability of the membrane. Humans contain cholesterol, which has a low affinity for amphotericin B. 

As discussed above, the vast majority of autoimmune diseases is associated with chronic inflammation. The therapy thus rests on two principles ... 

DHPs are potent arterial vasodilators. They act on resistance vessels and therefore reduce peripheral vascular resistance, lower arterial blood pressure, and antagonize vasospasms in coronary or peripheral arteries. By reducing afterload, DHPs also reduce cardiac oxygen demand. Together with their vascular spasmolytic effect, this explains most of the beneficial actions of DHPs in angina pectoris. Most DHPs are only licensed for the therapy of hypertension, some of them also for the treatment of angina pectoris and vasospastic (Prinzmetal) angina. 

Many of the agents currently in use for the therapy of cancer can trigger apoptosis in cancer cells. Cancer-associated alterations of the genes that regulate apoptosis would therefore be predicted to affect sensitivity to these agents. 

The main clinical use of COMT inhibitors is as adjunct (or additional adjunct) in the therapy of Parkinson s disease. The standard therapy of Parkinson s disease is oral L-dopa (as a drug levodopa) given with a dopa decarboxylase (DDC) inhibitor (e.g. carbidopa and benserazide), which does not reach the brain. When the peripheral DDC is inhibited, the concentration of 3-O-methyldopa (3-OMD), a product of COMT, in plasma is many times that of L-dopa. Since the half-life of 3-OMD is about 15 h, compared to about 1 h for L-dopa, the concentration of 3-OMD remains particularly high during chronic therapy, especially if new slow release L-dopa preparations are used. A triple therapy (L-dopa plus DDC inhibitor plus COMT-inhibitor) will... 

Knowledge on cytokines has been exploited to improve the therapy of many diseases, basically in two ways ... 

Interleukin 2 (Aldesleukin, Proleukin ) is a major growth factor and activator of cytotoxic and other T-lymphocytes. It is applied in the therapy of metastas-ing renal carcinoma and melanoma. Side effects include... 

NO-sensitive GC represents the most important effector enzyme for the signalling molecule NO, which is synthesised by NO synthases in a Ca2+-dependent manner. NO-sensitive GC contains a prosthetic heme group, acting as the acceptor site for NO. Formation of the NO-heme complex leads to a conformational change, resulting in an increase of up to 200-fold in catalytic activity of the enzyme [1]. The organic nitrates (see below) commonly used in the therapy of coronary heart disease exert their effects via the stimulation of this enzyme. 

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