Prophylaxis

The term prophylaxis as used in this chapter is limited to medical countermeasures applied relatively shortly before penetration of a toxic agent into the organism. There is a question what will happen after the administration of the prophylactic drug. When the treatment is unnecessary, it can be described as prophylaxis. However, though successful prophylaxis can be observed for some OP, full protection of the organism without post-exposure treatment, especially for soman poisoning, remains open. When the treatment is involved after exposure, the term pre-treatment has become to be accepted. 

From a practical point of view, it is obvious that when the drug is administered prior to intoxication (either prophylaxis or pre-treatment) with the aim of protecting the organism against the toxic drug, exposure to these agents is expected and, therefore, postexposure therapy can very probably be used, i.e., pre-treatment could be used as the right term. For reasons of simplicity, the term prophylaxis is used in this article. 

The administration of present antidotes (anticholinergics, reactivators, and others) to prevent the effects of OP is also possible. The problem with this approach is how to achieve sufficient levels of antidotes for a relatively long time. Combinations of these approaches are also possible. 

Keeping AChE intact is a basic requirement for effective prophylaxis, i.e., to change the enzyme in a way that will make it resistant to OP. This can be achieved by using reversible inhibitors, which are able to inhibit AChE reversibly and after spontaneous recovery of the activity, normal AChE serves as a source of the active enzyme. 

There are many inhibitors of cholinesterases diminishing both AChE and BuChE activities to a comparable extent, as has been described by Aldridge (1969). Carbamates belong to a group of inhibitors having a wide variety in their effectiveness. They are biologically active because of their structural 

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The immunorestorative potential of inosiplex has been evaluated in several clinical conditions, including post-surgical trauma, cancer patients with concurrent viral infections, and cancer patients receiving radiotherapy or chemotherapy. For example, most (84%) of the surgery patients remained immunologicaHy depressed, but 56% of the inosiplex-treated surgery patients had complete restoration of normal skin test reactivity (probability level < 0.0005). The use of inosiplex as an adjuvant to chemotherapy or radiotherapy appears to be valuable in the prophylaxis against opportunistic infections. 

The sulfas also remain clinically useful in the treatment of chancroid, lymphogranuloma venereum, trachoma, inclusion conjunctivitis, and the fungus-related nocardiosis (7). In combination with pyrimethamine, they are recommended for toxoplasmosis (8) and have been used for chloroquine-resistant falciparium malaria (4,9). There has also been some use of sulfas for the prophylaxis of rheumatic fever. The sulfone, dapsone, remains an accepted treatment for all forms of leprosy (4). 

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). 

Nystatin is mainly used to treat vaginal and oral infections and localized skin lesions, including Candida intertrigo and Candida nappy dermatitis. It may also be used as prophylaxis during treatment with antibiotics. 

Malaria affects an estimated 270 million people and causes 2—3 million deaths annually, approximately one million of which occur in children under the age of five. While primarily an affliction of the tropics and subtropics, it has occurred as far north as the Arctic Circle. The disease essentially has been eradicated in most temperate-zone countries, but some 1100 cases of malaria in U.S. citizens returning from abroad were reported to the Centers for Disease Control during 1990. Malaria is seen today in Southeast Asia, Africa, and Central and South America. It is on the increase in Afghanistan, Brazil, China, India, Mexico, the Philippines, Sri Lanka, Thailand, and Vietnam. Escalation of the disease is because of the discontinued use of the insecticide DDT which effectively kills mosquito larvae, but has been found to be toxic to Hvestock and wildlife. Also, chloroquine (6), a reUable dmg for the prophylaxis and treatment of falcipamm malaria, is ineffective in many parts of the world because of the spread of dmg-resistant strains. 

Tissue Schizonticides. These eradicate the Hver stages of the parasite and thereby prevent their entry into the blood. As a class, therefore, they ate useful for prophylaxis. Some tissue schizonticides can act on the long-Hved tissue forms (hypnozoites) of P. vivax and P. ovale and thus can cure the latter infections by preventing relapses. 

Ivermectin is widely used as an endectocide for catde as an injectable, oral, topical, or slow release bolus for sheep as an injectable or oral formulation for swine as an injectable for horses as a paste or drench and for goats as an injectable or oral formulation. Ivermectin has recently been introduced for heartworm prophylaxis in dogs and it is being studied for use with cats, many other mammals, birds, fish, and reptiles. 

Acyclovir is more effective the more serious the disease and the earher it is given. It has been shown to be efficacious when used systemicaHy in the prophylaxis of HSV infections in immunosuppressed patients, ie, bone marrow transplant recipients (67). Acyclovir therapy appears to be superior to ara-A in the treatment of herpes simplex encephaUtis in humans (68). 

Passive transdermal dehvery systems on the market tend to be either matrix or membrane controUed. In matrix devices, the stmctural and molecular characteristics of the dmg-polymer matrix determine dmg release. Examples of polymer matrix-controUed diffusional systems for angina prophylaxis include Nitro-Dur and Nitrodisc, which provide transdermal dehvery of nitroglycerin [55-63-0], and Erandol, a tape that releases isosorbide dinitrate [87-33-2]. Matrix diffusional systems have been used for dehvering dmgs with a wide therapeutic index. 

I. P. Semmelweis, The Etiology, Conception and Prophylaxis of Childbed Fever, Harfleben. Pest, Vienna Leipsig, 1861. 

The philosophy of public health protection used by the AEC and pursued ever since, is the use of multiple independent barriers, each a significant shield for the public. The last barrier involves the removal of people from the area over which the radioactive plume is expected to pass, interdiction of food supplies and the use of prophylaxis to reduce the iodine dose. Blood... 

Emergency Action If it appears that the public will be affected by a radioactive release, people may evacuate from the expected area, remain indoors, or use iodineblocking prophylaxis. 

The recently introduced antimalanal halofantrine (6) is an orally active blood schizonucide reported to be more than 95% effective in the treatment of malaria [S] Mefloquine hydrochloride (7) contmues to be useful m the prophylaxis and treatment of malaria [9]... 

Tolrestat (28) is a long-acang aldose reductase inhibitor useful in the prophylaxis of diabetic neuropathy, retinopathy, and cataracts [24 25] Lastly, the intro-ducuon of fluorine into steroids probably ushered in the modem era of fluonnated drugs Many commercial products were introduced [2] Typical of the products are the anti inflammatory glucocorticoids dexamethasone (29 X = F, Y = H), para-methasone (29, X = H, Y = F), and flumethasone (29, X = H, Y = F)... 

The excessive production of sebum associated with acne has made life miserable for many an adolescent. Research on acne has, as a rule, concentrated on therapy rather than prophylaxis. A pyrimidone forms an interesting exception, being described as an anti seborrheic agent. Starting keto-ester 21 can, at least in principle, be obtained by y-... 

Verhiittung,/. (Metal.) working (off), smelting. Verhiitung, /. prevention, (Med.) prophylaxis. Verhiitungsmittel, n. preventive, prophylactic inhibitor. 

Cisplatin administration requires adequate hydration and forced diuresis to prevent kidney damage. Cisplatin is intensely emetogenic and its use requires adequate antiemetic prophylaxis. Myelosuppression is less evident than with other alkylating agents. 

Antidepressants are used in neuropathic pain and migraine prophylaxis. Tricyclics require monitoring of plasma drug concentrations to achieve optimal effect... 

Ventricular fibrillation should be terminated by electrical defibrillation. Alternatively, lidocaine can be injected intravenously. In cases with lower frequency, ventricular tachyarrhythmia class I diugs such as aj marine, flecainide or propafenone are more effective as a result of the use-dependence of lidocaine. For prophylaxis treatment, amiodarone or sotalol may be helpful or the implantation of a cardioverter-defibrillator system. Acute amiodarone (i.v. in higher doses) can also terminate ventricular tachyarrhythmias. This action, however, seems to be mediated by its INa-blocking side effects and not (or less) by its class III like effects. 

Fondaparinux, the factor Xa-binding pentasaccharide (Arixtra, MW 1,728 Da), is prepared synthetically, unlike UFH, LMWH and danaparoid, which are obtained from animal sources. Despite only inactivating free factor Xa, clinical trials indicate that fondaparinux is an effective antithrombotic agent, both for venous thromboembolism prophylaxis and treatment, as well as for acute coronary syndrome and ST elevation myocardial infarction [4]. 

Prevention of DVT and PE (antithrombotic prophylaxis) is another common indication for UFH, LMWH or coumarin, especially following surgery or immobilizing trauma. Fondaparinux is approved for prevention of DVT and PE after hip and knee surgery, and following abdominal surgery. 

Daily doses of 3-8 mg (6-8 times 0.5-1.0 mg) are used for the treatment of acute gouty arthritis. For prophylaxis, daily doses of 0.5-1.5 mg are used, but the use of colchicine for prophylaxis is controversial. 

MTX is part of curative therapeutic schedules for acute lymphoblastic leukemias (ALL), Burkitt s lymphoma, and choriocarcinoma. It was also used in adjuvant therapy of breast cancer. High dose MTX with leucovorin rescue can induce about 30% remissions in patients with metastatic osteogenic sarcoma. MTX is one of the few antineoplastic drugs that can be safely administered intrathecally for the treatment of meningeal metastases and leukemic infiltrations (routine prophylaxis in ALL). In addition, MTX can be used as an immunosuppressive agent for the treatment of severe rheumatoid arthritis and psoriasis. 

Patient databases with genetic profiles, e.g. for cardiovascular diseases, diabetes, cancer, etc. may play an important role in the future for individual health care, by integrating personal genetic profile into diagnosis, despite obvious ethical problems. The goal is to analyse a patient s individual genetic profile and compare it with a collection of reference profiles and other related information. This may improve individual diagnosis, prophylaxis, and therapy. 

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