Prophylaxis toxicity

For rrumy drugs, however, the effects are difficult to measure (or the drug is given for prophylaxis), toxicity and lack of efficacy are potential dangers, or the therapeutic index is narrow. In these circumstances, doses must be titrated carefully, and drug dosage is limited by toxicity rather than efficacy. 

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. 

Gout is an episodic disease, and the number of attacks varies widely from patient to patient. Thus the benefit of long-term prophylaxis against acute gout flares must be weighed against the cost and potential toxicity of therapy that may not be necessary in all patients. Asymptomatic hyperuricemia usually does not require treatment. 

Nevirapine is a non-nucleoside reverse transcriptase inhibitor used to treat HIV-infected patients that causes mild to severe skin rash and even Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) in a substantial proportion (16%) of patients. Nevirapine also induces hepatotoxicity. These adverse clinical symptoms may also occur in non-HIV subjects taking the drug as postoperative prophylaxis [15]. 

B too toxic for systemic use C a pro-drug of penciclovir D not indicated in acute genital herpes simplex E indicated for the prophylaxis of varicella zoster... 

Lithium is a drug with a narrow therapeutic index and therefore plasma concentrations are regularly monitored. Lithium is used in the prophylaxis and treatment of mania. Concurrent administration of lithium and diuretics, particularly the thiazides, is contraindicated as lithium excretion is reduced, resulting in increased plasma-lithium concentration and hence toxicity. 

Lactation The small concentrations of isoniazid in breast milk do not produce toxicity in the nursing newborn therefore, do not discourage breastfeeding. However, because levels of isoniazid are so low in breast milk, they cannot be relied upon for prophylaxis or therapy in nursing infants. 

Sulfadiazine and sulfisoxazole still play a useful role in the prophylaxis of group A streptococcal infections in patients with rheumatic fever who are hypersensitive to penicillin. This is tempered with the potential for toxicity and infection with resistant Streptococcus pyogenes. 

A number of 5-nitro-2-furaldehyde derivatives, called nitrofurans, are used in the treatment and/or prophylaxis of microbial infections, primarily in the urinary tract. Recent evidence suggests that the reduction of the 5-nitro group to the nitro anion results in bacterial toxicity. Intermediate metabolites modify various bacterial macromolecules that affect a variety of biochemical processes (e.g., DNA and RNA synthesis, protein synthesis) this observation may explain the lack of resistance development to these drugs. Evidence also indicates that the nitro anion undergoes recycling with the production of superoxide and other toxic oxygen compounds. It is presumed that the nitrofurans are selectively toxic to microbial cells because in humans, the slower reduction by mammalian cells prevents high serum concentrations. 

Although dapsone (Avlosulfon) was once used in the treatment and prophylaxis of chloroquine-resistant P. falciparum malaria, the toxicities associated with its administration (e.g., agranulocytosis, methemoglobinemia, hemolytic anemia) have severely reduced its use. 

Vitamins are vital for normal metabolism in body. They vary in their chemical structure and are supplied in very small quantity in diet, because they are not synthesized in body or their rate of production is not sufficient for maintenance of health. Vitamin deficiency leads to development of deficiency symptoms. Different vitamin preparations are available for treatment and prophylaxis. Most of the vitamins are nontoxic but on chronic administration can cause toxicity especially vitamin A and D. 

It is indicated in wet beriberi, dry beriberi, Wernicke s encephalopathy, prophylaxis of thiamine deficiency, hyperemesis gravidarum, Korsakoff s syndrome, chronic alcoholics, multiple neuritis, toxic and confusional states, delirium tremens and anorexia nervosa. 

Maintenance and prophylaxis with lithium, and perhaps other mood stabilizers, favorably alters the longitudinal course of a bipolar disorder. Thus, efforts to enhance long-term compliance are a necessary part of any overall strategy. The incidence of adverse or toxic events is relatively low, and close attention to the more clinically relevant consequences can usually prevent serious sequelae ( 198).An issue of critical importance for future research is the potential efficacy of alternative maintenance medication for those who fail to respond adequately to acute or long-term lithium therapy. 

Propranolol Nonselective competitive antagonist at adrenoceptors Decreased heart rate, cardiac output, and blood pressure decreases myocardial oxygen demand Prophylaxis of angina for other applications, see Chapters 10, 11, and 13 Oral and parenteral, 4-6 h duration of action Toxicity Asthma, atrioventricular block, acute heart failure, sedation Interactions Additive with all cardiac depressants... 

Verapamil, diltiazem Nonselective block of L-type calcium channels in vessels and heart Reduced vascular resistance, cardiac rate, and cardiac force results in decreased oxygen demand Prophylaxis of angina, hypertension, others Oral, IV, duration 4-8 h Toxicity Atrioventricular block, acute heart failure constipation, edema Interactions Additive with other cardiac depressants and hypotensive drugs... 

Nifedipine (a dihydropyridine) Block of vascular L-type calcium channels > cardiac channels Like verapamil and diltiazem less cardiac effect Prophylaxis of angina, hypertension Oral, duration 4-6 h Toxicity Excessive hypotension Interactions Additive with other vasodilators... 

Ranolazine Inhibits late sodium current in heart also may modify fatty acid oxidation Reduces cardiac oxygen demand fatty acid oxidation modification may improve efficiency of cardiac oxygen utilization Prophylaxis of angina Oral, duration 6-8 h Toxicity QT interval prolongation, nausea, constipation, dizziness Interactions Inhibitors of CYP3A increase ranolazine concentration and duration of action... 

Salmeterol Selective B2 agonist Slow onset, primarily preventive action potentiates corticosteroid effects Asthma prophylaxis Aerosol inhalation duration 12-24 h Toxicity Tremor, tachycardia, overdose arrhythmias... 

Fluticasone Alters gene expression Reduces mediators of inflammation powerful prophylaxis of exacerbations Asthma adjunct in COPD Aerosol duration hours Toxicity Limited by aerosol application candidal infection, vocal cord changes... 

Montelukast, zafirlukast Block leukotriene D4 receptors Block airway response to exercise and antigen challenge Prophylaxis of asthma, especially in children and in aspirin-induced asthma Oral duration hours Toxicity Minimal... 

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