E. Marlo. Southern University, New Orleans.

Clinical Uses Hemodynamic Effects Phenytoin cheap colchicine 0.5mg otc, like lidocaine cheap colchicine 0.5 mg visa, is more effective in the treat- The acute hemodynamic effects are slight and transient ment of ventricular than supraventricular arrhythmias. The pharmacokinetic characteristics of tocainide: Phenytoin finds its most effective use in the treat- ment of supraventricular and ventricular arrhythmias Oral bioavailability Approximately 100% associated with digitalis intoxication. The ability of Onset of action Not known phenytoin to improve digitalis-induced depression of Peak response 0. Plasma half-life 15 hours 16 Antiarrhythmic Drugs 179 Primary route of Hepatic Hemodynamic Effects metabolism Although its cardiovascular toxicity is minimal, mexile- Primary route of Renal (40% unchanged) tine should be used with caution in patients who are hy- excretion potensive or who exhibit severe left ventricular dys- Therapeutic serum 3–11 g /mL concentration function. Clinical Uses Pharmacokinetics Tocainide is indicated for the treatment of symptomatic The pharmacokinetic characteristics of mexiletine: ventricular arrhythmias refractory to more conventional therapy. Serious noncardiac adverse effects limit its use Oral bioavailability 90% to patients with life-threatening arrhythmias. Primary route of Primarily biliary; 10% renal Overall, however, approximately 20% of patients pre- excretion scribed tocainide discontinue therapy because of such Therapeutic serum 0. Serious immune-based side effects, such as pul- concentration monary fibrosis, have been reported, and blood dyscrasias, such as agranulocytosis and thrombocytope- Clinical Uses nia, may occur in up to 0. Mexiletine is useful as an antiarrhythmic agent in the management of patients with either acute or chronic Contraindications ventricular arrhythmias. While it is not at present an in- Patients who are hypersensitive to tocainide or to local dication for use, there is interest in using mexiletine to anesthetics of the amide type should not be exposed to treat the congenital long QT syndrome when an abnor- tocainide. The first signs of toxicity manifest as fine tremor of When used with other class IB antiarrhythmic drugs, to- the hands, followed by dizziness and blurred vision. The side effects of oral maintenance therapy include re- Mexiletine versible upper gastrointestinal distress, tremor, light- Mexiletine (Mexitil) is an antiarrhythmic agent with headedness, and coordination difficulties. These effects pharmacological and antiarrhythmic properties similar generally are not serious and can be reduced by down- to those of lidocaine and tocainide. Like tocainide, mex- ward dose adjustment or administering the drug with iletine is available for oral administration. Cardiovascular adverse effects, which are less common, include palpitations, chest pain, and angina or Electrophysiological Actions anginalike pain.

Clinical breast exam (CBE)—Examination of the There are rare generic colchicine 0.5 mg free shipping, genetic cancer syndromes that may breasts colchicine 0.5mg on line, performed by a physician or nurse. As a group, these comprise less Malignant—A tumor growth that spreads to than 1% of all breast cancer diagnoses. These health problems can initially doses of x rays, in an attempt to visualize the inner appear unrelated, but may be caused by alterations in a breast tissue. As an example, Cowden syndrome typi- Metastasis—The spreading of cancer from the cally involves early-onset thyroid and breast cancers, as original site to other locations in the body. An individual with Cowden syndrome may have Multifocal breast cancer—Multiple primary can- all or some of these symptoms. Primary cancer—The first or original cancer site, Other known cancer syndromes are caused by specific before any metastasis. Most cases of breast cancer occur in A small proportion of breast cancers is caused by women past the age of 50, and more commonly in indi- inherited genetic alterations. The discovery of BRCA2 (location 13q12) As of 2000, the prevalence of BRCA alterations in followed shortly in 1995. Women with alterations in the general population is estimated to be between 1/500 these genes have an increased risk for breast and ovarian and 1/1,000. However, there are specific alterations that cancer, and men have an increased risk for prostate are commonly found in certain ethnic groups. Men with a BRCA2 alteration have an increased Ashkenazi (Eastern European) Jewish population, two risk for breast cancer. Slightly increased risks for colon specific BRCA1 alterations and one BRCA2 alteration 174 GALE ENCYCLOPEDIA OF GENETIC DISORDERS are commonly seen and range in prevalence from 0.

The identification of a low Therapeutic Index margin of safety buy colchicine 0.5 mg on line, however colchicine 0.5mg low cost, dictates particular caution in Effective Dose its use; the appropriate dose for each individual must be The quantal dose–response curve represents esti- determined separately. In addition to this of drug safety would include a comparison of the lowest information, it also would be useful to have some way to dose that produces toxicity (e. A curve similar to that already discussed can be therapeutic index is a very rough measure of safety and constructed by plotting percent of animals killed by generally represents only the starting point in determin- phenobarbital against dose (Fig. Since the Usually, undesirable side effects occur in doses lower degree of safety associated with drug administration de- than the lethal doses. For example, phenobarbital in- pends on an adequate separation between doses produc- duces drowsiness and an associated temporary neuro- ing a therapeutic effect (e. Thus, an im- Since an entire dose–response relationship is deter- portant measure of safety for an anticonvulsant would mined from one animal, the curve cannot tell us about be the ratio ED50 (neurological impairment)/ED50 the degree of biological variation inherent in a popula- (seizure protection). The protective index for phenobarbital is approxi- family of dose–response curves, such as those given in mately 3. The ED50in this type of dose–response curve dose–response curves can be used in a variety of ways is the dose that produced 50% of the maximum re- to compare the clinical usefulness of drugs. In guinea pig e, the maximum re- a drug with a protective index of 1 is useless as an anti- sponse is an increase in heart rate of 80 beats per convulsant, since the dose that protects against convul- minute. An estimate More common than the quantal dose–response rela- of the variation within the population can be indicated tionship is the situation in which a single animal (or pa- by calculating a statistical parameter, such as a confi- tient) gives graded responses to graded doses; that is, dence interval. With It is also possible to construct quantal dose–response graded responses, one can obtain a complete dose– curves for drugs that produce graded responses. A good example is the so, one chooses a quantum of effect, for example, an in- effect of the drug levarterenol (L-norepinephrine) on crease in heart rate of 20 to 30 beats per minute above heart rate. Doses of the drug are then Results of experiments with levarterenol in guinea plotted against the frequency with which each dose pro- pigs are shown in Figure 2. The resulting graph has the what one might obtain from constructing complete same characteristics as the graph for the anticonvulsant dose–response curves in each of five different guinea activity of phenobarbital. Further increases in dose do not produce greater re- There are many reasons for the common practice of us- sponses. At the other extreme, in guinea pig e, doses be- ing geometric scales, some of which will become appar- low 0.