By W. Kippler. Warren Wilson College.

The plasma drug concentration (Ct) at any time (t) after administration is given by ln Ct= ln C0−kt (or log Ct ¼ log C0–kt/2 purchase 120 mg silvitra mastercard erectile dysfunction causes mayo. The two-compartment model is a more common model for distribution and elimination of drugs generic silvitra 120 mg without a prescription erectile dysfunction vacuum pumps australia. Time between a central compartment, such as the plasma space, and a second compartment, such as the aggregate tissues and fluids to which the drug distributes. After distribution, a linear decrease in the log drug concentration is observed if the elimina- tion phase is first order. For drugs that obey a two-compartment model, the value of C0 obtained by extrapolation of the elimination phase is used to calculate Vd, and the elimination rate constant, k, is obtained from the slope of the elimination phase. It refers to the elimination of a constant fraction of drug per unit time; that is, the rate of elimination is a linear function of the plasma drug concentration. First-order elimination occurs when elimination systems are not saturated by the drug. In this model, the plot of the log of the plasma concentration versus time will be concave upward, and a constant amount of drug will be eliminated per unit time (e. Zero-order elimination may occur when therapeutic doses of drugs exceed the capacity of elimination mechanisms. Half-life is the time it takes for the plasma drug concentration to be reduced by 50%. Half-life is determined from the log plasma drug concentration versus time profile for drugs fit- ting a one-compartment model or from the elimination phase for drugs fitting the two-com- partment model. As long as the dose administered does not exceed the capacity of the elimination systems (i. The half-life is related to the elimination rate constant (k) by the equation t1/2 ¼ 0. For all doses in which first-order elimination occurs, >95% of the drug will be eliminated in a time interval equal to five half-lives. If a drug that is eliminated by first-order kinetics is administered repeatedly (e. Levels will be at the high point of the steady state range shortly after a dose is administered; levels will be at the low point immediately before administration of the next dose. Hence, steady state designates an average plasma concentration and the range of fluctuations above and below that level. A shorter dosing interval decreases fluctuations, and a longer dosing interval increases them. On cessation of multidose administration, >95% of the drug will be eliminated in a time interval equal to five half-lives if first-order kinetics applies. Maintenance dose rate is the dose of a drug required per unit time to maintain a desired steady-state level in the plasma to sustain a specific therapeutic effect. One may understand this fundamental relationship in the following way: To remain at steady state, the dose rate must equal the elimination rate; that is, the rate at which the drug is added to the body must equal the rate at which it is eliminated. If one administers a drug at the maintenance dose rate, a steady state plasma concentration of drug will be reached in four to five half-lives. A large loading dose may be needed initially when the therapeutic concentration of a drug in the plasma must be achieved rapidly (e. To calculate the loading dose, select the desired plasma concentration of drug and multiply by the Vd: Loading dose = Desired [drug]plasma×Vd (amount or mass)=(mass/volume)×(volume) c. After administration of the loading dose (which rapidly achieves the desired plasma con- centration of drug), one administers the drug at the maintenance dose rate to maintain the drug concentration at the desired steady-state level. Review Test for Chapter 1 Directions: Each of the numbered items or incomplete statements in this section is followed by answers or by completions of the statement. Cortisol is capable of targeting intranuclear receptors secondary to its ability to 6. Which of the following is the term used to (A) Recruit intracellular kinases describe the elimination rate via metabolism (B) Undergo autophosphorylation catalyzed by alcohol dehydrogenase when the (C) Diffuse through lipid membranes enzyme is saturated? Which of the following parameters is used to (D) Biotransformation indicate the ability of a drug to produce the (E) Redistribution desired therapeutic effect relative to a toxic effect? A 69-year-old woman is being treated in (A) Potency the intensive care unit for presumed staphylo- (B) Intrinsic activity coccal sepsis.

Effect of source-to-collimator distance on overall system resolution for various types of collimators cheap silvitra 120mg online ginkgo biloba erectile dysfunction treatment. Bar phantoms consist of four sets of parallel lead bar strips arranged perpen- dicular to each other in four quadrants in a lucite holder (Fig order 120 mg silvitra with visa impotence liver disease. The widths and spacings of the strips are the same within each quadrant but differ in different quadrants. The Hine–Duley phantom consists of five groups of lead strips of different thicknesses and spacings arranged in par- allel fashion in a lucite holder (Fig. In all bar phantoms, the thick- ness of lead should be sufficient to stop photons of a given energy for which spatial resolution is being estimated. A 57Co flood source (described later under Quality Control) is placed on the top of it and an image is taken. For evaluation of spatial resolution for differ- Evaluation of Spatial Resolution 123 Fig. The image of the bar phantom obtained is visually inspected, and spatial resolution is estimated from the smallest strips or spacings distinguishable on the image (Fig. Obviously, this technique is qualitative and does not give a quantitative measure of the spatial resolution. A long plastic tubing filled with a radioactive solution is placed in the field of view of the detec- tor. Line spread function of a gamma camera equipped with a low-energy all- purpose parallel hole collimator obtained in (a) air and (b) water at different dis- tances using a 99mTc-line source. Such a distribution gives a spatial frequency ( ) in cycles per centimeter or cycles per millimeter. The contrast, or modulation (Ms), in the source activity is given by A max − min Ms = (10. Because the imaging devices are not absolutely perfect, it will portray the distribution of activity in the image with Cmax for the peak and Cmin for the valley, which are smaller in magnitude than Amax and Amin. This is true if the sinusoidal cycles are well sepa- rated and if the imaging device reproduces the image of each cycle faith- fully. Performance Parameters of Gamma Cameras When the distribution of activity is such that spatial frequency increases, the peaks and valleys come closer. It is important to note that small objects are better imaged at higher frequencies and large objects at lower frequencies. The mathematical expression of these functions is quite complex and can be found in reference physics books. System A gives better spatial resolution than systems B and C, and system B pro- vides better resolution than system C. Briefly, (a) the intrinsic photopeak efficiency of a detector decreases with increas- ing photon energy and with increasing source-to-detector distance (see Fig. The photo- peak efficiency of these crystals is about 90% for 140-keV photons of 99mTc and about 30% for 364-keV photons of 131I. Sensitivity of a gamma camera is most affected by the collimator effi- ciency, which is described next. Variation of geometric efficiency with source-to-collimator distance for various collimators. The constant K is a function of the shape and arrangement of holes in the collimator and varies between 0. The collimator efficiency for parallel-hole collimators increases with increasing diameter of the collimator holes and decreases with increasing collimator thickness (t) and septal thickness (a), which is quite opposite to Uniformity 129 spatial resolution [see Eq. Thus, for a given collimator, as the spatial resolution of a system increases, its sensitivity decreases, and vice versa. Note that collimator efficiency, Eg, for parallel-hole collimators is not affected by the source-to-detector distance for an extended planar source; that is, it essentially remains the same at different distances from the detector. Collimator efficiency varies with different types of colli- mators, and the values are shown as a function of source-to-collimator dis- tance in Figure 10. Uniformity It is always expected that a gamma camera should yield a uniform response throughout the field of view. That is, a point source counted at different locations in the field of view should give the same count rate by the detec- tor at all locations. However, even properly tuned and adjusted gamma cameras produce nonuniform images with count density variations of as much as 10%.

The number of rings in current scanners (18–32) buy silvitra 120mg on-line impotence hypertension medication, and the number of detectors per ring vary with the manufacturer generic silvitra 120mg mastercard impotence newsletter. The number of rings and, hence, the width of the array of rings define the axial field of view. Typically, each block is about 3-cm deep and grooved into 6 × 8, 7 × 8, or 8 × 8 elements by partial cuts through the crystal with a saw. The cuts are made at varying depths, with the deepest cut at the edge of the block. The cuts are filled with opaque reflective mate- rials to prevent spillover of light between elements. The block detectors are arranged in an array of full or partial rings with a diameter of 80 to 90cm. Different arrangements of block detectors adopted by manufacturers are shown in Figure 13. In the case of partial ring configurations, the blocks have to be rotated around the patient to obtain 360° acquisition of data. This uncertainty in detection time is called the timing resolution or coincidence timing window. The timing resolution results from the difference in pulse formation in the detector primarily due to statisti- cal variations in gain and scintillation decay time of the detector. Further- more, there is a time delay in the arrival of one photon relative to the other, because of the difference in distances traveled by the two photons, partic- 186 13. Because the velocity of light is 3 × 10 m/s, the difference between the arrival times of the two photons is about 3 to 4ns (time to travel 1m). After annihilation, two timing signals A and B are formed with timing width, say t, depending on the scanner system. Both A and B indicate that the timing window of the coincidence circuit must be at least 2t to detect all events in coincidence. Each detector is connected in coincidence with as many as half the total number of detectors in a ring and the data for each detec- tor are acquired in a “fan beam” projection. Thus the timing resolution or coincidence timing window has to be a minimum of 2t. The number of opposite detectors can vary from one to a maximum of half the total number of detectors present in a ring. Each detector element can be connected in coincidence to a maximum of half the total number N of opposite detector elements (N/2). The horizontal travel range of the scanning table varies with the designs of the scanners. The actual scan field is the maximum travel range of the scanning table minus the displacement distance. The mobile unit moves to different clients’ facilities on different days depending on the schedule. The van must meet the Department of Transportation’s over- load regulations, and the rules and regulations of fire safety and security of local authorities. Data Acquisition 191 Hybrid Gamma Cameras Conventional dual-head and triple-head gamma cameras (Fig. The hybrid cameras suffer from a disadvantage of low sensitivity due to low detection efficiency of NaI(Tl) crystal for 511-keV photons. In a full ring system, data are collected in 360° simulta- neously, whereas in the partial ring system, the rings are rotated around the patient for 360° data acquisition. First, the location of the detector pair in the ring is determined for each coincident event. Because each detector is connected to many opposite detectors in coin- cidence, which detector pair detected a coincidence event must be deter- mined. As in gamma cameras, the position X, Y of each detector in the ring is determined by ( + X = (13. If it is outside the window, it is rejected; otherwise, it is accepted for storage. It is not known where along the line of travel of the two photons the event occurred, because they are accepted within the set time window (say, 12ns) and their exact times of arrival are not compared. Data can be collected in both static and dynamic imaging using either the frame mode or the list mode, described in Chapter 11. The whole-body scan of the patient is obtained at dif- ferent axial positions of the bed.

These patients often have triggers of attacks generic 120mg silvitra with visa erectile dysfunction protocol download pdf, including menstruation cheap silvitra 120 mg fast delivery erectile dysfunction anxiety, steroids, calorie restriction, alcohol, and numerous drugs. Numerous studies have indicated important ben- efits in both primary and secondary prevention of cardiovascular disease. Statins are generally well tolerated, with an excellent safety profile over the years. Dyspepsia, headache, fatigue, and myal- gias may occur and are generally well tolerated. The risk of myopathy is increased in the presence of renal insufficiency and with concomitant use of certain medications, including some antibiotics, antifungal agents, some immunosuppressive drugs, and fibric acid derivatives. Liver transaminases should be checked before therapy is started and 4 to 8 weeks after- ward. The peak incidence is between 30 and 50 years of age, and women are af- fected more frequently than are men. During the initial phase of follicular destruction, there is a release of thyroglobulin and thyroid hormones. Patient A is consistent with the thyrotoxic phase of subacute thyroiditis except for the increased radioiodine uptake scan. Clinically, this is manifested as hypoglycemia unawareness and defective glucose counterregulation, with lack of glucagon and epinephrine secretion as glucose levels fall. Barrier methods (condoms, cervical cap, dia- phragm) have an actual efficacy between 82 and 88%. Oral contraceptives and intrauter- ine devices perform similarly, with 97% efficacy in preventing pregnancy in clinical practice. Notably, a decreased incidence of neuropathy, retinopathy, microalbuminuria, and nephropathy was shown in individuals with tight glycemic control. Given their prev- alence, the cost of screening, and the generally benign course of most nodules, the choice and order of screening tests have been very contentious. A small percentage of incidentally discovered nodules will represent thyroid cancer, however. An estimated prevalence of 3% in persons over age 40 years is a generally accepted figure. Most frequently, the disease is asymptomatic and is diagnosed only when the typical sclerotic bones are incidentally detected on x-ray examinations done for other reasons or when increased alkaline phosphatase activity is recognized dur- ing routine laboratory measurements. The etiology is unknown, but increased bone re- sorption followed by intensive bone repair is thought to be the mechanism that causes increased bone density and increased serum alkaline phosphatase activity as a marker of osteoblast activity. Because increased mineralization of bone takes place (although in an abnormal pattern), hypercalcemia is not present unless a severely affected patient be- comes immobilized. Hypercalcemia in fact would be an expected finding in a patient with primary hyperparathyroidism, bone metastases, or plasmacytoma, with plasmacy- toma typically producing no increase in alkaline phosphatase activity. Osteomalacia re- sulting from vitamin D deficiency is associated with bone pain and hypophosphatemia; normal or decreased serum calcium concentration produces secondary hyperparathy- roidism, further aggravating the defective bone mineralization. Hearing loss is very frequent, usually due to bony compression of the eighth cranial nerve. The most commonly affected areas include the pelvis, the skull, and the vertebral bodies. Physical findings of bony deformity such as frontal bossing of the skull or bowing of an extremity, an elevated alkaline phos- phatase level, or characteristic findings on plain radiographs, such as cortical thickening, lytic and sclerotic changes suffice. Increased osteoclastic activity, possibly initiated by viral infection and likely modulated by genetic factors, drives the pathogenesis of Paget’s disease. The disease tends to run in families, with a positive family history in 15–25% of patients. Purple skin striae and hirsutism occur 65% of the time in these pa- tients, and amenorrhea about 60% of the time. Patients with Cushing’s syndrome may also develop hyperglycemia, os- teoporosis, proximal muscle weakness, acne, hirsutism, leukocytosis, lymphopenia, and eosinopenia.