Cardizem

By I. Jerek. Lake Forest Graduate School of Management.

The figures below show how the blood vessels and vascular beds are organized both in series and in parallel order cardizem 180mg without prescription. Resistance is dependent on discount cardizem 120mg visa, and can be calculated from the physical properties of the fluid (i. In reality, fluid near the vessel wall is slowed dramatically as it has to move along a stationary surface (in the limit, the fluid at the wall has zero velocity). This slow moving outer layer of fluid then slows down the next layer closer to the center, setting up a "laminar" (i. The resulting velocity profile is parabolic or quadratic, as shown above,which means that velocity increases as a function of x2, where x is the distance from the vessel wall. Integrating the velocity profile allows us to derive the average velocity of the fluid. For this laminar flow, the average velocity (vave) is equal to half the velocity at the center (vmax), where x=r, the vessel radius. The overall result is that the average velocity (vave) is proportional to the vessel radius (r) squared. The other factors that affect velocity are the pressure (P) and viscosity g of the fluid, and the length (L) of the vessel. Pressure, as we have shown, is directly related to flow, which is directly related to velocity. The more viscous the fluid, the slower the velocity, so they are inversely related: v α 1/ 4. Finally, for a given pressure, the longer the vessel length (L) the less the velocity generated (think of how fast you can blow water out of a straw compared to a garden hose). For a cylindrical tube is, the exact relationship needs a factor of 1/8: vave = Pr2/8L 7. Note the fourth order dependence of flow (Q) on radius (r) - halving the radius reduces flow by a factor of 16! See if you can follow the calculation below, using the table below, to derive the relative resistance of the arterioles vs. Total Length Total (Mm) Cross- (Cm) Volume section (Cm²) al Area (Cm²) Aorta 10 1 0. To compare the resistance of the arteriolar bed to that of the capillary bed, we must start with the resistances of a single arteriole and capillary: Rart = (8/)Lart/rart4 Rcap = (8/)Lcap/rcap4 Taking the ratio between the two allows several factors to cancel out (we will assume that viscosity remains constant - a topic to be discussed later. However, the total resistance of a vascular bed is the combination of the resistances of all the individual vessels, which are organized in parallel. Thus, the total resistance is equal to the resistance of a single vessel divided by the number of vessels. Rart(total) = Rart/#arts Rcap(total) = Rcap/#caps Rart(total)/Rcap(total) = (Rart/Rcap)(#caps/#arts) Rart(total)/Rcap(total) = ( / )( / ) ~ 1. Given the larger cross-sectional area of the capillary bed and thus the much greater number of capillary vessels, the total resistance works out to be greater in the arteriolar bed by approximately 50%. Table 9 - Relative Resistance to Flow in the Vascular Bed: Calculated from Table 6 Poiseuille’s Law Aorta 4% Venules 4% Large arteries 5% Terminal veins 0. In the previous section we presented the conservation of mass and the resulting tradeoff between cross-sectional area and fluid velocity. In this section we will discuss the conservation of energy, where there is a balance between the potential energy and the kinetic energy of a fluid. This balance produces a tradeoff between pressure, a measure of potential energy, and velocity, a measure of kinetic energy. This will add to our understanding of the relationships among pressure, flow, velocity, and vessel geometry. Going back to our hot tub example, it takes "pressure work" to squeeze in under that pile in the tub. From the conservation of energy, the total energy (E) must remain constant as blood flows through the vascular tree. This, however, ignores any loss of energy due to frictional forces, which only applies over short distances where resistance is negligible. Just as we approximate the potential energy of a ball when we drop it from a height as equal to its kinetic energy when it hits the ground, we are applying conservation of energy to blood flow in order to gain a qualitative understanding of the relationship between pressure and velocity. This can be simplified by dividing by V: E/V = P + 1/2 v2 = constant Physics of Circulation - Michael McConnell, M. Equating the energies at two different points in the circulation yields: P1 + 1/2 v12 = P2 + 1/2 v22 G. First of all, gravity affects the hydrostatic pressure of any fluid, as we discussed at the very beginning: Pgrav = gd This causes the pressure to increase with depth, i. Note that the right atrium is used as the reference or zero point for the circulation, which is roughly the level where a blood pressure cuff is placed. While gravity does affect the hydrostatic blood pressure, that is not what determines blood flow. It is often assumed that pressure drives blood flow, such as from the high pressure arteries to the low pressure veins. If it were that simple then why, looking at the figure above, does blood flow from the aorta to the arteries in the feet, where the pressure is greater?

Stratfed sampling is only possible when it is known what proporton of the study populaton belongs to each stratum cardizem 180 mg lowest price. The investgator interviews as many people in each category as he can fnd untl he has flled his “quota” buy 60 mg cardizem with amex. This method is only useful when it is felt that a convenience sample would not provide the desired balance of elements in the populaton. However, in quanttatve research it is very important to do sample size calculatons before embarking on a study, because it may not be worthwhile to do a study at all if the feasible sample size is much less than the desirable sample size. Thus, the maximum sample size is determined by the availability of resources: tme, manpower, transport, and equipment. Sample size calculatons take into account the power of the study to “prove” fndings (ofen set at least 80-90%) and the signifcance level (ofen set at least 0. Sofware is available for sample size calculaton, provided certain simple parameters about the populaton to be studies are known. In selectng the sample it is important to determine the inclusion and exclusion criteria of subjects. Subjects may be excluded because they are biased, have pre- determined conditons that afect the current study, etc. The inclusion and exclusion criteria help the researcher determine the scope of the sample. So that we can collect informaton about our subject of study (people, objects,So that we can collect informaton about our subject of study (people, objects, phenomena) in a systematc way. If you follow the steps above, you should be able to identfy the appropriate technique. Learning points:Learning points: In any study, a variety of data collecton techniques can be used for one study. If possible, use or modify a pre-existng questonnaire (ask for permission to use and remember to acknowledge the source in your write-up). The researcher may decide to use a database code number to keep track of how many questonnaires are distributed and returned. When an interview technique is used, have a secton to identfy who did the interview and the date of interview. If it is self-administered, you may want a queston on whether the person had help in answering the questonnaire. Check each queston with the objectves of the study and use your list of variables as a guide for deciding how to phrase the queston in relaton to the data to be collected. Draw dummy tables of desired data based on the questonnaire to ensure that all informaton required can be captured. Where possible, every queston should be designed to be answered, even if this is in a negatve way, e. Check content validity with experts in the area – verify that important areas are addressed appropriately. Pre-test the questonnaire on individuals who are similar to (but not part of) your study populaton to ensure that: a. Internal consistency: This is checking to see if questons asking the same thing get similar answers from the same person. Test-retest reliability: This is checking if the same person will answer the same way on repeated testng on diferent days. If possible, use or modify a pre-existng checklist (ask for permission to use and remember to acknowledge the source in your write-up). Check each item with the objectves of the study and use your list of variables as a guide for deciding on the areas of data to be collected. In a waitng tme study, the tme measured could be defned, from patent registraton to patent entering the doctor’s ofce or exitng the consultaton room, or leaving the pharmacy. Draw dummy tables of desired data based on the checklist to ensure that all informaton required can be captured. Where possible, every item should be designed to be answered, even if this is in a negatve way, e. Check content validity with experts in the area – verify that important areas are addressed appropriately 16. Pre-test the checklist on recorded sources which are similar to (but not part of) the study populaton to ensure: a. Test-retest reliability: This is checking if the same person will answer the same way on repeated testng on diferent days. Inter-rater reliablity: This is checking to see if items checked by diferent data collectors yield the same answers. Usually you use one checklist per recorded source, though you may use a tabulated checklist for multple sources.

The ventricles are tripartite purchase cardizem 60mg, all containing sections defined most clearly from the ventricular septum discussed below cardizem 60mg. These are the inlet, muscular (or trabecular) and outlet positions of both ventricles. With regard to the left side of the heart, when viewed from the left side, the small finger-like left atrial appendage is seen anteriorly, and the entrance of the left pulmonary veins posteriorly. The lower border of the appendage is crenulated and its attachment to the body of the left atrium is narrow. The pectinate muscles of this atrium are much finer than its fellow on the right side, and do not extend out of the atrial appendage as its fellow on the right side does. The left atrial aspect of the atrial septum can be illuminated to demonstrate the thin septum primum which has a horseshoe curve. The left ventricle has two papillary muscles attached to the inferior and lateral walls and the septum is free of attachment of papillary muscles. The anterior leaflet of the mitral valve is in fibrous attachment with the non-coronary cusp of the aortic valve. The lack of septal attachment of the mitral valve and the fibrous continuity of the anterior mitral valve leaflet to the non-coronary cusp are two distinctive differences between the left and right ventricle. The septal surface of the left ventricle and its right-sided fellow form the smooth upper septal surface and fine apical trabeculations. Because of pressure differences the left ventricle is also thicker walled than the right ventricle. As noted previously, the ventricle can be divided into inlet, trabecular and outlet portions. There is a fourth component - the membranous septum - a little fibrous tissue lying under the aortic valve between the right and non-coronary cusps when seen on the left side, and just under the septal leaflet of the tricuspid valve when viewed from the right side. In slide 12, the conduction system of the heart contains cellular and fibrous elements. The automatic firing comes from the cellular elements within the sinoatrial and atrioventricular nodes, and also within the upper cells lying within the His–Purkinje system. A hierarchical firing is present where the faster rates lie within the highest (sinoatrial) area and the periodicity decreases as the Introduction To Cardiac & Tomographic Anatomy Of The Heart - Norman Silverman, M. The sinoatrial node is a small cigar- shaped structure lying between the atrial appendage and the superior cava almost on the surface of the heart. There are no actual connections between the two nodes, although the fibers tend to run in the areas between the appendages and vascular entry. The atrioventricular node lies within the triangle of Koch and then penetrates above the muscular and below the membranous septum, where it runs on the left ventricular septal surface for a small distance. As the bundle divides the right bundle runs back toward the right ventricle, perforating near the muscle of Lancisi within the right ventricle and then running toward the right ventricular apex under the septomarginal trabeculation. These bundles are also apically directed and enter in the papillary muscles from the apical route to terminate within these muscles. The left main coronary artery has a short course and divides into a left anterior descending coronary artery and a circumflex. Short branches usually arising from the circumflex artery and termed diagonal branches also arise fairly proximally. The proximal left coronary and its branches lie in the left portion of the coronary groove, and the left coronary and circumflex runs posterior to the pulmonary artery. The left anterior descending artery arises laterally to the pulmonary trunk on the surface to the heart. The proximal circumflex lies in the coronary groove under the left atrial appendage. The more distal branches of the circumflex are called the obtuse marginal branches. Posteriorly, in a minority of hearts, the posterior descending coronary artery terminates from the circumflex coronary artery, while in the majority of hearts the posterior descending usually arises from the terminal right coronary artery. The former circumstance is referred to as left-dominant, whereas the latter is referred to as a right dominant system. The left anterior coronary artery gives rise predominantly to several septal perforators and surface branches of the left ventricle, and some smaller branches to the right ventricle. Its first branches are to the sinoatrial node and the right ventricular outflow (conus). It supplies the right ventricle with branches as it circles the grove inferiorly and posteriorly. On the posterior surface of the heart it supplies the area of the atrioventricular node and branches to both ventricles. The posterior descending, arising from either vessel, gives arterial supply to both sinoatrial and atrioventricular nodes. The coronary arteries are terminal vessels, which means they do not have collateral branches under normal circumstances. The first slide shows dynamic real-time ultrasound images recorded in a child at 30 frames per second. The ultrasound now passes from the cardiac apex and permits accurate Introduction To Cardiac & Tomographic Anatomy Of The Heart - Norman Silverman, M.

These drug-based functional groups are then “clicked together” in three-dimensional space by being covalently attached to a rela- tively rigid hydrocarbon frame cardizem 60mg fast delivery. The number of functional groups determines the number of contact points between the drug molecule and the receptor macromolecule purchase 120 mg cardizem amex. A three-point pharmacophore will have three different intermolecular interactions between the drug and the receptor. A large number of points of contact is favorable from a pharmacody- namic perspective since it enables a more specific and unique drug–receptor interaction, concomitantly decreasing the likelihood of toxicity. However, a large number of points of contact is unfavorable from a pharmacokinetic perspective, since the resulting increased polarity of the drug molecule tends to decrease the pharmacological half-life and also to decrease the ability of the drug to diffuse across membranes during its dis- tribution throughout the body. In general, most neuroactive drugs have 2–4 points of contact, while most non-neuroactive drugs have 3–6 points of contact. Once the pharmacophore has been designed, the remainder of the molecular frag- ments (individually composed of metabophores or toxicophores or inert bioinactive spacers, but collectively referred to as molecular baggage) are assembled. One of the primary goals of the molecular baggage component is to hold the pharmacophore in a desired conformation such that it can interact with its receptor. If one is designing an intravenous drug with a short half-life, one may want to include an ester moiety. This would constitute a metabophore since the ester would be hydrolyzed, resulting in rapid inactivation of the whole molecule. Once the prototype drug molecule has been prepared and biologically evaluated, var- ious toxicities may become apparent during preliminary testing in animals. If the toxicophore is separate and distinct from the pharmacophore, a new toxicity-free molecule can be engineered. If there is too much overlap between the tox- icophore and the pharmacophore, it may not be possible to “design out” the toxicity. It is important to emphasize that a drug molecule may have many different toxicophores, reflecting different toxicities. A toxicophore is merely a pharmacophore that permits an undesirable interaction with an “untargeted” receptor. The multiphore method is versatile and is not restricted to de novo drug design, as the above discussion might imply. For example, if the drug molecule is discovered by accident or in a random screening process, the multiphore conceptualization is still applicable. Through structure–activity studies (discussed below) it is still possible to discern fragments that constitute the pharmacophore and potential toxicophores, and thus it is still possible to re-engineer the molecule for improved performance. The strength of the multiphore method is its treatment of drug molecules as collections of bioactive fragments. If one fragment is giving problems, it is possible to simply insert another biologically similar fragment (bioisostere) that will hopefully overcome the identified problem. It takes repeated rounds of re-evaluation and redesign before a final candidate drug molecule is developed. Optimization of the lead compound for the pharmacokinetic and pharmaceutical phases (section 3. Pre-clinical and clinical evaluation of the optimized lead compound analog (section 3. A lead compound (pronounced “led”- and not to be mistaken for a salt of element 82) is invariably an organic molecule that acts as a prototype drug around which future optimization is centered and focused. There are several well-tested methods for uncovering or identifying lead compounds as prototype agents around which to design and optimize a drug molecule: 1. Genomics/Proteomics Elegant though some of these may sound, serendipity has historically been the most successful discoverer of drugs. Can these traditional techniques be fur- ther exploited to help discover new and better drugs? Since the dawn of humankind, efforts have been made to discover remedies for the ailments of life. Although there are numerous examples of the trials and tribulations associated with these efforts, the story of epilepsy affords many instructive anecdotes. The failure of premodern physicians to develop adequate therapies reflected their inability to gain a viable mechanistic understanding of epilepsy. In primitive times, sur- gical “therapies” for epilepsy included trephining holes through the patient’s skull in order to release “evil humours and devil spirits. In early Roman times human blood was widely regarded as curative, and people with epilepsy frequently sucked the blood of fallen gladiators in a desperate attempt to find a cure. By the Middle Ages, alchemy and astronomy formed the scientific foundations of epilepsy therapy. These remedies ranged from grotesque therapies, such as the ingestion of dog bile or human urine, to the use of somewhat more innocuous precious stone amulets. During the Renaissance, these magi- cal treatments were rejected by the medical profession in favor of “rational and scientific” Galenic therapies.