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Digoxin

By L. Hernando. Palmer College of Chiropractic.

The resting myocardial cell tends to be highly vation and inactivation of multiple ion channels order digoxin 0.25mg on line arteria y vena poplitea, which permeable to K and less so to Na and Ca ; therefore purchase 0.25mg digoxin arrhythmia prevalence, allows the flow of charged ions across the sarcolemmal a net diffusion of K flows out of the cell, leaving behind membrane. As a result, the interior of teins possessing two important features: an ion selective the cell becomes electronegative, and two opposing pore that allows the passage of a specific cation or an- forces are established: a chemical force due to a con- ion and regulatory components that respond to chemi- centration gradient and a counteracting electrostatic cal stimulation or changes in the transmembrane poten- force established by the negatively charged ions within tial by opening or closing. The application of a subthreshold stimulus (#1) produces a depolarizing current that fails to result in excitation of the myocardial cell. The application of a threshold stimulus (#2) reaches the threshold potential (TP) and results in an inward current and an action potential. Major transmembrane currents carried by specific ions entering the cell through selective ion channels are depicted to the right. Antiarrhythmic agents alter the electrophysiologic properties of the cardiac cells by modulating one or more of the transmembrane currents, especially the fast inward sodium current and the transmembrane currents carried by the potassium ion (IK and IK- ATP). INA fast inward sodium current; ICA “L”-type calcium current; Ito transient outward cur- rent; INa-Ca sodium-calcium exchange current; IK-ATP adenosine triphosphate-sensitive potas- sium current; IK inward rectifying potassium current; IK delayed rectifying potassium current. The interval during which the myocyte cannot be which this occurs may be calculated using the Nernst stimulated is the absolute refractory period. After the equation: myocyte returns to a hyperpolarized resting potential, the channels cycle through the inactivated state back to Ex 61 log([x] /[x]i o) the rested or closed conformation and again are avail- able to open in response to a stimulus of sufficient in- In this equation, x is the ion in question, [x] is the tensity. The rate of recovery of the Na channels from i concentration inside the cell, and [x]o is the concentra- voltage-dependent inactivation is one determinant of tion outside the cell. The refractory period defines the maximal rate at which is almost identical to the normal resting mem- which the cardiac cells will respond to applied stimuli brane potential of 90 mV. The den- ionic species to the resting membrane potential is sity of available sodium channels in the cell membrane smaller because of the low transmembrane permeabil- also determines the rate at which an impulse is con- ity at hyperpolarized resting membrane potentials. The maximal upstroke An examination of the relationship of [K ] ] and velocity of phase 0 (V ) is a major determinant of the o max [K ] ] in the Nernst equation shows that an increase in speed of impulse conduction within the myocardium i the [K ] will result in a decrease in the membrane rest- and therefore is important in initiation and mainte- o ing potential (less negative). Genetic mutations in the sodium lar concentration of another ion (Na,Ca,Mg,Cl ) channel resulting in a sustained inward leak current may also modify the resting potential. If the depolariz- Phase 1 ing stimulus raises the membrane potential above a At the peak of the action potential upstroke, a short threshold value, sodium channels within the sarcolem- rapid period of repolarization occurs and the membrane mal membrane change their conformation and open potential returns toward 0 mV. This produces a spike their ion-selective pore, allowing Na to enter the cell and dome configuration of the action potential and is a driven by the electrochemical gradient. The open result of the inactivation of the INa and activation of a sodium channels raise the membrane potential toward short-lived outward current called the transient outward the equilibrium potential of sodium ( 65 mV) and set current (Ito). Ito is composed of two distinct channels car- into motion the intricate and precisely coordinated se- ried by either potassium or chloride. The distribution of ries of ion channel openings and closings leading to the Ito is heterogeneous throughout the myocardium and characteristic action potential. Ito is present in both the The action potential has been divided into five atrium and the ventricular myocardium. Within the ven- phases, rapid depolarization (phase 0), early repolariza- tricle, Ito is present in the epicardium and absent in the tion (phase 1), plateau (phase 2), rapid repolarization endocardium. Consequently, the epicardium repolarizes (phase 3) and finally the resting phase in myocytes or more rapidly than the endocardium; this is the basis for slow diastolic depolarization (phase 4). The last is a the QRS complex and the T-wave on the surface elec- property in cells with the potential for automaticity (de- trocardiogram having an identical axis as opposed to an fined later). Action Potential Phase 0: Rapid Depolarization Phase 2: Action Potential Plateau Phase 0 of the action potential encompasses the rapid Phase 2 is characterized by a net balance between in- depolarization of the myocyte induced principally by ward (depolarizing) and outward (repolarizing) ion cur- the opening of voltage gated sodium channels. Interestingly, nels changes, and they enter an inactivated state in the current flow during the plateau phase is small, and which they cannot be recruited to participate in gener- therefore, perturbations in any of the currents partici- ating a subsequent action potential for a defined inter- pating in this phase (either through genetic mutations 16 Antiarrhythmic Drugs 163 or pharmacologically) may result in profound alter- laying repolarization. Ca enters the cell the various subtypes of I inhibit proper channel function K through voltage-dependent channels highly selective and result in the LQTS. The channel (L-type calcium channel) Phase 4 possesses slow inactivation kinetics resulting in a long- In normal atrial and ventricular myocytes, phase 4 is lasting current. This current is outward potassium leak current and ion exchangers carried predominantly through delayed rectifier potas- previously described.

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The incidence of rethrombosis and rein- Urokinase (Abbokinase) is a two-polypeptide chain farction is greater when thrombolytic drugs with shorter serine protease that does not bind avidly to fibrin and that plasma half-lives are used digoxin 0.25 mg discount arteria supraorbitalis. Concurrent administration directly activates both circulating and fibrin-bound plas- with heparin followed by warfarin digoxin 0.25mg lowest price hypertension icd 9, as well as antiplatelet minogen. Urokinase is derived from hu- ticoagulant and antiplatelet drugs may contribute to man cells and thus is not antigenic. Adverse Effects Second- and Third-generation The principal adverse effect associated with throm - Thrombolytic Drugs bolytic therapy is bleeding due to fibrinogenolysis or fibrinolysis at the site of vascular injury. H ypo- The principal physiological activator of plasm inogen in fibrinogenem ia m ay occur and should be m onitored the blood, tissue-type plasm inogen activator (t-PA, al- with laboratory tests. A t effective throm bolytic doses, teplase) (Activase), has a high binding affinity for fibrin the second- and third-generation agents cause less ex- and produces, after IV adm inistration, a fibrin-selective tensive fibrinogenolysis, but bleeding occurs with a sim - activation of plasm inogen. Life-threatening intracra- solute; circulating plasm inogen also m ay be activated nial bleeding m ay necessitate stoppage of therapy, by large doses or lengthy treatm ent. A fter intravenous adm inistration of whole blood, platelets or fresh frozen adm inistration, alteplase is m ore efficacious than strep- plasm a, protam ine (if heparin is present), and an an- tokinase in establishing coronary reperfusion. The rate of rethrom bosis after t- PA is greater than after streptokinase, possibly because The contraindications to the use of throm bolytic drugs alteplase is rapidly cleared from the blood (half-life is 5 are sim ilar to those for the anticoagulant drugs. Reocclusion m ay be lessened by adm inistration diopulm onary resuscitation (traum a to thorax is possi- of heparin and antiplatelet drugs. Two genetically engineered variants of hum an t-PA First-Generation Thrombolytic Drugs have better pharm acological properties than alteplase. Streptokinase (Streptase, Kabikinase), a nonenzym atic Reteplase (Retavase) contains only the peptide dom ains protein from Lancefield group C -hem olytic strepto- required for fibrin binding and protease activity. These 22 Anticoagulant, Antiplatelet, and Fibrinolytic (Thrombolytic) Drugs 265 changes increase potency and speed the onset of action. They also are useful adjuncts to co- Reteplase m ay penetrate further into the fibrin clot agulation factor replacem ent during dental surgery in than alteplase. A nistreplase (Eminase) consists of streptokinase in a Agents for Controlling Blood Loss noncovalent 1:1 complex with plasminogen. A nistreplase is catalytically inert because of acylation of the catalytic Cardiopulm onary bypass, with extracorporeal circula- site of plasminogen. However, the affinity of plasmino- tion during cardiac artery bypass graft or heart valve re- gen binding to fibrin is maintained. It has a long catalytic placem ent surgery, causes transient hem ostatic defects half-life (90 minutes), and the time required for nonen- in blood cells and perioperative bleeding. The protease zymatic deacylation lengthens its thrombolytic effect af- inhibitor aprotinin (Trasylol) inhibits kallikrein (coagu- ter IV injection. A nistreplase is more effective than lation phase) and plasm in (fibrinolysis) and protects streptokinase in establishing coronary reperfusion, but it platelets from m echanical injury. H yperplasm inem ia resulting from throm bolytic therapy M anufacture of these substances involves extraction exposes fibrinogen and other coagulation factors, plas- from hum an blood or recom binant technology. They in- m inogen, and 2-antiplasm in to nonspecific proteolysis clude antihem ophilic factor (factor VIII) (Alphanate, by plasm in, a process norm ally regulated by 2-antiplas- Bioclate, others) for hem ophilia A patients, factor IX m in. Consum ption of these factors and extensive fibrin concentrate (Bebulin, AlphaNine, M ononine, others) dissolution leads to hem orrhage. The binding of plas- for hem ophilia B patients, and factor VIIa (NovoSeven) m inogen to fibrin involves interactions with lysine- for hem ophilia and Von W illebrand patients. W hich of the following statem ents describe why ANSW ERS warfarin is not used to prevent blood coagulation in 1. W arfarin does not produce an anticoagulant blood collection devices used at blood donating effect in vitro. W arfarin does not require conversion into an (B) The anticoagulant effect of warfarin occurs active drug. W arfarin is m etabolized in the liver by P450 (E) W arfarin is chem ically unstable and is de- enzym e system and is appreciably m etabolized be- graded unless m ade fresh and used im m ediately. A ll of the following statem ents about warfarin are seen in patients taking warfarin if a second drug dis- true EXCEPT which one? Throm bocytopenia is a frequent side effect as- (D ) W arfarin is elim inated from the body un- sociation with heparin.

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Many of these patients presenting with these conditions have additional diagnoses and a wide variety of general symptoms discount 0.25 mg digoxin amex prehypertension jnc 8. Improvement in these additional symptoms during the course of chiropractic treatment has provided much of the impetus for anecdotal claims of benefit in the treatment of other conditions order 0.25 mg digoxin visa blood pressure chart uk, including internal disorders. The three most frequently diagnosed non-musculoskeletal complaints treated by chiropractors are asthma, otitis media and migraine headaches. Only a very small percentage (1–10%) of patients seeking chiropractic care do so for non-musculoskeletal symptoms. Given these statistics, it is somewhat ironic that overzealous claims made by some chiropractors concerning the treatment of a tiny fraction of chiropractic patients produce the greatest amount of friction between chiropractors and the medical community. The strongly musculoskeletal bias of the conditions presenting to chiropractic offices probably results from the fact that patients are most likely to view chiropractors as being particularly effective in the treatment of these conditions. This distribution of patients may also result from the fact that conditions such as back and neck pain are often refractory to conventional medical care. It is not surprising, then, that the greatest amount Chiropractic 37 of evidence for a beneficial effect of chiropractic and spinal manipulation is in the treatment of back pain, neck pain and headache (see below and Chapter 15. Historically, most chiropractic patients saw medical physicians first, and only sought chiropractic care when all else failed. Therefore, the quality of chiropractic education in the primary analysis and diagnosis of patients has become of greater importance. REIMBURSEMENT The nature of reimbursement for chiropractic services has changed, along with the maturation of the chiropractic profession and the fact that the general population has increasingly viewed chiropractic as a viable alternative or adjunctive method of treatment. To some extent, changes in reimbursement patterns have also been driven by trends in medicine as well as social and reimbursement policy in general. Up to the 1960s, the vast majority of chiropractic treatments were provided on a fee- for-service basis. One milestone in the movement away from this was the inclusion of chiropractic in the original Medicare law. This inclusion was legislated in a rather narrow fashion and with tight restrictions on issues ranging from the types of conditions to be treated and the reimbursements provided. Nonetheless, it provided some impetus towards incorporation of chiropractic services in other third-party payer systems. Since chiropractors were often involved in treating patients with neck and back injuries, there was also involvement in the personal injury arena. With the more recent growth of health maintenance organizations (HMOs), there has been slowly evolving inclusion of chiropractors in many of these plans. Some have restricted access strictly on the basis of referral from primary care providers, while a growing number of plans permit self-referral, usually under a system of strict guidelines for numbers of treatments. Integration of chiropractic into the US armed services is proceeding after the conclusion of a pilot program exploring the feasibility of such involvement. Additionally, the US Veterans Administration health-care system will be incorporating chiropractors, although the precise nature of this involvement is still being established. In the early 1990s the primary sources of payment for chiropractic services included 6 private insurance and direct payments from the patient. Other forms of payment, including Medicaid and managed care, contributed the remaining 10%. However, with the growing integration of chiropractic services into 10 managed care, the portion related to HMOs is expected to grow significantly. There has been considerable debate, both inside and outside the profession, regarding the role(s) chiropractors should play in the health-care delivery system. The most common way in which chiropractors practice is as limited musculoskeletal specialists, dealing primarily with painful conditions either independently or, increasingly, as part of an interdisciplinary team. There are those within the profession who advocate chiropractors as primary health-care gatekeepers with a particular emphasis on ambulatory musculoskeletal conditions. There are some chiropractors still advocating a broad practice as general primary (alternative/complementary) health-care providers not limited 13,14 to musculoskeletal conditions. Although all three of the sepractice models can be found within the chiropractic profession, all studies have shown that chiropractors treat a limited array of conditions, with up to two-thirds of patients presenting with low back 6,12,15 pain. Chiropractic has become so commonly utilized and tightly woven into the fabric of health care in the USA that some have argued that it has entered the health-care 14,16–18 mainstream. Indeed, there are a growing number of examples of integration of chiropractic services into medical clinics and HMOs. Chiropractors are permitted membership in all major spine societies including the North American Spine Society, the American Back Society and the International Society for the Study of the Lumbar Spine, and there is a recently formed society specifically to encourage co-operation between chiropractors and neurosurgeons.

Clinical features Infection may track from bladder and urethra along the vas to the epi- didymis (acute epididymitis) buy digoxin 0.25mg with amex heart attack zip. The operation of bilateral vasectomy is a common procedure for male sterilization purchase digoxin 0.25mg visa pulse pressure cardiac output. The vas is identified by its very firm consistency which, in coaching days, was likened to whipcord but which today might, more aptly, be compared with fine plastic tubing. The seminal vesicles These are coiled sacculated tubes 2in (5cm) long which can be unravelled to three times that length. They lie, one on each side, extraperitoneally at the bladder base, lateral to the termination of the vasa. In spite of their name, they do not act as receptacles for semen, although their secretion does contribute considerably to the seminal fluid. Clinical features The vesicles can be felt on rectal examination if enlarged; this occurs typi- cally in tuberculous infection. The bony and ligamentous pelvis The pelvis is made up of the innominate bones, the sacrum and the coccyx, bound to each other by dense ligaments. The ilium with its iliac crest running between the anterior and posterior superior iliac spines; below each of these are the corresponding inferior spines. Well-defined ridges on its lateral surface are the strong muscle markings of the glutei. Its inner aspect bears the large auricular surface which articulates with the sacrum. The iliopectineal line runs forward from the apex of the auricular surface and demarcates the true from the false pelvis. The bony and ligamentous pelvis 125 Iliac crest Anterior gluteal line Anterior superior spine Posterior gluteal line Posterior superior spine Inferior gluteal line Posterior inferior spine Anterior inferior spine Greater sciatic notch Acetabulum Iliopectineal eminence Ischial spine Superior ramus Lesser sciatic notch Pubic tubercle Obturator foramen Body of pubis Fig. The ischium has a vertically disposed body, bearing the ischial spine on its posterior border which demarcates an upper (greater) and lower (lesser), sciatic notch. The inferior pole of the body bears the ischial tuberosity then projects forwards almost at right angles into the ischial ramus to meet the inferior pubic ramus. The obturator foramen lies bounded by the body and rami of the pubis and the body and ramus of the ischium. All three bones fuse at the acetabulum which forms the socket for the femoral head, for which it bears a wide crescentic articular surface. The pelvis is tilted in the erect position so that the plane of its inlet is at an angle 60° to the horizontal. The anterior border of its upper part is termed the sacral promontory and is readily felt at laparotomy. Its anterior aspect presents a central mass, a row of four anterior sacral foramina on each side (transmitting the upper four sacral anterior primary rami), and, lateral to these, the lateral masses of the sacrum. The superior aspect of the lateral mass on each side forms a fan-shaped surface termed the ala. Note that the central mass is roughly rectangular—the triangular shape of the sacrum is due to the rapid shrinkage in size of the lateral masses of the sacrum from above down. Posteriorly lies the sacral canal, continuing the vertebral canal, bounded by short pedicles, strong laminae and diminutive spinous processes. Perfo- rating through from the sacral canal is a row of four posterior sacral foramina on each side. Inferiorly, the canal terminates in the sacral hiatus, which trans- mits the 5th sacral nerve. On its lateral aspect, the sacrum presents an auricular facet for articula- tion with the corresponding surface of the ilium. The 5th lumbar vertebra may occasionally fuse with the sacrum in whole or in part; alternatively, the 1st sacral segment may be partially or completely separated from the rest of the sacrum. Beyond this the sacral canal is filled with the fatty tissue of the extradural space, the cauda equina and the filum terminale. Even if the hip joints are fixed, this swing of the pelvis enables the patient to walk reasonably well. Joints and ligamentous connections of the pelvis The symphysis pubis is the name given to the cartilaginous joint between the pubic bones.

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