Directorate of Technical Education
KERALA (Government of Kerala)



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By: G. Rasarus, M.B. B.CH. B.A.O., M.B.B.Ch., Ph.D.

Vice Chair, Rush Medical College

Digoxin is primarily eliminated unchanged by the kidney (~75%) so its clearance is predominately influenced by renal function menstrual underwear buy evista 60mg fast delivery. Hospitalized patients with severe or acute heart failure may need to have serum creatinine determinations 2–3 times weekly to monitor renal function menopause youngest age trusted evista 60mg, while ambulatory patients with stable heart failure may only need yearly serum creatinine measurements menstrual depression buy cheap evista on line. Digoxin pharmacokinetics are not effected by obesity (>30% over ideal body weight), so volume of distribution and dosage estimates should be based on ideal body weight. Digoxin total ( Wt 70 body stores decrease to where V is digoxin 6–10 μg/kg because of reduced volume of distribution in volume of distribution. L/70 kg, Wt is body weight in kg (use ideal body weight if >30% overweight) and CrCl is creatinine clearance in mL/min. In patients with good renal function (creatinine clearance >80 mL/min), the effect on digoxin total clear- ance is negligable. But in patients with poor renal func- tion, (creatinine clearance <30 mL/min) nonrenal clear- ance is a primary elimination pathway. Hyperthyroidism 24 hours or 1 day 7 L/kg Hyperthyroid patients are with normal renal hypermetabolic and have function higher digoxin renal and nonrenal clearances. Nonrenal clearance (denoted by the y-intercept) is lower for patients with moderate-severe heart failure because reduced cardiac output results in decreased liver blood flow and digoxin hepatic clearance. Unbound digoxin molecules displaced from tissue binding sites move into the blood causing the decreased volume of distribution [↓V = Vb + (fb / ↑f ) V ,t t where V is digoxin volume of distribution, Vb is blood volume, Vt is tissue volume, fb is the unbound fraction of digoxin in the blood, and ft is the unbound fraction of digoxin in the tissues]. The equation that estimates digoxin volume of distribution using creatinine clearance is: ⎛ 298 ⋅ CrCl ⎞ V 226 Wt 70 ⎝ 29. However, due to pharmacokinetic variability, some patients may need a peri- odic booster dose to increase digoxin concentrations (see Special Dosing Consideration section at end of chapter). Liver blood flow is an important factor in the determination of hepatic clearance for drugs because it is the vehicle that delivers drug molecules to the liver for possible elimination. Thyroid homone regulates basal metabolic rate, and thyroid status will influence every major organ system in the body including the heart (heart rate and cardiac output), liver (liver blood flow and microsomal drug-metabolizing enzyme function), and kidney (renal blood flow and glomerular filtration rate). Patients who are hypothyroid will have slower metabolic rates and eliminate digoxin more slowly than euthryoid patients (t1/2 = 48 hours with normal renal function). Generally, these patients require higher digoxin doses to control ventricular rate because of the increase in digoxin clearance. Similar to other drugs, digoxin clearance is lower in neonates and premature infants because renal and hepatic function are not completely developed. In older babies and young children (6 months to 8 years old) renal and hepatic function are fully developed and half-lives can be as short as 18 hours. Older children (≥12 years old) have mean digoxin half-lives (t1/2 = 36 hours) that are similar to those found in adults. Also, volume of distribution is larger in infants and children compared to adults as is found with many other drugs. Malabsorption of oral digoxin has been reported in patients with severe diarrhea, radi- ation treatments to the abdomen and gastrointestinal hypermotility. Inhibition of P-glycoprotein, a drug efflux pump which is found in the kidney, liver, and intestine, appears to be involved in the majority of digoxin interactions. Verapamil, diltiazem, and bepridil inhibit digoxin clearance and increase mean digoxin steady-state concentrations by various degrees. Diltiazem and bepridil therapy each increase aver- age digoxin steady-state serum concentrations by about 30%. In addition to this drug interaction mechanism, aminodarone also simultaneously increases digoxin oral bioavailability, and it is likely that P-glycoprotein inhibition is involved in the drug interaction between these two drugs. Because amiodarone has a very long half-life (~50 hours), the onset of the drug interaction with digoxin can be very long.

In addition to the benzodiazepines pregnancy yoga pants order evista 60 mg, barbiturates womens health alliance cary ob gyn purchase 60mg evista overnight delivery, and the newer hypnotics (eg women's health center port st lucie purchase 60 mg evista fast delivery, zolpidem), many other drugs with central nervous system effects can modify the function of this important ionotropic receptor. These include alcohol and certain intravenous anesthetics (etomidate, propofol) in addition to thiopental. Central nervous system excitatory agents that act on the chloride channel include picrotoxin and bicuculline. Sedation—Benzodiazepines, barbiturates, and most older sedative-hypnotic drugs exert calming effects with concomitant reduction of anxiety at relatively low doses. In most cases, however, the anxiolytic actions of sedative- hypnotics are accompanied by some depressant effects on psychomotor and cognitive functions. In experimental animal models, benzodiazepines and older sedative-hypnotic drugs are able to disinhibit punishment-suppressed behavior. This disinhibition has been equated with antianxiety effects of sedative-hypnotics, and it is not a characteristic of all drugs that have sedative effects, eg, the tricyclic antidepressants and antihistamines. However, the disinhibition of previously suppressed behavior may be more related to behavioral disinhibitory effects of sedative-hypnotics, including euphoria, impaired judgment, and loss of self-control, which can occur at dosages in the range of those used for management of anxiety. The benzodiazepines also exert dose-dependent anterograde amnesic effects (inability to remember events occurring during the drug’s duration of action). The effects of sedative-hypnotics on the stages of sleep depend on several factors, including the specific drug, the dose, and the frequency of its administration. Despite possible reductions in slow-wave sleep, there are no reports of disturbances in the secretion of pituitary or adrenal hormones when either barbiturates or benzodiazepines are used as hypnotics. The use of sedative-hypnotics for more than 1–2 weeks leads to some tolerance to their effects on sleep patterns. However, the suitability of a particular agent as an adjunct in anesthesia depends mainly on the physicochemical properties that determine its rapidity of onset and duration of effect. Among the barbiturates, thiopental and methohexital are very lipid-soluble, penetrating brain tissue rapidly following intravenous administration, a characteristic favoring their use for the induction of anesthesia. Rapid tissue redistribution (not rapid elimination) accounts for the short duration of action of these drugs, a feature useful in recovery from anesthesia. Benzodiazepines—including diazepam, lorazepam, and midazolam—are used intravenously in anesthesia (see Chapter 25), often in combination with other agents. Not surprisingly, benzodiazepines given in large doses as adjuncts to general anesthetics may contribute to a persistent postanesthetic respiratory depression. Several benzodiazepines—including clonazepam, nitrazepam, lorazepam, and diazepam—are sufficiently selective to be clinically useful in the management of seizures (see Chapter 24). Of the barbiturates, phenobarbital and metharbital (converted to phenobarbital in the body) are effective in the treatment of generalized tonic-clonic seizures, though not the drugs of first choice. Muscle relaxation—Certain drugs in the sedative-hypnotic class, particularly members of the carbamate (eg, meprobamate) and benzodiazepine groups, exert inhibitory effects on polysynaptic reflexes and internuncial transmission and at high doses may also depress transmission at the skeletal neuromuscular junction. Somewhat selective actions of this type that lead to muscle relaxation can be readily demonstrated in animals and have led to claims of usefulness for relaxing contracted voluntary muscle in muscle spasm (see Clinical Pharmacology). Effects on respiration and cardiovascular function—At hypnotic doses in healthy patients, the effects of sedative- hypnotics on respiration are comparable to changes during natural sleep. However, even at therapeutic doses, sedative- hypnotics can produce significant respiratory depression in patients with pulmonary disease. Effects on respiration are dose-related, and depression of the medullary respiratory center is the usual cause of death due to overdose of sedative- hypnotics. At doses up to those causing hypnosis, no significant effects on the cardiovascular system are observed in healthy patients. However, in hypovolemic states, heart failure, and other diseases that impair cardiovascular function, normal doses of sedative-hypnotics may cause cardiovascular depression, probably as a result of actions on the medullary vasomotor centers. At toxic doses, myocardial contractility and vascular tone may both be depressed by central and peripheral effects, possibly via facilitation of the actions of adenosine, leading to circulatory collapse.

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It arises from the anterior inferior iliac spine and notch from which the ligamentum teres passes to the fovea on the inserts at either end of the trochanteric line menstruation 2 weeks apart 60mg evista amex. The capsule (c) Ischiofemoral ligamentafibres arise from the ischium and some attaches to the femur anteriorly at the trochanteric line and to the bases encircle laterally to attach to the base of the greater trochanter menopause 55 years old generic evista 60 mg without a prescription. Posteriorly the capsule attaches to the femur at a The majority of the fibres pregnancy emotions discount evista 60mg on-line, however, spiral and blend with the higher levelaapproximately 1 cm above the trochanteric crest. This is an outpouching of synovial 2 Vessels in the ligamentum teres which enter the head through membrane through a defect in the anterior capsular wall under the small foramina in the fovea. The hip joint and gluteal region 103 Gluteus medius Gluteus medius Gluteus minimus Gluteus maximus Superior gluteal artery and nerve Inferior gluteal nerve Piriformis Obturator internus and gemelli Femoral insertion Inferior gluteal artery of gluteus maximus Quadratus femoris Posterior cutaneous nerve of thigh Internal pudendal nerve and artery Sciatic nerve Vastus lateralis Biceps femoris Adductor magnus Semimembranosus Opening in adductor magnus Semitendinosus Biceps (short head) Biceps (long head) Sciatic nerve Semimembranosus tendon Gastrocnemius Fig. Lateral rotation (0–45°): piriformis, obturators, the gemelli, Flexion (0–120°): iliacus and psoas predominantly. Medial rotation (0–45°): tensor fasciae latae, gluteus medius and Extension (0–20°): gluteus maximus and the hamstrings. Adduction (0–30°): adductor magnus, longus and brevis predomin- Circumduction: this is a combination of all movements utilizing all antly. Pertrochanteric Extracapsular The smaller diagram shows how the sacrotuberous and sacrospinous ligaments resist rotation of the sacrum Fig. Fractures near the head can cause avascular necrosis because of the disruption of the arterial supply to the head The fractured neck of femur (Fig. This occurs as the adductors, hamstrings and rectus femoris pull Nerves: of the gluteal region include the: sciatic nerve (L4,5,S1–3), upwards on the distal fragment whilst piriformis, the gemelli, obtur- posterior cutaneous nerve of the thigh, superior (L4,5,S1,2) and in- ators, gluteus maximus and gravity produce lateral rotation. The fold occurs as the overly- circumflex arteries, and the first perforating branch of the profunda, to ing skin is bound to the underlying deep fascia and not, as is often form the trochanteric and cruciate anastomoses, respectively. The greater and lesser The hip joint and gluteal region 105 47 The thigh Diaphragm Iliacus Right crus Femoral triangle Quadratus Tensor fasciae Inguinal ligament lumborum latae Psoas tendon Psoas major Pectineus Iliacus Adductor longus Inguinal ligament Rectus femoris Gracilis Pectineus Sartorius Adductor longus Vastus lateralis Vastus medialis Iliotibial tract Adductor magnus Opening in adductor magnus (for passage Patellar of femoral vessels retinacula Ligamentum patellae to popliteal fossa) Fig. Psoas, iliacus and the adductor The femoral triangle is outlined group of muscles The thigh is divided into flexor, extensor and adductor compartments. On the lateral side the fascia lata is condensed to form the iliotibial The membranous superficial fascia of the abdominal wall fuses to the tract (Fig. The tract is attached above to the iliac crest and fascia lata, the deep fascia of the lower limb, at the skin crease of the receives the insertions of tensor fasciae latae and three-quarters of glu- hip joint just below the inguinal ligament. The deep fascia of the thigh (fascia lata) The saphenous opening is a gap in the deep fascia which is filled with This layer of strong fascia covers the thigh. The lateral border of the inguinal ligament and bony margins of the pelvis and below to the tibial opening, the falciform margin, curves in front of the femoral vessels condyles, head of the fibula and patella. Three fascial septa pass from whereas on the medial side it curves behind to attach to the iliopectineal the deep surface of the fascia lata to insert onto the linea aspera of the line (Fig. The great saphenous vein pierces the cribriform fascia femur and consequently divide the thigh into three compartments. Superficial branches of the femoral artery and lymphatics are also transmitted through the saphenous opening. The saphenous opening is in the Contents of the subcutaneous tissue include: upper part of the triangle. The back of the thigh fuse and evaginate to form the femoral sheath below the inguinal liga- receives its sensory supply from the posterior cutaneous nerve of the ment. Superficial arteries: these include the four superficial branches of the femoral artery: the superficial circumflex iliac artery, superficial The contents of the anterior compartment of the thigh epigastric artery, superficial external pudendal artery and the deep (Fig.

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Contrast agents Intra-arterial and intravenous contrast agents not only To demonstrate specifc structures womens health kalispell order evista discount, such as bowel loops or help in visualizing the arteries and veins but because they arteries women's health lichi buy evista with a visa, it may be necessary to fll these structures with a are excreted by the urinary system menstruation odor 60 mg evista sale, can also be used to substance that attenuates X-rays more than bowel loops or visualize the kidneys, ureter, and bladder in a process arteries do normally. Barium sulfate, an Subtraction angiography insoluble salt, is a nontoxic, relatively high-density agent that is extremely useful in the examination of the gastro­ During angiography it is often difcult to appreciate the intestinal tract. When barium sulfate suspension is contrast agent in the vessels through the overlying bony ingested it attenuates X-rays and can therefore be used to structures. Simply, one or add air to the barium sulfate suspension, by either ingest­ two images are obtained before the injection of contrast ing "fzzy" granules or directly instilling air into the body media. In this case, iodine-based through the arteries into the veins and around the circula­ molecules are suitable contrast agents. By adding the "negative precontrast image" to the because it has a relatively high atomic mass and so mark­ positive postcontrast images, the bones and soft tissues edly attenuates X-rays, but also, importantly, it is naturally are subtracted to produce a solitary image of contrast excreted via the urinary system. Before the advent of digital imaging this was a nous contrast agents are extremely safe and are well toler­ challenge, but now the use of computers has made this ated by most patients. Rarely, some patients have an technique relatively straightforward and instantaneous anaphylactic reaction to intra-arterial or intravenous (Fig. Ultrasonography of the body is widely used for all aspects Doppler ultrasound enables determination of flow, its of medicine. Sound waves bounce off moving (not electromagnetic radiation) generated by piezoelectric structures and are returned. Precise measurements of blood flow and blood velocity can The sound waves are then interpreted by a powerful therefore be obtained, which in turn can indicate sites of computer, and a real-time image is produced on the blockage in blood vessels. Ultrasound is also widely used to assess the eyes, neck, soft The patient lies on a bed, an X-ray tube passes tissues, and peripheral musculoskeletal system. A computer carries out a complex mathematical sound of the esophagus, stomach, and duodenum is now routine. Endocavity ultrasound is carried out most com­ monly to assess the genital tract in women using a transvaginal or transrectal route. Magnetic resonance imaging Nuclear magnetic resonance imaging was frst described in 1946 and used to determine the structure of complex mol­ ecules. The complexity of the physics necessary to obtain an image is beyond the scope of this textbook, but the reader should be aware of how the image is produced and the types of images typically seen in routine medical practice. When a pulse of radio waves is passed through the patient the magnets are deflected, and as they return to their aligned position they emit small radio pulses. The strength and frequency of the emitted pulses and the time it takes for the protons to return to their pre-excited state produce a signal. Byaltering the sequence ofpulses towhich the protons are subjected, different properties of the protons can be assessed. These two types of imaging sequences provide differences in image contrast, which accentuate and optimize different tissue characteristics. For an area to be visualized, the patient must receive a gamma ray emitter, which must have a number of proper­ ties to be useful, including: Nuclear medicine imaging Nuclear medicine involves imaging using gamma rays, • a reasonable half-life (e. When injected intothe body thisradiopharmaceutical spe­ cifcallybinds to bone, allowing assessment of the skeleton. Similarly, combining technetium-99m with other com­ pounds permits assessment of other parts of the body, for example the urinary tract and cerebral blood flow. Depending on how the radiopharmaceutical is absorbed, distributed, metabolized, and excreted by the body afer injection, images are obtained using a gamma camera (Fig. Imaging is necessary in most clinical specialties to diag­ Gastrointestinal contrast examinations nose pathological changes to tissues. It is paramount to High-density contrast medium is ingested to opacify the appreciate what is normal and what is abnormal.


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