Blood flows

The rate-determining step in the absorption of dmg esters such as fluphenazine decanoate (which has an aqueous solubility of about 1 part per million) is the hydrolysis of the dmg at the surface of the oil droplet. Hydrolysis of the fluphenazine decanoate to its soluble alcohol therefore depends on the state of dispersion and surface area of the droplets. Dispersing the droplets by mbbing the site of injection or by violent exercise can result in excessive dosage, with toxic effects. Exercise also causes increased blood flow and, as absorption is a dynamic process requiring the sweeping away of the dmg from the localised absorption site, this increased flow increases the rate of dmg dispersal. 

The age of the patient should influence the behaviour of the injection as ageing will affect vascular blood flow and fatty deposits, but age has not been specifically isolated as a factor in studies to date. In some disease states it is possible to predict that the outcome of an i.m. injection might be different from that in normal patients for example, in patients with circulatory shock, hypotension, congestive heart failure and myxoedema, where blood flow to skeletal muscle is decreased. 

The absorption of drugs in solution from intramuscular and subcutaneous sites of injection is limited by the perfusion rate. Failure to recognize this important concept has resulted in patient death. For example, morphine sulfate is often administered subcutaneously in a dose of 10 mg per 70 kg of body weight. This dose is sufficient to produce analgesia in 70% of patients with moderate to severe pain. However, in the setting of circulatory collapse and shock (e.g., septic shock in bacteremia due to release of endotoxin) in which the peripheral circulation may be impaired, morphine is not absorbed. Cases have been reported in which the lack of analgesia prompted the additional injection of morphine, all of which remained at the injection site and in the subcutaneous capillary bed. When the peripheral circulation improved, the massive amount of morphine that had collected became absorbed and death ensued, which was primarily due to respiratory depression. 

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The pumping action of the heart rather than gravity is responsible for blood flow hence the term pgl can be set equal to zero in Eq. (9.29) and the result solved for 77 ... 

Destmction of the aluminum complex with ammonia then permits hydrocarbon extraction of the alkaloid. The alkaloid is subsequently both isolated and used as its tartrate salt. This nonnarcotic dmg, for which tolerance may develop, is frequently used orally with caffeine (16) for treatment of migraine it acts to constrict cerebral blood vessels, thus reducing blood flow to the brain. 

Among the examples of monoindole bases being discussed, vincamine (109) is the principal alkaloid of Vinca minorC. and has received some notoriety because it apparently causes some improvement in the abiUties of sufferers of cerebral arteriosclerosis (78). It is beheved that this is the result of increasing cerebral blood flow with the accompanying increase in oxygenation of tissue as a result of its action as a vasodilator. 

This procedure offers the possibiUty of remote noncontact velocity measurement, where no probes disturb the flow. It is thus compatible for use with hot or corrosive gases. Commercial laser velocimeters have become weU-developed measurement tools. Examples of laser velocimetry include remote measurement of wind velocity, measurement of vortex air flow near the wing tips of large aircraft, and in vivo measurement of the velocity of blood flow. 

Blood flow attributable to capillary force residence time regulated at will... 

Long-lasting vasoconstriction is produced by the ETs in almost all arteries and veins and several studies have shown that ET-1 causes a reduction in renal blood flow and urinary sodium excretion. ET-1 has been reported to be a potent mitogen in fibroblasts and aortic smooth muscle cells and to cause contraction of rat stomach strips, rat colon and guinea pig ileum. In the central nervous system, ETs have been shown to modulate neurotransmitter release. 

Kidney Function. Prostanoids influence a variety of kidney functions including renal blood flow, secretion of renin, glomerular filtration rate, and salt and water excretion. They do not have a critical role in modulating normal kidney function but play an important role when the kidney is under stress. Eor example, PGE2 and -I2 are renal vasodilators (70,71) and both are released as a result of various vasoconstrictor stimuli. They thus counterbalance the vasoconstrictor effects of the stimulus and prevent renal ischemia. The renal side effects of NSAIDS are primarily observed when normal kidney function is compromised. 

One of the remarkable features of the heart, which is about the size of a fist, is that the pumping action or contractions (- 70 times/min) of atria and ventricles are simultaneous. Deoxygenated blood is pumped out to the lungs from one side of the heart at the same time oxygenated blood is pumped out from the other side to the aorta and onward through the body. The entire process of blood flow between the atria, ventricles, and the principal vessels is in unison, controlled in part by four one-way valves. The atrioventricular valves, tricuspid on the right and mitral on the left, prevent blood from flowing... 

In addition to its internal blood flow operation, the heart has its own system of blood vessels to keep the muscle wall of the heart, the myocardium, supphed with oxygenated blood (Fig. 3a). The coronary arteries, which branch from the aorta to the right and left sides of the heart, are vital to maintaining that supply. The heart is an extraordinary electromechanical muscle that can be trained to increase blood flow to the body sixfold. It can range from 5 to 30 L /min during exertion. 

Vascular grafts are tubular devices implanted throughout the body to replace blood vessels which have become obstmcted by plaque, atherosclerosis, or otherwise weakened by an aneurysm. Grafts are used most often in peripheral bypass surgery to restore arterial blood flow in the legs. 

Ca.rdia.c-AssistDevices. The principal cardiac-assist device, the intra-aortic balloon pump (lABP), is used primarily to support patients before or after open-heart surgery, or patients who go into cardiogenic shock. As of the mid-1990s, the lABP was being used more often to stabilize heart attack victims, especially in community hospitals which do not provide open-heart surgery. The procedure consists of a balloon catheter inserted into the aorta which expands and contracts to assist blood flow into the circulatory system and to reduce the heart s workload by about 20%. The disposable balloon is powered by an external pump console. 

In other applications of CT, orally administered barium sulfate or a water-soluble iodinated CM is used to opacify the GI tract. Xenon, atomic number 54, exhibits similar x-ray absorption properties to those of iodine. It rapidly diffuses across the blood brain barrier after inhalation to saturate different tissues of brain as a function of its lipid solubility. In preliminary investigations (99), xenon gas inhalation prior to brain CT has provided useful information for evaluations of local cerebral blood flow and cerebral tissue abnormalities. Xenon exhibits an anesthetic effect at high concentrations but otherwise is free of physiological effects because of its nonreactive nature. 

Some P-adrenoceptor blockers have intrinsic sympathomimetic activity (ISA) or partial agonist activity (PAA). They activate P-adrenoceptors before blocking them. Theoretically, patients taking P-adrenoceptor blockers with ISA should not have cold extremities because the dmg produces minimal decreases in peripheral blood flow (smaller increases in resistance). In addition, these agents should produce minimal depression of heart rate and cardiac output, either at rest or during exercise (36). 

Propranolol. Propranolol (Table 1), a Class II antiarrhythmic agent, is usefiil in the management of hypertrophic subaortic stenosis, especially for the treatment of exertional or other stress-induced angina by improving blood flow. The dmg can increase exercise tolerance in patients suffering from angina. Propranolol has been shown to have cardioprotective action in post-MI patients (37—39,98,99,108). 

Moreover, digitahs has indirect effects on the circulation, which in normal hearts results in a small increase in arterial pressure, peripheral resistance, and cardiac output (114). The effects of digitahs on the circulation of an individual experiencing congestive heart failure are much more dramatic, however. The increased cardiac output, for example, increases renal blood flow which can reheve in part the edema of CHF associated with salt and water retention (114). 

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