Blood penetration

Antidotes to phenol. Isopropanol (isopropyl alcohol) and polyethylene glycol seem to be the most effective local antidotes, both histologically and because they slow down blood penetration. Immediately rinsing the area of skin that has come into contact with the phenol with plenty of water gets rid of some of the toxin and prevents precipitation of some of the epidermal proteins. 

In mammals, phallotoxins, and certainly also virotoxins, are absorbed from the intestines into the blood only slowly, if at all (in contrast to the amatoxins). After intraperitoneal injection they rapidly reach the liver and exert their similar toxic effect there. They weaken the structure of the hepatocyte membrane, hence blood penetrates the Uver cells and the periphery is depleted of blood to such an extent that anemic shock occurs from internal bleeding. A cause of damage to the membranes is supposedly the very strong binding of phallotoxins and virotoxins to F-actin that under the lipid-bilayer stabilizes the membrane. At this point a brief discussion of actin is necessary. 

AAAs present in three different types or shapes. Fusiform aneurysms, the most typical, are mostly symmetrical bulges that occur around the entire circumference of the aorta. These are sometimes referred to as false aneurysms or pseudoaneurysms, because layers of the wall of the aorta are missing (as opposed to the presence of all three layers in a true aneurysm). An aortic dissection, on the other hand, is when blood penetrates the inner layer of the aortic wall, and flows between the layers, similar to delamination. This typically occurs in the thoracic region of the aorta, but can sometimes occur in the abdominal region. Figure 21.3 shows these various types of aneurysms. 

Specific barriers may serve to limit dmg distribution. The placental barrier is of obvious importance to dmg action in the fetus. Dmg transfers across the placenta primarily by Hpid solubiHty. Hence, this barrier is not particularly restrictive. Similarly, the Hpid solubiHty of a dmg is a primary deterrninant in access to the brain and cerebrospinal fluid. Generally, hydrophilic or charged dmgs can also penetrate to these latter areas, but the result is slow and incomplete. The blood brain barrier is composed of cells having tight junctions which are much less permeable to solutes than are the endotheHal cells of other tissues. 

Florfenicol concentrations in tissues and body fluids of male veal calves were studied after 11 mg/kg intramuscular doses adininistered at 12-h intervals (42). Concentrations of florfenicol in the lungs, heart, skeletal muscle, synovia, spleen, pancreas, large intestine, and small intestine were similar to the corresponding semm concentrations indicating excellent penetration of florfenicol into these tissues. Because the florfenicol concentration in these tissues decreased over time as did the corresponding semm concentrations, it was deemed that florfenicol equiUbrated rapidly between these tissues and the blood. Thus semm concentrations of florfenicol can be used as an indicator of dmg concentrations in these tissues. 

A contusion is an injury to soft tissue in which the skin is not penetrated, but swelling of broken blood vessels causes a bmise. The bmise is caused by a blow of excessive force to muscle, tendon, or ligament tissue. A bmise, also known as a hematoma, is caused when blood coagulates around the injury causing swelling and discoloring skin. Most contusions are mild and respond well to rest, ice, compression, and elevation of the injured area. 

Absorption, Transport, and Excretion. The vitamin is absorbed through the mouth, the stomach, and predominantly through the distal portion of the small intestine, and hence, penetrates into the bloodstream. Ascorbic acid is widely distributed to the cells of the body and is mainly present in the white blood cells (leukocytes). The ascorbic acid concentration in these cells is about 150 times its concentration in the plasma (150,151). Dehydroascorbic acid is the main form in the red blood cells (erythrocytes). White blood cells are involved in the destmction of bacteria. 

The filariform larva found in moist soils may be either ingested or penetrate the skin of its host. It is then carried through the circulatory system to the lungs and migrates up the respiratory tree into the digestive tract. The worms feed on intestinal tissue and blood. Some worms may persist in humans as long as nine years. Infestations cause cutaneous reactions, pulmonary lesions, intestinal ulcerations, and anemia. 

Another dideoxypyrimidine nucleoside active against human immunodeficiency vims is 3 -azido-2/3 -dideoxyuridine [84472-85-5] (AZDU or CS-87, 64) C H N O. Since its synthesis, (167) CS-87 has been identified as a promising antiHIV agent (168) and is currentiy undergoing phase I clinical trials in patients with AIDS and AIDS-related complex. It appears to be less potent than AZT against HIV in a peripheral blood mononuclear (PBM) cell screening system and in MT-4 cell lines. This lower activity in PBM cells appears to be related to a lower affinity of CS-87 for the enzyme responsible for its initial phosphorylation (169). However, CS-87 has significantly lower toxicity on bone marrow cells than AZT (170) and penetration of the CNS as a 5 -dihydropyridine derivative. 

The Cardiac Cycle. The heart (Eig. lb) performs its function as a pump as a result of a rhythmical spread of a wave of excitation (depolarization) that excites the atrial and ventricular muscle masses to contract sequentially. Maximum pump efficiency occurs when the atrial or ventricular muscle masses contract synchronously (see Eig. 1). The wave of excitation begins with the generation of electrical impulses within the SA node and spreads through the atria. The SA node is referred to as the pacemaker of the heart and exhibits automaticity, ie, it depolarizes and repolarizes spontaneously. The wave then excites sequentially the AV node the bundle of His, ie, the penetrating portion of the AV node the bundle branches, ie, the branching portions of the AV node the terminal Purkinje fibers and finally the ventricular myocardium. After the wave of excitation depolarizes these various stmetures of the heart, repolarization occurs so that each of the stmetures is ready for the next wave of excitation. Until repolarization occurs the stmetures are said to be refractory to excitation. During repolarization of the atria and ventricles, the muscles relax, allowing the chambers of the heart to fill with blood that is to be expelled with the next wave of excitation and resultant contraction. This process repeats itself 60—100 times or beats per minute... 

P-Adrenoceptor Blockers. There is no satisfactory mechanism to explain the antihypertensive activity of P-adrenoceptor blockers (see Table 1) in humans particularly after chronic treatment (228,231—233). Reductions in heart rate correlate well with decreases in blood pressure and this may be an important mechanism. Other proposed mechanisms include reduction in PRA, reduction in cardiac output, and a central action. However, pindolol produces an antihypertensive effect without lowering PRA. In long-term treatment, the cardiac output is restored despite the decrease in arterial blood pressure and total peripheral resistance. Atenolol (Table 1), which does not penetrate into the brain is an efficacious antihypertensive agent. In short-term treatment, the blood flow to most organs (except the brain) is reduced and the total peripheral resistance may increase. 

Methyldopa, through its metaboHte, CX-methyInorepinephrine formed in the brain, acts on the postsynaptic tt2-adrenoceptor in the central nervous system. It reduces the adrenergic outflow to the cardiovascular system, thereby decreasing arterial blood pressure. If the conversion of methyldopa to CX-methyl norepinephrine in the brain is prevented by a dopamine -hydroxylase inhibitor capable of penetrating into the brain, it loses its antihypertensive effects. 

Exercise also increases skin circulation and perspiration, which both enhance dermal penetration of compounds into the body. Furthermore, skin lesions, such as wounds and dermatitis, can increase the permeability of the skin to chemicals. Also, exposure of the skin to solvents and removal of skin fat increase dermal penetration of a number of compounds. Compounds penetrate the skin more readily in places where the skin is thin, like the face, hands and scrotum. Increased dermal blood flow due to exercise facilitates the penetration of the skin by chemicals. 

All fluorinating agents should be considered toxic in different amounts and, therefore, handled accordingly Nonvolatile fluorides, however, are not too dangerous in this respect, because it is unlikely that they will be swallowed or that they will penetrate into the blood stream What is extremely dangerous is inhalation of volatile fluorides, that is, gases, liquids, or solids with considerable vapor pressure Such fluorides are indicated in the tables in this chapter... 

Properties.—Yellow-green liquid with a peculiar penetrating and sweet smell, which, on inhaling, causes a rush of blood to the head, b. p. 96° sp. gr. 0 902. See Appc77tUx. p. 240. 

The sedation side effect commonly observed on administration of classical antihistaminic drugs has been attributed in part to the ease with which many of these compounds cross the blood brain barrier. There have been developed recently a series of agoits, for example, terfenadine (198), which cause reduced sedation by virtue of decreased penetration into the CNS. This is achieved by making them more hydrophilic. Synthesis of a related compound, ebastine (197),... 

Cancer chemothCTapeutic agents as a rule poorly penetrate the blood brain barrier. Brain tumors are thus not readily treatable by chemotherapy. Diaziquone (at one time known as AZQ) is an exception to this generalization. Treatment of chloranil (213) with the anion from urethane gives intermediate 214, probably by an addition elimination scheme. Displacement of the remaining halogen with aziridine yields diaziquone (215) [.55J. 

Blood poisoning can occur if an inorganic oxide such as As2 03 is allowed to penetrate an open wound. Of course, oxides such as Na20 and CaO have a markedly corrosive action on all body tissue (Ref 38). The specific toxicities of selected inorganic oxides are presented below... 

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