By I. Benito. Portland State University.

Opioids and Opiates 133 Situations involving poly substance usage maybe less straightforward buy cheap motrin 600 mg online, but clini- cal judgment and supportive measures are usually employed before receiving results of a toxic screen motrin 600 mg with visa. Screening techniques must be able to detect parent compounds and their active metabolites in serum or urine cheap motrin 400 mg with visa. Urine drug screens can provide a qualitative method to detect many opioids, including propoxyphene, codeine, methadone, meperidine, and morphine. Quantitative results on opiates from serum are not helpful in the routine management of overdoses. The serum drug screen maybe helpful in detecting the pres- ence of agent other than opiates, such as acetaminophen that may require its specific antidote (N-acetyl cystein) therapy. Management of Opioid Overdose Management of opioid overdoses focuses on stabilization. Initial assessment and establishment of effective ventilation and oxygenation followed by ensuring adequate homodynamic support are followed. Oral or nasal airway place- ment may be required and in fact is vital in comatose patients. However, caution is advised with their use, to prevent vomiting and or aspiration. Endotracheal intubation is indicated in severely compromised patients in whom there is a real risk in aspiration or in patients who do not respond satisfactory to opioid antagonists. The options for opioid antagonists include nalox- one, naltrexone, and the longer acting antagonist nalmefene (35,36). This pure opiate antagonist with great affinity to µ receptors should be titrated according to the severity of poisoning. Naloxone remains the drug of choice as the initial reversal agent in suspected opioid overdose, given its short half-life and ability to titrate for the effect. The need for immediate results (usually in the form of increased ventilation) is balanced by the potential unpleasant of inducing withdrawal symptoms in the chronic abuser. In the patient who presents with respiratory arrest, precipitation of some acute withdrawal symptoms may be unavoidable. To minimize this risk, naloxone should be given in small increments, titrated to the response. Naloxone can be administered iv, im, sc, endotracheally, or intralingually (37–39). For respiratory depression or arrest, 2 mg iv is sug- gested initially, to be repeated 2–5 min (or sooner if the patient is indeed in respira- tory arrest) up to 10 mg. If no response is observed after 10 mg of naloxone, it is unlikely that opioids by themselves are playing a significant role in the patient’s clinical status. Certain opiate overdoses such as codeine, propoxifen, pentazocine, methadone, and diphenoxylate may require repetitive or continuous administration. In cases of leaked opium body packing, repetitive or continuous naloxone administration is needed. This decrease in gastrointestinal motility suggests that there may be some benefit to gastrointestinal emptying several hours after ingestion. Gastric aspiration and lavage is affected in debulking large amounts of ingestant; it may also be beneficial with smaller amounts of ingestant due to delayed gastric motility in the obtuse patient. Endotracheal intubation should be performed prior to the placement of orogastric or nasogastric tubes, to protect against aspiration in comatose patients. Activated charcoal and cathartics (magnesium citrate or sorbi- tol) should be administered after gastric emptying if bowel sounds are present. Repeti- tive dosing of activated charcoal may be beneficial in cases in which large amounts of ingestant such as body packers are suspected. Muscle rigidity, though possible after all narcotics, appears to be more common after administration of bolus doses of fentanyl or its congeners. Rigidity can be treated with depolarizing or nondepolarizing neuromuscular blocking agents while controlling the patient’s ventilation (3). The pharmacological interactions can be divided into pharmacokinetics and pharmacodynamics. In a randomized crossover study in 22 nor- mal male and female subjects, it was revealed that oxycodone in sustained-release form had no significant interactions with food intake. However, both bioavailability and Cmax were significantly altered by high-fat meal after taking immediate-release form of oxycodone (43). It was shown that food has no effect on the pharmacokinetics of morphine following doses of immediate-release solution and the modified-release prep- arations. Opioids and Opiates 135 gests that care should be taken by physicians in changes of modified-release formulations (44).

In addition observe several medium-sized thin-walled veins buy 600mg motrin free shipping, which are collapsed and hence have an irregular lumen buy generic motrin 600 mg online. This is a cross section of a large vein which has been opened up and laid flat before sectioning buy 400mg motrin. Observe the bundles of smooth muscle cells (red) and collagen (blue), which make up the thick adventitia. Calcium channels support slow propagation and help control action potential duration E. Calcium channels as targets of “calcium blockers” and sympathetic neurotransmitter In the last lecture we saw that the action potentials in different regions of the heart show considerable diversity. Unlike spikes in skeletal muscle, cardiac modifying action potentials not only trigger contractions but also have contraction considerable influence on contractility In this lecture, we will deal with the ionic basis for cardiac action potentials. Not surprisingly in view of these different functions, the underlying ionic mechanisms in various parts of the heart are somewhat different. The upstroke of the cardiac action potential closely resembles the spike in other excitable tissues. In ventricular and atrial muscle and in Purkinje fibers (where rapid conduction is critical) the ionic basis is quite similar to nerve. The rapidly rising phase is generated by an increase in Na conductance (gNa) as in the squid giant axon. If most of the external Na ions are replaced by choline (or NaCl replaced by dextrose) the following changes are observed: 1. The action potential is briefer (the plateau configuration is much less pronounced). This suggests that some Na current may also contribute to maintaining the plateau. Similar changes take place when Purkinje fibers or working heart muscle are treated with tetrodotoxin, a specific sodium channel blocker. Although such changes do not occur within the clinical range of plasma sodium concentrations, changes in other ion concentrations (K+, Ca2+) have indirect effects on the impulse generating mechanism which prove to be very important. We have suggested that the Na channel mechanism in heart is similar to that in nerve or skeletal muscle. But heart differs from other excitable cells in one important sense: it has a much longer refractory period, lasting tenths of a second rather than a few milliseconds. During the refractory period the muscle is completely unresponsive to electrical stimuli. This behavior was noted as long ago as 1876 by the French physiologist Marey, who observed that stimuli falling within the early part of mechanical systole were unsuccessful in eliciting any additional contraction. More recently, electrical recording has shown that the refractoriness is associated with the absence of a propagated action potential. There is an intermediate situation between full refractoriness and no refractoriness. A stronger-than-usual stimulus is needed to produce this response, and once it is generated, it propagates very slowly. Such poorly-propagated responses arise in cases of defects in heart rhythm (arrhythmias). An erratic pacemaker, or the existence of more than one pacemaker can give rise to premature "stimuli". The poorly- propagating response will cause excitation of some regions, but not of others; these regions will therefore show varying excitability for the next pacemaker signal, and eventually, complete asynchrony may result. The above figure shows that the ability to propagate a second action potential is restored rapidly once repolarization has proceeded to a sufficiently negative level (about 10-20 mV positive to the usual resting potential). In fact, agents which shorten or prolong the action potential also produce similar changes in the duration of refractoriness. This point may be puzzling, since the plateau potential exceeds (is positive to) the threshold for eliciting an action potential in the first place. In heart, as in nerve, gNa is switched on by a sudden depolarization from the resting potential. The membrane potential must be returned to a level near the resting potential in order to reverse the inactivation process. As the inactivation is removed, the sodium channels become available once again for rapid opening in response to a depolarization beyond threshold, as shown in the figure on the following page. Weidmann was the first to show how membrane potential influenced the availability of sodium channels in heart. He used the rate-of-rise of action potentials as a means of measuring sodium current, and studied the effect of changes in the steady potential preceding sudden stimuli: H. The availability of sodium channels is strongly dependent on membrane potential over the range between -90 mV and -60 mV. This explains the gradual recovery of excitability during the final repolarization phase of the action potential. One function of the plateau, then, is to postpone the recovery of excitability, thereby preventing premature excitation (why would re- excitation during systole be detrimental?

Tobacco smoke comprises several-hundred different chemicals motrin 400mg sale, including nicotine and carbon monoxide in greatest abundance generic 600mg motrin mastercard. There are several- thousands of publications on the risks of tobacco use during pregnancy buy motrin 600mg on line, including exten- sive reviews (Fredricsson and Gilljam, 1992; Landesman-Dwyer and Emanuel, 1979; McIntosh, 1984a,b; Nash and Persaud, 1988; Rosenberg, 1987; Stillman et al. Approximately 20 percent of pregnant women smoke tobacco in some studies (Rantakallio et al. The ear- liest finding was increased frequencies of prematurity (estimated by lowered birth weight) among smokers (Simpson, 1957), which was later confirmed (Herriot et al. It later became apparent that lowered birth weight was not due to prematurity, but was in fact intrauterine growth retardation (Rubin et al. Low birth weight Several-hundred thousand women who smoked during pregnancy have been studied (Anonymous, 1993; Cnattingius et al. Smoking more heavily during pregnancy results in infants that are more growth retarded. In addition, passive expo- sure to smoke was also related to reduced birth weight (Bardy et al. However, growth is apparently not delayed when there is exposure to tobacco smoke postnatally (Day et al. Importantly, birth weight was unaffected in infants whose mothers ceased smoking early in pregnancy (i. Birth defects The purported teratogenic relationship between smoking or use of tobacco during preg- nancy is unlikely, but, if it does exist, is very small (1 percent or less). The possibility Tobacco use in pregnancy 327 that tobacco is a teratogen has been analyzed in dozens of epidemiological studies, involving over 100 000 children (McIntosh 1984a; Stillman et al. The frequency of major congenital anomalies is generally not increased among mothers who smoke tobacco during pregnancy (Andrews and McGarry, 1972; Christianson, 1980; Erickson, 1991; Evans et al. Some investigators found significant associations between cigarette smoking and birth defects, such as craniosynostosis (Alderman et al. A nonspecific collection of birth defects (gastroschisis, limb reduction defects, strabismus, and congenital heart dis- ease) have been reported to be increased in frequency among infants born to smokers (Aro, 1983; Christianson, 1980; Czeizel et al. Cleft palate and orofacial clefts have been reported to be increased in frequency (Andrews and McGarry, 1972; Ericson et al. The association of tobacco with clefting remains controversial because other large studies found no such association (Frazier et al. For example, in one study no association was found with maternal tobacco smoking among 288 067 infants, of whom 10 223 had congenital anomalies (Malloy et al. In a cohort of 67 609 pregnancies, an increased frequency of anencephalic infants was found among progeny of women who smoked heavily during gestation (greater than 20 cigarettes per day) (Evans et al. Notably, smoking is more prevalent in the lower social classes, as is the incidence of anencephaly. A similar trend was not found among Black women, who have a lower rate of anencephaly than White women, and no trend with smoking was found for smoking and anencephaly for this ethnic group. If the risk of congenital anomalies is increased above the background rate among infants whose mothers smoke tobacco during pregnancy it is very small at 1 percent or less. Childhood cancer Very weak evidence suggests that cancer during childhood is associated with in utero exposure to tobacco smoke (McKinney et al. Pregnancy complications An increased frequency of premature rupture of membranes (Underwood et al. Smoking was reported to be a risk factor for gynecol- ogical diseases, ovarian cycle disturbance, spontaneous abortion, pregnancy toxicosis, premature delivery, and chronic fetal hypoxia (Sheveleva et al. Preterm delivery, placenta previa, perinatal mortality, and other complications of pregnancy have shown 328 Substance abuse during pregnancy an increase among women who smoke (Anonymous, 1993; English and Eskenzai, 1992; Guinn et al. Animal studies Nicotine and cigarette smoking in animals has also been studied and reduced fetal weight was found. Notably, a very early study showed that rabbits exposed to the equiv- alent of 20 cigarettes per day gave birth to fetuses that were 7 percent lighter than con- trols (Schoeneck, 1941). However, catch-up growth in the neonatal period fully compensates for fetal growth retardation for active smokers. Phencyclidine is no longer available as a pharmaceutical prepa- ration, but was formerly used as an anesthetic and analgesic in human but mainly vet- erinary medicine. Pentazocine is a synthetic narcotic analgesic given medically by par- enteral, oral, or rectal routes to relieve moderate to severe pain. In the early 1970s it was in wide use in Chicago, and popular among inner-city drug users as a ‘high’ less expen- sive than, but similar to, heroin (Senay, 1985). Data are available for 86 infants born to women who used Ts and blues during pregnancy (n = 13, 50, and 23, respectively) (Chasnoff et al. Infants born to Ts and blues abusers have fetal growth retardation and suffer from peri- natal complications more frequently than controls (Chasnoff et al. The frequency of congenital anomalies was not increased among these 86 infants (Chasnoff et al.