By H. Baldar. Cornell College, Iowa.
Ketoprofen inhibits lipoxygenase and COX celexa 20 mg with amex medications list template, Clinical Uses order celexa 10mg otc medications causing gout, Adverse Effects, thus decreasing the production of both leukotrienes and and Contraindications prostaglandins. The principal differ- All of these drugs produce analgesic effects, antipyresis, ences among these drugs lie in the time to onset and du- and antiinﬂammatory effects. Naproxen has a long half-life, whereas of gastric irritation, headache, nausea, and other side ef- fenoprofen and ketoprofen have short half-lives. All of fects, including hematological effects and coronary the drugs are extensively metabolized in the liver and re- vasoconstriction, they are not useful as an initial treat- quire adequate kidney function for clearance of the ment for pain. Indomethacin is useful in but clearly all are bound to a relatively high degree and the treatment of acute gout, osteoarthritis, ankylosing can interfere with the binding of other drugs that com- spondylitis, and acceleration of the closure of the ductus pete for plasma protein binding (as described for as- arteriosus in premature infants. The one exception is ketoprofen, which although indomethacin to prevent preterm labor are the result of highly bound to plasma proteins, does not appear to al- its effects on prostaglandin synthesis. Indomethacin is contraindicated in pregnancy, in asthmatics, and in those with gastric ul- Clinical Uses, Adverse Effects, cers or other ulceration of the GI tract. The drug should duction of mild to moderate pain and fever, and for pain be used with caution in such patients. Side effects of the drugs are similar to but less severe than those described for Fenamates the salicylates. Those who are sensitive to salicylates also may be sensitive to and have adverse reactions Meclofenamate (Meclomen) and mefenamic acid when taking ibuprofen and related drugs. Acute hyper- (Ponstel) exhibit potency and side effects similar to sensitivity to ibuprofen has been reported in patients those of other nonsalicylate NSAIDs. The hypersensitivity reaction to sulindac can drugs produce serious side effects, have a short duration be fatal. The con- agents indicated for mild to moderate pain, treatment current use of ibuprofen with aspirin reduces the anti- of dysmenorrhea, rheumatoid arthritis, and osteoarthri- inﬂammatory effects of both drugs. These drugs are metabolized via glucuronidation in traindicated in patients with aspirin sensitivity leading the liver and excreted via the kidney. Thus, fenamates to bronchiolar constriction and in patients with an- require normal liver and kidney function for excretion gioedema. As with all NSAIDs, renal and liver function and are contraindicated in patients with either liver or should be normal for adequate clearance of the drugs. Overdose with fenamates leads to seizures that are sometimes insensitive to traditional treatment with benzodiazepines. In cases of overdose with Pyrazolone Derivatives meclofenamate dialysis may be required to restore ﬂuid and electrolyte balance. Phenylbutazone (Butazolidin) is metabolized to oxy- phenbutazone (Phlogistol), and both compounds have all of the activities associated with the NSAIDs. Their Arylpropionic Acid Derivatives use is accompanied by serious adverse reactions, such as Chemistry and Mechanism of Action anemia, nephritis, renal failure or necrosis, and liver Ibuprofen (Advil), ﬂurbiprofen (Ansaid), fenoprofen damage. Because of their toxicity, they are prescribed (Nalfon), ketoprofen (Orudis), and naproxen (Naprosyn) only for the treatment of pain associated with gout or are all 2-substituted propionic acid derivatives. They phlebitis or as a last resort for other painful inﬂamma- block the production of prostaglandins via inhibition of tory diseases resistant to newer and less toxic treat- COX and therefore are similar to the salicylates in that ments. Interactions with a large number of other drugs 316 IV DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM (similar to those described for aspirin) occur, since Nabumetone (Relafen) has antiinﬂammatory, an- phenylbutazone displaces several drugs from plasma tipyretic, and analgesic properties. The drug is contraindicated in chil- liver enzymes to an active metabolite that is a potent dren and in the elderly with diminished renal function. Although nabumetone shares many of The consequences of overdose occur slowly and can in- the adverse effects of other NSAIDs, it appears to pro- clude liver damage, renal failure, and shock. Supportive measures include ventilation, dialysis, and gastric lavage with activated COX-2 Inhibitors charcoal, as well as the use of benzodiazepines to con- Chemistry trol convulsions. Both lack a carboxylic group present in most NSAIDs and therefore are able to Piroxicam (Feldene) is the prototypical oxicam deriva- orient into the COX-2 enzyme in a selective manner that tive, with analgesic, antipyretic, and antiinﬂammatory differs from that of other NSAIDs. Side effects are similar to those encountered with other NSAIDs: Mechanism of Action gastric disturbances, tinnitus, and headache.
The duration of an oscillatory potential would correspond to an episode of relatively stable activity in the neuronal territory exhibiting it purchase 10 mg celexa otc medicine research. Shifts in power among frequency bands discount celexa 20 mg visa treatment impetigo, or in correlation strength among oscillatory potentials in different regions, indicate functional transitions within the motor system from one state to another. During stationary (postural) states, cortical oscillations provide an economic way of driving motor units. Partial synchronization of the discharge of corticomotoneuronal cells would allow them to recruit motor units while maintaining as low a ﬁring rate as possible. It is possible that motor cortical oscillations may provide an economical means of driving motor units or spinal interneurons during dynamic as well as stationary phases of motor control. The circuitry for generating theta oscillations was localized to superﬁcial cortical layers. Rhythmic activity required intact glutamatergic transmission as well as inhibition. By analogy with the hippocampus, the inhibitory interneurons in the network probably have a slow spiking frequency, and terminate on distal dendrites of pyramidal neurons. Although the circuit to generate it may be present, theta rhythm is not conspic- uous in motor cortical recordings. Relationships of theta oscillations to movement typically involve neighboring regions. For example, in cats, a widespread 5-Hz LFP oscillation with foci in somatosensory (S1) and in the visual cortex correlates to general disinterest in the environment and drowsiness. The authors developed an autoregressive model of the linear dynamics of EEG, and found that abrupt short transients of model coefﬁcients occured during the movement preparatory period, related to dynamic changes. These transients marked temporal nonstationarities in the alpha, beta, and gamma bands that seemed to reﬂect boundaries separating successive phases of motor preparation. When the EEG was averaged with respect to the ﬁrst Copyright © 2005 CRC Press LLC ECoG (mean) : µV A 75 0 3 single trials B 300 0 300 EMG (f. These theta plus gamma oscillations were observed mainly over the supplementary motor area (SMA), premotor and parietal cortex. The authors interpreted the oscillatory bursts as markers of the succession of dynamic stages in the production of movement. Some leads showing this activity were in the rolandic area, or over the cingulate motor area. The theta rhythm was obviously not driving movement, but it could have been inﬂuencing a premotor network involved in setting up the motor performance. Because the theta rhythm was phase-locked to EMG onset, there is a possibility that it was used as a temporal reference for preparatory activity, analogous to the use of theta rhythm in hippocampus for coding spatial position. The theta activity was much more prominent during virtual movement on the videoscreen than while “standing still. Andersen and Eccles postulated that groups of thalamocortical neurons were synchronized into a common rhythm by mutual axon collateral inhibition (via the reticular nucleus) and postinhibitory rebound. Today more emphasis is placed on the complementary oscil- latory mechanisms within the cortex itself, but both thalamus and cortex are important. Jasper and Stefanis25 showed that one to two shocks of intralaminar thalamus were sufﬁcient to elicit a spindle of “recruit- ing responses,” at about 10 Hz, in cat motor cortex (Figure 7. The surface negative peak of the spindle oscillation corresponded with a wave of depolarization and spiking in pyramidal tract neurons. They suggested that the rhythm of oscillatory waves was determined by inhibitory phasing of alternating excitatory and inhibitory postsynaptic potentials (PSPs), facilitated by postinhibitory rebound hyperexcitabil- ity. Since antidromic activation of PT cells also could elicit the oscillation (although not quite as well as thalamic stimulation), recurrent collaterals of pyramidal cells probably contributed to the rhythmogenic feedback loop. Above all, synchronization of a population of neurons into a common oscillatory cycle is accomplished by intracellular PT cell + 30 mV − 1 mV layer 1 LFP stim 1 sec FIGURE 7. A double shock stimulus to the intralaminar thalamus, marked by two solid circles, triggers a subsequent spindle oscillation in the cat motor cortex. Simultaneous recordings were made of the mem- brane potential of a PT cell, and of the LFP in overlying cortical layer 1. Note that the PT cell is regularly depolarized in synchrony with the negative peak of each LFP cycle, and occasionally discharges.
Symptoms of toxicity from local anesthetics includes twitching order 40mg celexa otc medications joint pain, restlessness buy generic celexa 20 mg symptoms low blood sugar, drowsiness, light-headedness, and seizures. Use fine-toothed forceps (Adson or Brown-Adson) with gentle pressure to handle skin edges to decrease trauma. The toothed forceps are less traumatic to the skin than other forceps with flat surfaces that may crush the tissue. On the face, simply covering with antibiotic ointment is often used, especially around the eyes or mouth. Finally, keep tetanus and antibacterial prophylaxis in mind, particularly for contami- nated wounds (Table 17–3, page 350). Critical to any suturing technique is making certain that the edges of the wound closely approximate without overlapping or inversion and that there is no tension. Remember “approximation without strangulation” or eversion T A B L E 1 7 – 2 L o c a l A n e s t h e t i c C o m p a r i s o n C h a r t f o r C o m m o n l y U s e d I n j e c t a b l e A g e n t s M a x i m u m D o s e P r o p r i e t a r y V o l u m e i n A g e n t N a m e s O n s e t D u r a t i o n m g / k g 7 0 - k g A d u l t * B u p i v a c a i n e M a r c a i n e, 7 – 3 0 m i n 5 – 7 h 3 7 0 m L o f S e n s o r i c a i n e 0. Source: Based on guidelines from the Centers for Disease Control and reported in MMWR. SURGICAL KNOTS There are two basic knot-tying techniques: the handed tie and the instrument tie. The two- handed tie is easier to learn than the one-handed tie, although one-handed ties may be more useful in certain situations (eg, with deep cavities or where speed is essential). Some pro- 17 grams frown on one-handed tying, especially for physicians early in their careers. Instru- ment ties are more useful for closing skin and for emergency room laceration repair. Figures 17–7, page 355, and 17–8, page 356, show the technique for tying a two-handed square knot. SUTURE REMOVAL The longer that suture material is left in place, the more scarring it will produce. Using a topical antibiotic (Polysporin, others) ointment on the wound is helpful in decreasing suture tract epithelialization. This epithelialization results from crusting around the suture that in- creases suture marks and subsequent scarring. Sutures can be safely removed when a wound has developed sufficient tensile strength. Situations vary greatly, but general guidelines for 17 Suturing Techniques and Wound Care 351 Correct method Unequal distance Skin inversion Skin overlap Excessive tension FIGURE 17–1 Proper method for simple interrupted suturing of a skin wound com- pared with incorrect techniques that result in poor scars from skin overlap, skin inver- sion, or necrosis of the skin edges because of excessive tension. It allows rapid closure, but depends on only two knots for security and may not allow precise approximation of the skin edges. It allows precise approximation of the skin edges with little tension, but may result in more scarring than a simple stitch. Any suture material or skin clips can be removed earlier if they have been reinforced with a deep absorbable suture or with the application of Steri- Strips after the suture is removed. Steri-Strips will stay in place more securely if tincture of benzoin (spray or solution) is applied to the skin and allowed to dry before the Steri-Strips are applied. Cut the suture as close to the skin as possible so that a minimal amount of “dirty su- ture” is dragged through the wound. The use of skin staples is commonplace in the operating room because of the rapidity of closure and the nonreactive nature of the steel staples. These are typically removed 3–5 d after surgery (abdominal incisions) as shown in Figure 17–10. Because these are removed fairly quickly, reinforce the incision with Steri-Strips. When removing skin staples, make sure that the staple is completely reformed (see Figure 17–10) before re- moval to decrease patient discomfort. These are ideal for linear cosmetic closures be- cause they eliminate possible cross-hatching deformities.
HYDRALAZINE AND NITRATES Loop Diuretics A major advance in the pharmacological management of CHF has been the demonstration that afterload re- Diuretics and their mechanisms of action will be dis- duction improved survival cheap 20mg celexa amex medicine rock. Loop diuretics generic 40mg celexa with amex symptoms you need glasses, such as reduction was developed for the treatment of mitral re- furosemide (Lasix), block the Na –K –2Cl symporter gurgitation. The resultant cular resistance, as reﬂected in lower arterial blood pres- effect is delivery of more Na to the distal tubule and sure, resulted in an increase in the percentage of blood enhanced urinary loss of Na and water. Unfortunately, that ﬂowed from the left ventricle to the aorta as op- the resultant increase in urinary excretion of H and K posed to the left atrium (decreased regurgitant fraction). The potential for arrhythmias is The decrease in backup of blood into the lungs provided exacerbated by the loss of Mg and Ca and an un- considerable symptomatic relief from dyspnea, fatigue, derlying vulnerability of the myocardium in CHF. It was reasoned that patients with CHF However, loop diuretics are still part of the mainstay of often also have mitral regurgitation and might similarly therapy for CHF despite these potential problems and beneﬁt from more forward (left ventricle to aorta), as the absence of well-controlled multicenter clinical trials. Moreover, tors were added to digitalis and furosemide was the ﬁrst furosemide was accepted as the standard of care in all to demonstrate a signiﬁcant improvement in survival in of the clinical trials that form the basis for recom- CHF. The use of the potassium- adrenoceptor blocking agent or the combination of sparing diuretic spironolactone has been shown to im- the direct vasodilator hydralazine and a nitric oxide– prove survival and is discussed below. There were fewer deaths among the patients on the combina- Spironolactone tion of hydralazine and nitrates. Patients taking prazosin did not beneﬁt, probably because chronic therapy with Spironolactone (Aldactone) is the only diuretic that has prazosin results in tachyphylaxis. The mechanisms of ac- been shown in a double-blind multicenter prospective tion of prazosin, hydralazine, and organic nitrates are clinical trial to improve survival in CHF. It is unclear at present whether the addition of spirono- The relative ease of administration and superior efﬁ- lactone to a combination of digitalis,ACE inhibitor, and cacy of angiotensin-converting enzyme inhibitors and a -blocker will also confer additional beneﬁt. The demonstration of the sur- the epithelial cells in the late distal tubule and collect- vival beneﬁt conferred by vasodilator therapy resulted 156 III DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM in a paradigm shift in the approach to CHF. The ognized that the way to improve survival in heart failure use of an ACE inhibitor results in the elaboration of was not by directly addressing the weakened heart more kinins and less angiotensin II. Thus, the beneﬁts pump but rather by reversing the inappropriate periph- of ACE inhibitors may derive from their elaboration of eral vasoconstriction that results from neurohumoral more kinins in addition to their inhibition of an- activation. Captopril (Capoten) was the original prototype Efforts to elucidate the mechanisms responsible for product, and it was administered three times a day. Prospective multicenter double-blind tive pathways for forming angiotensin II independent of placebo-controlled clinical trials have repeatedly the conversion of angiotensin I to angiotensin II. Other demonstrated an early and persistent survival beneﬁt cellular enzymes, such as chymases and trypsin, can also with ACE inhibitors in CHF patients. And ﬁnally, at least two dis- were found superior to hydralazine and nitrates in a di- tinct angiotensin II receptors have been cloned and se- rect comparison. ACE inhibitors are now clearly the quenced; they are confusingly named the type 1 and agents of ﬁrst choice in the pharmacological manage- type 2 angiotensin II (AT-1;AT-2) receptors. There are also a number of additional rea- Elaboration of angiotensin II can result in either of sons to use ACE inhibitors. The HOPE trial and other two effects on an individual cell, depending on the rela- studies demonstrated additional survival and renal pro- tive numbers of AT-1 and AT-2 receptors. Relatively se- tective beneﬁts of ACE inhibition in diabetic and/or hy- lective AT-1 receptor blockers have been developed in pertensive patients long before they develop CHF. Thus far, clinical studies indicate that ARBs ACE inhibitors has evolved along with our growing ap- may be as effective as ACE inhibitors and have fewer preciation of the physiological and pathophysiological side effects. Initially, angiotensin II was shown inhibitor as the ﬁrst-line therapy before using an ARB, to be elaborated in response to low blood ﬂow to the such as valsartan or losartan. Low ﬂow to can induce a very troubling cough in susceptible indi- the kidney occurs when damage to the heart results in a viduals as a result of the increase in kinins. Renin in the liver converts an- For many years the prevailing view was that -blockers giotensinogen to angiotensin I. Since cardiac output is a function of cellular ionized free calcium causes vasoconstriction by stroke volume times heart rate (CO SV HR), an in- vascular smooth muscle cells, aldosterone secretion by creased heart rate would be necessary to maintain an adrenal glomerulosa cells, increased central sympa- adequate cardiac output in the presence of the rela- thetic outﬂow, and enhanced thirst.