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Most patients experience marked relief within 24 hours; swelling subsides over the next few days purchase lopressor 12.5mg fast delivery. However cheap lopressor online american express, because the duration of treatment is brief buy cheap lopressor 100 mg, the risk for these complications is low. Because of their effects on carbohydrate metabolism, glucocorticoids should be avoided, when possible, in patients prone to hyperglycemia. Colchicine Colchicine [Colcrys, Mitigare] is an antiinflammatory agent with effects specific for gout. Acute Gouty Arthritis High-dose colchicine can produce dramatic relief of an acute gouty attack. Prophylaxis of Gouty Attacks When taken during asymptomatic periods, low-dose colchicine can decrease the frequency and intensity of acute flare-ups. Colchicine may also be given for prophylaxis when urate-lowering therapy is initiated because there is a tendency for gouty episodes to increase at this time. Mechanism of Action We do not fully understand how colchicine relieves or prevents episodes of gout. It may work, at least in part, by inhibiting leukocyte infiltration: in the absence of leukocytes, there is no phagocytosis of uric acid and no subsequent release of lysosomal enzymes. Because microtubules are also required for cell division, colchicine is toxic to any tissue that has a large percentage of proliferating cells. Pharmacokinetics Colchicine is readily absorbed after oral dosing, in both the presence and absence of food. Large amounts reenter the intestine through the bile and intestinal secretions and then undergo reabsorption. When given for gout prophylaxis (as opposed to familiar Mediterranean fever), colchicine is not recommended for patients younger than 16 years. Allopurinol may be given to children younger than 6 years for the purpose of treating hyperuricemia associated with cancer therapy. Probenecid has been given to children as young as 2 years for purposes unrelated to gout. Of the xanthine oxidase inhibitors, both febuxostat and allopurinol are Pregnancy Risk Category C; however, animal studies with febuxostat have demonstrated an increase in fetal mortality. For patients taking xanthine oxidase inhibitors, Canadian labeling contraindicates breastfeeding. Gastrointestinal Effects The most characteristic side effects are nausea, vomiting, diarrhea, and abdominal pain. Myelosuppression Injury to rapidly proliferating cells can suppress bone marrow function and can thereby cause leukopenia, granulocytopenia, thrombocytopenia, and pancytopenia. Accordingly, colchicine should be used with caution in patients with hematologic disorders. Myopathy Colchicine can cause rhabdomyolysis (muscle breakdown) during long-term low-dose therapy. Risk is increased in patients with renal and hepatic impairment and in those taking statin drugs (e. Patients should be monitored for signs of muscle injury (tenderness, pain, weakness). Drug Interactions Statins As noted, atorvastatin, simvastatin, and other statins can increase the risk for colchicine-induced muscle injury. For both acute therapy and long-term prophylaxis, dosage should be adjusted on the basis of liver function, kidney function, and use of interacting drugs. Prescribing information for Mitigare, but not Colcrys, includes contraindications for hepatic or renal impairment. It should be avoided during pregnancy, unless the perceived benefits outweigh the potential risks. The goal is to promote dissolution of urate crystals, prevent new crystal formation, prevent disease progression, reduce the frequency of acute attacks, and improve quality of life. Four drugs—allopurinol, febuxostat, probenecid, and pegloticase—are used to reduce uric acid levels. Pegloticase converts uric acid to allantoin, a compound that is readily excreted by the kidney. These drugs lack antiinflammatory and analgesic actions, so they are not useful against an acute gouty attack. These drugs lower plasma urate by three mechanisms: allopurinol and febuxostat reduce uric acid formation, pegloticase catalyzes conversion of uric acid to allantoin, and probenecid facilitates uric acid excretion by the kidney. Xanthine Oxidase Inhibitors: Allopurinol and Febuxostat Two xanthine oxidase inhibitors are now available: allopurinol and febuxostat. Because experience with allopurinol is more extensive, and febuxostat is much more expensive, allopurinol is often preferred. Allopurinol Therapeutic Uses Allopurinol [Zyloprim] is the current drug of choice for chronic tophaceous gout. By reducing blood uric acid levels, allopurinol prevents new tophus formation and causes regression of tophi that have already formed, thereby allowing joint function to improve. Reversal of hyperuricemia also decreases the risk for nephropathy from deposition of urate crystals in the kidney. Allopurinol can be used for hyperuricemia that develops secondary to cancer chemotherapy and to certain blood dyscrasias, such as polycythemia vera, myeloid metaplasia, and leukemia. To minimize hyperuricemia, allopurinol should be administered before chemotherapy starts. Pharmacokinetics Allopurinol is well absorbed after oral dosing and then undergoes rapid conversion to alloxanthine, an active metabolite. Because alloxanthine has a prolonged half-life (about 25 hours), therapeutic effects are long lasting. The most serious toxicity is a rare but potentially fatal hypersensitivity syndrome, characterized by rash, fever, eosinophilia, and dysfunction of the liver and kidneys. Many patients recover spontaneously; others may require hemodialysis or glucocorticoid therapy. Prolonged use (more than 3 years) may cause cataracts; periodic ophthalmic examinations are recommended. The risk for drug accumulation can be a problem if administered to patients with renal impairment. Drug Interactions Allopurinol can inhibit hepatic drug-metabolizing enzymes, thereby delaying the inactivation of other drugs. This interaction is of particular concern for patients taking warfarin, whose dosage should be reduced. The combination of allopurinol plus ampicillin is associated with a high incidence of rash; if rash develops, allopurinol should be discontinued immediately. P ro t o t y p e D r u g s Drugs for Gout Xanthine Oxidase Inhibitor Allopurinol Uricosuric Agent Probenecid Recombinant Uric Acid Oxidase Pegloticase Febuxostat Febuxostat [Uloric] is an alternative to allopurinol. Adverse effects of febuxostat, which are uncommon, include liver function abnormalities, nausea, arthralgia, and rash. High doses (80 mg/day) are associated with a small increase in cardiovascular events.

Liraglutide is administered subcutaneously; as with any injection order lopressor from india, local site reactions such as redness or pruritus may occur best order for lopressor. Several uncommon effects warranting special precautions occur in less than 1% of patients taking liraglutide buy 25mg lopressor mastercard. These include acute pancreatitis, renal impairment (likely associated with dehydration secondary to nausea, vomiting, and diarrhea) and acute gallbladder disease (typically associated with significant or rapid weight loss regardless of medication). Contraindications Liraglutide is known to cause thyroid cancer development in rodents, so cautious use is warranted until the effects on humans are known. B l a c k B o x Wa r n i n g : L i r a g l u t i d e ( S a x e n d a ) Liraglutide is associated with a risk for thyroid C-cell tumors based on studies in rodents. Life span−associated contraindications are provided the box for Patient- Centered Care across the Life Span: Weight Loss. Drug Interactions Liraglutide may potentiate the hypoglycemic effect of drugs given for glycemic control in diabetes mellitus. Combination Products There are currently two combination products approved for weight loss. Each combination is unique with different mechanisms of action and different side effect profiles. Phentermine, as mentioned previously, is a sympathomimetic amine already approved for short-term management of obesity. Topiramate is currently approved for seizure disorders (see Chapter 19) and prophylaxis of migraine (see Chapter 23). Possible mechanisms for topiramate include antagonism of glutamate (an excitatory neurotransmitter), modulation of receptors for gamma-aminobutyric acid, and inhibition of carbonic anhydrase. In a 56-week trial, phentermine/topiramate produced a 10% reduction in weight and a significant decrease in systolic blood pressure. Adverse Effects The most common adverse effects are dry mouth, constipation, altered taste, nausea, blurred vision, dizziness, insomnia, and numbness and tingling in the limbs. The most serious effects are memory impairment, difficulty concentrating, hypertension and tachycardia, birth defects, acute myopia with angle-closure glaucoma, acidosis, and, for patients who take insulin secretagogues or insulin, an increased risk for hypoglycemia beyond that of antidiabetic drugs alone. Contraindications There are life span−associated contraindications with phentermine/topiramate (see the box for Patient-Centered Care across the Life Span: Weight Loss). When given with the antiepileptic drugs carbamazepine or phenytoin, levels of topiramate (which is also an antiepileptic drug) may be increased. Administration with carbonic anhydrase inhibitors increases the risk for metabolic acidosis, whereas administration with diuretics that are not potassium sparing increases the risk for hypokalemia. Finally, studies show that concomitant administration with oral contraceptives increases the estrogen level while decreasing the progestin level. Naltrexone/Bupropion Actions and Use The anorexiant naltrexone/bupropion (Contrave) combines the effects of a dopamine and norepinephrine-reuptake inhibitor with an opioid antagonist. The mechanism of action by which this drug combination promotes weight loss is unknown, but it has been hypothesized that it acts on the regulation of appetite in the hypothalamus and on the mesolimbic dopamine system, which is the key reward pathway in the brain. Approximately 5% of patients experience an increase in blood pressure, dry mouth, diarrhea, abdominal discomfort, anxiety, and fatigue. B l a c k B o x Wa r n i n g : N a l t re x o n e a n d B u p ro p i o n ( C o n t r a v e ) The naltrexone/bupropion combination is associated with an increased risk for suicidal ideation and suicide attempts in children, adolescents, and young adults. Contraindications This product is contraindicated for patients taking other products containing bupropion. Because naltrexone is an opioid antagonist, it will decrease the ability of opioid analgesics to relieve pain. B l a c k B o x Wa r n i n g : N a l t re x o n e a n d B u p ro p i o n ( C o n t r a v e ) When the naltrexone/bupropion combination is given to patients who are taking or discontinuing bupropion (Aplenzin, Budeprion, Bupropion, Wellbutrin, Zyban), severe neuropsychiatric reactions, including depression, mania, psychosis, and homicidal ideation, have occurred. It should not be used for weight loss in patients with uncontrolled hypertension, seizure disorders, or eating disorders such as anorexia or bulimia. Patients who are undergoing alcohol, barbiturate, or benzodiazepine withdrawal should not take this drug. Life span−associated contraindications are listed in the box for Patient-Centered Care across the Life Span: Weight Loss. Drug Interactions Drug interactions are numerous and reflect interactions of the individual agents. Inhibitors of these enzymes can increase naltrexone/bupropion levels, requiring a lowered dosage. A Note Regarding Drugs for Weight Loss Weight-loss drugs share a disturbing history: they receive regulatory approval, undergo widespread use, and then are withdrawn owing to discovery of serious adverse effects. It is quite likely that new drugs may be approved by the time you read this chapter. It is also possible that drugs in this chapter, especially those most recently approved, will have been taken off the market. A ‘dietary ingredient’ may be one, or any combination, of the following substances: a vitamin, a mineral, an herb or other botanical, an amino acid, a dietary substance for use by people to supplement the diet by increasing the total dietary intake, a concentrate, metabolite, constituent, or extract. Some people like the sense of empowerment that comes from self- diagnosis and self-prescribing. Others may turn to supplements out of anger or frustration with their health care providers. In addition, supplements may be a way to save money: because these products are available without prescription, they can be purchased without the cost of visiting a prescriber. However, perhaps the strongest force driving the demand for nutritional supplements is aggressive marketing. In addition, the label must not claim that the product can be used to diagnose, prevent, treat, or cure a disease. In fact, it must state the opposite: this product is not intended to diagnose, treat, cure, or prevent any disease. Furthermore, regardless of what the label says, common sense assumes that people will take herbal products with the intent to prevent or treat disease. Adverse Effects With dietary supplements, as with conventional drugs, the manufacturer is responsible for safety. With conventional drugs, opposite logic and regulations apply: drugs are presumed dangerous until rigorous testing by the manufacturer reveals an absence of serious adverse effects. Because of this system, the number of dangerous drugs that reach the market is kept to a minimum. Ask yourself, “Which product would I be more comfortable using—one that has been tested for adverse effects before I take it, or one that is evaluated for adverse effects only after it caused me harm? A few examples illustrate the problem: • A combination product used to “cleanse the bowel” caused life- threatening heart block. Analysis revealed contamination with Digitalis lanata, a plant with powerful effects on the heart.

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Adverse Effects Intravenous Therapy Intravenous acyclovir is generally well tolerated cheap lopressor 50 mg mastercard. Reversible nephrotoxicity order lopressor australia, indicated by elevations in serum creatinine and blood urea nitrogen purchase 50mg lopressor, occurs in some patients. The risk for renal injury is increased by dehydration and by use of other nephrotoxic drugs. Kidney damage can be minimized by infusing acyclovir slowly (over 1 hour) and by ensuring adequate hydration during the infusion and for 2 hours after. Neurologic toxicity—agitation, tremors, delirium, hallucinations, and myoclonus—occurs rarely, primarily in patients with renal impairment. In patients on dialysis, very low doses can cause severe neurotoxicity, characterized by delirium and coma. Topical acyclovir frequently causes transient local burning or stinging; systemic reactions do not occur. Oral acyclovir is safe during pregnancy, so it can be used to suppress recurrent genital herpes near term. P a t i e n t E d u c a t i o n Acyclovir Advise patients to apply the drug with a finger cot or rubber glove to avoid viral transfer to other body sites or other people. Inform patients with herpes simplex genitalis that acyclovir only decreases symptoms; it does not eliminate the virus and does not produce cure. Advise patients to cleanse the affected area with soap and water 3 to 4 times a day, drying thoroughly after each wash. Advise patients to avoid all sexual contact while lesions are present and to use a condom even when lesions are absent. Patients should use a finger cot or rubber glove to avoid viral transfer to other parts of the body or to other people. Acyclovir [Zovirax] is supplied as a 5% cream for topical therapy of recurrent herpes labialis (cold sores) in patients at least 12 years old. Oral acyclovir [Zovirax] is available in capsules (200 mg), tablets (400 and 800 mg), and a suspension (200 mg/5 mL). To minimize the risk for renal damage, hydrate the patient during the infusion and for 2 hours after. The dosage for children under 12 years is 10 mg/kg infused every 8 hours for 7 days. The dosage for children under 12 years is 20 mg/kg infused every 8 hours for 7 days. The dosage for children younger than 12 years is 15 to 20 mg/kg/day divided into three doses to be infused every 8 hours for 5 days. With the exception of herpes labialis, there are limits on use for each condition. Pharmacokinetics Oral valacyclovir undergoes rapid absorption followed by rapid and essentially complete conversion to acyclovir. In contrast, when valacyclovir is given orally, the effective bioavailability of acyclovir is greatly increased—to about 55%. Therefore valacyclovir represents a more efficient way of getting acyclovir into the body. After conversion of valacyclovir to acyclovir, the kinetics are the same as if acyclovir itself had been given. Adverse Effects No doubt you noticed the emphasis on using valacyclovir primarily for immunocompetent patients. Preparations, Dosage, and Administration Valacyclovir [Valtrex] is available in 500- and 1000-mg oral capsules. For patients with herpes zoster, the recommended dosage is 1000 mg 3 times a day for 7 days. For patients with herpes simplex genitalis, the dosage is 1 g twice daily for 10 days (for the initial episode), or 500 mg twice daily for 3 days (for episodic recurrences). For patients with herpes labialis, 2 g/dose should be taken 12 hours apart for 1 day. For immunocompetent children aged 2 to 18 years with chickenpox, dosage is 20 mg/kg (up to a maximum of 1 g) 3 times a day. Famciclovir Famciclovir [Famvir] is a prodrug used to treat acute herpes zoster and genital herpes infection. As a result, the amount of penciclovir produced is the same whether famciclovir is taken with or without food. In patients with renal impairment, the plasma half-life of penciclovir is prolonged. Under clinical conditions, formation of penciclovir triphosphate requires viral thymidine kinase. Therapeutic Use Famciclovir is approved for treatment of acute herpes zoster (shingles) and herpes simplex genitalis. In patients with herpes zoster, the drug can decrease the time to full crusting from 7 days down to 5 days. Famciclovir does not decrease the incidence of postherpetic neuralgia but can decrease the duration (from 112 days down to 61 days). In patients with genital herpes simplex infection, famciclovir is active against the first episode and recurrent episodes. In clinical trials, the only headache and nausea were reported by more than 10% of the subjects. Preparations, Dosage, and Administration Preparations Famciclovir [Famvir] is supplied in tablets (125, 250, and 500 mg) for oral dosing, with or without food. In patients with renal impairment, the dose should be reduced and the interval between doses should be increased to 12 hours or 24 hours, depending on the degree of impairment. Herpes Simplex Genitalis For initial episodes, the dosage is 250 mg 3 times a day for 7 to 10 days. For episodic recurrence, there are three dosage regimens available: (1) 125 mg twice a day for 5 days; (2) 500 mg as a single dose on day 1 followed by 250 mg twice a day on day 2, or (3) two 1000-mg doses 12 hours apart. Herpes Labialis For cold sores that are recurrent, the dosage is a single 1500-mg dose at the first signs of symptoms. Topical Drugs for Herpes Labialis We have three topical drugs for recurrent herpes labialis (cold sores). Penciclovir is supplied as a 1% cream to be applied every 2 hours (except when sleeping) for 4 days. In clinical trials, benefits were modest: the average time to healing and duration of pain were decreased by just half a day, from 5 days down to 4. Docosanol Cream Docosanol [Abreva] is a topical preparation indicated for recurrent herpes labialis. As a result, viable virions can remain attached to the cell surface for a long time. Because docosanol does not affect processes of replication, it is unlikely to promote resistance.

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Experimentally discount lopressor 12.5mg with visa, it has been shown that combining flaring sutures with spreader grafts produces a statistically significant improvement in three-dimensional cross-sectional surface area order 25mg lopressor. Note: The asterisks in (b) and (c) denote the middle-third cartilage spreader grafts discount 100 mg lopressor overnight delivery. The grafts are then The revision rhinoplasty patient often presents with both func- sutured into position with a horizontal mattress “sandwich” tional and aesthetic problems. Usually, the patient has signifi- suture of 4–0 long-acting monofilament absorbable suture cant emotional and psychological issues relating to his or her. These can to widen a narrow nose, to straighten a deviated nose, to occur secondary to overresection of infrastructure or from lengthen a short nose, or to improve a functionally obstructed unfortunate occurrences with healing and scar contracture. Commonly, in an effort to remove a nasal hump and nar- Successful revision rhinoplasty requires the surgeon to under- row a wide nose, structural support to the middle nasal third is stand the complex interplay between normal nasal anatomy compromised. This creates an unaesthetic overly narrow nose and the scar tissue created from prior surgeries. They are usually placed centrally in the supratip of the nose but can be placed laterally to augment or support the side of the nose. These grafts may be placed endonasally or sutured into position through an open approach. If placed centrally (butterfly graft), a curved graft shape, with the convex side outward, will provide optimal support and profile contour. The surgeon should bevel the edges improved internal nasal valve, improved nasal breathing, and improved of the onlay graft to minimize the chance for palpable or visu- width of the nasal vault. Reduction rhinoplastyand nasal patency: change in the cross-sec- tional area of the nose evaluated byacoustic rhinometry. The long-term effects of open cos- had previous trauma with loss of support of the right nasal third. Arch Otolaryngol Head Neck Surg has created nasal obstruction on the right side and a deviated 1996; 122: 41–45 external nose. Facial Plast left side, and placement of a unilateral right spreader graft and right Surg Clin North Am 1993; 1: 23–38 nasal onlay graft to create nasal symmetry and improved nasal [10] Murakami C. The flaring suture to augment the repair of the dysfunctional nasal The surgeon must diagnose the weakness in the nasal infrastruc- valve. Plast Reconstr Surg 1998; 101: 1120–1122 ture and formulate a plan to reconstruct the nose. Spreader graft: a method of reconstructing the roof of the middle forces of wound contraction after the revision operation. If carefully diagnosed and 1999; 7: 333–345 463 Revision Rhinoplasty 60 Secondary Rhinoplasty: anagem ent of the Overresected Dorsum Rollin K. Daniel and Ali Sajjadian Any discussion of grafting the dorsum in secondary rhinoplasty properties of the irradiated cartilage such as greater absorption must take into account the different indications (aesthetic, aug- and loss of stiffness, which are directly proportional to the radi- mentation, and structure) as well as recent changes in materials ation dose. Even though in a few patients grafts for revising the overresected dorsum will become clear as replacement with fibrous scar tissue can provide satisfactory the various alternative materials and techniques are analyzed. Recently, the problem has become even more challenging by the emer- There are many types of human dermis grafts available for rhi- gence of graft-depleted patients where septal and ear cartilage noplasty. Thus, the challenge is very real and the types of grafts various processing techniques used on donated human skin tis- almost limitless. The goal is to remove the epidermis and cells that can lead and would include: availability, biocompatibility, minimal to tissue rejection and graft failure. It is best reserved as a camou- material include the following: (1) autografts, obtained from flaging graft for patients who need minimal tissue for correc- the patient including cartilage, bone, fascia, and dermis; (2) tion of visible or palpable dorsal irregularities. This product is homografts, derived from tissues donated by members of the not for use in patients with large tissue requirement given its same species that include irradiated cartilage and acellular der- unpredictable rate of absorption. Furthermore, acellular dermis mis; and (3) alloplastic implants, made from a variety of syn- should not be used in patients who need a structural graft. Alternatively, During the past 40 years, silicone has been used for augmenta- alloplastic materials have been associated with varying inciden- tion rhinoplasty. However, they are readily avail- employed to augment the dorsum, project the tip, and lengthen able with no harvest-related morbidity and can be easily tail- the columella. There is no donor site morbidity or any risk of absorp- native grafts is warranted. Because these implants do not allow soft tissue ingrowth, their mobility within the capsule can result in chronic soft tis- 60. These factors lead to an Irradiated cartilage graft is considered by some surgeons as a increased risk of exposure, infection, and extrusion. Even in good option for augmenting the nasal dorsum including saddle ideal patients such as the Asian nose where there is a thick soft nose deformity. The graft is easily accessible with no donor site tissue pocket, complications are very common. However, there can be a wide variability in physical placement, translucency, infection, and extrusion are frequent 464 Secondary Rhinoplasty: Management of the Overresected Dorsum and have been documented up to 20 years after surgery. When silicone implants are used in secon- flage of deficiencies in different portions of the nose. Juni had to Advantages for the patients include minimal recovery time and remove 42% of 72 dorsal implants used in secondary rhino- minimal cost. Many patients do not like the limited duration (6 to 12 mucosal lining, thus precluding direct contamination from the months) and need for repeated procedures. Last, the risk of hypersensitivity reaction and “biofilm” for- mation exist, which can be very problematic. There have been reports of 1 to 5% Autografts (derived from the patient’s own tissues including infection and extrusion when used in rhinoplasty surgery. The advantages typically outweigh the concerns about the donor site morbidity or absorption. It worth noting that septum, auricular, and costal can be carved easily, and is noncompressible. They consist pri- implants have large pores that permit significant tissue marily of chondrocytes and surrounding matrix, which is type ingrowth and implant fixation. These com- plications are thought to be related to shedding particles with Septal cartilage is composed of hyaline cartilage, which renders resultant chronic inflammatory response and infection. It is typically straight and Removal of infected implants may be necessary and can result can be carved to appropriate shape and size. It is easily inserted in large soft tissue loss, deformity, and visible irregularities. The tissue ingrowth makes their removal very Harvesting is straightforward and easily done with minimal difficult as compared with removing silicone implants. When available in sec- in the surrounding soft tissue and serve as a nidus for contin- ondary cases, septum can be used for a variety of structural ued infection. Immediate and definitive reconstruction is con- purposes such as struts, battens, or spreader grafts.

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