Angela L. Turpin, MD

• Associate Medical Director of Diabetes Program
• Assistant Professor of Pediatrics
• University of Missouri?ansas City School of Medicine
• Children? Mercy Hospitals & Clinics
• Kansas City, Missouri

Note that the iodine content in kelp may precipitate hyperthyroidism medicine vending machine generic 100 ml duphalac with amex, and prolonged or excessive intake is inadvisable symptoms women heart attack order duphalac 100ml on line. Constituents the thallus of kelp contains polysaccharides including alginic acid (the major component) symptoms quit drinking buy duphalac 100 ml cheap, fucoidan and laminarin (sulfated polysaccharide esters) medications with acetaminophen cheap duphalac 100ml line, free phloroglucinol and its high-molecular-weight polymers the phlorotannins and fucols and galactolipids medicine quest 100 ml duphalac free shipping. The iodine content can be high treatment xerostomia duphalac 100ml on-line, and kelp may be standardised to the total iodine content medications hydroxyzine duphalac 100ml cheap. Kelp also contains vitamins and minerals treatment improvement protocol buy 100 ml duphalac visa, particularly ascorbic acid (vitamin C), and it is a moderate source of vitamin K1 (phytomenadione). Kelp may be contaminated Interactions overview Kelp is probably unlikely to interact with warfarin, because, although it is a moderate source of vitamin K1, and therefore has the potential to reduce the effect of warfarin and related anticoagulants, sufficient vitamin K is very unlikely to be attained with usual doses of kelp supplements. K 265 266 Kelp Importance and management the interaction of warfarin with vitamin K from foods is a very wellestablished, well-documented and clinically important drug­food interaction, expected to occur with every coumarin or indanedione anticoagulant because they have a common mode of action. However, the evidence suggests that, in patients with normal vitamin K1 status, in general, clinically relevant changes in coagulation status require large continued changes in intake of vitamin K1 from foods, which would be highly unlikely to be attained from usual doses of kelp supplements. Fucoids in kelp are very unlikely to be orally active, so kelp supplements would be unlikely to have any anticoagulant activity. Taking the evidence together, there appears to be no reason why patients taking warfarin should particularly avoid taking kelp supplements. A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds. Kelp + Anticoagulants Unintentional and unwanted antagonism of warfarin occurred in one patient when she ate seaweed sushi. It has been suggested that kelp contains substances with anticoagulant activity, but the evidence for this is theoretical. It was estimated that she had consumed only about 45 micrograms of vitamin K1, which would not usually be sufficient to interact. However, if her vitamin K stores were low, this amount could have accounted for a large percentage of her vitamin K intake or stores, and might therefore have interacted. Also, when the kelp is used to prepare an infusion, it would be unlikely to contain much vitamin K1, because the vitamin is not water soluble. Experimental evidence In experimental studies, fucoidans from brown seaweeds including kelp have demonstrated anticoagulant activity. For example, in one in vitro study, the fucoidan from Fucus serratus had anticoagulant activity, as measured by activated partial thromboplastin time; this was roughly equivalent to 19 units of heparin per mg. The fucoidans from Fucus vesiculosus and Ascophyllum nodosum had a smaller effect (roughly equivalent to 9 and 13 units of heparin per mg, respectively). Fucoidans from kelp may act like heparin and inhibit thrombin activity, and therefore have some anticoagulant effects. However, they are large polysaccharides, and are therefore unlikely to be orally active. Other species used include Pueraria mirifica Airy Shaw & Suvatabandhu (Thai kudzu, Kwao Kreu Kao) and Pueraria phaseoloides (Roxb. Constituents the major isoflavone constituent of the root of Pueraria lobata is puerarin, which is the 8-C-glucoside of daidzein, but there are many others, such as puerarin hydroxy- and methoxy- derivatives and their glycosides, daidzein and its O-glycoside daidzin, biochanin A, genistein and formononetin derivatives. Pueraria mirifica root contains similar constituents to Pueraria lobata, the major difference being lower amounts of daidzein. Much of the research carried out on kudzu has been on the effects of isolated puerarin. It also has a popular reputation for being able to lower alcohol consumption and to treat symptoms of alcohol intoxication. This effect has not been reported for other isoflavonecontaining herbs and the possible mechanism of action is unknown. Kudzu has also been used for migraine and hypertension, pain and stiffness, and angina. The phytoestrogenic properties are well known, and puerarin is thought to be the major component with this effect, which has been well documented in animals. For further details about the general and specific effects of isoflavones, see isoflavones, page 258. For information on the pharmacokinetics of its main isoflavone constituent puerarin, see isoflavones, page 258. Interactions overview Studies in rats suggest that kudzu can increase the effects of methotrexate. Kudzu contains oestrogenic compounds and therefore it may interact with oestrogens and oestrogen antagonists. Potential interactions of isoflavone constituents of kudzu are covered under isoflavones; see antibacterials, page 260, antidiabetics, page 260, benzodiazepines, page 260, miscellaneous cardiovascular drugs, page 260, digoxin, page 261, fexofenadine, page 261, nicotine, page 261, paclitaxel, page 261, and theophylline, page 263. Use and indications Kudzu contains isoflavones and is used as a phytoestrogen for menopausal symptoms, with a particular emphasis on K 267 268 Kudzu Kudzu + Antibacterials No data for kudzu found. For the theoretical possibility that broadspectrum antibacterials might reduce the metabolism of the isoflavone constituents of kudzu, such as puerarin and daidzin, by colonic bacteria, and so alter their efficacy, see Isoflavones + Antibacterials, page 260. Kudzu + Methotrexate the interaction between kudzu and methotrexate is based on experimental evidence only. Experimental evidence In a pharmacokinetic study in rats, the use of a kudzu root decoction significantly decreased the elimination and resulted in markedly increased exposure to methotrexate. With intravenous methotrexate, the concurrent use of the kudzu decoction at 4 g/kg increased the half-life by 54% and decreased the clearance by 48%. Nevertheless, the findings suggest that kudzu might markedly increase the effects of methotrexate. The risks are likely to be greatest with high-dose methotrexate (for neoplastic diseases) and in patients with impaired renal function, but less in those given low doses (5 to 25 mg weekly) for psoriasis or rheumatoid arthritis and with normal kidney function. Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats. For comment on the blood-glucoselowering effects of puerarin, a major isoflavone constituent of kudzu, see Isoflavones + Antidiabetics, page 260. Puerarin, a major isoflavone constituent of kudzu, has been reported to be a weak benzodiazepine antagonist, see Isoflavones + Benzodiazepines, page 260. For a discussion of the evidence that puerarin, an isoflavone present in kudzu, might inhibit platelet aggregation, see Isoflavones + Cardiovascular drugs; Miscellaneous, page 260. For the possibility that high-dose biochanin A, an isoflavone present in kudzu, might increase digoxin levels, see Isoflavones + Digoxin, page 261. Kudzu + Nicotine For discussion of a study showing that daidzein and genistein present in kudzu caused a minor decrease in the metabolism of nicotine, see Isoflavones + Nicotine, page 261. Kudzu + Fexofenadine For the possibility that high-dose biochanin A, an isoflavone in kudzu, may slightly decrease fexofenadine levels in rats, see Isoflavones + Fexofenadine, page 261. K Kudzu + Oestrogens or Oestrogen antagonists Kudzu contains oestrogenic compounds. This may result in additive effects to oestrogens or it may oppose the effects of oestrogens. Similarly, kudzu may have additive effects to oestrogen antagonists or oppose the effects of oestrogen antagonists. Evidence, mechanism, importance and management Kudzu has a long history of use for menopausal symptoms, and is known to contain isoflavones (plant oestrogens). Numerous in vitro and animal studies have demonstrated oestrogenic effects for the herb (too many to cite here). Theoretically, the isoflavones from kudzu might have oestrogen antagonistic effects when they are given with potent oestrogenic drugs, as their oestrogenic effects are weaker and they might competitively inhibit the conventional oestrogenic drugs. Conversely, because of their oestrogenic effects it is possible that they might reduce the efficacy of potent oestrogen antagonists. Although many studies have been carried out, clinical information on the potential interaction of kudzu with oestrogens or oestrogen antagonists is sparse. On the basis of the postulated oestrogenic effects of kudzu and the theoretical mechanisms of antagonism, some have recommended caution if kudzu is given with other oestrogens including hormonal contraceptives, or with oestrogen antagonists such as tamoxifen. However, isoflavones from plants are widely consumed as part of the traditional diet in many parts of the world, and there is no clear evidence that this affects response to hormonal contraceptives or oestrogen antagonists such as tamoxifen. For further information on the oestrogenic effects of isoflavone supplements, see Isoflavones + Tamoxifen, page 262. Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause. For the possibility that the isoflavones biochanin A and genistein present in kudzu might increase paclitaxel levels, see Isoflavones + Paclitaxel, page 261. For the possibility that high doses of daidzein present in kudzu might modestly increase theophylline levels, see Isoflavones + Theophylline, page 263. Use and indications Lapacho is used traditionally for infectious diseases of bacterial, protozoal, fungal and viral origin, to enhance the immune system, and as an anti-inflammatory agent. It is also used as an anticancer therapy, especially in South America, and, although there is experimental evidence to support some of these uses, good clinical evidence is not available. Constituents Naphthoquinones are the major active constituents of the inner bark, the most important of which is lapachol, with deoxylapachol and - and -lapachone and others. Other constituents that may contribute to the pharmacological activity of lapacho include: iridoid glycosides such as ajugol; lignans based on secoisolariciresinol and cycloolivil; isocoumarin glycosides based on 6-hydroxymellein; phenolic glycosides of methoxyphenol derivatives and vanillyl 4hydroxybenzoate; various aldehydes; and volatile constituents such as 4-methoxybenzaldehyde, elemicin, trans-anethole and 4-methoxybenzyl alcohol. Interactions overview Lapachol is reported to have anticoagulant properties, which may be additive with those of conventional anticoagulants. L 270 Lapacho 271 Lapacho + Anticoagulants Lapacho may have anticoagulant effects and therefore, theoretically, concurrent use of conventional anticoagulants may be additive. However, it has been stated that lapachol (the main active constituent of lapacho) was originally withdrawn from clinical study because of its anticoagulant adverse effects,1 but the original data do not appear to be available. Experimental evidence An in vitro study in rat liver microsomes found that lapachol is a potent inhibitor of vitamin K epoxide reductase. They do this by inhibiting vitamin K epoxide reductase, which reduces the synthesis of vitamin K. This action appears to be shared by lapachol, and therefore the concurrent use of lapacho and anticoagulants may be additive. Importance and management Evidence is extremely limited, but the fact that lapachol was withdrawn from clinical studies due to its anticoagulant effects adds weight to the theoretical mechanism. Until more is known it would seem prudent to discuss the possible increase in anticoagulant effects with any patient taking an anticoagulant, who also wishes to take lapacho. Lapachol inhibition of vitamin K epoxide reductase and vitamin K quinine reductase. Pharmacokinetics Prolonged intake of high doses of liquorice extract, or its constituent glycyrrhizin, on probe cytochrome P450 isoenzyme substrates was investigated in mice. In a single-dose study in 2 healthy subjects, plasma levels of glycyrrhetic acid were much lower after administration of aqueous liquorice root extract 21 g (containing 1600 mg glycyrrhizin) than after the same 1600-mg dose of pure glycyrrhizin. This suggests that the biological activity of a given dose of glycyrrhizin might be greater if taken as the pure form than as liquorice. These findings therefore suggest that the effect of liquorice might be less than that of pure glycyrrhizin at the same dose. Constituents Liquorice has a great number of active compounds of different classes that act in different ways. The most important constituents are usually considered to be the oleanane-type triterpenes, mainly glycyrrhizin (glycyrrhizic or glycyrrhizinic acid), to which it is usually standardised, and its aglycone glycyrrhetinic acid. There are also numerous phenolics and flavonoids of the chalcone and isoflavone type, and many natural coumarins such as liqcoumarin, umbelliferone, glabrocoumarones A and B, herniarin and glycyrin. Interactions overview Liquorice appears to diminish the effects of antihypertensives and may have additive effects on potassium depletion if given in large quantities with laxatives and corticosteroids. Iron absorption may be decreased by liquorice, whereas antibacterials may diminish the effects of liquorice. A case report describes raised digoxin levels and toxicity in a patient taking liquorice. Although it has been suggested that liquorice may enhance the effects of warfarin, there appears to be no evidence to support this. See under bupleurum, page 89, for possible interactions of liquorice given as part of these preparations. Use and indications the dried root and stolons of liquorice are used as an expectorant, antispasmodic and anti-inflammatory, and to treat peptic and duodenal ulcers. Liquorice is widely used in traditional oriental systems of medicine, and as a flavouring ingredient in food. It has mineralocorticoid and oestrogenic L 272 Liquorice 273 Liquorice + Antihypertensives Liquorice may cause fluid retention and therefore reduce the effects of antihypertensives. Clinical evidence In 11 patients with treated hypertension, liquorice 100 g daily for 4 weeks (equivalent to glycyrrhetinic acid 150 mg daily) increased mean blood pressure by 15. The group taking the largest quantity of liquorice experienced the greatest rise in systolic blood pressure, and was the only group to have a statistically significant rise in diastolic blood pressure. Experimental evidence Because of the quality of the clinical evidence, experimental data have not been cited. In addition, the potassium-depleting effect of liquorice would be expected to be additive with loop and thiazide diuretics. The mineralocorticoid effect of liquorice is due to the content of glycyrrhetinic acid (a metabolite of glycyrrhizic acid), and therefore deglycyrrhizinated liquorice would not have this effect. Importance and management the ability of liquorice to increase blood pressure is well established. The dose required to produce this effect might vary between individuals, and the evidence from the study cited suggests that patients with hypertension might be more sensitive to its effect. It is probably not appropriate for patients taking antihypertensive drugs to be treated with liquorice, especially if their hypertension is not well controlled. Although liquorice-containing confectionary and other foodstuffs have also been implicated in this interaction it is usually when it has been consumed to excess. It seems unlikely that the occasional consumption of small amounts of these products will cause a notable effect. Nevertheless, in patients with poorly controlled blood pressure it may be prudent to ask about liquorice consumption to establish whether this could be a factor. Note also that the potassium-depleting effect of liquorice would be additive with that of potassium-depleting diuretics such as loop diuretics and thiazides. Sigurjуnsdуttir HБ, Franzson L, Manhem K, Ragnarsson J, Sigurdsson G, Wallerstedt S. Liquorice + Caffeine For mention that sho-saiko-to (of which liquorice is one of 7 constituents) only slightly reduced the metabolism of caffeine in one study, see Bupleurum + Caffeine, page 90. Liquorice + Carbamazepine For mention that sho-saiko-to (of which liquorice is one of 7 constituents) did not affect the metabolism of carbamazepine in an animal study, see Bupleurum + Carbamazepine, page 90. Liquorice + Corticosteroids Liquorice, if given in large quantities with corticosteroids, may cause additive hypokalaemia. Clinical evidence (a) Dexamethasone In a parallel group study, 6 patients were given glycyrrhizin 225 mg daily for 7 days, and 6 patients were given the same dose of glycyrrhizin and dexamethasone 1. The mineralocorticoid effects of glycyrrhizin were significantly reduced by dexamethasone; cortisol plasma concentrations and urinary excretions were reduced by up to 70%. Note that glycyrrhizin had no effect on endogenous cortisol levels in 7 control subjects without adrenal insufficiency. It is likely that the effects of the elevated digoxin levels were exacerbated by the hypokalaemia possibly caused by the herbal laxative. The theoretical basis for an interaction between liquorice and digoxin is well established, but there are few actual cases. Any herbal preparation that can reduce potassium levels would be expected to increase the risk of digoxin toxicity. This is likely to be additive with other concurrent medications that a patient may also be taking that can cause hypokalaemia, such as loop diuretics. It would be prudent to exercise caution in patients who are taking digitalis glycosides and who regularly use/abuse laxatives including liquorice and/or anthraquinone-containing substances such as rhubarb. However, note that, if these laxatives are used as recommended (at a dose producing a comfortable soft-formed motion), then this interaction is probably unlikely to be important. Congestive heart failure caused by digitalis toxicity in an elderly man taking a licorice-containing chinese herbal laxative. Therefore, it cannot be assumed that liquorice will inhibit the inactivation of all corticosteroids. Dexamethasone appears to attenuate the mineralocorticoid effects of glycyrrhizin because it suppresses endogenous cortisol secretion (causes adrenal suppression). Other corticosteroids would be expected to interact similarly if given in adrenal-suppressant doses. Importance and management the clinical importance of these observations is uncertain. Doses of corticosteroids sufficient to cause adrenal suppression would be expected to reduce the mineralocorticoid activity of liquorice, but mineralocorticoid activity might still occur. Glycyrrhizin (an active constituent of liquorice) and its metabolite glycyrrhetinic acid slightly increased the plasma levels of hydrocortisone and prednisolone and markedly potentiated the cutaneous effects of hydrocortisone. This suggests that liquorice will slightly potentiate the effects of these steroids. Nevertheless, it might be prudent to monitor the concurrent use of liquorice and corticosteroids, especially if liquorice ingestion is prolonged or if large doses are taken, as additive effects on water and sodium retention and potassium depletion may occur. Glycyrrhizin induces mineralocorticoid activity through alterations in cortisol metabolism in the human kidney. The inhibitory effects of glycyrrhizin and glycyrrhetinic acid on the metabolism of cortisol and prednisolone ­ in vivo and in vitro studies. Effect of oral administration of glycyrrhizin on the pharmacokinetics of prednisolone. Effect of glycyrrhizin on the pharmacokinetics of prednisolone following low dosage of prednisolone hemisuccinate. Licorice inhibits 11-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action.

Note that oral dronabinol (9-tetrahydrocannabinol) has caused seizures in clinical use medicine used during the civil war purchase duphalac 100 ml fast delivery, and the manufacturer recommends caution in those with a seizure disorder medicine 751 m order duphalac 100 ml visa. Cannabidiol ­ antiepileptic drug comparisons and interactions in experimentally induced seizures in rats 92507 treatment code order duphalac 100ml overnight delivery. C Cannabis + Sildenafil Myocardial infarction occurred in a man who had smoked cannabis and taken a tablet of sildenafil symptoms queasy stomach and headache buy duphalac 100 ml lowest price. Clinical evidence A 41-year old man with no history of cardiac disease experienced a myocardial infarction after smoking cannabis and recreationally taking a tablet of sildenafil (strength not specified) symptoms schizophrenia safe duphalac 100ml. These included Cannabis + Irinotecan treatment atrial fibrillation purchase 100ml duphalac visa, page 111 medicine 5658 generic duphalac 100ml visa, and Cannabis + Docetaxel medicine reminder alarm purchase duphalac 100 ml on line, page 110. Importance and management the vasodilatory effects of sildenafil necessitate caution in its use in patients with cardiovascular disease; myocardial infarction has rarely been associated with its use. The contribution of an interaction to this case is unclear, but bear the possibility in mind in the event of adverse effects on concurrent use. Myocardial infarction following the combined recreational use of Viagra and cannabis. Evidence, mechanism, importance and management One study found that tobacco or cannabis smoking similarly caused higher total clearances of theophylline (given as oral aminophylline) than in non-smokers (about 74 mL/kg per hour compared with 114 Cannabis C 52 mL/kg per hour), and that clearance was even higher (93 mL/kg per hour) in those who smoked both. Little is known about the effects of smoking cannabis on theophylline levels, but be alert for the need to increase the theophylline dosage in regular users. Factors affecting theophylline clearances: age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates, and ethanol. Cannabis + Tricyclic antidepressants Tachycardia has been described when patients taking tricyclic antidepressants smoked cannabis. Evidence, mechanism, importance and management A 21-year-old woman taking nortriptyline 30 mg daily experienced marked tachycardia (an increase from 90 to 160 bpm) after smoking a cannabis cigarette. Direct information is limited but it has been suggested that concurrent use should be avoided. Marked sinus tachycardia resulting from the synergistic effects of marijuana and nortriptyline. Case study: adverse effects of smoking marijuana while receiving tricyclic antidepressants. Capsicum Capsicum species (Solanaceae) Synonym(s) and related species Caspic, Cayenne, Cayenne pepper, Chili pepper, Chilli pepper, Hot pepper, Paprika, Red pepper, Tabasco pepper. A further in vitro study has shown that the acute use of capsaicin inhibits P-glycoprotein whereas longterm exposure induces P-glycoprotein, see digoxin, page 116. Constituents the pungent principles of capsicum are the capsaicinoids (to which it may be standardised), present in concentrations up to 1. The major components are capsaicin, 6,7-dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin and homocapsaicin. Other constituents include the carotenoid pigments (capsanthin, capsorubin, carotene, lutein), vitamins including A and C, and a small amount of volatile oil. Use and indications Capsicum possesses stimulant, antispasmodic, carminative and counterirritant effects, which has led to its use in conditions such as colic and flatulent dyspepsia, and to increase peripheral circulation. Topical preparations are used for neuralgia including rheumatic pains and unbroken chilblains. Capsicum is frequently eaten as part of the diet and, in particular, diets that contain spicy foods. It has been estimated that the average consumption of dietary spice from capsicum fruit is 2. As the capsaicin content in capsicum fruit is approximately 1%, the daily dietary intake Interactions overview Capsicum has the potential to decrease the absorption of aspirin, increase the absorption of ciprofloxacin and theophylline, and alter the absorption of cefalexin and digoxin. However, the clinical effects of these changes are unknown, not established or not clinically significant. Capsicum may also decrease the metabolism of pentobarbital and phenazone, but it does not alter the metabolism of theophylline or quinine, which suggests that it has selective effects on hepatic enzymes. Metabolism of capsaicinoids by P450 enzymes: a review of recent findings on reaction mechanisms, bio-activation, and detoxification processes. Similar, but greater, results were found when aspirin was given to rats that had been treated with Capsicum annuum extract for 4 weeks. However, the clinical significance of this effect is unclear, especially as the capsaicin dose used in the study is 10-fold greater than the expected dietary intake in countries where a spicy diet is typically eaten, and many times higher than the expected exposure if capsaicin is given as a cream, or ingested as a medicinal product. Ingestion of chilli pepper (Capsicum annuum) reduces salicylate bioavailability after oral aspirin administration in the rat. Capsicum + Ciprofloxacin the interaction between capsicum and ciprofloxacin is based on experimental evidence only. Experimental evidence A study in which rats were given oral ciprofloxacin 20 mg/kg with placebo, or capsaicin in concentrations of 0. The doses of the antibacterial and capsaicin were chosen to reflect those likely to be encountered clinically, and those encountered within dietary levels, respectively. Therefore if these findings are replicated in humans it seems possible that a clinically relevant rise in ciprofloxacin levels could occur; however, given the magnitude of the rise, the effect seems most likely to be beneficial rather than adverse, although more study is needed to establish this. Sumano-Lуpez H, Gutiйrrez-Olvera L, Aguilera-Jimйnez R, Gutiйrrez-Olvera C, Jimйnez-Gуmez F. Administration of ciprofloxacin and capsaicin in rats to achieve higher maximal serum concentrations. C Capsicum + Digoxin the interaction between capsicum and digoxin is based on experimental evidence only. Capsicum + Cefalexin the interaction between capsicum and cefalexin is based on experimental evidence only. Experimental evidence An in vitro study using animal tissue found that high concentrations of capsaicin instilled into rat intestines resulted in a lower rate of absorption of cefalexin. Although the rate of cefalexin absorption was decreased the total amount of cefalexin absorbed was not studied, and therefore no conclusions can be drawn on the possible clinical relevance of the findings. Experimental evidence In an in vitro study, P-glycoprotein function was assessed by looking at the transport of digoxin, a known substrate of this transporter protein. In the presence of capsaicin the transport of digoxin across cells was enhanced, suggesting that capsaicin induces P-glycoprotein. Importance and management Evidence is limited and difficult to extrapolate to a clinical situation. The study found that the acute use of capsaicin inhibited P-glycoprotein, whereas long-term exposure induced P-glycoprotein. Clinically, P-glycoprotein induction has resulted in reduced digoxin absorption from the intestine and increased biliary excretion, the end result being a reduction in digoxin levels. Whether capsaicin would initially raise then subsequently lower digoxin levels remains to be established, but it may be prudent to consider the possibility of this effect if large doses of capsaicin are given systemically. Therefore if patients taking pentobarbital are given systemic capsacicin it may be prudent to warn them that prolonged drowsiness may occur. Interaction of capsaicinoids with drugmetabolizing systems: relationship to toxicity. Capsicum + Phenazone (Antipyrine) Capsicum + Iron compounds Capsicum modestly reduces the absorption of dietary iron. Clinical evidence In a randomised, crossover study, 30 healthy women were given a standard Thai meal (fortified with about 4 mg of isotopically labelled ferrous sulfate), with soup, to which 4. Importance and management the study suggests that capsicum inhibits the absorption of dietary levels of iron. The levels of capsicum used were high, but they are not unusual in a typical Thai meal. However, consider this interaction if a patient taking capsicum supplements has a poor response to iron replacement therapy. Tuntipopipat S, Judprasong K, Zeder C, Wasantwisut E, Winichagoon P, Charoenkiatkul S, Hurrell R, Walczyk T. Chili, but not turmeric, inhibits iron absorption in young women from an iron-fortified composite meal. C the interaction between capsicum and phenazone is based on experimental evidence only. Experimental evidence In a placebo-controlled study, rats were given capsaicin 25 mg/kg daily for 7 days, followed by a single 10-mg intravenous dose of phenazone. Although rises in phenazone levels of this magnitude may be of clinical relevance, the dose of capsicum used in the study was very high, so it seems unlikely that these effects would be reproduced with clinical or dietary quantities of capsaicin. Capsicum + Quinine Capsicum + Pentobarbital the interaction between capsicum and pentobarbital is based on experimental evidence only. Experimental evidence In a placebo-controlled study, rats were given a single 10-mg/kg subcutaneous dose of capsaicin followed 6 hours later by pentobarbital. The sleeping time of rats in response to the pentobarbital was more than doubled by capsaicin. If the findings are replicated the information regarding the use of capsicum with quinine is based on experimental evidence only. Experimental evidence In a placebo-controlled study, rats were given capsaicin 25 mg/kg daily for 7 days, followed by a single 25-mg/kg intravenous dose of quinine. Importance and management the available evidence suggests that no pharmacokinetic interaction would be expected between capsaicin and quinine. It would therefore appear that no specific additional precautions are necessary if patients taking theophylline also take capsaicin. Theophylline pharmacokinetics and metabolism in rabbits following single and repeated administration of Capsicum fruit. Effects of capsicum fruit on theophylline absorption and bioavailability in rabbits. Effects of capsaicin on the pharmacokinetics of antipyrine, theophylline and quinine in rats. Capsicum + Theophylline Although capsicum may slightly increase the absorption of theophylline, it does not appear to be clinically relevant. Capsicum did not affect the pharmacokinetics of theophylline, apart from a 40% increase in the elimination rate constant after the single dose of capsicum. C Pharmacokinetics For information on the pharmacokinetics of an anthraquinone glycoside present in cascara, see under aloes, page 27. Interactions overview No interactions with cascara found; however, cascara (by virtue of its anthraquinone content) is expected to share some of the interactions of a number of other anthraquinonecontaining laxatives, such as aloes, page 27 and senna, page 349. Of particular relevance are the interactions with corticosteroids, digitalis glycosides and potassium-depleting diuretics. Constituents Anthraquinone glycosides are major components of cascara and include cascarosides A, B, C, D, E and F, aloins A and B, and chrysaloins A and B. Aloe-emodin, barbaloin, crysophanol, emodin, frangulin and physcion are also present in small amounts, as are resins and tannins. This serves as a reminder that in vitro studies cannot be directly extrapolated to the clinical situation, and that the findings need confirmation in a clinical setting. Note that there are two chemotypes of Uncaria tomentosa, one primarily containing the tetracyclic oxindole alkaloids, isorhynochophylline and rhynchopylline, and one primarily containing the pentacyclic oxindole alkaloids, (iso)pteropodine and (iso)mitraphylline. An in vitro evaluation of human cytochrome P450 3A4 inhibition be selected commercial herbal extracts and tinctures. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. In various preclinical studies, antiviral, anti-inflammatory, antirheumatic, immunostimulating, antimutagenic, antitumour and hypotensive properties have been shown. Importance and management Evidence appears to be limited to experimental data and an interaction is not established. Concurrent use need not be avoided, but patients should be made aware of the possibility of increased antihypertensive effects. Hypotensive and hemodynamic effects of isorhynchophylline in conscious rats and anaesthetised dogs. Warn patients to discuss any episode of prolonged bleeding with a healthcare professional. There were no safety concerns from the use of the combination when compared with placebo, and a modest clinical benefit. Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of Uncaria tomentosa for the treatment of rheumatoid arthritis. Importance and management Evidence appears to be limited to one case report from which it is difficult to draw general conclusions. No evidence of protease inhibitor-related toxicity was found and the patient reported no adverse effects. The supplement was stopped and by day 15 the levels of all three drugs had returned to within normal limits. Not to be confused with celery stem, which is commonly eaten as a salad vegetable. Use and indications Celery seed is traditionally used for joint inflammation (including rheumatism), gout and urinary tract inflammation. C Pharmacokinetics No relevant pharmacokinetic data found for celery seed, but see flavonoids, page 186, and natural coumarins, page 297, for information on these constituents present in the herb. Other important constituents are the flavonoids (notably apigenin and isoquercitrin) and natural coumarins (bergapten, isoimperatorin, osthenol, umbelliferone and 8-hydroxy-5-methoxypsoralen), some of which may cause photosensitivity; however, celery seed oil has been reported to be non-phototoxic in humans. Note that celery stem contains much lower levels of the phototoxic natural coumarins; even so, cases of phototoxicity have been reported. For information on the interactions of individual flavonoids present in celery seed, see flavonoids, page 186. Although celery seed contains natural coumarins, the quantity of these constituents is not established, and therefore the propensity of celery seed to interact with other drugs because of their presence is unclear. Consider natural coumarins, page 297, for further discussion of the interactions of coumarin-containing herbs. Alkaloids of the pyridine type, including gentianine, gentianidine, gentioflavine, are also found in trace amounts. The triterpenoids - and -amyrin, erythrodiol, crataegolic acid, oleanolic acid and sitosterol are also present Use and indications Centaury is used for disorders of the upper digestive tract, mainly dyspepsia. Constituents the iridoids (bitters) are considered to be the main active constituents of centaury, and include gentiopicroside (about 2%), with centapicrin, gentioflavoside, sweroside and swertiamarin and m-hydroxybenzoylesters of sweroside, and catapicrin. Highly methylated xanthones, including eustomin and 8-demethyleustomin, have been found Pharmacokinetics No relevant pharmacokinetic data found. Constituents the flowerheads of German chamomile contain essential oil composed mainly of (-)-bisabolol. Chamazulene (1 to 15%), another volatile oil found in chamomile, is formed from matricin during steam distillation of the oil. Other constituents present in chamomile include flavonoids (apigenin, luteolin, quercetin, rutin), and the natural coumarins umbelliferone and its methyl ether, heniarin. C Use and indications German chamomile is used for dyspepsia, flatulence and travel sickness, especially when the gastrointestinal disturbance is associated with nervous disorders. German chamomile is widely used in babies and children as a mild sedative, and to treat colic and teething pain. Interactions overview An isolated case of bleeding in a patient taking warfarin and using chamomile products has been reported. For information on the interactions of individual flavonoids present in German chamomile, see under flavonoids, page 186. Pharmacokinetics In vitro studies have found that a commercial ethanolic extract of Matricaria chamomilla and a crude Matricaria 125 126 Chamomile, German complications 5 days after she started using two chamomile products. C Chamomile, German + Iron compounds Chamomile tea (an infusion of Matricaria chamomilla) does not appear to affect iron absorption. Evidence, mechanism, importance and management A study in 13 healthy subjects found that chamomile tea (an infusion of Matricaria chamomilla) sweetened with panela (an unrefined cane sugar sweetener containing fructose) did not affect the absorption of iron from an iron-fortified bread, when compared with the absorption of iron from the bread alone. This is much less than the tannin content of black tea, which is known to reduce iron absorption. This level of tannins did not appear to affect iron absorption in this particular study and it would therefore appear that chamomile tea may be taken without impairing iron absorption. Mechanism German chamomile contains the natural coumarin compounds, umbelliferone and heniarin, However, these compounds do not possess the minimum structural requirements (a C-4 hydroxyl substituent and a C-3 non-polar carbon substituent) required for anticoagulant activity. Importance and management this appears to be the first report of an interaction between warfarin and German chamomile. There seem to be no reports of German chamomile alone causing anticoagulation, and the natural coumarin constituents of German chamomile do not appear to possess anticoagulant activity, which might suggest that the risk of an additive effect is small. Furthermore, a pharmacokinetic basis for this interaction has not been established. It may be better to advise patients to discuss the use of any herbal products that they wish to try, and to increase monitoring if this is thought advisable. Chamazulene is formed from a natural precursor during steam distillation of the oil. C Use and indications Roman chamomile is used as a carminative, anti-emetic, antispasmodic, and sedative for dyspepsia, nausea and vomiting, anorexia and dysmenorrhoea. Pharmacokinetics Constituents the flowerheads contain an essential oil composed mainly of esters of angelic and tiglic acids, with 1,8-cineole, transpinocarveol, trans-pinocarvone, chamazulene, farnesol, nerolidol, various germacranolide-type sesquiterpene lactones, amyl and isobutyl alcohols, and anthemol. The flavonoids apigenin, luteolin, quercetin with their glycosides, and the natural coumarin scopoletin-7-glucoside, are also present. For information on the pharmacokinetics of individual flavonoids found in Roman chamomile, see under flavonoids, page 186. Interactions overview No interactions with Roman chamomile found, but, for information on the interactions of individual flavonoids found in Roman chamomile, see under flavonoids, page 186. It has also been used to treat other diseases such as cancer, venereal disease and tuberculosis. Its use as a herbal remedy is not recommended due to reports of hepatotoxicity and renal toxicity. The herb also contains flavonoids, which include isorhamnetin, kaempferol and quercetin, and their derivatives. There is also a volatile oil present containing calamene, eudesmol, limonene, - and -pinene, and 2-rossalene. A cytotoxic naphthoquinone derivative, larreantin, has been isolated from the roots. For information on the pharmacokinetics of individual flavonoids present in chaparral, see under flavonoids, page 186.

About half of all patients treated will respond to androgen therapy hb treatment 100 ml duphalac with visa, and a subset of those who initially respond may become refractory over time symptoms 9 days before period generic 100 ml duphalac amex. For patients for whom hematopoietic stem cell transplant is indicated symptoms 5 days before missed period buy duphalac 100 ml amex, delay in going to transplant may increase transplant-associated risks medicine 802 buy cheap duphalac 100 ml. Since there is no evidence that androgens can forestall bone marrow failure medicine in ukraine cheap duphalac 100 ml without a prescription, treatment is initiated when cytopenias drop to clinically significant levels but before the marrow becomes completely devoid of hematopoietic stem cells for androgens to stimulate treatment 7 february cheap duphalac 100ml fast delivery. The standard recommended androgen is oxymetholone medicines 604 billion memory miracle order 100ml duphalac with visa, with a starting dose of 2-5 mg/kg/day rounded to the nearest 1/4 tablet (50 mg tablets are available in the United States treatment management company discount duphalac 100 ml otc, while 10 mg tablets are available in many countries in Europe). If the patient responds to the initial dose with a stabilization of or increase in the hemoglobin level, the daily dose may be tapered in 1/2 tablet decrements after 3 months. Thereafter, a reasonable taper schedule might involve gradually decreasing the androgen dose at 2-4 month intervals. The family should be counseled about the possible side effects of androgen therapy and the child, especially teenagers, should be forewarned about them. Every effort should be made to minimize the side effects by tapering the dose whenever possible. Aggressive acne treatment with topical benzoyl peroxide and topical antibiotics (clindamycin or erythromycin) may make the treatment more tolerable. Since the masculinizing side effects of oxymetholone are particularly troublesome in girls and women, some female patients have been treated with a different androgen, danazol, which is hypothesized to produce fewer of these side effects. It has not been established whether, dose for dose, danazol is as effective and, at the same time, less masculinizing than oxymetholone. Clinical trials comparing efficacy and side effects of different androgens are currently being developed. The use of low dose (5-10 mg every other day) prednisone in an attempt to attenuate the premature epiphyseal closure by androgens has been advocated by some physicians. There are no data to support any sparing of androgen toxicity with the use of low dose prednisone. Furthermore, prednisone therapy carries a risk of 60 Fanconi Anemia: Guidelines for Diagnosis and Management additional bone toxicities, such as avascular necrosis or osteoporosis. Unfortunately, transaminases do not always correlate with the degree of liver inflammation on liver biopsy. If liver transaminases increase to 3-5 times above normal, the androgen dose can be tapered until the blood tests improve. Androgen-associated liver adenomas can resolve after androgens are discontinued, but some may persist even years after androgens are stopped. If screening tests raise a concern for adenocarcinoma, a liver biopsy (generally performed as an open procedure to minimize bleeding risk) should be considered. These formulations offer the advantage of decreased injection frequency (a particularly appealing prospect for thrombocytopenic patients). A bone marrow aspirate/biopsy with cytogenetics is recommended prior to the initiation of cytokine treatment, given the theoretical risk of stimulating growth of a leukemic clone. It is reasonable to monitor the bone marrow morphology and cytogenetics every six months while patients are treated with cytokines. There are currently no studies demonstrating a causal relationship between cytokine therapy and leukemogenesis. Investigational protocols For those patients who fail to respond to androgens or cytokines and have no acceptable transplant donor or pose an unacceptably high transplant risk, investigational protocols for new therapies may be considered (see Chapter 12). Early discussion with a transplant expert is recommended to allow families the option of initiating the procedure at an optimal time for the patient. This suggestion for "preemptive transplantation" is highly controversial since some patients who might never progress to significant marrow failure would be unnecessarily subjected to both early and late mortality risk and potential morbidity associated with transplant. A careful discussion with a hematologist and transplant physician is warranted for families interested in this investigational approach. Selection of a donor requires additional confirmatory testing as well as determination of donor availability. This stage accrues a substantial charge and is not undertaken until active plans for transplant are underway. Information regarding the number of potential donors available is helpful in estimating the time likely required to complete a full donor search if the marrow failure progresses. Severe marrow failure: · Consider unrelated donor hematopoietic stem cell transplant for eligible candidates. Severe marrow failure unresponsive to androgens/ cytokines and high transplant risks: · Consider investigational protocols. It remains unclear whether pre-transplant chemotherapy improves or worsens outcomes. Close monitoring of the hemoglobin is necessary, as outlined above, so that treatment may be instituted before transfusion with packed red blood cells is required. The hemoglobin level at which treatment is started should be modified upward for patients who live at high altitude, where the normal range for hemoglobin levels is higher. When treatment is anticipated, it should be initiated under the care of a hematologist. As discussed above, treatment options for anemia consist of bone marrow transplant or androgens. High transfusion burden may adversely affect transplant outcomes, so timely consideration of transplant is recommended. Some physicians advocate a more aggressive and regularly scheduled transfusion program to maintain as normal a quality of life as possible for patients with bone marrow failure. These physicians reason that the patient should maximize the benefit of transfusion therapy. Using the latter approach, a patient would be transfused to maintain a minimal trough hemoglobin of 7-8 g/dl. A post-transfusion hemoglobin level of 10-12 g/dl is generally sufficient to allow for normal activity, growth, and development in children. Extended antigen matching may be important for patients in certain racial groups, where minor antigen mismatch is more commonly encountered. The use of family members as directed donors may cause alloimmunization to an antigen that would increase the risk of graft rejection after sibling donor hematopoietic stem cell transplant. Secondary iron overload Each mL of transfused packed red cells contains approximately 0. Since the human body lacks mechanisms to actively eliminate excess iron, patients who receive multiple red blood cell transfusions are at risk for accumulating toxic levels of iron overload. The liver is a primary site of iron accumulation, and hepatic fibrosis and cirrhosis may result. Cardiac decompensation may be sudden and acute despite regular monitoring with electrocardiograms and measurements of cardiac function. Iron also targets endocrine organs such as the pituitary, pancreas, thyroid, and parathyroid (Table 5). Table 5: Clinical Complications of Iron Overload Liver disease with fibrosis and cirrhosis Cardiac failure, arrhythmias Hypopituitarism: central hypogonadism growth hormone deficiency central hypothyroidism Poor growth Diabetes mellitus Primary hypothyroidism Primary hypogonadism Hypoparathyroidism While ferritin levels are often followed as a convenient marker for total body iron load, their interpretation is complicated by additional factors such as acute or chronic inflammation and infection or hepatitis. The gold standard for the measurement of total body iron has been a liver biopsy; however, hepatic iron distribution may be uneven, particularly with cirrhosis and, thus, liver biopsies may be limited by sampling error. Elevated liver iron >15mg/g dry weight is associated with a high risk of cardiac toxicity. Bleeding or infection as possible complications of the surgical biopsy procedure are of heightened concern in patients who are thrombocytopenic or neutropenic. Guidelines for the institution of iron chelation therapy in bone marrow failure patients are based on those established for thalassemia patients, with the caveat that thalassemia patients who undergo accelerated, albeit ineffective, erythropoiesis, often have concomitant increases in iron absorption and are transfused to the point of suppressing endogenous hematopoiesis. Total red cell volumes transfused, particularly for infants and small children, as well as total body iron status as reflected in liver iron, cardiac iron, and ferritin levels must be carefully monitored. As a general guide, chelation is considered when the total red cell volume transfused reaches 200mL/kg (roughly corresponds to a total of 12-18 red cell transfusions) or the liver iron reaches 7mg/g dry weight. Chronically transfused patients heading to a hematopoietic stem cell transplant may also benefit from total body iron measurements and chelation therapy to reduce iron levels. In situations where liver iron measurements are not clinically available, a serum ferritin persistently greater than 1,500 without other apparent etiologies has been used as a surrogate, albeit imperfect (see prior discussion), marker. Although generally effective, its use is complicated by the need for parenteral infusion (subcutaneously or intravenously). Furthermore, deferoxamine must be administered over prolonged periods of time since only a small proportion of total body iron is available for chelation at any given moment and the half-life of deferoxamine is short. Subcutaneous infusions pose risks of bleeding or infection in patients with thrombocytopenia or neutropenia. Side effects of deferoxamine include loss of hearing or vision, particularly when desferoxamine doses are high relative to iron stores. Immediate cessation of deferoxamine and medical evaluation is warranted if such symptoms arise. Deferoxamine therapy is associated with an increased risk of Yersinia enterocolitica infection, and the drug should be stopped for unexplained fevers pending the results of blood cultures and infection work-up. Given the disadvantages of a parenterally administered drug, deferasirox offers an attractive alternative for iron chelation. Deferasirox is conveniently administered orally once a day as a slurry on an empty stomach. Clinical experience with deferasirox is limited, but short- and long-term side effects reported to date are generally mild. Patients who continue to have unacceptable iron levels on deferasirox despite dose escalation may benefit from switching back to deferoxamine until goal iron levels have been achieved. Studies suggest that deferiprone may be more efficient than deferoxamine at removing cardiac iron. Its utility is limited by its side effects, which include agranulocytosis, arthritis, and hepatic fibrosis. For patients with severe iron overload or with cardiac functional compromise (arrhythmias or failing left ventricular function), continuous high dose. Thrombocytopenia Bone marrow transplant should be considered when the platelet counts fall below 50,000/mm3. If transplant is not pursued, then thrombocytopenia should be treated with androgens as the platelet count declines to 30,000/mm3. As noted above, a longer trial of oxymetholone, up to six months, is required before treatment is discontinued for lack of a platelet response. Platelet transfusion is indicated in patients with severe bruising, bleeding or undergoing invasive procedures. Single donor apheresis platelets should be provided in an effort to decrease the risk of alloimmunization and to decrease the risk of infection from exposure to multiple donors. Amicar (epsilon aminocaproic acid) may be used as an adjunct to platelet transfusion in the patient with mucosal bleeding. The drug is given at a dose of 50-100 mg/kg every six hours, with a maximum dose of around 12 grams/day. Drugs that inhibit platelet function, such as aspirin or non-steroidal anti-inflammatory drugs. Activities carrying a high risk of significant trauma (particularly to the head or trunk) should be avoided. Patients with fever and neutropenia should have a thorough examination and cultures, and should receive broad spectrum antibiotics until the cultures are found to be negative and the fever resolves. Precautions to minimize the risk of infections from endogenous bacterial flora should be instituted according to local guidelines. Sedation and analgesia for invasive procedures Given the need for frequent evaluation of the bone marrow, adequate sedation and analgesia should be offered to every patient undergoing bone marrow aspiration and biopsy. The use of local anesthetic alone may not be sufficient to alleviate the anxiety and pain that is associated with frequent, repeated bone marrow aspirations. The use of intravenous propofol, fentanyl and midazolam, or similar regimens used in accordance with the guidelines established by the American Academy of Pediatrics, is strongly recommended. Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study. Testosterone-induced remission in aplastic anemia of both acquired and congenital types. Prolonged administration of granulocyte colony-stimulating factor (filgrastim) to patients with Fanconi anemia: a pilot study. Evaluation of granulocyte-macrophage colony-stimulating factor for treatment of pancytopenia in children with Fanconi anemia. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk beta-thalassemia. Polypharmacy As with any complex disease process, the involvement of multiple subspecialists introduces the risk that medications prescribed by one physician will interact adversely with those prescribed by another. It is essential that all subspecialists communicate with the primary physician, usually the hematologist/oncologist, to coordinate care. In some cases, digital radiographs may require less radiation than cut films and are thus preferred. Esophagealatresiaandtracheoesophagealfistula Long-term complications of esophageal atresia and tracheoesophageal fistula are related to the severity of the primary lesion and the quality of the repair. A longer gap between the proximal and distal segments makes the repair more difficult and increases the risk of late strictures. Respiratory symptoms, including cough, pneumonia, and wheezing may suggest the need for bronchoscopy. If the esophageal segments are very short or if significant complications occur, colon interposition to replace the esophagus may be required. This procedure is associated with many complications, including anastamotic leaks and swallowing problems, particularly pain with solids and frequent reflux and vomiting. Complications occur in 12-15% of patients and include abdominal pain, chronic alkaline reflux, and blind loop syndrome. There is frequently poor duodenal motility above the anastomosis with recurrent obstruction-like episodes. Anal atresia After anal atresia repair, 30% of patients have fecal incontinence, 50% have occasional soiling, and an undetermined number have constipation with or without encopresis. Patients and their families must be questioned during routine clinic visits regarding gastrointestinal symptoms, as it is common for patients to fail to spontaneously disclose these concerns. Nausea can result from infections, particularly urinary tract infections or sinusitis. This is 80 Fanconi Anemia: Guidelines for Diagnosis and Management usually a transient problem, resolving with resolution of the infection or stopping the medication. Abdominal pain may result from partial obstruction caused by complications of anatomic abnormalities, abnormal gastrointestinal motility, small bowel overgrowth or gallbladder disease. Possible causes of diarrhea include opportunistic infection of the gastrointestinal tract, small bowel overgrowth, medications, and short bowel with malabsorption. Constipation with encopresis is common, and families may mistake encopresis for diarrhea. If the patient has nonspecific poor oral intake, with or without nausea and abdominal pain, evaluation for evidence of occult infection may be useful. Laboratory studies, including urine culture and measurement of serum C-reactive protein or erythrocyte sedimentation rate, may point to infection or systemic inflammation. Patients with diarrhea should have stool examination for ova and parasites, giardia antigen, cryptosporidium, and other opportunistic agents. While small bowel cultures are diagnostic in suspected small bowel overgrowth, duodenal intubation is relatively contraindicated in a patient with both increased radiation sensitivity and increased risk for bleeding. Gastroesophageal reflux, gastritis, and other peptic disease can be diagnosed either clinically or by endoscopic biopsy, without the need for imaging. Peptic disorders should be treated with proton pump inhibitors (omeprazole 1 to 2 mg/kg/day or lansoprazole 0. For small children who cannot take pills or capsules, some pharmacies compound suspensions. The most reliable proton pump inhibitor therapy is given by prescribing suspensions made dose-by-dose, using either proprietary suspension packets or effervescent tablets. Alternatively, a proton pump inhibitor capsule can be opened, and the estimated amount of beads necessary for the dose placed on a small spoonful of applesauce and given immediately. Gastric emptying delay can be suspected clinically, when patients complain of nausea, early satiety and vomiting of food eaten several hours earlier. The most common study used is the nuclear medicine gastric emptying study, which involves radiation. Omitting a gastric emptying study and initiating a trial of medical therapy is acceptable to avoid radiation exposure. A trial of erythromycin (5 mg/kg/dose, three times per day) or metoclopramide (< 6 yrs old: 0. Prior to 82 Fanconi Anemia: Guidelines for Diagnosis and Management prescribing, the physician must determine if the patient is on any medication that may interact adversely with the gastric emptying medication. An important interaction for erythromycin is the azole group (fluconazole, itraconazole or ketoconazole). In cases of severe, intractable nausea without a detectable cause, a trial of ondansetron may be warranted if there is no improvement with metoclopramide or domperidone. Evaluation by a pediatric endocrinologist would be appropriate for this group of children. Attention must also be paid to children losing weight or slowing their growth rate. When poor weight gain or weight loss is documented, both poor oral intake and/or diarrhea with malabsorption must be considered. Analysis of a prospective three-day dietary record may indicate deficits in protein and calorie intake. Dietary counseling, with or without evaluation by a feeding specialist, may be enough to improve oral intake in some patients. Even children with adequate weight-for-height may benefit from a vitamin-mineral supplement given daily. Supplemental feeds are formula feeds delivered directly into the stomach or small intestine, bypassing appetite and food interest.

It also assists in the debridement of the root canal treatment that works buy 100 ml duphalac mastercard, increasing the dissolution of necrotic tissue medicine 44 159 discount 100ml duphalac. Diagnostic periapical radiograph (arrow at radiolucent area) and a radiolucent area (Figure 3 symptoms 2016 flu duphalac 100 ml low price. The new generation of paper points with markings is an effective mean for measurements · Copious irrigation with 0 medications used for adhd buy discount duphalac 100 ml on line. ClinicalandRadiographicFollow-up · the tooth was asymptomatic and functional 12 months post-operatively (Figure 3 symptoms zinc overdose discount duphalac 100ml. Its relatively good success rate has been attributed to its (a) high pH administering medications 7th edition generic duphalac 100ml free shipping, (b) calcium ions treatment kitty colds cheap 100 ml duphalac free shipping, (c) hydroxyl ions symptoms gluten intolerance buy duphalac 100 ml free shipping, and (d) antibacterial effect (Fava and Saunders 1999). The aim of the second visit is to complete the debridement and remove the tissue remnants (Hasselgren, Olsson, and Cvek 1988). At the next appointment, if the barrier is incomplete and the patient feels the touch of a file, the apexification procedure is repeated until a complete barrier is formed. When an apical barrier is formed, a root canal filling is performed using either lateral condensation with Gutta Percha point or using the warm Gutta Percha technique (Rafter 2005). Apexification includes a coronal access that should be wide enough to include the pulp horns to prevent future contamination and discoloration. The length of the root canal in immature teeth can be determined radiographically and by using the paper point method. The debridement of the root canal should be done with minimal instrumentation to prevent damage to the thin dentin walls. Irrigation with disinfecting solutions should be done carefully, avoiding pushing the solutions beyond the apex. Twelve months post-op radiograph caretakers and the patient should bear in mind that this tooth may be lost in the future. CommonComplicationsandAlternative TreatmentPlans Common Complications · After apexification, the crown-root ratio is not favorable because the root is shorter than in a mature tooth; therefore, the prognosis of the tooth may be hampered. It was assumed that the size of the blunderbuss apex before treatment influenced the type and time of closure (Yates 1988). The frequency of fractures among immature teeth ranged from 77% in teeth with the least developed roots to 28% in teeth with the most developed roots. The prognosis may be further compromised by the placement of a temporary coronal seal (Tronstad et al. A histological and quantitative histomorphometric study of apexification of nonvital permanent incisors of vervet monkeys after repeated root filling with a calcium hydroxide paste. Prognosis of luxated non-vital maxillary incisors treated with calcium hydroxide and filled with gutta percha. Effects of calcium hydroxide and sodium hypochlorite on the dissolution of necrotic porcine muscle tissue. Soft tissue dissolution capacity of currently used and potential endodontic irrigants. Influence of coronal restorations on the periapical health of endodontically treated teeth. DentalHistory · Has a dental home · Eats a regular balanced diet · Fair oral hygiene habits, brushes his teeth twice a day unsupervised · Uses a fluoride-containing toothpaste · Lives in an optimally fluoridated area · Dental trauma at age 7 · Cooperative G. Intra-oralExam Soft Tissues · No significant findings Hard Tissues · No significant findings Occlusal Evaluation of Mixed Dentition · Class I permanent molars and primary canines, anterior crowding, overjet: 5 mm, overbite: 50% Dental Exam · Minimal plaque · Caries free · First permanent molars with amalgam restorations Figure 3. Obturation of the root canal can be done with a vertical condensation of warm Gutta Percha in the remainder of the canal. Periapical radiograph of the maxillary right permanent central incisor (arrow at radiolucent area) I. DiagnosticTools · Periapical radiograph of the maxillary right permanent central incisor (Figure 3. DifferentialDiagnosis · Remnants of the dental sac · Periapical true cyst · Non-odontogenic lesion K. ClinicalandRadiographicFollow-up · the tooth is asymptomatic and functional 12 months post-operatively (Figure 3. The size of the periapical radiolucency diminished; full healing is expected Figure 3. The tooth can be restored with minimal delay, preventing the risk of root fracture and re-infection. Radiograph showing obturation of the root canal 128 ClinicalCasesinPediatricDentistry N. PrognosisandDiscussion · Due to their thin dentinal walls, these teeth are prone to fracture. Therefore, a mouth guard is suggested to decrease the risk of injury in risky situations (sports, biking, etc. The post only retains the core and crown, but does not strengthen the tooth itself (Davy, Dilley, and Krejci 1981). Immature root filled teeth are often compromised by inappropriate post space preparation, coronal leakage, and secondary caries around prefabricated posts, or too large custom posts. It may be advantageous to use a light transmitting post and composite resin to internally strengthen the tooth (Sapir et al. CommonComplicationandAlternative TreatmentPlans Common Complications · After apexification, the immature root is short and the crown:root ratio is not favorable. Determination of stress patterns in root-filled teeth incorporating various dowel designs. A novel multidisciplinary approach for the treatment of an intruded immature permanent incisor. Histologic assessment of mineral trioxide aggregate as a root-end filling in monkeys. DentalHistory · Has a dental home · Eats a balanced diet, not fond of sweets, loves salty snacks, and drinks mostly tap water · Poor oral hygiene, brushes without supervision twice a day · Uses toothpaste containing fluoride · Water fluoridation level is 0. Extra-oralExam · Bilaterally enlarged submandibular lymph nodes · Slightly incompetent lips Figure 3. PresentingPatient · 7-year-old Caucasian female · New patient presenting as an emergency B. ChiefComplaintandHistoryofPresent Injury · Her father stated that the patient "has had excruciating pain in the upper front tooth since yesterday" · Trauma history: One month ago patient was playing with a ball, slipped, and fractured the maxillary left permanent central incisor. A few days later a composite coronal restoration was placed at a private dental clinic. During the day and the following night the pain became unbearable, with some relief by nonsteroidal anti-inflammatory drugs C. Intra-oralExam Soft Tissues · Generalized gingivitis Hard Tissues · Maxillary left permanent central incisor (Figure 3. DiagnosticTools · Periapical radiograph of the maxillary left permanent central incisor (Figure 3. DifferentialDiagnosis · Acute periradicular periodontitis (pulp necrosis) · Acute periradicular abscess (pulp necrosis) · Normal dental sac K. The file should be inserted 2 to 3 mm short of the apical foramen to prevent damage to vital apical tissues (Figure 3. ClinicalandRadiographicFollow-up · At three-month follow-up the radiograph (Figure 3. The temporary sealing material was replaced by a composite resin restoration · At the six-month follow-up visit (Figure 3. PrognosisandDiscussion · Pulp necrosis following traumatic injuries is mainly related to the type and severity of the injury as well as to the stage of root development. Endodontic intervention is indicated when the pulp is necrotic or when there are clinical and radiographic signs of infection (Barnett 2002). The advantage of pulp revascularization is the possibility of further root development and strengthening of the dentin walls by deposition of hard tissue (Banchs and Trope 2004, Chueh and Huang 2006). Regeneration of pulp tissue in a necrotic infected tooth with apical periodontitis was thought to be impossible. However, recent research suggests that creating the unique circumstances that exist in revascularized avulsed cases allows regeneration of tissue to take place. CommonComplicationsandAlternative TreatmentPlans Complications · Green-gray discoloration of the crown is sometimes evident after using 3 mix, which presents an esthetic problem · Drug tolerance is a potential risk and, as a result, the disinfecting action will be impaired · A systemic allergic reaction to the antibiotics can be life threatening Alternative Treatment Plans · When signs of pulp infection are persistent after the use of the 3 mix. Revascularization of immature permanent teeth with apical periodontitis: New treatment protocol? Immature teeth with periradicular periodontitis or abscess undergoing apexogenesis: A paradigm shift. Pulp revascularization of necrotic bilateral bicuspids using a modified novel technique to eliminate potential coronal discolouration: a case report. Sterilization of infected root-canal dentine by topical application of a mixture of ciprofloxacin, metronidazole and minocycline in situ. Permanent,immaturetooth(thewidertheapical foramenthebetterthechancefor revascularization),necroticpulp(chronic periradicularperiodontitisorsinustractmaybe present),noknownallergytoanyofthe antibioticsused 2. Asystemic allergicreactiontotheantibioticscanbe life-threatening 136 ClinicalCasesinPediatricDentistry 4 OrofacialTrauma Dennis J. PresentingPatient · 2-year-, 7-month-old male · New patient presenting as an emergency B. ChiefComplaintandHistoryofPresent Injury · Mother stated, "My son was running and hit the stairs in our house" · Child was running in home, fell and hit cement stairs three hours ago. No loss of consciousness · Child was taken to local emergency room and cleared of any closed head trauma · Child is in no distress C. SocialHistory · Patient is only child · Mother is the primary caregiver and stays at home · Low socio-economic status 138 ClinicalCasesinPediatricDentistry the preschool years represent a peak in incidence of dental trauma, with some reports citing incidence as high at 35% (Hargreaves et al. MedicalHistory · History of recurrent otitis media infections per mother · No known drug or food allergies, no medications, vaccinations are up to date E. Vitality testing of questionable value on primary teeth and recognition of pulpal necrosis is typically based on clinical presentation (Pugliesi et al. There are several theorized sources of tooth discoloration in children including systemic illness and certain medications. While some dental staining, such as those due to tetracycline, are well-documented, others such as extrinsic amoxicillin-clavulanic acid staining are less studied and subsequently less thoroughly understood (Garcia-Lуpez et al. Extra-oralExam · Soft tissue injuries: Bruising noted on lip · No other significant findings H. Intra-oralExam Soft Tissues · No significant findings Hard Tissues · No significant findings Occlusal Evaluation of Primary Dentition · Mesial step molar and class I canines Other · Minimal plaque accumulation noted · Caries-free dentition · Maxillary right primary lateral incisor: Slight mobility, brown discoloration noted middle third · Maxillary right primary central incisor: Slight mobility · Maxillary left primary central incisor: Intruded to gingival margin (Figure 4. DiagnosticTools · Radiographs not possible due to very poor patient cooperation · Vitality tests deferred J. DiagnosisandProblemList Diagnosis · Maxillary right primary lateral incisor, right primary central incisor, and left primary lateral incisor: Subluxation · Maxillary left primary central incisor: Intrusion Figure 4. Intra-oral photo showing intrusion of maxillary left primary central incisor Figure 4. Treatment · No treatment is indicated at this time (see Flowchart A at the end of this chapter) · Advise parent of potential damage to permanent tooth bud, including potential hypocalcifications · Discharge instructions · Avoid incising on injured segment until instructed otherwise · Watch for clinical signs such as presence of parulis or fistula · Follow-up treatment · Patient was seen for follow-up at one and two months with minimal re-eruption noted · Four-month follow-up: Per mother, patient is asymptomatic; the maxillary left primary central incisor has fully re-erupted into position L. PrognosisandDiscussion · the overall prognosis for this tooth is based on the observation that it did re-erupt. The four-month post-op radiograph demonstrated no periapical resorption or radiolucency. The full understanding of the impact of the trauma is limited to the two-dimensional radiograph, and the successful eruption of the permanent incisor is a benchmark for the overall success of treatment M. ComplicationsandAlternativeTreatment Plan · If the root tip had become exposed through gingival tissues, extraction would be indicated due to the poor healing prognosis · If the tooth failed to re-erupt after six months of evaluation, an extraction would be the recommended course of treatment because any partial ankylotic changes could impede the path of eruption of the permanent incisor · It is not unusual to have a concomitant root fracture on a primary incisor. If the coronal fractured segment poses any type of aspiration risk, then the recommendation is extraction of the coronal segment while leaving the apical segment alone Figure 4. Radiograph showing no periapical resorption or radiolucency associated with the maxillary left primary central incisor Figure 4. Intra-oral photo showing re-eruption of maxillary left primary central incisor 140 ClinicalCasesinPediatricDentistry Figure 4. Influence on the type of dental trauma on the pulp vitality and the time until treatment: a study in patients ages 0­3 years. Traumatic injuries to the primary dentition and effects on permanent successors-a clinical follow-up study. Falls are typically the most common type of injury, and while the anecdotal belief is that increased supervision will prevent injuries, reports in the literature cite that only about 20% of parents believe increased supervision will prevent falls/injuries (Eberl et al. PresentingPatient · 4-year-, 6-month-old Caucasian male · New patient presenting as an emergency B. ChiefComplaintandHistoryofPresent Injury · Mom states, "My son knocked his teeth yesterday, and now they look brownish. SocialHistory · Patient has no siblings · Mother is the primary caregiver and stays at home · Low socio-economic status D. MedicalHistory · History of recurrent otitis media infections · No known drug or food allergies, no medications, vaccinations are up to date E. If the last tetanus booster was five or more years prior and the wound is contaminated with soil/debris, another tetanus toxoid booster is indicated (Broder et al. Intra-oral photo of maxillary right and left primary central incisors Occlusal Evaluation of Primary Dentition · No significant findings Other · Caries-free dentition I. DiagnosticTools · Periapical radiograph shows root fracture in the middle third of the maxillary right and left primary central incisors · Vitality tests deferred J. DiagnosisandProblemList Diagnosis · Maxillary right and left primary lateral incisors: subluxation · Maxillary right and left primary central incisors: middle root fractures K. Treatment · No treatment is indicated at this time (see Flowchart B at the end of this chapter) · Discharge instructions: Avoid incising on injured segment until instructed otherwise. Watch for clinical signs such as presence of parulis or fistula · Fair oral hygiene with little adult supervision. PrognosisandDiscussion · Root fractures located on the apical third present a good prognosis. Teeth with root fractures in the middle segment should be observed closely as in the case presented. Cases in which there is significant mobility of the coronal segment and/ or mobility of the coronal segment result in poor outcomes M. ComplicationsandAlternativeTreatment Plan · If the fracture had been located in the coronal third, the recommendation would be to remove the coronal segment because the prognosis is poor. Interposition of granulation tissue the most common forms of root fracture healing are calcified tissue and interposition of connective tissue (Cvek et al. Correlation between parental perception and actual childhood patterns of bicycle helmet use and riding practices: implications for designing injury prevention strategies. Development of clinical and radiographic signs associated with dark discolored primary incisors following traumatic injuries: a prospective controlled study. Prevention of traumatic dental lesions: cognitive research on the role of mouthguards during sport activities in paediatric age. Facial photographs Nausea/vomiting Headache Lethargy/irritability/confusion Loss of consciousness Ask patient and parent if they know where the broken tooth fragment is. Rule out aspiration or impaction of the fragment in soft tissue wounds of the lips or tongue Confirm that tetanus immunizations are up to date if there are soft tissue injuries contaminated with soil (Broder et al. PresentingPatient · 8-year-, 7-month-old African-American female · New patient presenting as an emergency B. ChiefComplaintandHistoryofPresent Injury · Mother reports, "My daughter fell off her bicycle and broke her tooth. The grandmother had no transportation so the patient waited until her mother returned home from work to come to the clinic. DentalHistory · No dental home · Mother reports infrequent dental exams through local school program · Diet high in refined carbohydrates · Poor oral hygiene · Child reports brushing with fluoridated toothpaste once per day · Community water is optimally fluoridated · No previous history of dental trauma G. DiagnosticTools · Periapical radiograph demonstrates immature apices of maxillary incisors (Figure 4. Pulp canal obliteration is the most common sequela to luxation injuries to immature permanent teeth Rule out other injuries. Intraoral photos showing maxillary right permanent central incisor-complicated fracture (pulp exposure) Optimal care indicates treatment as soon as possible after the injury. Patient behavior, lack of availability of facilities and materials, or management of more serious injuries may delay treatment. Successful outcomes have been reported when treatment of complicated crown fractures is delayed up to several days, so the clinician may elect to defer treatment until the following morning, if necessary, to assure optimal treatment the treatment objective is to complete a debridement of inflamed or infected pulp tissue while maintaining healthy pulp tissue. This is particularly important in immature teeth in order for complete root maturation (apexogenesis) to occur Figure 4. Periapical radiograph demonstrating immature apices of maxillary incisors 148 ClinicalCasesinPediatricDentistry (Cvek 1978, Flores et al. ComprehensiveTreatment · See Flowchart C at the end of the this chapter · Maxillary right permanent incisor: Partial pulpotomy (Cvek technique, see Fundamental Point 3) · Isolate tooth with rubber dam · Gently remove 1. Final restoration may be completed at same appointment if it can be done atraumatically. However, final restoration should be deferred if tooth is mobile · Suture gingival lacerations (if indicated). Prescribe over-the-counter acetaminophen or ibuprofen for pain, as needed Discharge Instructions · Avoid incising on injured tooth until tenderness resolves · Instruct parents to watch for clinical signs including tooth discoloration and presence of parulis or fistula · Instruct child to report increased pain or mobility Follow-up Treatment · Two-week post-op visit · Clinical exam: Assess vitality with cold and electric pulp tests; assess color, mobility, and pain to percussion · Complete final restoration of tooth if not done at first appointment · Six-week post-op visit · Clinical exam: Repeat assessment above · Radiographic exam: Assess for signs of pulp necrosis, periapical radiolucency, or inflammatory resorption, and for continuing root development · Repeat same post-op assessments at six months and one year. PrognosisandDiscussion · Prognosis depends on maintaining vitality of the pulp in the maxillary right permanent central incisor. The goal is to achieve full root maturation by removing inflamed pulp tissue while retaining healthy pulp in the root canal and crown. While a direct pulp cap may be simpler and quicker to perform than a partial pulpotomy, the consequences of failure (pulp necrosis) are dire in a tooth with an immature apex. Lacking a vital pulp makes the chances of the tooth achieving complete root maturation markedly decreased. Continuing root development in immature teeth is a sign of a positive treatment outcome (Flores et al.

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