Skin

Skin reactions have been observed after intramuscular injection of phytomenadione. The English-language literature on adverse skin reactions associated with intramuscular or subcutaneous phyto-menadione has been reviewed (8). Vitamin K is generally well tolerated subcutaneously or intramuscularly. However, erythematous eczematous plaques have been well documented. Of 39 skin reactions due to Table 1 Classification of hemorrhagic disease of the newborn Table 1 Classification of hemorrhagic...

References

Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994 47(1) 153-205. 2. Erlich KS, Mills J, Chatis P, Mertz GJ, Busch DF, Follansbee SE, Grant RM, Crumpacker CS. Acyclovir-resistant Herpes simplex virus infections in patients with the acquired immunodeficiency syndrome. N Engl J Med 1989 320(5) 293-6. 3. Sacks SL, Wanklin RJ, Reece DE, Hicks KA, Tyler KL, Coen DM. Progressive esophagitis from...

Liver

Although rarely severe, any increase in liver enzyme activity justifies careful and regular monitoring of liver function and the results may be a reason for withdrawing treatment (SED-8, 1118) (21). In a retrospective study, hepatitis was found in 21 (2 ) of 1035 renal transplant patients, and it was suggested that hepatitis B or C infection increases the risk of azathioprine hepatotoxicity (22). In 29 cardiac transplant recipients who had had probable azathioprine-induced liver dysfunction,...

Taxus species

Taxus (yew) trees contain alkaloids called taxanes that have anticancer activity and are the basis of the semi-synthetic anticancer drugs paclitaxel and docetaxel (see separate monographs), which are based on taxol, from Taxus brevifolia. Taxus baccata has been used as a means of suicide (1-3), successfully, because of cardiac dysrhythmias (4). Taxoids from Taxus cuspidata (the Japanese yew) inhibit P glycoprotein and are candidates for reversing multidrug resistance in cancer cells (5). Taxus...

Rhus species

Rhus is used as a traditional remedy for gastrointestinal complaints in Korea. Anacardium (anacardium) Buchanania (buchanania) Campnospera Comocladia (maidenplum) Cotinus (smoke tree) Dracontomelon (dracontomelon) Gluta (gluta) Lithrea (lithrea) Malosma (laurel sumac) Mangifera (mango) Melanorrhoea (melanorrhoea) Metopium (Florida poison tree) Pistacia (pistachio) Rhus (sumac) Schinus (pepper tree) Schinopsis (schinopsis) Sclerocarya (sclerocarya) Semecarpus (semecarpus) Spondias (mombin)...

General adverse effects

The frequencies of severe adverse effects of aldesleukin (7) are listed in Table 1 and the most frequent reasons for withdrawal of high-dose intravenous aldesleukin in Table 2. Table 1 The frequencies of severe adverse effects of aldesleukin Supraventricular dysrhythmias 3 Myocardial damage (angina, infarction) 4 Adult respiratory distress syndrome < 1 Behavioral changes 28 Hematologic Pruritus and erythema 4 Musculoskeletal Table 2 The most frequent reasons for withdrawal of high-dose...

The safety of fenoterol in severe asthma

Debate continues about the safety of fenoterol in the treatment of severe asthma. A sharp rise in asthma mortality in 1977 in New Zealand provoked debate about the safety of beta2-adrenoceptor agonists, especially the short-acting compound fenoterol. This led to the withdrawal of fenoterol in New Zealand and amendment of the American Asthma Guidelines, suggesting caution in the regular use of beta2-adrenoceptor agonists (1). Although there is evidence linking fenoterol to increased morbidity...

Use in noninfective conditions

Levamisole has immunostimulatory activity by modulating the cell-mediated immune response and restoring T cell functions. It has therefore been used extensively and for extended periods of time in various rheumatic and other chronic diseases, in aphthous ulceration, nephrotic syndrome, warts, and malignancies, such as cancers of the head and neck and, in combination with 5-fluorouracil, colorectal cancer (SEDA-20, 348). Under these conditions, its adverse effects are more frequent and rather...

General Information

Bucricaine (centbucridine) is a quinolone derivative with local anesthetic activity. Nausea, vomiting, bradycardia, backache, shivering, and hypotension can occur with a similar incidence to that of lidocaine (SED-12, 256) (1). It has been suggested that bucricaine is more potent than lidocaine and has few cardiovascular and nervous system adverse effects in animals, at high doses. One study in humans suggested that bucricaine may be associated with fewer cardiovascular adverse effects than...

Nervous system

Peripheral nerve block is created by injecting ethanol around the selected nerve. The effect of alcohol on nerve tissue has been examined in animal models and in postmortem specimens from patients who received neurolytic blocks (8,9). In general, alcohol causes destruction of nerve fibers, with subsequent Wallerian degeneration. The basal lamina around the Schwann cell usually remains intact. This leaves a tract available for axon regeneration without the formation of a neuroma. If the cell...

Oenothera biennis

The seeds of Oenothera biennis (evening primrose, fever plant, king's cure-all, night willow herb, scabish, sundrop, tree primrose) yield evening primrose oil, which contains gamma-linolenic acid and has been used in various disorders, such as atopic eczema, premenstrual syndrome, and benign breast pain, but is probably not efficacious (1,2). Evening primrose oil has generally only minor adverse effects, such as nausea, diarrhea, and headache. In three patients evening primrose oil triggered...

Immunologic

Allergic reactions, including anaphylaxis, from chlor-hexidine are reported with all types of use and are well documented. However, chlorhexidine may still not be suspected as a possible cause of anaphylaxis when several agents are used in the anesthetized surgical patient, and hypersensitivity to chlorhexidine may not be tested for (37). If a reaction occurs during anesthesia, there is often doubt about the exact agent responsible patch-testing will help if there is doubt about causality. The...

Valeriana species

Valeriana (all-heal, amantilla, heliotrope, valerian), 400900 mg 30-60 minutes before bedtime, is a traditional herbal sleep remedy (1), but although it has subjective effects on sleep objective sleep measures have been inconsistently affected (2). The roots of members of the Valeriana (valerian) species contain valepotriates, which have alkylating properties. Valtrate isovaltrate and dihy-drovaltrate are mutagenic in bacterial test systems in the presence of a metabolic activator, and their...

Drugs that influence CYP3A

Midazolam is selectively metabolized by CYP3A4, with which several drugs interact, influencing its pharmaco-kinetics and pharmacodynamics. Itraconazole, an inhibitor of CYP3A, and rifampicin, an inducer of CYP3A, altered the pharmacokinetics and pharmacodynamics of oral midazolam in nine healthy volunteers (42). The half-life was prolonged from 2.7 to 7.6 hours by itraconazole and reduced to 1.0 hour by rifampicin. These effects were still present, although less marked, at 4 days after...

Comparative studies

In a double-blind, multicenter trial in 328 patients with H. pylori infection and non-ulcer dyspepsia, omeprazole 20 mg bd, amoxicillin 1 g bd, and clarithromycin 500 mg bd were compared with omeprazole alone. The rate of success and quality of life were similar in both groups. There were no serious adverse events. However, there were 12 withdrawals in the group given omeprazole and antibiotics and two in the group given omeprazole alone. Diarrhea occurred in 63 patients in those given...

Intraarticular and periarticular administration

Local injections of glucocorticoids into and around the joints can have a dramatic therapeutic effect, but the catabolic effect can have serious consequences, including adverse effects on joint structure (395) and on local tendons, subcutaneous atrophy, and possibly osteonecrosis. Provided the state of the joint is carefully inspected before any new injection is given, and the interval between the injections is not less than 4 weeks, the risk seems to be small enough to justify treatment in...

Surveillance of adverse events following immunization

Currently, in many highly developed countries in which the incidences of dangerous infectious diseases have been markedly reduced through immunization, there are controversial discussions about the balance of benefits and harms in immunization. Vaccine adverse events, both those caused by vaccines (that is true adverse reactions) and those associated with immunization only by coincidence, become more visible than the natural disease. Not surprisingly, vaccine safety concerns have become...

Topical administration to the eye

Glucocorticoids that have been used for local ophthalmic treatment include medrysone, fluorometholone, tetrahy-droxytriamcinolone, and clobetasone. Loteprednol etabo-nate 0.5 increases intraocular pressure less than dexamethasone. Studies on animal models of uveitis and two randomized double-masked trials showed that lote-prednol etabonate 0.5 was less potent than dexametha-sone, prednisolone acetate 1 , or fluorometholone, which may partly explain the improved toxicity profile of loteprednol...

Polio vaccines as a possible cause of AIDS

There is a hypothesis that the HIV virus might have jumped the species barrier from monkey to people via a contaminated polio vaccine because the vaccine was manufactured in primary monkey kidney tissue known to be sometimes contaminated with monkey viruses. The existing evidence, including tests of poliovirus seed stocks, more than 20 vaccine lots, and serum samples from vaccine recipients makes this hypothesis highly improbable (6,7). Contamination of polio vaccines with simian papovavirus 40...

Psychological psychiatric

At first thought to occur only after therapeutic doses of mefloquine, it is now clear that neuropsychiatric reactions occur after prophylactic use as well. The incidence is estimated at about one in 13 000 with prophylactic use, but as high as one in 215 with therapeutic use (SEDA-17, 329). Combination with other drugs that affect the nervous system can result in unpredictable reactions. The symptoms vary in type and severity non-cooperation, disorientation, mental confusion, hallucinations,...

Mechanism of action

A77 1726 inhibits dihydro-rate dehydrogenase, the rate-limiting enzyme in pyrimidine synthesis. It inhibits the proliferation of T and B cells, and probably acts via the production and action of interleukin-2. Besides its immu-nomodulatory action, A77 1726 also has an anti-inflammatory action by inhibition of nuclear factor kappa B (NFkB), tumor necrosis factor alfa (TNF-a), and interleukin 1 beta (IL-1,0), and increased production of transforming growth factor beta-1 (TGF-,01) (2-5).

Warfarin

Azithromycin can increase the effect of warfarin (183), perhaps by inhibiting its metabolism. Despite only modest effects of macrolides on serum warfarin concentrations and increases in prothrombin time (119), morbidity caused by hemorrhage may be significant, as illustrated by several case reports (184-188). It is likely that this interaction is potentiated by other factors, such as old age or dietary restrictions (119). However, a retrospective analysis of 3995 patients treated with...

Drug Administration Drug formulations

Drugs that have similar names are not infrequently confused. The name of Sanofi-Synthelabo's brand of sodium polystyrene sulfonate, Kayexalate, could be confused with the names of proprietary brands of potassium chloride, such as Kay-Cee-L and Kay-Ciel. Furthermore, some formulations of potassium chloride are formulated in packaging that resembles that of Kayexalate. There have been two deaths when potassium chloride was given instead of sodium polystyrene sulfonate for hyperkalemia (31).

Age

Small children have usually been considered as being relatively more sensitive to the effects of overdosage, but it has been calculated that on a mg kg body weight basis, adults are in fact equally sensitive. Young children seem to be truly more susceptible to gastric irritation. Patients with a history of mania or epilepsy should be careful in taking chloroquine (9). The hypoxemic effects of chloroquine, reflecting cardiac and respiratory toxicity, pose a particular problem in the newborn, in...

Organs and Systems Respiratory

Intravenous injection of solubilized'' psychoactive pills containing talc can produce microemboli in small pulmonary vessels, leading to talc granulomatosis, a common finding in drug abusers. Medications intended for oral use can be injected or sniffed, together with talc particles. Pulmonary hypertension due to talc microemboli is a well-known cause of respiratory failure in heroin addicts. A heroin addicted patient, who had been followed up for 6 months for increasing dyspnea due to chronic...

Drug Drug Interactions Alcohol

Although ethanol itself has no effect on bleeding time, it enhances the effect of aspirin when given simultaneously or up to at least 36 hours after aspirin ingestion (99). Ethanol also promotes gastric bleeding. The FDA has announced its intention to require alcohol warnings on all over-the-counter pain medications that contain acetylsalicylic acid, salicylates, paracetamol, ibuprofen, ketoprofen, or naproxen. The proposed warnings are aimed at alerting consumers to the specific risks incurred...

Organs and Systems Liver

Hepatotoxicity is the most important adverse effect of antituberculosis drug therapy. Isoniazid, rifampicin, and pyrazinamide are the main culprits. There is wide variability in the risk of hepatotoxic reactions reported from different parts of the world or in different populations (for example African-American women in the postpartum period) (SEDA-24, 353). The risks of hepatotoxicity differ with different antituberculosis drug combinations. There are mild to moderate increases in liver...

See also Individual agents General Information

The benzodiazepines typically share hypnotic, anxiolytic, myorelaxant, and anticonvulsant activity. Because their efficacy and tolerability are generally good, especially in the short term, they have been used extensively and are likely to continue to be used for many years to come. However, their less specific use in the medically or psychia-trically ill, and in healthy individuals experiencing the stresses of life or non-specific symptoms has often been inappropriate and sometimes dangerous...

Organs and Systems Cardiovascular

Alcohol is one of many drugs that cause or aggravate systemic hypertension. Acute alcohol exposure has an inconsistent effect on blood pressure, but cross-sectional population studies have shown a relation between chronic alcohol consumption and blood pressure, and the prevalence of hypertension up to three times higher in heavy drinkers (5). Although the mechanism of hypertension caused by chronic alcohol consumption is not known, it is suspected that it is partly related to repeated episodes...

General adverse reactions

In a survey of more than 2000 patients treated with iso-niazid, the most frequent adverse effects were rash (2 ), fever (1.2 ), jaundice (0.6 ), and peripheral neuropathy (0.2 ). Seizures can also occur. Isoniazid prolongs the half-life of rifampicin and other drugs metabolized by the liver. Morbilliform, maculopapular, purpuric, and urticarial rashes, with or without fever, are considered to be of allergic origin. Hematological adverse effects consist of agranulocytosis, thrombocytopenia, pure...

Metabolism

Although there is a long list of causes of metabolic acido-sis with an increased anion gap (6,7), clinical clues can help diagnosis. A case report has illustrated the acute metabolic and hemodynamic effects of ingestion of a massive load of oral citric acid. The principal findings included a metabolic acidosis accompanied by an increase in the plasma anion gap, not due to lactic acidosis, hyper-kalemia, and the abrupt onset of hypotension (8). A 42-year-old previously healthy male prisoner...

Mahonia species

Barberry is a vernacular name for members of the Berber s species, such as Berber s vulgaris (European barberry), but is also used to refer to members of the Mahonia species, such as Mahonia aquifolium and Mahonia nervosa. In the USA only the latter species have had official status as a source of barberry, but Berberis vulgaris is said to serve similar medicinal purposes and to contain similar principles. Its root bark yields the quaternary isoquinoline alkaloid berberine and several other...

Prostaglandins in ophthalmology

Topical PGE2 and PGF2a significantly reduce intraocular pressure for at least 24 hours and are used in the treatment of glaucoma. Derivatives of the isopropyl ester of PGF2a appear to be the most effective. Transient ocular adverse effects include conjunctival hyperemia, local irritation, intermittent photophobia, and pain in the eye (66-68). Newer derivatives, such as latanoprost, travoprost, and bimatoprost, appear to be better tolerated, with less severe and less frequent adverse effects...

Long Term Effects Drug withdrawal

The more intensive diuretic treatment is the greater the risk from sudden withdrawal. In one series of 38 patients, taking 20-40 mg furosemide or equivalent, generally for heart failure, withdrawal was attempted when all had been free of heart failure or hypertension for at least 3 months it was followed by clinical or radiological relapse in 29 and one of the patients died (21). In another five patients, withdrawal in three led to severe symptoms necessitating admission to hospital (SEDA-10,...

Nicotinic acid derivatives

Nicotinic acid derivatives include acipimox, aluminium nicotinate, nicotinyl alcohol, and xanthinol nicotinate. The adverse effects of these compounds appear to be identical to those of nicotinic acid. Acipimox (S-methylpyrazine-2-carboxylic acid 4-oxide) is structurally related to nicotinic acid. Flushing and gastrointestinal disturbances, but there were no effects on blood glucose or uric acid in 7137 patients, of whom 15 stopped taking the drug because of adverse effects (12). In another...

Drug resistance

The relative frequency of resistance to macrolides, lincosamides, and streptogramins (MLS resistance) has been assessed in a series of 2091 staphylococcus isolates collected during a 3-week period in 1995 in 32 French hospitals. A total of 294 strains (144 Staphylococcus aureus, 150 coagulase-negative staphylococci) exhibited resistance to at least one of these groups of antibiotics. Resistance to pristinamycin was phenotypically detected in ten S. aureus strains (seven isolates from the same...

Drug Drug Interactions

Ritonavir can interact with carbamazepine (20). A 49-year-old woman with a long history of HIV infection developed worsening ataxia leading to two falls. Four days before admission she had had her antiretroviral drugs changed from zidovudine, lamivudine, and indinavir to ritonavir, saquinavir, and efavirenz. She was also taking carbamazepine to control generalized seizures resulting from a previous right thalamic infarction. The change in antiretroviral therapy resulted in an increase in serum...

Leukodepleted blood products

As in several other countries, the Health Council of the Netherlands has prepared recommendations on the need for routine leukodepletion by filtration of blood. The presence of leukocytes in blood products has no beneficial effect for the recipient, except in special cases, such as patients undergoing organ transplantation (41). Apart from preventing the adverse effects associated with leukocyte transfusion, it has been postulated that the risk of transmission of new variant Creutzfeldt-Jakob...

Morphine

See also Opioid analgesics General Information Morphine and its two glucuronides may have neuroexcita-tory effects and affinity for non-opioid receptors (glycine and or N-methyl-d-aspartate), effects that will not be antagonized by naloxone. Furthermore, these other opioid effects may be related to the mechanism of some adverse effects, including hyperalgesia, allodynia, and myoclonus, which are increasingly being reported after high doses of morphine, but which do not seem to occur after...

Drug Drug Interactions Furosemide

Acetazolamide inhibits cerebrospinal fluid production, and its effects are augmented by furosemide, suggesting a role for this combination in infants with ventricular dilatation resulting from severe periventricular hemorrhage. The International Posthaemorrhagic Ventricular Drug Trial Group has reported the results of a randomized, controlled trial of standard therapy alone or with the addition of acetazolamide plus furosemide in the first 151 of 177 randomized patients (27). The addition of...

Placebocontrolled studies

The effect of adding acarbose (maximum 100 mg tds) or placebo to insulin (15) or metformin (16) has been investigated in 1946 patients with type 2 diabetes. The results were comparable with the results of the UK Prospective Diabetes Study (17). After 3 years, 39 were still using acarbose compared with 58 using placebo. The main reasons for stopping were flatulence (30 versus 12 ) or diarrhea (16 versus 8 ). After 3 years the HbA1c concentration was 0.5 lower (median 8.1 versus 8.6 ). Acarbose...

Gastrointestinal

Abdominal discomfort is frequent with metformin (15-25 ), and nausea, vomiting, and diarrhea occur even in the absence of lactic acidosis. Other effects include flatulence, abdominal bloating, anorexia, and a metallic taste. Anorexia and weight loss are often seen at the beginning of treatment. Phenformin can cause hemorrhagic gastritis (65). The gastrointestinal adverse effects of metformin can be reduced by giving the metformin during or immediately after meals, starting with a low dose and...

Melatonin

Melatonin has a hypotensive effect in both normotensive and hypertensive subjects. In a double-blind, randomized, crossover study designed to evaluate whether evening ingestion of melatonin potentiates the antihypertensive effect of nifedipine monotherapy in 50 patients with well-controlled mild to moderate hypertension aged 38-65 years (28 men, 22 women), there was a surprising significant increase in blood pressure and heart rate throughout 24 hours (56). The authors suggested that there was...

Bleeding disorders

Treatment with beta-lactam antibiotics can result in impaired hemostasis and bleeding. The true incidence of bleeding is difficult to assess, since many non-antibiotic factors can be involved, such as malnutrition with vitamin K depletion (87), renal insufficiency (88), and serious infection (89). Cancer, the use of cytotoxic drugs, and surgery have made conclusive interpretation of coagulation disorders difficult (90). Between the different beta-lactam antibiotics, the reported incidence of...

Fetotoxicity

The adverse effects of beta-adrenoceptor antagonists on the fetus have been reviewed (319). Beta blockers cross the placenta, and can have adverse maternal and fetal effects. Studies of the use of beta-blockers during pregnancy have generally been small, and the gestational age at the start of the study was generally 29-33 weeks, leaving substantially unanswered the possibility that treatment of more patients and or longer treatment durations may reveal unrecognized adverse events. These...

Citrullus colocynthis

The dried pulp of the fruit of Citrullus colocynthis (colocynth) is a drastic laxative, which contains toxic cucurbitacins. Apodanthera (apodanthera) Benincasa (benincasa) Brandegea (starvine) Bryonia (bryony) Cayaponia (melonleaf) Citrullus (watermelon) Coccinia (coccinia) Ctenolepis (ctenolepis) Cucumis (melon) Cucumeropsis (cucumeropsis) Cucurbita (gourd) Cyclanthera (cyclanthera) Doyerea (doyeria) Ecballium (squirting cucumber) Echinocystis (echinocystis) Echinopepon (balsam apple) Fevillea...

Respiratory

Most people tolerate aspirin well, but not patients with asthma, of whom there is a subgroup in whom aspirin precipitates asthmatic attacks (61,62). This is a distinct clinical syndrome, called aspirin-induced asthma, which affects about 10 of adults with asthma (63). Aspirin-induced asthma is usually accompanied by naso-ocular symptoms and can be triggered not only by aspirin, but by several NSAIDs, a fact that makes immunological cross-reactivity most unlikely. The propensity of an NSAID to...

Amphotericin

In vitro studies and experiments in animals have given conflicting results relating to potential antagonism between the effects of fluconazole and amphotericin on Candida species (71). However, large, randomized, double-blind comparisons of fluconazole with and without amphotericin for 5 days in non-neutropenic patients with candidemia showed no evidence of antagonism, but faster clearance of the organism from the blood and a trend toward an improved outcome in those who received the...

Iodophors

Iodophors are labile complexes of elemental iodine with macromolecular carriers that both increase the solubility and provide sustained release of iodine. Povidone-iodine is a water-soluble iodophor that is used as an antiseptic and is said to be free of the undesirable effects of iodine tincture. However, iodine can be absorbed from it through burned areas (16), vaginal mucosa (17), oral mucosa (18), and in children even with normal skin (19). Povidone-iodine is discussed in a separate...

Citalopram

The effect of ketoconazole on the pharmacokinetics of citalopram has been studied in a double-blind, three-way, crossover trial in 18 men and women (38). The subjects received three treatments with a 14-day washout period a single dose of ketoconazole 200 mg plus placebo, a single dose of citalopram 40 mg plus placebo, and a single dose of ketoconazole 200 mg plus a single dose of citalopram 40 mg. There were no changes in the pharmacokinetics of citalopram after co-administration of...

Ciclosporin

The combination of itraconazole with ciclosporin leads to a marked increase in blood ciclosporin concentrations, and this can result in a rise in serum creatinine, clearly pointing to renal damage as a result of the high ciclosporin concentrations (SED-12, 681) (69,70-72). However, an interaction has not been demonstrated in all cases (73). Two cases of rhabdomyolysis caused by itraconazole in heart transplant recipients taking long-term ciclosporin and simvastatin have been reported (74,75)....

Second Generation Effects Teratogenicity

The mixture of doxylamine succinate and pyridoxine (at one time combined with dicycloverine), known under the brand names of Bendectin and Debendox, was withdrawn after a campaign had incriminated it as a teratogen. Used mainly in some English-speaking countries, it was used primarily to treat nausea and vomiting during pregnancy in circumstances in which, in other countries, dietary measures and or low doses of antihistamines alone are more customary. No consistent picture of the congenital...

Etretinate and isotretinoin

Since the beginning of the 1980s two synthetic retinoids, etretinate (the ethyl ester of trimethoxymethyl-phenyl retinoic acid Tigason Tegison) and isotretinoin (13-cis-retinoic acid Acutane Roaccutane), have been successfully administered for a variety of skin disorders, all of which involve disordered epidermal or epithelial cell growth and differentiation as prominent pathogenic features, for example psoriasis, ichthyosis, Darier's disease, lichen planus, and pityriasis rubra pilaris....

Pancuronium

Antagonism to pancuronium has been found with theophylline concentrations in excess of the recommended target range (SEDA-5, 4). Aminophylline appears to facilitate neuromuscular transmission, perhaps by increasing neurotransmitter release through raising cyclic AMP concentrations at the neuromuscular junction by phosphodiesterase inhibition (72). This would account for the antagonism of pancuro-nium-induced blockade that has been reported to occur in the presence of very high serum...

Hematologic

Patients with end-stage liver failure, portal hypertension, and associated pulmonary artery hypertension (portopul-monary hypertension) have a high mortality when undergoing liver transplantation. Successful transplantation in these patients may depend on efforts to reduce pulmonary artery pressure. To this end, some centers are using a continuous intravenous infusion of epoprostenol, which has been shown to improve symptoms, extend life span, and reduce pulmonary artery pressure in patients...

Teratogenicity

Vitamin K antagonists, including hydroxycoumarin derivatives and indan-1,3-dione-derived drugs, can be teratogenic and can also induce bleeding in the fetus (71,72,76-79). Adverse fetal outcomes occur in about one-third of pregnancies after either oral anticoagulants or heparin (77). This surprisingly high figure, which is often quoted, should be tempered by the consideration that these data are largely (if not exclusively) derived from women with heart valves taking relatively large doses of...

Dysosma pleianthum bajiaolian

Dysosma pleianthum (bajiaolian), a species of mayapple, has been widely used for thousands of years in China as a general remedy and for the treatment of snake bite, weakness, condyloma acuminata, lymphadenopathy, and tumors. Podophyllotoxin is one of its main ingredients. Five people who drank infusions of bajiaolian developed nausea, vomiting, diarrhea, abdominal pain, thrombocy-topenia, leukopenia, abnormal liver function tests, sensory ataxia, altered consciousness, and persistent...

Oral anticoagulants

Since dimeticone is a surfactant, one might expect it to enhance the absorption of drugs, and there are some reports that this happens with ethyl biscoumacetate (17). 5. Krska J, John DN, Hansford D, Kennedy EJ. Drug utilization evaluation of nonprescription H2-receptor antagonists and alginate-containing preparations for dyspepsia. Br J Clin Pharmacol 2000 49(4) 363-8. 6. Lifschitz CH, Irving CS, Smith EO. Effect of a simethicone-containing tablet on colonic gas elimination in breath. Dig Dis...

Albumin microspheres

Albunex is a suspension of air-filled human albumin microspheres. In an assessment of the safety of Albunex (Molecular Biosystem Inc USA, Nycomed, Oslo Norway) in imaging the left ventricle in 52 patients, there were no major or minor adverse events and no changes in vital signs (2). Optison is a second-generation contrast agent based on sonicated human albumin (albumin microspheres containing the gas perfluoropropane). In 191 patients with chronic pulmonary disease and or cardiomyopathy (aged...

Second Generation Effects Pregnancy

Use of beta2-adrenoceptor agonists in threatened premature labor The adverse effects of the beta2-adrenoceptor agonists when given (as a rule by injection) to arrest premature uterine contractions are very similar to those experienced when the classic drug in the series (salbutamol) is used for other purposes. In the special circumstances of obstetrics, however, there are several particular safety problems. Probably most or all beta2-agonists could be used in obstetrics as well as in asthma,...

Relation of toxicity to pharmacokinetics

The pharmacokinetics of fluorouracil have been determined in 19 patients receiving fluorouracil by protracted intravenous infusion of 190-600 mg m2 day (5). The steady-state fluorouracil plasma concentration and AUC were significantly lower in the nine patients who had WHO grade 2 toxicity or less compared with the nine patients who had greater than grade 2 toxicity. In contrast, there was no difference in fluorouracil plasma concentrations between the 10 responders and the nine patients who...

Relation to dose

Many reactions to beta-lactam antibiotics are clearly not immune mediated. These include bleeding disorders, neu-rotoxicity, and most cases of diarrhea. In addition, many reactions, the pathogenesis of which is still being discussed, clearly depend on the daily and the cumulative dose of beta-lactam antibiotics and hence the duration of treatment. Although the rare, but well-understood, immune hemolysis after penicillin is seen mostly with high-dose and long-term treatment, dose dependency and...

Renal disease

The hydrophilic drugs atenolol and sotalol are eliminated largely unchanged in the urine with deteriorating renal function their half-lives can be prolonged as much as 10fold (330,331). Other beta-adrenoceptor antagonists, for example acebutolol and metoprolol, have active metabolites that can accumulate (332). Massive retention of the metabolite propranolol gluconate has also been reported in patients with renal insufficiency taking long-term oral propranolol (333) this metabolite is then...

Reproductive system

There is a risk of ovarian hyperstimulation when an ovulation-inducing drug is followed by rapid ovarian enlargement with peritoneal effusion. The incidence of these complications varies with the product and dosage schedule used in experienced hands, the frequency of complications may be no more than about 4 . In an unusual case reported in detail from Saudi Arabia, a 28-year-old woman receiving gonadotropins developed acute respiratory distress, abdominal pain, and severe hyponatremia...

Residronate

Residronate is a pyridinylbisphosphonate with potent antiresorptive properties. In animal studies it was about 1000 times more potent than etidronate and 3-5 times more potent than alendronate (13), which enables the use of a lower dose and a shorter treatment regimen, with consequent potential minimization of adverse effects. In a randomized, double-blind, multicenter study of the efficacy, safety, and tolerability of residronate in 62 patients taking oral residronate for Paget's disease of...

Retinal damage

An apparent association between severe retinopathy of prematurity and dexamethasone therapy has been shown in a retrospective study (SEDA-20, 372) (62). Infants treated with dexamethasone required longer periods of mechanical ventilation (44 versus 26 days), had a longer duration of supplemental oxygen (57 versus 29 days), had a higher incidence of patent ductus arteriosus (28 38 versus 18 52), and required surfactant therapy more often for respiratory distress syndrome (17 38 versus 11 52)....

Rheum palmatum

Rheum palmatum (rhubarb) contains the anthranoids sen-nosides and rhein. In a study of patients taking regular doses of rhubarb-containing Kampo medicines (extracts or decoctions) and patients taking excess doses there was tolerance to initial stimulant pain in the abdomen during excess use (7). The authors proposed that the absence of tenderness on pressure over the umbilical region could predict increasing or excess use of rhubarb. In 14 616 patients who used various Kampo medicines, some of...

Rifamycins

Clarithromycin is one of the core drugs for MAC infections in both HIV-infected and non-infected patients. For this indication, doses of up to 2000 mg day are used, typically in combination with other drugs. The interaction of clarithromycin with the rifamycins is complex. Clarithromycin inhibits CYP3A4, while both rifampicin and rifabutin induce P450 cytochromes, including CYP3A4, resulting in enhanced metabolism of drugs. The changes in serum concentrations of clari-thromycin and its...

Risperidone andor sertraline

An interaction of tetracycline with risperidone and or sertraline has been described (188). A 15-year-old youth with Asperger's syndrome, Tourette's syndrome, and obsessive-compulsive disorder was stabilized on risperidone 1.5 mg bd and sertraline 100 mg od and had marked improvement in his social skills and tics, until he was given tetracycline 250 mg bd for acne. Within 2 weeks his tics were acutely exacerbated with pronounced neck jerking and guttural sounds. The sertraline was increased to...

Risperidone

Combined treatment with atypical neuroleptic drugs and SSRIs is common and case reports have suggested that SSRIs can increase risperidone concentrations and increase the risk of extrapyramidal disorders (SEDA-23, 18). Severe parkinsonism with urinary retention occurred when fluoxetine 20 mg day was added to risperidone 2 mg day in a 46-year-old man with schizophrenia. Risperidone had been prescribed at this dose for 1 month without any adverse effects, and the authors considered that a...

Ritodrine

See also Beta2-adrenoceptor agonists General Information Ritodrine is a beta2-adrenoceptor agonist used in the treatment of premature labor. The hemodynamic effects of ritodrine have been assessed in 12 fetuses by cardiac and extracardiac Doppler sonography (1). Ritodrine significantly increased maternal and fetal heart rates, left cardiac stroke volume, and cardiac output. There was also an increase in the pulsatility index of the middle cerebral artery and a fall in the pulsatility index of...

Ritonavir

Ritonavir is an inhibitor of HIV protease and a potent inhibitor of CYP3A4 and CYP2D6. The interaction between ritonavir and intravenous fentanyl has been investigated in 12 healthy volunteers in a double-blind, placebo-controlled, crossover study (84). The volunteers took ritonavir 600 mg on day 1, ritonavir 900 mg and intravenous fentanyl 5 mg kg on day 2, and ritonavir 300 mg or placebo on day 3. Ritonavir reduced the clearance of fentanyl by 67 by inhibiting its metabolism. This could...

Rocuronium bromide

See also Neuromuscular blocking drugs General Information Rocuronium is a steroidal agent related chemically to vecuronium. It is less potent than vecuronium and has a quicker onset of action. The plasma clearance of rocuronium is primarily due to liver uptake and biliary excretion (1). About one-third of an injected dose is excreted unchanged in the urine (1). Good intubating conditions may be expected 90-120 seconds after the injection of 0.6 mg kg rocuronium. Increasing the dose to 1 mg kg...

Ropivacaine

In a prospective, randomized, double-blind study, the analgesic effect and adverse effects profile of epidural ropivacaine (2 mg ml) alone was compared with three different fentanyl ropivacaine combinations (fentanyl 1, 2, and 4 mg ml) for up to 72 hours of postoperative analgesia in 244 patients after major abdominal surgery, most commonly colorectal surgery (85). Hypotension was significantly more common with fentanyl 4 mg (52 ) compared with the other three groups (31-34 ) in the first 24...

Routes of administration

Nitrates can be administered by various routes. For example, glyceryl trinitrate is used not only as traditional sublingual tablets but also in the form of modified-release tablets, buccal tablets, aerosolized oral spray, intravenous injection, and topical ointment or skin patches for percutaneous absorption (23). These different formulations have been developed largely as a means of controlling the onset and duration of action of glyceryl trinitrate, since in conventional oral form its action...

Roxithromycin

The effect of omeprazole on roxithromycin concentrations in plasma and gastric tissue has been investigated in 12 healthy volunteers who took omeprazole 20 mg bd with or without roxithromycin 300 mg bd over 6 days (38). The medications were well tolerated, with only mild adverse events. The more frequent adverse events were nausea, bloating, and diarrhea. Omeprazole and roxithromycin did not alter the systemic availability of each other. However, omeprazole increased the local concentration of...

Salts of antimony

Meglumine antimoniate is a pentavalent antimonial chemically similar to sodium stibogluconate and is considered to have similar efficacy and toxicity. Meglutamine antimoniate solution contains pentavalent antimony 8.5 and stibogluconate 10 . Sodium stibogluconate is a pentavalent antimonial that contains pentavalent antimony 10 . Stibocaptate is a trivalent antimony compound, whose toxic effects, especially its acute adverse effects, are similar to those of the pentavalent compounds.

Salvia species

In China, the root of Salvia miltiorrhiza (danshen) has been used traditionally for the treatment of coronary diseases. The leaf of Salvia officinalis (sage) contains 1.0-2.5 of essential oil, consisting of 35-60 of thujone. A patient taking warfarin and who had taken a decoction of S. miltiorrhiza presented with a prolonged bleeding time and melena (12) and other cases have been reported (13). Pharmacodynamic and pharmacokinetic studies in rats have shown that danshen increases the absorption...

Saquinavir

See also Protease inhibitors General Information Of all protease inhibitors, saquinavir is the most potent in vitro. However, owing to poor systemic availability (less than 4 ), it is the least potent of all protease inhibitors in use, although a formulation with increased availability has been marketed. However, when saqui-navir is given together with ritonavir, the strong inhibitory effect on CYP3A4 of the latter results in high plasma concentrations of saquinavir. This interaction has been...

Searching the online edition

The print edition of this Reference Work contains two indexes, the Index of Drug Names'' and the Index of Adverse Reactions''. Both indexes are print oriented and point at pages in the main text in which a reaction is discussed or a drug name used. In the online environment these are redundant as freestanding indexes since on ScienceDirect simple searches can achieve the same results more efficiently and quickly. In addition, whilst the print Index of Adverse Reactions'' was necessarily...

Second Generation Effects

Citalopram has been reported to cause sleep disturbance in a breast-fed infant (19). A 29-year-old woman took citalopram (40 mg day) while breast feeding her 5-week-old daughter. The maternal citalopram concentrations were 99 ng ml in the serum and 205 ng ml in the breast milk. The serum concentration in the infant was 13 ng ml, and the child's sleep was fitful and disturbed. The dosage of citalopram was reduced to 20 mg day and the two feeds after each daily dose were replaced by artificial...

Second Generation Effects Fertility

Leflunomide did not affect fertility in rats (87). Teratogenicity In oral embryocytotoxicity and teratogenicity studies in rats and rabbits, leflunomide was embryocytotoxic (growth retardation, embryolethality) and teratogenic (malformations of the head, rump, vertebral column, ribs, and limbs) (87). Not only is leflunomide teratogenic and fetotoxic in animals, but its active metabolite is detectable in plasma up to 2 years after withdrawal. Therefore, the fetus could have in utero exposure to...

Second Generation Effects Fetotoxicity

Alfentanil 10 mg kg in normal parturients does not reduce Apgar scores, but a higher dose (15-30 mg kg) is recommended for attenuation of the stress'' response in non-pregnant patients. In a randomized, placebo-controlled, double-blind study alfentanil was used in 40 patients in a dose of 10 mg kg 1 minute before induction of anesthesia in 40 uncomplicated cesarean deliveries to determine whether it would reduce the maternal stress response after tracheal intubation without subsequent neonatal...

Sedation for endoscopy

Gastrointestinal endoscopy is one of the most commonly performed invasive procedures in clinical practice (for example about 500 000 procedures per annum in Australasia). Propofol is a short-acting intravenous anesthetic with a rapid onset of action and a short half-life, making it eminently suitable for day procedures. However, the use of propofol by non-anesthetists has been controversial because of the perceived risks of its low therapeutic ratio. The incidence of adverse events related to...

Sedation for surgery under regional anesthesia

Sedation during prolonged surgical procedures under regional anesthesia can be quite challenging. The beta2 adrenoceptor agonist dexmedetomidine has potent sedative and analgesic-sparing properties. In therapeutic doses it does not cause respiratory depression, making it attractive for infusion sedation. However, it causes reduced sympathetic outflow, which might cause untoward hemo-dynamic upset during intraoperative sedation. Dexmedetomidine has been compared with propofol in a prospective...

See also Adrenoceptor agonists General Information

As a non-selective beta-adrenergic receptor stimulant, isoprenaline produces a wide range of adrenergic effects. Those that involve the heart present the most marked problems in practice. Doses of up to 10 micrograms minute are used to improve the peripheral circulation in shock. In respiratory disease, isoprenaline in sublingual tablets (up to 10 mg) and inhalers were used in the past, but have been supplanted by selective beta2-adrenoceptor agonists. Isoprenaline inhalers sometimes provided...

See also Alphaadrenoceptor antagonists General Information

Alfuzosin is a uroselective alpha1-adrenoceptor antagonist used to relieve the symptoms of prostatic hyperplasia (1). Its safety has been investigated in a large prospective 3-year open trial in 3228 patients with benign prostatic hyperpla-sia. There were no unexpected adverse effects. Only 4.2 of the patients dropped out owing to adverse effects. In a large database of 7093 patients with lower urinary tract symptoms related to benign prostatic hyperplasia treated for up to 3 years with...

See also Anticholinergic drugs General Information

Benzatropine and etybenzatropine (ethylbenzatropine) are anticholinergic drugs. They represent attempts to combine atropine-like and antihistaminic effects in single molecules. The dose is determined individually and varies from 0.5 to 6 mg day for benzatropine and 6 to 30 mg day for etybenzatropine. Although the adverse reactions are essentially those of the anticholinergic drugs, sedation is very likely to occur and these drugs should not be used in patients who need to drive motor vehicles....

See also Antidysrhythmic drugs General Information

Adenosine and adenosine triphosphate (ATP), its phosphorylated derivative, have been used to treat acute paroxysmal supraventricular tachycardias and adenosine has also been used in the diagnosis of narrow-and broad-complex tachycardias (SEDA-16, 176). Several reviews of the clinical pharmacology, actions, therapeutic uses, and adverse reactions and interactions of adenosine and ATP have appeared (1-4). After intravenous administration adenosine enters cells, disappearing from the blood with a...

See also Antiepileptic drugs General Information

Lamotrigine is widely used in the management of partial and generalized seizures. It has a favorable tolerability profile, even though neurological adverse effects and hypersensitiv-ity reactions are sometimes troublesome. Its pharmacology, clinical pharmacology, adverse effects, and interactions have been reviewed (1). Its adverse events are primarily neurological, gastrointestinal, and dermatological and are typically mild or moderate and transient, with the exception of a potentially serious...

See also Antifungal azoles General Information

Genaconazole is an N-substituted triazole with a wide antifungal spectrum. Its absorption is slow, with peak concentrations 2-4 hours after a single dose and mean peak concentrations markedly higher after 16 days of administration. The mean elimination half-life is about 90-100 hours (1). It has high tissue penetration, including the CNS, and good broad-spectrum antifungal activity. However, it causes hepatocellular carcinoma in animals and the manufacturers stopped developing it because of...

See also Antihistamines General Information

Cetirizine is a non-sedating metabolite of hydroxyzine (SEDA-18, 181) (SEDA-19, 172) (SEDA-21, 172) (SEDA-22, 178). There is only minor hepatic metabolism of cetirizine (1), which is excreted unchanged in the urine. It has not been associated with dysrhythmias. Skin reactions have been reported, and the anticoagulant activity of acenocoumarol may be potentiated (SEDA-22, 178). Seasonal allergic rhinitis affects about 10 of schoolage children, and there is evidence of a significant impact of the...

See also Antituberculosis drugs General Information

Pyrazinamide is a pyrazine analogue of nicotinamide. It is bactericidal for Mycobacterium tuberculosis in an acid environment and within macrophages (1). Regimens that include pyrazinamide produce significantly more rapid rates of sputum conversion than any other combination. Pyrazinamide is therefore especially appropriate in the initial phase of treatment. In the 6-month regimen of the American Thoracic Society, pyrazinamide was used together with isoniazid and rifampicin for the first 2...

See also Betalactam antibiotics General Information

Carbapenems differ from penicillins and cephalosporins by a methylene substitution for sulfur in the five-membered beta-ring structure. Imipenem and mero-penem belong to this class of compounds. In the last 25 years, various natural carbapenems have been discovered (1). However, their potential is limited by chemical instability. Imipenem (N-formimidoylthienamycin), the first carbapenem in use, is therefore a stabilized synthetic compound. To overcome a second difficulty, namely inactivation by...

See also Calcium channel blockers General Information

Isradipine is a dihydropyridine calcium channel blocker. The MIDAS study (1) was a randomized trial of isradipine versus hydrochlorothiazide over 3 years in 883 patients, designed primarily to assess the effect on the rate of progression of medial intimal thickness in carotid arteries. The control of diastolic blood pressure was equivalent in both groups, but mean systolic blood pressure was 3.5 mmHg higher in isradipine group at 6 months, a significant difference that persisted throughout the...

See also Coagulation proteins General Information

Prothrombin complex products contain constant amounts of clotting factors II, VII, IX, and X, bypassing the need for factor VIII in the clotting cascade. They are used to reverse the effects of oral anticoagulants (for example during surgery or bleeding episodes) (1) and to treat bleeding episodes in hemophiliacs with inhibitors of factor VIII (2). Prothrombin complex achieves more rapid and effective reversal of acquired coagulation defects than fresh frozen plasma. However, a potential...

See also Cytostatic and immunosuppressant drugs General Information

Fludarabine phosphate is a purine nucleoside antitumor agent, which inhibits adenosine deaminase. It is mainly used to treat chronic lymphocytic leukemia. Dose-limiting myelotoxicity, nausea and vomiting, and raised liver enzymes were observed during early clinical studies. The most common adverse effect is myelosuppression (WHO grade 3 or 4), and other common adverse effects include infections and gastrointestinal disturbances, although these are usually of mild to moderate intensity (WHO...

See also Disinfectants and antiseptics General Information

The lower aliphatic alcohols (ethanol, isopropanol, 2-propanol, N-propanol, and 1-propanol) are widely used for skin antisepsis. In appropriate concentrations, these alcohols are bactericidal to most of the common pathogenic bacteria, but some rare species survive and can grow, especially since these alcohols are inactive against dried spores. Seven cases of gaseous edema were observed in the former German Democratic Republic (GDR) after intramuscular injections following rubbing of the skin...

See also Diuretics General Information

Eplerenone is a potassium-sparing diuretic. It is similar to spironolactone as an aldosterone antagonist, but has less affinity for androgen and progesterone receptors and may therefore have fewer adverse effects (1). Eplerenone is metabolized by CYP3A4 (2) and should not be given with inhibitors of CYP3A4 because of the risk of hyperkalemia (3). Eplerenone has been compared with spironolactone in patients with heart failure (NYHA classes II-IV). In a dose-finding study, 321 patients maintained...

See also Estrogens General Information

For a complete account of the adverse effects of estrogens, readers should consult the following monographs as well as this one Hormonal contraceptives oral Hormone replacement therapy estrogens Hormone replacement therapy estrogens + androgens Hormone replacement therapy estrogens + proges-togens A review of the English language literature has shown that in the USA, the source of most of the evidence, the two most commonly used forms of emergency contraception are the Yuzpe regimen (high-dose...