Side Effects Of Drug Resistance

The increasing rate of antimicrobial drug resistance has been a matter of great concern and is the most serious unwanted effect of these drugs. However, in spite of the fact that the problem is now very well recognized (SEDA-25, 279), it continues to grow. Most antimicrobial drugs are natural products, that is they are produced by micro-organisms such as bacteria or fungi, often found in the soil. In fact, they can be looked upon as nature's regulatory principle for microbial society....

Organs and Systems Cardiovascular

Because dofetilide prolongs the QT interval, there is a risk of ventricular tachydysrhythmias, which have often been reported, after both intravenous and oral administration. In 154 patients with implantable cardioverter-defibrillators randomly assigned to dofetilide or placebo, there were pause-dependent runs of polymorphic ventricular tachycardia in 15 of the 87 patients who received dofetilide and in only five of the 87 who received placebo (57). There were five early events (at less than 3...

Gastrointestinal

Nausea, vomiting, and gastric intolerance are relatively uncommon and mild. However, there have been reports of severe diarrhea requiring drug withdrawal. Eosinophilic colitis (47) and lymphocytic colitis (SEDA-22, 85) are rare reactions. A report of two cases has suggested that carbamazepine can cause colitis as part of the anticonvulsant hypersensi-tivity syndrome (48). A 47-year-old man developed fever, lymphadenopathy, flu-like symptoms, facial edema, a skin rash, and diarrhea after taking...

Delirium

Excessive anxiety and tremulousness, hyperexcitability, confusion, and hallucinations were all reported more often with triazolam than with temazepam or flurazepam, when spontaneous reporting was analysed (81). Whether this is dose-related, and perhaps related to the rapid changes in blood concentration with triazolam, is not clear. Delirium is common, particularly in elderly people, who may have impaired drug clearance, and must always be regarded as possibly drug-induced. Of considerable...

Drug Administration Drug formulations

Guidelines for depot neuroleptic drug treatment in schizophrenia were developed during a consensus conference held in 1995 in Siena in Italy, since when a thorough review devoted to depot neuroleptic drugs has been published (496). The authors reported that depot neuroleptic drugs are associated with significantly fewer relapses and rehospitalizations than oral neuro-leptic drugs. The potential disadvantages of depot drugs include patient reluctance to accept injections or a sense of being too...

Teratogenicity

Teratogenic effects of glucocorticoids, which have been demonstrated in animal experiments since 1950, have not generally been confirmed in man. The question whether a disease that has had to be treated with glucocorticoids in pregnancy or the glucocorticoid treatment itself may have caused congenital anomalies reported anecdotally usually cannot be answered in any individual case. Dexamethasone, for instance, given in a suppressive dosage, seems to have been therapeutically effective in...

Organs and Systems Immunologic

Immediate-type hypersensitivity reactions (acute, systemic urticaria after the third immunization) occurred in two of 39 volunteers immunized with a synthetic multi-antigen peptide vaccine (PfCS-MAP1NYU) against P. fal-ciparum sporozoites, with detection of serum IgE MAP antibody (8). Immediate pain at the injection site was associated with the adjuvant QS-21, and delayed local inflammatory reactions were associated with high titers of circulating IgG anti-MAP antibody. Skin tests using...

Organic salts

Organomercurials have been a common cause of allergic contact dermatitis or rash (22) and even exfoliative dermatitis has been described (23). Some reagents for intra-cutaneous testing (tuberculin, etc.) may contain thiomersal, which can cause sensitization and thus elicit false-positive delayed-type skin reactions. Mercury compounds inhibit most lymphocyte functions (SEDA-21, 240). An early indicator of an immunological response to mercury exposure, for example in occupational medicine,...

Indometacin

Severe systemic hypertension developed in a patient who took indometacin shortly after taking an appetite suppressant (Trimolets) containing phenylpropanolamine (20). The hypertension was attributed to inhibition of prosta-glandin synthesis by indometacin, which exacerbated the sympathomimetic effects of phenylpropanolamine. However, in 14 young, healthy, normotensive women who were randomized double-blind to modified-release phenylpropanolamine 75 mg day or placebo for 4 days, modified-release...

References

Meyers AM, Feldman C, Sonnekus MI, Ninin DT, Margolius LP, Whalley NA. Chronic laxative abusers with pseudo-idiopathic oedema and autonomous pseudo-Bartter's syndrome. A spectrum of metabolic madness, or new lights on an old disease S Afr Med J 1990 78(11) 631-6. 2. Chicouri MJ. Estudo clinico do psyllium husk associado a parafina microencapsulada no tratamento da constipacao intestinal essencial. Rev Bras Med 2001 58 672-6. 3. Dettmar PW, Sykes J. A multi-centre, general practice comparison of...

Immunologic

Allergic reactions have been attributed to phytome-nadione, menadione, and vitamin K4. In mice, menadione caused marked hypodynamia and hypothermia. This effect was potentiated by riboflavin. Allergic reactions to the systemic administration of vitamin K are immuno-logically mediated, and generally arise in patients with coagulation or liver problems. Intradermal tests with phytomenadione and menadione caused an allergic skin reaction 7-22 days after injection in 13 of 145 healthy subjects. The...

Drug additives

The addition of dextran to a lidocaine + adrenaline solution used for infiltration reduced the absorption of both (62). Alkalinization of local anesthetic solutions should theoretically lead to a faster onset of effect and prolonged anesthesia. However, raising the pH of the solution can cause the local anesthetic to precipitate out of solution, and one study with 2 lidocaine has shown no difference in quality or onset of anesthesia (SEDA-20, 129). Adrenaline 1 100 000, added to lidocaine 2 ,...

Long Term Effects Tumorigenicity

There is great concern about the potential development of malignancy after blockade of tumor necrosis factor alfa, and it is biologically plausible. However, it is unclear whether this is a drug-related or a disease-related phenomenon. There have been several cases of lymphoproliferative disease (B cell non-Hodgkin's lymphoma and nodular sclerosing Hodgkin's disease) in the 9 months after infliximab infusion in patients with Crohn's disease (63). The FDA received reports of 26 cases of...

Pharmacoeconomics

A further consideration, the economic evaluation of drugs, has become an issue, although not without criticism (44). In its most rigorous form the cost of drug therapy is measured against the aggregate number of years of improved health that such therapy might be expected to bring (45). These so-called quality-adjusted life years'' (QUALYs) are reduced if a drug has an adverse effect, so that the net benefit of a drug that prolongs life but makes that life miserable may well be a negative...

Combinations of vaccines

Since immunization against diphtheria, tetanus, and pertussis is recommended at the same age as immunization against Haemophilus influenzae, children must usually receive two intramuscular injections at separate sites during the same visit. Combined vaccines, for example DTP Hib vaccines, requiring one injection, could be preferable and are commercially available. Results of clinical trials comparing the safety and efficacy of combined and simultaneously administrated vaccines (Hib, DTP, MMR,...

Myroxylon species

Balsam of Peru is derived from species of Myroxylon such as Myroxylon balsamum and Myroxylon pereirae and has been used in medicinal and cosmetic ointments for centuries. It contains about 25 different substances, including triterpenoids, and can cause allergic reactions. Its sensitizing constituents have been determined (63). Balsam of Peru is a topical photosensitizer (SEDA-19, 162) and can cause contact urticaria (64,65). A systemic contact dermatitis has been reported after oral...

Perfluorocarbons

NC100100 (Nycomed, Oslo, Norway) is composed of stabilized perfluorocarbon microbubbles. In a randomized comparison of 99mtechnetium sestamibi single-photon emission-computed tomography (SPECT) and NC100100 in the assessment of myocardial perfusion in 203 patients with myocardial infarction, NC100100 was well tolerated, with no serious adverse events or deaths (10). Similarly there were no clinically important changes in vital signs, laboratory parameters, or electrocardiography. NC100100...

Drug Drug Interactions General

Drug mechanisms that result in potentiation of the hypoglycemic effects of the sulfonylureas include prolongation of the half-life by inhibition of metabolism or excretion (phenylbutazone, coumarins, chloramphenicol, doxycycline, bezafibrate, probenecid, sulfaphena-zole, naproxen, fenyramidol) competition with plasma protein binding sites (NSAIDs, salicylates, and sulfonamides) potentiation of their hypoglycemic action by inhibition of gluconeogenesis, enhancement of oxidation of glucose, or...

General Information Measles vaccine

Live measles virus vaccine is available in monovalent (measles only) form and in combinations measles-rubella (MR) and measles-mumps-rubella (MMR) vaccines. Measles vaccines based on further attenuated strains (beyond the level of the original strain, for example the Edmonston B strain or Schwarz strain) produces a mild or subclinical and non-communicable infection. Inactivated measles vaccine was not distributed after 1967 (owing to lack of efficacy). Reports of the atypical measles syndrome...

Drug Administration

Low-dose intrathecal morphine (0.3 mg) plus 0.5 spinal bupivacaine and patient-controlled intravenous morphine (given as a 1 mg bolus with a 5-minute lockout period) has been compared with patient-controlled intravenous morphine alone in 38 patients undergoing knee surgery in a randomized, double-blind study (40). The former combination provided effective analgesia with a low and non-significant incidence of emesis, pruritus, and respiratory depression. Oral morphine is more effective after...

Dysosma pleianthum

Dysosma pleianthum (bajiaolian), a species of May apple, is a traditional Chinese herbal medicine rich in podo-phyllotoxin. It has been widely used in China for thousands of years as a general remedy and for the treatment of snake bite, weakness, condyloma accuminata, lymphadenopathy, and tumors. Five people developed nausea, vomiting, diarrhea, abdominal pain, thrombocytopenia, leukopenia, abnormal liver function tests, sensory ataxia, altered consciousness, and persistent peripheral tingling...

Drug Drug Interactions Ethanol

Ethanol and retinol are converted to their corresponding aldehydes by isozymes of alcohol dehydrogenase and other dehydrogenases. The pathways of retinol metabolism have been described in hepatic microsomes, partly involving cytochrome P450 isozymes, which can also metabolize various drugs. Multiple interactions of retinol, ethanol, and other drugs can therefore occur (91). It is not therefore surprising that prolonged use of alcohol, drugs, or both not only results in reduced dietary intake of...

Drug Drug Interactions Clarithromycin

A pharmacokinetic study has shown a minor interaction of amprenavir with clarithromycin in healthy men (8). The mean AUC, Cmaxss and Cminss of amprenavir increased by 18, 15, and 39 respectively. Amprenavir had no effect on the AUC of clarithromycin, but the median imax.ss increased by 2 hours, renal clearance increased by 34 , and the AUC for 14-(R)-hydroxy-clarithromycin fell by 35 . These effects were felt not to be clinically important and dosage adjustment was not recommended.

General Information

Pristinamycin (rINN) is a synergistic combination of streptogramin A (pristinamycin IIA) and streptogramin B (pristinamycin IB). It is active against the main bacteria that cause respiratory tract infections and could be useful in the treatment of acute or recurrent sinusitis, community-acquired pneumonia, or periodontal infection with Actinobacillus actinomycetemcomitans (1-5). Quinupristin (rINN) and dalfopristin (rINN) are two semisynthetic pristinamycin derivatives that are given in...

Disopyramide

Severe cardiac dysrhythmias and major hypoglycemia have occurred in patients taking disopyramide with some macrolide antibiotics, especially erythromycin and clarithromycin (153). In a 76-year old woman, severe prolongation of the QTc interval and self-terminating torsade de pointes were induced by the combined use of clarithromycin and disopyramide concomitant hypokalemia may have contributed to the cardiac dysrhythmia (154). Symptomatic hypoglycemia developed in a 59-year-old man treated with...

Metabolism

The thiazolidinediones can cause hypoglycemia both when used alone or in combination with other hypo-glycemic drugs (47). The thiazolidinediones increase body weight. With troglitazone the increase in body weight is accompanied by changed fat distribution, but central fat, in part responsible for the cardiovascular changes seen in diabetes, remains the same weight gain is accompanied by increased subcutaneous fat (48). In one study, troglitazone increased body weight, adipo-cyte size, leptin...

Secondgeneration antihistamines

The second-generation antihistamines include acrivastine, astemizole, azelastine, carebastine, cetirizine, ebastine, loratadine, mizolastine, and terfenadine. They are used orally and some of them can be given by local application to the nose and eyes (2,16). They are relatively free from anticholinergic, antiserotonergic, and alpha-adrenergic activity. They cause markedly less sedation, perhaps because they penetrate the central nervous system less well than the first-generation...

Illicium species

Illicium anisatum contains sesquiterpenoids, such as anisatin, anisotin, neoanisatin, and pseudoanisatin. Illicium religiosum (Japanese star anise) contains shikimic acid, anisatin and neoanisatin. Illicium verum (Chinese star anise) contains the monoterpenoid transanethole. Chinese star anise has been used to treat infant colic, but can be confused with Japanese star anise, which contains the neurotoxin anisatin. Safrole is a mutagenic and animal carcinogenic mono-terpenoid. It is the major...

Organs and Systems

A 70-year-old patient with a metastatic carcinoid tumor of the liver presented with a hypertensive crisis after being given pethidine 10 mg hour by continuous intravenous infusion (4). The patient remained hypertensive with a systolic blood pressure of 210 mmHg, even after chemoembolization of the tumor. The blood pressure fell when pethidine was withdrawn and nitroprusside was given. The serum 5-HT concentration was 15 mmol l (reference range 0.17-0.26) and the urine 5-hydroxyindoleacetic...

Drug Drug Interactions Trimethoprim

The interaction kinetics and safety profile of oral ganciclovir when co-administered with trimethoprim have been investigated in HIV- and CMV-seropositive patients (17). Trimethoprim significantly reduced the renal clearance of ganciclovir and prolonged its half-life, although the changes are unlikely to be clinically important. Ganciclovir did not alter trimethoprim pharmacokinetics, with the exception of a 13 increase in Cmin. Ganciclovir was well tolerated when given alone or in this...

Drug Administration Drug overdose

Verapamil poisoning can cause cardiac toxicity with cardiogenic shock, conduction abnormalities (including life-threatening dysrhythmias), hypotension, and death. A 15-year-old woman survived a total of 65 minutes cardiac arrest after taking 7200 mg of verapamil and 240 mg of paroxetine, which potentiates verapamil toxicity (19). Despite the length of cardiopulmonary resuscitation, with evidence of subsequent myocardial damage and renal impairment, she was discharged 17 days after admission,...

Diagnosis of Adverse Drug Reactions

The adverse effects of indinavir have been retrospectively evaluated and correlated with indinavir trough concentration in 63 patients taking indinavir + ritonavir 800 100 mg bd (49). The median indinavir trough concentration of 1446 ng ml was associated with 60 of measured toxicity. Of 49 patients with an indinavir trough concentration over 500 ng ml, 46 had at least one dosage adjustment the main reason for dosage adjustment was toxicity (n 43). The common adverse effects affected the skin...

Doses

The optimal dosage of levothyroxine should be based on repeated measurements of T3 and TSH serum concentrations. The daily recommended dose depends on the aim of the therapy. Thyroid replacement therapy for control of spontaneous or iatrogenic hypothyroidism should aim at a dosage of levothyroxine that maintains TSH concentrations within the low reference range. This will usually be associated with a free T4 concentration in the high reference range and a T3 concentration within the reference...

Food Drug Interactions Grapefruit juice

Since halofantrine is metabolized to N-debutyl-halofan-trine by CYP3A4, grapefruit juice increases its systemic availability (14). Twelve healthy men and women took halofantrine 500 mg with water, orange juice, or grapefruit juice (250 ml day for 3 days and once 12 hours before halofantrine) in a crossover study. Compared with water, grapefruit juice significantly increased halofantrine AUC and Cmax 2.8-fold and 3.2-fold respectively there was no significant change in half-life. Maximum QTc...

See also Neuromuscular blocking drugs General Information

Vecuronium is a monoquaternary analogue of pancuronium, with a similar speed of onset, a duration of action of 15-30 minutes, rapid spontaneous recovery, and virtually no cumulative effects (1). Being monoquaternary, it is more lipophilic than pancuronium. About 30 is bound to plasma proteins. It is deacetylated in the liver, the principal metabolite being 3-desacetylvecuronium, which is believed to have about 50 of the neuromuscular blocking potency of the parent drug in man small amounts of...

Liver

A 67-year-old woman developed acute hepatocellular and cholestatic liver damage after taking celecoxib 100 mg day for 1 week (6). Celecoxib was withdrawn and the liver function tests normalized within 2 weeks. There have been three case reports of acute cholestatic hepatitis in patients taking celecoxib. A 55-year-old non-alcoholic obese woman, who was allergic to sulfa drugs, presented with a 5-day history of jaundice, malaise, and a pruritic rash that began 3 weeks after she started to take...

Thrombocytopenia Due To Thiamphenicol

The first death resulting from bone marrow aplasia induced by chloramphenicol eye-drops was described in 1955 (17). Chloramphenicol causes two types of bone marrow damage (18). A frequent, early, dose-related, reversible suppression of the formation of erythrocytes, thrombocytes, and granulocytes (early toxicity). A rare, late type of bone marrow aplasia, a hypersus-ceptibility reaction, which is generally irreversible, and has a high mortality rate (aplastic anemia) (19-21). Chloramphenicol...

Organs and Systems Respiratory

Bronchospasm may be a consequence of penicillin allergy (7-12). Acute severe dyspnea with cyanosis has also been observed without symptoms of bronchial obstruction or pulmonary edema (13). Specific mechanisms for such cases have yet to be identified. Allergic pneumonitis and transient eosinophilic pulmonary infiltrate (Loeffler's syndrome) are rare. These syndromes have also been observed with penicillin hyper-sensitivity (14-16). In one case, an alveolar allergic reaction, probably due to...

Second Generation Effects Fetotoxicity

Various types of nephrotoxicity have been described with nimesulide (SEDA-22, 119) (SEDA-23, 121). Two reports have illustrated the potential danger of using it as a toco-lytic (18) or during late pregnancy (19). In both cases, maternal ingestion of nimesulide was accompanied by irreversible neonatal renal insufficiency. In the second case, renal biopsy showed abnormal tubular differentiation and signs of tubulointerstitial nephritis. The mechanism of this adverse reaction is not known, but it...

Skin

Skin reactions ranging from exanthems to severe adverse events have been reported in association with diltiazem (SED-13, 513) (SEDA-18, 215) (SEDA-22, 216). Three cases of skin reactions (hypersensitivity syndrome reaction, pruritic exanthematous eruption, and acute generalized exanthematous pustulosis) possibly induced by diltiazem have been described and the literature on skin reactions associated with calcium antagonists has been reviewed. The number of diltiazem-induced cutaneous events was...

Drug Drug Interactions Busulfan

During long-term follow-up of patients treated with busulfan and hydroxycarbamide for essential thrombo-cythemia, seven patients (13 ) taking hydroxycarbamide developed secondary acute leukemia, myelodysplasia, or solid tumors, compared with only one of the control group none of the 20 patients who had never been treated with chemotherapy developed secondary malignancies compared with three of the 77 given hydroxycarbamide only and five of the 15 given busulfan plus hydroxycarba-mide. This...

Drug Drug Interactions Anticonvulsant drugs

An interaction of anticonvulsant drugs with the metabolism of folate has been described (SEDA-13, 348) (see also the section on Nervous system in this monograph). Folic acid can alter the metabolism of phenytoin. In one case folic acid 5 mg day reduced the serum phenytoin concentration to below the target range, and a breakthrough seizure occurred (25). The Km of phenytoin metabolism was significantly reduced, suggesting competitive inhibition of metabolism. In another series folic acid reduced...

See also Vaccines General Information

Haemophilus influenzae causes several infectious diseases in man, the most serious being meningitis. Most cases of Haemophilus influenzae infection are due to type b of the organism (Hib). Two types of Hib vaccines have been developed Hib capsular polysaccharide (PRP) vaccines are first-generation Hib vaccines, while Hib conjugate vaccines are second-generation vaccines. The capsular polysaccharide vaccines do not protect infants and children under 18 months, whereas Hib conjugate vaccines have...

Hematologic

DoTS classification (BMJ 2003 327 1222-1225) Dose-relation hypersusceptibility effect Time-course intermediate or delayed Susceptibility factors genetic age Clozapine-induced agranulocytosis was originally determined to be 0.21 in a selected Finnish population (SED-9, 83) (105), and the drug was withdrawn, only to be cautiously reintroduced in some countries a decade later, with hematological monitoring. With mandatory hematological monitoring by the Clozaril Patient Management System in the...

Drug Drug Interactions Azithromycin

The effect of co-administration of azithromycin on plasma concentrations of desloratadine has been examined in a randomized third-party-blind, placebo-controlled, parallel-group study in 90 healthy volunteers (18). An initial loading dose of azithromycin (500 mg) was given on day 3, followed by 250 mg od for 4 days. Concomitant azithromycin had little effect (< 15 ) on either the Cmax or AUC of desloratadine, and there were no statistically significant increases in the PR, QT, QTc interval,...

Angelica sinensis

Angelica sinensis, known in China as dong quai'' or dang gui,'' contains antioxidants (8), inhibits the growth of cancer cells in vitro (9) and stimulates immune function in experimental animals (10). It has been used to treat amenorrhea (11) and menopausal hot flushes (12), and to reduce pulmonary hypertension in patients with chronic obstructive pulmonary disease (13). Angelica sinensis can cause hypertension (14). A 32-year-old woman, 3 weeks post-partum, developed acute headache, weakness,...

Ammi majus and Ammi visnaga

Ammi majus is also known as bishop's weed or large bullwort, and Ammi visnaga as toothpick weed. They have numerous active ingredients, including ammirin, angenoma-lin, kellactone, majurin, and marmesin, furanocoumarins (psoralen, bergapten, isopimpinellin, imperatorin, umbelli-prenin, xanthotoxin), and flavonol triglycosides (kaemp-ferol, isorhamnetin). In modern times they have been used to treat vitiligo, since they contain psoralens, and have several different pharmacological effects in...

Long Term Effects Drug abuse

Methylphenidate shares the pharmacological properties and the abuse potential of the amphetamines. When given intravenously, it activates psychotic symptoms in schizophrenic patients if administered during the active phase of their illness, but not after remission. It failed to produce a psychotic reaction in most manic or depressed patients or in healthy subjects (27). Adults with childhood-onset ADHD had an earlier onset of psychoactive substance use disorders, independent of any psychiatric...

Organs and Systems Ear nose throat

Endotracheal intubation is less traumatic when it is facilitated by a muscle relaxant. Vocal cord hematoma after intubation occurred in six of 36 patients when only fenta-nyl plus propofol was used, compared with one of 37 when atracurium was added (9). Drug accumulation will result in paralysis lasting from hours to days. Occasionally, however, paralysis can persist for weeks or even months because of relaxant-associated myopathy (10). Muscle weakness, causing difficulties in the subsequent...

References On The Side Effects Diabetes Drugs

Desmopressin (DDAVP) in the treatment of bleeding disorders the first 20 years. Blood 1997 90(7) 2515-21. 2. Holmberg L, Nilsson IM, Borge L, Gunnarsson M, Sjorin E. Platelet aggregation induced by 1-desamino-8-D-arginine vasopressin (DDAVP) in Type IIB von Willebrand's disease. N Engl J Med 1983 309(14) 816-21. 3. Sutor AH. Desmopressin (DDAVP) in bleeding disorders of childhood. Semin Thromb Hemost 1998 24(6) 555-66. 4. Lethagen S, Ragnarson Tennvall G. Self-treatment with...

Vinorelbine rINN

Vinorelbine has become a pivotal agent for treating adjuvant non-small cell lung cancer (stages IB-III) and the palliative treatment of non-small cell lung cancer (stages IIIB and IV), often in combination with drugs like cisplatin. In addition, vinorelbine plays an important part in the treatment of advanced and metastatic breast cancer. Its role in the treatment of advanced cervical cancer is still under investigation. The usual intravenous dosage is 20-30 mg m2 (vinorelbine base) given once...

Nervous system

Delayed onset oculogyric crisis and generalized dystonia occurred in a 19-year-old man after intranasal heroin use, possibly due to bilateral hypoxic infarction of the palli-dum and pallidothalamic tracts (10). There has been one report of mixed transcortical aphasia attributed to heroin (11). Myoclonic spasm has been reported about 24 hours after withdrawal of an epidural infusion of diamorphine (SEDA-16, 81). Demyelination has been attributed to diamorphine (12). A 41-year-old chronic...

Alkylating cytostatic agents Nlost derivatives

Park DS, Vassilopoulou Sellin R, Tu S. Estramustine-related hypocalcemia in patients with prostate carcinoma and osteoblastic metastases. Urology 2001 58(1) 105. 13. Zackheim HS, Epstein EH Jr, McNutt NS, Grekin DA, Crain WR. Topical carmustine (BCNU) for mycosis fun-goides and related disorders a 10-year experience. J Am Acad Dermatol 1983 9(3) 363-74. 14. Ellis ME, Weiss RB, Kuperminc M. Nephrotoxicity of lomustine. A case report and literature review. Cancer Chemother Pharmacol 1985...

Drug Drug Interactions

Neuroleptic drugs can reduce or block the pressor effects of alpha-adrenoceptor agonists. When using drugs with both alpha- and beta-adrenoceptor activity, neuroleptic drug blockade of alpha-adrenoceptors can lead to unopposed beta predominance, resulting in severe hypotension (508). A neuroleptic malignant-like syndrome occurred when norephedrine was combined with neuroleptic drugs (338). Alcohol-induced CNS and respiratory depression is enhanced by neuroleptic drugs (509), but enhancement can...

Boric acid

See also Disinfectants and antiseptics General Information In the past, boric acid was falsely considered to be relatively non-toxic, and had an unwarranted reputation as a germicide. However, it is only bacteriostatic, even in a saturated aqueous solution, and can cause adverse reactions. Boric acid has often proved poisonous, either by ingestion or after local use. Cases from the world literature have been reviewed (1,2). In 172 cases of boric acid intoxication, including 83 deaths, 37 deaths...

Drug overdose

The most important complication of overdosage of digitalis in all age groups is disturbance of cardiac conduction, but in addition any dysrhythmia can occur. Death can result from asystole or ventricular fibrillation. Hyperkalemia is common, and the higher the plasma potassium concentration the poorer the prognosis (157). Other common effects of overdosage are nausea, vomiting, and central nervous system and visual disturbances (66). Accidental overdose of digoxin in a 22-month-old boy caused...

Conjugated meningococcal vaccines

Success with the protein-conjugate formulations of Hemophilus influenzae vaccines has facilitated research and development on conjugated meningococcal vaccines with preference for monovalent group C or bivalent group A group C vaccines. Conjugated meningococcal vaccines of serogroup C made by various manufacturers were first licensed in 1999 in the UK and then (at the end of 2000) in many other countries, including some other member states of the European Union (Belgium, Germany, Greece,...

Drug Drug Interactions Ciclosporin

In 42 patients who had received a kidney transplant, cases were treated with ciprofloxacin in the first 1-6 months after transplantation, and matched controls (two per case) were not. The proportion of cases with at least one episode of biopsy-proven rejection 1-3 months after transplantation (45 ) was significantly higher than in the controls (19 ). The authors speculated that ciprofloxacin increases rejection rates in renal transplant recipients by antagonizing ciclosporin-dependent...

Drug Drug Interactions Clozapine

Raised clozapine blood concentrations have been reported after the introduction of lisinopril (10). A 39-year-old man with schizophrenia and diabetes, who had taken clozapine 300 mg day and glipizide 10 mg day for a year, took lisinopril 5 mg day for newly diagnosed hypertension. On several occasions afterwards he had roughly a doubling of his blood concentrations of clozapine and norclozapine. He had typical effects of clozapine toxicity. After replacement of lisinopril by diltiazem, the blood...

Second Generation Effects Teratogenicity

Diethylstilbestrol was used extensively in pregnancies between 1940 and about 1975, in the belief that it could protect threatened pregnancies and counter the risk of spontaneous abortion. Toward the end of that period, increasingly clear evidence emerged that diethylstilbestrol could have an adverse effect on the second generation that did not become apparent until puberty or adulthood, and perhaps could also appear in the third generation (10). It appears to be the only estrogen with this...

Inorganic salts

Chronic mercurialism with nervous system involvement, renal insufficiency, and progressive colitis has been described after the long-term use of remedies containing inorganic mercury. Such remedies may also explain the persistence of other unexplained disorders, such as pink disease. Inorganic and organic mercury compounds may cause allergic dermatitis (SEDA-22, 247) (28). Frank poisoning from these sources, although uncommon today, is still possible, and occasional case reports appear...

See also Vitamins and Vitamin A Retinoids General Information

The carotenoids are a class of hydrocarbons (carotenes) and their oxygenated derivatives (xanthophylls) that consist of eight isoprenoid units joined in such a manner that the arrangement of the units is reversed at the center of the molecule, so that the two central methyl groups are in a 1,6-positional relationship and the remaining nonterminal methyl groups are in a 1,5-positional relationship. Their nomenclature has been standardized by IUPAC and their formal names are all based on the term...

Oral contraceptive steroids

There have been anecdotal reports that oral antibiotics reduced the efficacy of oral contraceptives. The proposed mechanism is that the antibiotics reduce the amount of gut bacteria that normally deconjugate excreted estrogens prior to reabsorption. However, in small formal studies this effect has not been confirmed (345-347). It is nevertheless possible that this is the mechanism, but that it occurs in too few women to be detected in small formal studies. As early as 1971, it was observed that...

Pneumococcal polysaccharide vaccine

The question of whether revaccination with 23-valent pneumococcal polysaccharide vaccine (PPV) at least 5 years after the first vaccination is associated with more frequent or more serious adverse events than those after the first vaccination has been studied in patients aged 5074 years who had never been vaccinated with PPV (n 901) or who had been vaccinated once at least 5 years before enrolment (n 513) (8). After one dose of PPV, local injection site reactions and prevaccination...

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...

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...

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...

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...

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...

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...

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...

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...

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...