Other Compounds

Metronidazole (SED-14, 977 SEDA-23, 309 SEDA-25, 350 see also Chapter 26) Metronidazole is used for the treatment of protozoal infections, including amebiasis, gia-rdiasis, and trichomoniasis. Nausea, a metallic taste, a disulfiram-reaction with alcohol, and peripheral neuropathy are well-recognized adverse effects. Nervous system Encephalopathy associated with metronidazole has been reported in a patient with chronic renal insufficiency (54A). A 58-year-old woman with end-stage renal...

Ginkgo biloba maidenhair tree

Nervous system A 78-year-old man and an 84-year-old woman with previously well controlled epilepsy presented with recurrent seizures (33A). There were no obvious reasons for these events, and the investigator suspected self-medication with Ginkgo biloba extracts. Both patients had started taking Ginkgo within 2 weeks of the start of the seizures. The herbal remedy was withdrawn and both patients remained seizure-free several months later. No other change of medication was made. The author...

Gonadotrophinreleasing hormone antagonists SED14 1523 SEDA24 504 SEDA25 521

Competitive gonadorelin receptor antagonists inhibit gonadotrophin secretion without the initial flare seen with gonadorelin agonists, and without receptor down-regulation. Potential applications include treatment of prostate cancer and prevention of premature LH surges in in vitro fertilization. Skin Injection sites reactions (pain, itching, redness, swelling, or bruising) are common. In 226 women randomized to subcutaneous ganirelix and 111 to triptorelin there were local symptoms in 12 of...

Cognitive effects of topiramate

All antiepileptic drugs have been associated with adverse cognitive events, and many, sometimes contradictory, studies of classical antiepileptic drugs have been published (59R). Cognitive adverse effects are large for phenobarbital, and possibly larger for phenytoin than for carbamazepine or valproic acid (59R). Most often cognitive adverse events result in mild general psychomotor slowing. Although the severity of cognitive adverse effects is considered mild to moderate for most antiepileptic...

Citric acid

Cardiovascular Citric acid toxicity has been reported previously, but only after intravenous administration. It was originally seen with massive transfusion of blood products with citrate as the anticoagulant. Two case reports have described accidental intravenous administration of citrate or citric acid, and at a maximum serum concentration of citrate (4.1 mmol l) there were profound alterations in blood pressure and QT interval these were reversed by calcium infusion (6Ac). Metabolism...

Effects of longterm exposure to cannabis

Is cannabis neurotoxic Although there have been claims that chronic cannabis use can permanently damage the brain, there is little scientific evidence to support this (3R, 4R, 5R, 42R). Some studies have shown modest impairment of the ability to focus attention and filter out irrelevant information in ex-cannabis users (25r), but other studies have failed to show any long-term impairment in cognitive function (43e). There is little evidence that cannabis impairs work performance or leads to an...

Corticosteroids and prostaglandins

Editor's note In this chapter adverse effects arising from the oral or intravenous administration of corticosteroids are covered in the section on systemic glucocorticosteroids. Other routes of administration are dealt with in the section after that, apart from inhalation and nasal administration, which are dealt with in Chapter 16, and topical administration, which is covered in Chapter 14. (SED-14, 1369 SEDA-23, 427 SEDA-24, 450 SEDA-25, 465) Respiratory In a double-blind, randomized,...

Rifampicin

Urinary tract Acute interstitial nephritis has been reported after first-time daily rifampicin administration (17A). A 61-year-old alcoholic developed non-oliguric rapidly progressive renal insufficiency 10 weeks after starting to take daily rifampicin, isoniazid, ethambutol, and pyrazinamide for pulmonary tuberculosis. There was proteinuria but a normal sediment. Renal biopsy showed acute interstitial nephritis. He improved when rifampicin was replaced by sparfloxacin. Acute renal...

Moxifloxacin

In a multicenter, prospective, double-blind, randomized trial in 455 patients with community-acquired pneumonia oral moxifloxacin 200 mg day or 400 mg day for 10 days resulted in a bacteriological response of 91 (98C). Most adverse events, possibly or probably related to moxifloxacin, were generally mild or moderate and were mostly related to the digestive system diarrhea, nausea, and abdominal pain with 200 mg day diarrhea, liver function abnormalities, and nausea with 400 mg day. The drugs...

Other Peripheral Vasodilators

Sildenafil (SED-14, 636 SEDA-23, 215 SEDA-24, 231 SEDA-25, 238) The adverse effects of a single dose of silde-nafil 50 mg have been evaluated in a placebo-controlled study in 40 young healthy volunteers (5c). The most commonly reported adverse effects with sildenafil and placebo respectively were flushing (75 and 0 ), headache (50 and 5 ), and dyspepsia (15 and 5 ). This adverse effects profile was similar to that observed in clinical trials. Heart rate changed significantly, but blood pressure...

Conclusions

The medical and recreational uses of cannabis are associated with some adverse effects. While the acute toxicity of cannabis is low, long-term use is associated with cognitive impairment and can lead to dependence in a proportion of regular users. The medical uses of cannabis are complicated by the narrow therapeutic window between the desired effects and intoxication. Smoking cannabis involves the additional risks of chronic lung damage and possibly cancer. The adverse effects of cannabis are...

Lopinavirritonavir

Sensory systems Ototoxicity has not previously been reported with antiretroviral drugs, but has recently been attributed to lopinavir ritonavir (54a). A 46-year-old man took a regimen containing lopinavir ritonavir, and 4 weeks later complained of reduced auditory acuity accompanied by lancinating pain. Audiology showed mild to moderate bilateral sensorineural hearing loss. On withdrawal and use of efavirenz his hearing recovered. Based on the time-course and the effect of withdrawal, lopinavir...

Epidural anesthesia

Patient-controlled epidural analgesia is increasingly being used, as it reduces the need for adjustment of epidural infusion rates by anesthetic personnel. In a retrospective survey of 1057 patients who received postoperative patient-controlled epidural analgesia using bupivacaine 0.1 plus fentanyl 5 micrograms ml, on the first postoperative day 93 of the patients had adequate analgesia and 96 reported no nausea two patients had an episode of respiratory depression and one patient was...

Compositae

There are over 20 000 species in the family of Compositae, including arnica, chamomile, chrysanthemum, dandelion, gerbera, and marigold. Arnica, chamomile, and marigold are used in cosmetics and topical therapeutics. Delayed hypersensitivity reactions to the Compositae can arise from sesquiterpene lactones. To detect contact allergy to sesquiterpene lactones, a mixture of lactones (alantolactone, costunolide, and dehydrocostus lactone) is used. However, Com-positae contain other sensitizers,...

Pyrimethamine plus sulfadoxine

Pyrimethamine + sulfadoxine (Fansidar ) prevents Pneumocystis carinii pneumonia and toxoplasmosis. In a single-arm, open, prospective study between 1990 and 1995 (before HAART) the prophylactic efficacy of Fansidar was evaluated in 95 HIV-infected patients with successfully treated Pneumocystis carinii pneumonia and no history of toxoplasma encephalitis (49C). Patients took Fansidar (25-500 mg) with folinic acid (15 mg) twice weekly and were followed for a median of 19 (range 1-72) months. Five...

Minocycline

Immunologic Serum sickness Serum sickness was first described by von Pirquet and Schick in 1905 and was regarded as a syndrome resulting from the administration of heterolo-gous serum or other foreign proteins. The im-munopathology of classic serum sickness results from antigen-antibody complex formation with a foreign protein as the antigen. Characteristic symptoms include fever, cutaneous eruptions, edema, arthralgias, and lymphadenopa-thy. The incidence of classical serum sickness has fallen...

Travoprost

Travoprost is a derivative of fluprostenol and prostaglandin F2a and it has intraocular pressure-lowering activity. It causes changes in iris pigmentation (3.1-5.0 ) and changes in eyelash characteristics, including length, thickness, density, and color (44-57 ), similar to those described with latanoprost, after 12 months (32C). 1. Matsumoto T, Tamaki T, Kawakami M, Yoshida M, Ando M, Yamada H. Early complications of high-dose methylprednisolone sodium succinate treatment in the follow-up of...

Vancomycin

In a prospective study to determine if standardized vancomycin doses could produce adequate serum concentrations in 25 full-term neonates with sepsis, 13 had adequate peak vancomycin serum concentrations (20-40 mg ml) and one had a peak concentration with a risk of ototoxicity (over 40 g ml) (134c). Only 12 had adequate trough concentrations (5-10 mg ml) and seven had a risk of nephrotoxicity (over 10 g ml). There was no significant difference between peak or trough concentrations and good or...

Interferon alfa

In 1530 patients with chronic hepatitis C pe-gylated interferon alfa-2b had a similar profile of adverse effects to unmodified interferon alfa-2b, but with more frequent dose-limiting neutropenia (1C). No particular adverse effect has emerged since the use of this new formulation. Respiratory The first case of pulmonary artery hypertension has been reported (2A). A 23-year-old man taking hydroxycarbamide (1.5 g day) and interferon alfa-2b (less than 10 MU day) for chronic lymphocytic leukemia...

Adverse effects of the chemically modified tetracyclines CMTs

The adverse effects profile of the classical tetra-cyclines, such as doxycycline and minocycline, is well established. However, the adverse effects profile of the CMTs has not been elucidated. What can be expected Recent reviews form a good starting point (31r, 43e). In brief, CMTs are more active in interfering with mammalian processes than the classical tetracyclines, which is the main justification for their use in non-infective problems. From a qualitative point of view, it might be...

Laurus nobilis laurel oil

Laurel (Laurus nobilis) has well-known analgesic, diaphoretic, antipyretic, and diuretic effects (46r), and is widely used in rheumatic, pyrexial, and infective disorders (47R), as well as in the perfume and soap industries (46R). Skin Laurel contact allergy is usually seen in aromatherapists or their clients (48A,49C, 50A). A 55-year-old woman developed erythema and edema over her knees (48A ). She had applied laurel oil, obtained from a herbalist, to her knees to relieve joint pain 15 days...

Perfluorocarbons

Perfluorocarbons have gained wide acceptance in the surgical management of complicated retinal detachment (7R). These heavy low-viscosity liquids are inert, are optically clear, and have a high specific gravity and good surface tension. Their chemical and physical properties make them a suitable temporary intraoperative tool to flatten the retina during surgery. Although the high surface tension allows closure of retinal breaks and prevents the perfluorocarbons from flowing into the subretinal...

Liposomal Amphotericin B LAmB

In order to determine the maximum tolerated dosage of liposomal amphotericin B, a phase I II study was conducted in 44 adult patients with proven (n 21) or probable (n 23) infections due to Aspergillus spp. and other filamentous fungi (7C). The dosages were 7.5, 10, 12.5, and 15 mg kg day. The number of infusions was 1-83 with a median duration of 11 days. The maximum tolerated dosage was at least 15 mg kg. Infusion-related reactions included fever in eight and chills and rigors in five of 43...

Diamorphine heroin

Nervous system Reflex sympathetic dystrophy, in which there is an excessive or abnormal sympathetic nervous system response in a limb, has been associated with rhabdomyolysis secondary to heroin abuse (62A). A 37-year-old male heroin smoker developed tea-colored urine and pain, swelling, and tenderness in both feet. He had acute renal insufficiency and rhabdomyolysis and was treated with hemodialy-sis. Urine toxicology was negative. He also had persistent burning pain in both feet, with cool,...

Anticholinergic drugs

The adverse effects of the antimuscarinic anti-cholinergic drugs in patients with incontinence and bladder overactivity has been emphasized in several recent reviews (55M, 56C, 57M, 58C). The findings are not unexpected dry mouth is by far the most commonly reported adverse effect, with a frequency of about 40 in patients taking 2 mg of the immediate-release formulation bd. The next most common effects are consistently headache, constipation, and abdominal discomfort. Hallucinations and...

Helicobacter Pylori Eradication Regimens

(SEDA-23, 384 SEDA-24, 404, SEDA-25, 422) Many studies of Helicobacter pylori eradication therapies have been reported in the year under review. Regimens for Helicobacter pylori eradication usually include a proton pump inhibitor or H2 receptor antagonist, two or three antibiotics, and less commonly bismuth compounds or sucralfate. Adverse effects are related to the individual drugs used. Pseudomembranous colitis has been reported in a 86-year-old woman with non-ulcer dyspepsia a few days after...

R The role of endothelin receptor antagonists in hypertension

It is disappointing that mechanistically novel antihypertensive drugs have not emerged during the last decade or two. The only real novelty of the last decade was the addition of angiotensin II receptor antagonists as a refinement of the approach introduced with ACE inhibitors. The expectations for direct renin antagonists have not been realized. Some of the cornerstone classes of antihypertensive drugs, such as the diuretics, beta-adrenoceptor antagonists, calcium channel blockers, and direct...

Catechol Omethyl transferase inhibitors

Tolcapone was very effective but was withdrawn in 1998 because of liver toxicity. It has been replaced by entacapone, which appears to lack this serious adverse effect, although some neurologists also consider it to be less effective. In 40 patients (mean age 64 years, 22 men) who took tolcapone for 3-7 months and were given entacapone in dosages titrated to 800-2000 mg day after a transition period of 3-6 months with co-beneldopa, the improvements in on and off times were less impressive than...

General

Recent reviews have increased our understanding not only of the adverse effects profiles of individual drugs (170R) but also of the factors that contribute to the adverse effects of chemotherapy, which are not purely related to the pharmacology of the cytostatic drugs themselves. For example, there are some dramatic scheduling effects, particularly in hematologi-cal toxicity, depending on whether the patient receives doxorubicin followed by docetaxel or the same doses but in reverse order...

Celecoxib

Psychiatric There have been two reports of visual hallucinations in patients taking cele-coxib. A 79-year-old woman presented to her optometrist with a 2-day history of seeing orange spots in both visual fields 2 months after starting to take celecoxib 100 mg day (94A). Physical examination and a CT scan were normal. Celecoxib was withdrawn and her symptoms resolved within 3 days. An 81-year-old woman took celecoxib 100 mg day, and over the next 2 weeks developed delirium and auditory and...

Drugs Used In Dysrhythmias

The efficacy of a large range of antidysrhyth-mic drugs in converting atrial fibrillation to sinus rhythm acutely and in maintaining it during long-term treatment has been the subject of a systematic review (54M). Adverse effects were too sporadically reported to be suitable for proper review. The results are summarized in Table 1. Cardiovascular The prodysrhythmic risks of using antidysrhythmic drugs have been mentioned in the context of a set of guidelines on the management of patients with...

Positive inotropic drugs and drugs used in dysrhythmias

CARDIAC GLYCOSIDES (SED-14, 523 SEDA-23, 193 SEDA-24, 197 SEDA-25, 205) Cardiovascular Digoxin has previously been reported to cause ventricular fibrillation in children with Wolff-Parkinson-White syndrome (1A, 2a). There has now been another report A male infant, whose narrow-complex tachycardia at birth had responded to adenosine, was treated with digoxin and 1 week later, during trans-esophageal electrophysiology, developed coarse ventricular fibrillation after the induction of a...

CNS effects of secondgeneration antihistamines

There is a widespread tendency to consider the second-generation antihistamines as non-sedating drugs. Indeed, when they are used in their recommended dosages in objective studies in healthy volunteers, the CNS depressant effects of fexofenadine (26C, 27C), loratadine (28r), and mizolastine (29R) appear to be no greater than those seen with placebo. However, the issue is further complicated by evidence that sedation in allergic disease (and subsequent impairment in performance and learning) may...

Citrus auranticum bergamot

Skin In aromatherapy volatile plant oils (often incorrectly termed essential oils) are used and are usually applied by gentle massage. Bergamot oil (Citrus auranticum spp. bergamia) is often used in this way. It has photosensitive and melanogenic properties and is potentially phototoxic and photomutagenic. Two patients had localized and disseminated bullous phototoxic skin reactions 48-72 hours after exposure to bergamot aromatherapy and ultraviolet light (30A). One developed bullous skin...

Methylphenidate

Two reviews have addressed the diagnosis and management of attention-deficit hyperkinetic disorder (ADHD) and have summarized the effects of stimulants, including those of methylphenidate and adderal (a mixture of equal components of d-amphetamine saccharate, d,l-amphetamine aspartate, d-amphetamine sulfate, and d,l-amphetamine sulfate, which seems to be gaining popularity in the treatment of ADHD) (26r, 27r). The results of the National Institute of Mental Health Collaborative Multimodal...

Types Of Contrast Agents

Iodinated water soluble contrast agents are of four types High-osmolar ionic monomer (e.g. diatri-zoate, iothalamate, metrizoate). Low-osmolar ionic dimers (e.g. ioxaglate). Low-osmolar non-ionic monomers (e.g. io-pitridole, iohexol, iomeprole, iopamidole, io-promide, ioversol). Iso-osmolar non-ionic dimer (e.g. iodixonal, iotrolan). They are mainly used intravascularly, but can also be injected into body cavities, particularly the low-osmolar contrast agents. The high-osmolar water-soluble...

British drug safety

In 1963, the UK Ministry of Health invited Professor Sir Derrick Dunlop to head a new agency, the Committee on Safety of Drugs (CSD), which would advise on measures for the future protection of the community against adverse reactions to therapeutic drugs. One important need was the introduction of a system for the licensing of new drugs. The CSD was to have only a small central medical and administrative Secretariat, but its operations would depend on suitable academics and others who could...

Phenolic Compounds

(SED-14, 773 SEDA-23, 248 SEDA-24, 271) Phenol is a benzyl alcohol and a major oxidized metabolite of benzene. Although it can be prepared in an aqueous solution or in glycerin, it appears to be more effective when mixed in aqueous compounds. At a concentration of 0.2 it is bacteriostatic and at over 1 bacteriocidal (10R). In addition to its uses as an antiseptic and disinfectant, phenol is also used as a sclerosant, as a local anesthetic on the skin, and as an analgesic, by injection into...

Mesalazine 5aminosalicylic acid mesalamine

In a randomized open trial in 227 patients with mild to moderate ulcerative colitis, mesalazine 4 g day given as prolonged-release granules bd and qds was as effective as prolonged-release tablets given qds (51c). All the treatments were well tolerated and the frequencies of adverse effects were similar in the treatment groups. The patients preferred twice-daily dosing. Daily mesalazine 4 g orally plus placebo enema and mesalazine 2 g orally plus mesalazine 2 g rectally as a liquid enema have...

Sertindole

Sertindole was suspended in January 2000, following concerns about reports of cardiac dysrhythmias and sudden death (SEDA-22, 71 SEDA-25, 71). To gather further information, data collected for prescription-event-monitoring (PEM) studies have been analysed (107c). Patients taking sertindole (n 462 5482 months of observation) were compared with patients taking risperidone or olanzapine (n 16542 139987 months of observation). There were seven deaths in the sertindole group and 415 in the other,...

Cytostatic drugs

Editor's note The wide range of cytostatic drugs, the multitude of their adverse effects, and the fact that they are generally used in combinations ofseveral agents all make it impossible to provide as detailed a review of the adverse effects of all the drugs in this field as the Annual gives in others. This year most of this chapter is devoted to a special review of the adverse effects of the platins by Drs Lipp, Bokemeyer, and Hartmann. The rest of the chapter is by Dr Stanley, who thanks...

Myrrh

Myrrh is an oleo gum resin obtained from the stem of Commiphora molmol, a tree that grows in north-east Africa and the Arabian Peninsula. In mice, myrrh showed no mutagenic effects and was a potent cytotoxic drug against solid tumor cells (21e). The antitumor potential of C. molmol was comparable with that of cy-clophosphamide. Studies in hamsters suggested an anti-schistosomal activity of myrrh (22c). Myrrh and schistosomiasis The efficacy and adverse effects of myrrh and the most effective...

Itraconazole

Data on the safety of itraconazole have been collected in an open randomized multicenter study in 277 adults with cancer and neutropenia (28c). Itraconazole oral solution (100 mg bd, n 144) was compared with a combination of amphotericin capsules and nystatin oral suspension (n 133). Adverse events were reported in about 45 of patients in each group. The most frequent were vomiting (14 vs. 12 patients), diarrhea (12 vs. 9), nausea (5 vs. 12), and rash (2 vs. 13 patients). There were no...

Caudal anesthesia

Caudal block with bupivacaine in children provides adequate analgesia in the early postoperative period, but additional analgesia is often required as the block wears off. Two studies have looked at adjuvants to prolong the analgesic effect. The first was a randomized, controlled trial in 60 boys undergoing unilateral herniorrhaphy (7C). They received 0.25 bupivacaine 1 ml kg or the same dose of bupivacaine plus 1.5 mg kg tramadol, or tramadol 1.5 mg kg alone made up to the same volume. Caudal...

Acetylsalicylic acid aspirin and related compounds SED14 233 SEDA23 116 SEDA24 121 SEDA25 132

Gastrointestinal The question of whether the risk of gastrointestinal complications with the long-term use of aspirin is dose-related is controversial (SEDA-21, 100 SEDA-25, 132). A systematic review of 17 epidemiological studies conducted between 1990 and 2001 has provided further data on this topic (10M). The effect of aspirin dosage was investigated in five studies. There was a greater risk of gastrointestinal complications with aspirin in dosages over 300 mg day than in dosages of 300 mg...

Brachial plexus anesthesia

Respiratory Brachial plexus blockade is often used in patients with cardiorespiratory disease undergoing upper limb surgery. However, the procedure carries certain significant risks, one being blockade of the phrenic nerve, resulting in paralysis of the ipsilateral hemidi-aphragm. This can rarely cause severe respiratory compromise, depending on pre-existing lung dysfunction. In unpremedicated patients who underwent supraclavicular brachial plexus block for upper limb surgery, blocks were...

Opioid Receptor Agonists

Alfentanil (SED-14, 211 SEDA 23, 98 SEDA-24, 104 SEDA 25, 110) Alfentanil is a potent short-acting opioid with a rapid onset and short duration of action. It is therefore the ideal analgesic for focused and ambulatory interventions. In a prospective, uncontrolled study in three consecutive groups of out-patients undergoing shock-wave lithotripsy, group 1 (152 patients) had an induction dose of a combination of propofol 0.8 mg kg and alfentanil 8 g kg in group 2 (78 patients) and group 3 (250...

Toremifene

The unwanted gynecological effects of toremi-fene (40 mg dd), when used in breast cancer, have been compared with those of tamoxifen (20 mg day) in 167 women (77Cr). There were vasomotor symptoms in 35 of the women before the start of the trial, but the incidence rose to some 60 with both products during the first year. Vaginal dryness, present in 6 at baseline, increased with both drugs to around 26 and endometrial thickness increased from a mean of 3.9 mm to 6.8 mm. The endometrium became...

Miscellaneous Compounds Nimesulide

Liver Further reports of the potential hepa-totoxicity of nimesulide continue to appear (SEDA-25, 135 122A-124A). A wide range of types of liver damage have been documented (125A). Some patients have required liver transplantation (126A) and deaths have occurred (127A). The pathogenic mechanism of these unpredictable, sometimes severe, reactions is uncertain (128r, 129r). In recent months in some countries nimesulide has been withdrawn from the market or its use has been restricted. DRUGS...

Thiuram

Thiurams are a group of chemicals that have been in commercial use since the 1920s. Their main uses are as accelerators and vulcanizing agents during rubber processing and as fungicides on seeds and plants. Skin Allergic contact dermatitis following exposure to thiuram compounds in rubber products, such as disposable rubber gloves, is well recognized (41R). A 49-year-old man developed acute pruritic dermatitis of the hand, which settled quickly with oral corticosteroids and antibiotics (42c)....

Hydromorphone SEDA24106

Intolerable adverse effects or inadequate analgesia occur in 10-15 of patients with chronic pain given continuous intrathecal morphine. Hydromorphone is a semisynthetic derivative of morphine used extensively in the management of cancer pain. It is more soluble than morphine, has a slightly shorter duration of action, and is about five times more potent when given systemically. In a retrospective review of 37 patients with chronic non-malignant pain (mostly from failed lumbosacral spine...

Oral Hypoglycemic Drugs

A retrospective analysis of a pharmacy database of over 60 million Americans has shown that many do not persist in taking particular oral hypoglycemic drugs (51C). Of 11.6 million patients identified as continuously benefit-eligible for mail and retail prescriptions, 136 466 had received a first prescription for an oral hypo-glycemic drug between 1 October 1997 and 31 March 1999. The 12-month persistence rate ranged from 31 for a-glucosidase inhibitors to 60 for metformin. Compliance rates were...

The cardiotoxic effects of antihistamines

Several antihistamines can cause ventricular dysrhythmias of the torsade de pointes type (4r), first reported with astemizole (5r) and later with terfenadine (6r). With a few exceptions, antihistamines are rapidly and completely absorbed after oral administration peak plasma concentrations are reached after 1-4 hours and are highly variable, owing to differences in metabolism and tissue distribution (2r). Many of the second-generation anti-histamines (e.g. astemizole, ebastine, lorata-dine, and...

Cotrimoxazole trimethoprim plus sulfamethoxazole

Co-trimoxazole remains the first-line agent in the therapy and prophylaxis of Pneumocystis carinii pneumonia. HIV-infected patients are susceptible to adverse events, particularly fever or rash. The US Centre for Disease Control (CDC) recommends a dose of co-trimoxazole containing trimethoprim 150 mg m2 day and sul-famethoxazole 750 mg m2 day for Pneumocys-tis carinii prophylaxis in HIV-infected children. In a retrospective study of the records of 49 HIV-infected children who met CDC criteria...

Amphotericin B deoxycholate DAMB

Urinary tract The epidemiology of the nephrotoxicity of conventional amphotericin B has been investigated in a retrospective study in 494 adult in-patients who received two or more doses (1c). Nephrotoxicity was defined as a 50-100 increase in the baseline crea-tinine concentration. The median cumulative dose was 240 mg and most of the patients received it for empirical therapy. Overall, 139 patients (28 ) had renal toxicity, including 58 (12 ) with moderate to severe nephrotoxicity. For each...

Hydroxyethyl starch hetastarch

Skin In a retrospective study of the dose-dependency of pruritus caused by hydroxyethyl starch, 50 consecutive patients were evaluated by questionnaire about 6 months after treatment 37 returned the questionnaires, of whom 20 reported pruritus, lasting an average of 15 weeks (3c). There was significantly more pruritus in patients who received more than 5 l of hydroxyethyl starch compared with those who received less than 5 l. The pruritus had a delayed onset and occurred in acute bouts lasting...

Theophylline

Risk factors Age Developmental differences in the balance between metabolic and renal elimination pathways determine the unique toxicokinetics of theophylline in neonates. Three premature neonates received inadvertent intravenous doses of theophylline for apnea of prematurity (6a). All the neonates had sinus tachycardia and agitation. Maximum serum theophylline concentrations were 55-123 mg l theophylline-derived caffeine concentrations plateaued at 8.4-13 mg l and did not fall during the...

Fluvastatin

Liver A woman presented with clinical and laboratory signs of cholestatic and necrotic acute hepatitis (19A). A 61-year-old woman developed symptoms of acute hepatitis 6 weeks after she began to take fluvastatin sodium 20 mg day for hypercholesterolemia. Ultrasonography and liver biopsy confirmed the diagnosis of non-obstructive intrahepatic jaundice. Studies of viral markers and autoimmune factors excluded viral hepatitis and autoimmune hepatitis. There was a high serum concentration of a...

The baclofen withdrawal syndrome

Long-term administration of baclofen is widely used in patients with muscle spasticity resulting from a variety of cerebral and spinal chord lesions. As with other GABA receptor agonists, withdrawal reactions will occur if it is stopped abruptly. Patients can present with different symptoms, not all ofwhich would be considered classical of drug withdrawal. Some interesting aspects of withdrawal symptoms after baclofen administration have been highlighted in three recent reports. Clinical...

Metals

A 19-year-old woman presented with multiple itchy nodules on the outer aspects of the upper arms at the sites of previous vaccine injections (5A). There were several nodules, ranging from a few millimeters to 1 cm in diameter, some with overlying hyperpigmented skin. She had been receiving hyposensitization vaccines to treat recurrent extrinsic asthma and rhinitis for the previous 4 years. A skin biopsy showed a normal epidermis and upper dermis. There were multifocal unen-capsulated...

Cotrimoxazole

The relation between the onset of adverse reactions to co-trimoxazole in HIV-infected patients and the subsequent development of toxoplasmosis, other AIDS-defining events, and survival has been studied in 592 French patients (226C). A low CD4 cell count when co-trimoxazole was introduced was the only factor associated with the onset of adverse reactions. The occurrence of toxoplasmosis and first AIDS-defining events was significantly and independently linked to a low CD4 cell count when...

Colophonium and gum resins

Colophonium, a natural unmodified gum resin used in cosmetics such as mascara, lipsticks, creams, and hair removal products, is a known contact allergen. Modifications have been made to colophonium, resulting in a variety of ester gums. In a retrospective study, 1270 patients with leg ulcers were tested for contact allergy with colophonium and the modified ester gum Table 1. Contact allergy to ingredients of topical drugs and cosmetics Alkylammonium amidobenzoate (Osmaron B) Surfactant, mild...

Drugs Active Against Cytomegalovirus

Five antiviral drugs that are active against cy-tomegalovirus have been approved and are available for use. Mainstays for treatment continue to be intravenous ganciclovir and fos-carnet, possibly because of their established efficacy and safety. Valganciclovir, an oral prodrug that is rapidly hydrolysed by plasma esterases to ganciclovir, has recently been added. It has high systemic availability and causes adverse reactions as often as an equivalent dose of intravenous ganciclovir. Cidofovir...

Phenytoin and fosphenytoin

(SED-14, 180 SEDA-23, 89 SEDA-24, 90 SEDA-25, 90) Immunologic Hypersensitivity to phenytoin (which had been previously well tolerated) after a hypersensitivity reaction to carbamazepine has been reported (46A). A 19-year-old man with partial epilepsy took phenytoin 300 mg day for over 6 months. Carba-mazepine was introduced and after about 6 weeks (while taking phenytoin 300 mg day and carbamazepine 600 mg day), he developed fever, anorexia, a sore throat, bloody diarrhea, a diffuse,...

Allergic reactions to rocuronium

During the last few years several allergic reactions to rocuronium have been reported. Based on data from the UK, Australia, and France, it had been suggested that the incidence of such reactions after rocuronium administration paralleled its frequency of use, as assessed by its market share, implying that rocuronium did not have unusual allergenic properties (4C-6C). Also, the incidence ofhypotension, tachycardia, or reduced oxygen saturation (which might suggest an anaphylactoid reaction) was...

Cyanamide

Skin Rashes due to cyanamide have been reported in two cases (10c). A 37-year-old man developed itchy erythema on his trunk and legs after taking cyanamide (dose not specified) for 3 days. He had an eosinophilia of 22 . Patch testing with cyanamide was positive. The eruption subsided after withdrawal of cyanamide. A 60-year-old man developed keratotic erythema on his trunk and extremities after taking cyanamide (dose not specified) for 1 month. Patch testing with cyanamide was positive. The...

Lithium

Mine the World Health Organization International Drug Monitory Database for information on antipsychotic drugs and heart muscle disorders found 17 case reports involving lithium (4r). There was a significant association with lithium and cardiomyopathy, but not with myocarditis. However, a causal relation could not be established. Two reviews of drug-related congenital malformation briefly mentioned lithium and cardiovascular teratogenesis, but no new information was provided (5r, 6r). Likewise,...

Diltiazem

Nervous system Parkinsonism associated with diltiazem has been reported (14A). A 53-year-old man with hypertension took dilti-azem 60-120 mg day for 5 years and then developed Parkinsonism. His neurological symptoms were treated without success and only after the substitution of diltiazem with an ACE inhibitor did his Parkinsonian symptoms began to regress, with eventual complete recovery. Skin Four cases of photodistributed hyper-pigmentation associated with long-term administration of a...

Lorazepam

Nervous system The effects of lorazepam and diazepam on false memories and related states of awareness have been investigated in 36 healthy volunteers, randomly assigned to one of three groups (placebo, diazepam 0.3 mg kg, lorazepam 0.038 mg kg) (12C). The results suggested that diazepam and lorazepam cause impaired conscious recollection associated with true, but not false, memories. The effects of lorazepam on three neuropsy-chiatric measures ofattention and psychomotor performance have been...

Buffergel

Since there is an urgent need for topical mi-crobicides that women can administer vaginally to protect themselves from HIV infection and possibly other sexually transmitted diseases and pregnancy, BufferGel (ReProtect LLC, Baltimore, MD), an aqueous gel of a spermicidal microbicide, formulated at pH 3.9, which acidifies twice its volume of semen to a pH of 5 and maintains the protective acidity of the vagina, should be ideal. The safety of BufferGel has been evaluated in a high-dose tolerance...

Tenofovir

Tenofovir is the newest member of this class, and, in contrast to the others, it only needs to be phosphorylated twice intracellularly before it is pharmacologically active. Adverse effects have been reported as flatulence, raised transaminases, raised creatine kinase, and rarely a raised serum creatinine (26c). However, teno-fovir does not currently appear to be nephro-toxic. DRUGS ACTIVE AGAINST HUMAN IMMUNODEFICIENCY VIRUS NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTI) (SED-14, 996...

Acitretin

Nervous system The possible negative effects of short-term oral acitretin 1 mg kg day on peripheral nerve function have been assessed in a small prospective study in 13 patients (69c). Patients with conditions related to peripheral neuropathy were excluded. There was a fall in the mean amplitude of the sensory action potential of the superficial peroneal nerve after 1 and 3 months of therapy. There was a significant change in one or more neurophysiological parameters in three of 13 patients...

Verapamil

Cardiovascular Another case of cardiogenic shock after the ingestion of verapamil has been reported, but on this occasion with a small dose (32a). A 78-year-old woman with a history of biventric-ular heart failure had cardiogenic shock after she took a single tablet of verapamil 80 mg. She was resuscitated with artificial ventilation, dobutamine, noradrenaline, and calcium gluconate. Toxicologi-cal analysis showed an unexpectedly high plasma verapamil concentration, which was attributed to...

Progesterone Antagonists

(SED-14, 1471 SEDA-21, 422 SEDA-25, 492) Mifepristone (RU 486) The optimal dose of mifepristone to secure an abortion without excessive adverse effects is not known. In a study in nearly 900 women there was no appreciable difference between oral doses of 200 or 600 mg, followed after 48 hours by gemeprost 1 mg vaginally (87C). The similarity of adverse reactions with the lower and higher doses of mifepristone has been confirmed by others (88Cr). However, in another study mifepristone 0.5 mg,...

Ljp 394

LJP 394 is an investigational drug under development as a selective immunomodulator for the treatment of systemic lupus erythemato-sus. It reduces serum dsDNA antibodies and splenic dsDNA antibody-producing cells in BXSB mice and causes improved renal function and histopathology, as well as prolonged survival (150E). In a phase 2, partially randomized, doubleblind, placebo-controlled study of three different doses of LJP394 in 58 patients, seven did not receive all doses of LJP394 because of...

Dorzolamide

Skin Topical dorzolamide caused severe periorbital dermatitis after an average exposure time of 20 weeks in 14 patients (7c). Although the dermatitis may resolve when dorzolamide is withdrawn, this does not always occur, and in some patients all topical medications containing benzalkonium chloride must be withdrawn. Allergic contact blepharoconjunctivitis has also been reported with dorzolamide in a 72-year-old man (8A). THIAZIDE AND LOOP DIURETICS (SED-14, 656 SEDA-23, 228 SEDA-24, 250...

Vitamin B6 pyridoxine

In India, pyridoxine hydrochloride, along with thiamine and cyanocobalamin, is often injected or given orally as a neurotonic to large numbers of people. Skin Contact hypersensitivity to pyridoxine is rare. Only three cases of allergy to pyridox-ine have been reported in hair lotion (24A), a corticosteroid cream (25A), and a skin cream (Iruxol) (26a). There have also been a few reports of photosensitivity due to pyridoxine hydrochloride (27A-29A). Occupational systemic contact dermatitis with...

Special hazards of smoked cannabis

Traditionally the use of cannabis both in Oriental and Western medicine involved taking the drug by mouth, but most current use in the West involves the inhalation of cannabis smoke. Unfortunately, although smoking is a remarkably efficient means of delivering an accurately gauged dose of THC it also carries special hazards. Although THC itself appears to be relatively safe, the same cannot be said of marijuana smoke. Cannabis smoke and smoking behavior Although there has been relatively little...

Terbinafine

Hematologic With increasing use of terbina-fine world-wide, anecdotal cases of hematolog-ical toxicity are being reported. The projected rate of all blood dyscrasias associated with terbinafine has been estimated to be 32 per million patient-years (50A). Agranulocytosis occurred in a 15-year-old who took terbinafine 250 mg day for toenail onychomy-cosis and tinea pedis (51A ). This effect was noted 4 weeks after starting terbinafine and resolved within 1 week after its withdrawal. As the...

Index of drugs

Notes For any therapy, see under the specific item and the class for example lisinopril and angiotensin-converting enzyme inhibitors. Boldface page numbers refer to main discussions. abacavir, 330 acamprosate, 540 acarbose gastrointestinal system, 467 liver, 467 metabolic effects, 467 metformin concentration, 468 ACE inhibitors. see angiotensin converting enzyme inhibitors aceclofenac, 115 acetaminophen. see paracetamol acetazolamide electrolyte balance, 238 immunologic system, 239 overdose,...

Lincomycin

Skin Precautions are necessary to avoid ultraviolet radiation after taking photoreactive drugs (154e). Metabolism of lincomycin can lead to the formation of reactive oxygen species and cause tissue injury and damage to various cellular macromolecules, which can result in phototoxicity. MACROLIDES (SED-14,873 SEDA-23, 273 SEDA-24, 295 SEDA-25, 306) The basic structure of macrolides is characterized by a lactonic cycle with two osidic chains, and they are classified according to the number of...

Drug Interactions

In a review of the pharmacokinetics of mood stabilizers and new anticonvulsants, lithium drug interactions were only briefly mentioned (102r). Anesthetics Sinus bradycardia (36 bpm) developed in a 44-year-old woman taking lithium, fentanyl, and propofol (15A) (see also Cardiovascular). Antibiotics A 40-year-old woman developed nausea, malaise, impaired concentration, trembling, unsteadiness, diarrhea, and muscle spasm in association with a serum lithium concentration of 2.1 mmol l while taking...

Miocamycin

Drug interactions CYP3A4 is mainly responsible for catalysing the hydroxylation of miocamycin metabolites. Some macrolide antibiotics cause drug interactions that result in altered metabolism of concomitantly administered drugs by the formation of a metabolic intermediate complex with CYP450 or competitive inhibition of the CYP450 (157R). The resulting interactions can cause rhabdomyol-ysis (associated with the co-administration of some statins, e.g. lovastatin or simvastatin),...

Alltrans retinoic acid

A novel intravenous liposomal formulation of all-trans retinoic acid (Atragen , Aronex Pharmaceuticals Inc, The Woodlands, TX), which provides a reliable dose for patients who are unable to swallow or absorb medications, has been evaluated in 69 patients with acute promyelocytic leukemia (5C). Liposomal all-trans retinoic acid (90 mg m2) was given every other day until complete remission or a maximum of 56 days. Treatment after complete remission was liposomal all-trans retinoic acid with or...

Delayed reactions to iodinated watersoluble contrast agents

Delayed contrast reactions usually occur after 1 hour but within 7 days of contrast injection. Several of the reported delayed adverse effects, such as headache, musculoskeletal pain, and flu-like symptoms, may not be caused by the contrast agents, but delayed allergic-like skin reactions are most likely to be. Delayed skin reactions tend to be commoner with non-ionic dimers than with other types of contrast agents (SEDA-22, 499). Delayed reactions are generally benign, but not always. The...

Miscellaneous Nefopam

In an open trial 120 patients undergoing elective hepatic resection were randomized to receive postoperative intravenous patient-controlled analgesia with morphine either alone or in combination with nefopam (20 mg 4-hourly) or propacetamol (2 g 6-hourly) (132C). Nefopam plus morphine was the most effective treatment. Adverse effects, especially sedation, were comparable in the three groups, but there was significantly more nausea in the morphine group and more sweating in the nefopam group...

Methylenedioxymethamphetamine ecstasy MDMA

Concern has been raised about the increasing use of ecstasy in Europe in the last 10 years (10Cr), particularly the UK and the Netherlands. MDMA and drugs such as its N-demethylated derivative (MDA), 3,4-methyl-enedioxyethylamphetamine (MDEA), N-meth-ylbenzodioxazolylbutamine (MBDB), and 4-bromo-2,5-dimethoxyphenylethylamine (2-CB or Nexus) are often grouped together as ecstasy. Some have used the term enacto-gen, meaning touching within, to describe MDMA. The patterns and trends of substance...

Bryostatin

Bryostatin 1 is a naturally occurring macro-cyclic lactone derived from the marine invertebrate Bugula neritina. It is a protein kinase C partial agonist. In preclinical and phase I clinical studies it had promising antitumor and immunomodulating effects. It amplifies expansion of myeloid and erythroid progenitor cells stimulated by the cytokines GM-CSF, M-CSF, and IL-3. Similarly, it induces the production of peripheral blood mononuclear cells with enhanced lymphokine-activated killer cell...

Tobramycin

Sensory systems Histological examination of the temporal bones from two individuals with ototoxicity due to tobramycin showed reductions in the numbers of both ganglion cells and hair cells (24c). Spiral ganglion cell loss was not necessarily subadjacent to areas of hair cell loss in cases of aminoglycoside ototoxicity. Instead, there may be a reduction in the number of ganglion cells in segments of the cochlea with normal-appearing hair cells. Respiratory Nebulized antipseudomonal antibiotics...

Triphenylmethane dyes SED14 761

Gentian violet is a triphenylmethane dye that is used as a topical antifungal and antiseptic. It was also used in the treatment of oral candidiasis for more than 70 years, until concerns arose over its mutagenic and carcinogenic effects in animal studies. In the UK its licence is restricted to topical application on unbroken skin and it is no longer recommended for application to mucous membranes or open wounds. In the USA gentian violet is still used as a topical therapy for thrush,...

Chloroquine and hydroxychloroquine

Chloroquine remains effective against most non-falciparam malaria, but owing to widespread resistance has limited efficacy in the management of P. falciparum infections. Nevertheless, because of its low cost and wide availability it is still widely used in many countries. Amodiaquine and chloroquine have been compared in an open randomized trial in uncomplicated falciparum malaria in Nigerian 2003 Elsevier Science B.V. All rights reserved. Side Effects of Drugs, Annual 26 J.K. Aronson, ed....

Albendazole mebendazole and thiabendazole

Benzimidazoles and human neurocysticerco- sis The controversies in the management of neurocysticercosis have been described in an excellent review (1R). Cysticercosis is caused by the larval stage of the pork tapeworm Tenia solium. Neurocysticercosis is the most severe and common clinical manifestation and probably the most frequent parasitic infection of the central nervous system. Tenia solium is endemic in Latin America, Asia, and sub-Saharan Africa. However, the management of neurological...

Ecballium elaterium squirting cucumber SED141658

Ecballium elaterium is used in the Mediterranean as a purgative and in treating sinusitis. In a retrospective chart analysis in a Greek ENT department 42 patients with allergic reactions to this remedy, including upper airway edema, were identified (31c). Treatment with corticosteroids and antihistamines resulted in full recovery in all cases. Echinacea (SED-14, 1658 SEDA-25, 569) A 41-year-old man, who had taken Echinacea intermittently for the previous 18 months, had four episodes of erythema...

Clarithromycin

In a multicenter, double-blind, randomized comparison of cefprozil, 500 mg bd for 5 days and clarithromycin 500 mg bd for 10 days in 295 subjects with an acute exacerbation of chronic bronchitis, the most common adverse effects of clarithromycin were nausea (8 ), diarrhea (12 ), taste disturbance (8 ), and dry mouth (5 ) (172C). Cardiovascular In a prospective, nonrandomized study, phlebitis occurred in 15 of 19 patients treated with intravenous erythromycin (incidence rate of 0.40 episodes...

Leukotriene Receptor Antagonists Seda24 184 Seda25 197

The safety and tolerability of montelukast in patients aged 6 years or more have been evaluated in a meta-analysis of pooled data from 11 multicenter, randomized studies and five long-term extension studies (55M). In 3386 adults (aged 15-85 years) and 336 children (aged 6-14 years), the overall incidence of clinical and laboratory adverse events was similar among patients taking montelukast and placebo. There were no clinically important differences in individual adverse events between the two...

Midodrine

Orthostatic hypotension forms a potentially very disabling component of several types of autonomic disturbance. It is relatively common in all age groups, but the cause varies. It is commonly due to drugs (such as diuretics, antihypertensive drugs, and neuroleptic drugs) and to neurocardiogenic or vasovagal syncope, which occurs at all ages, usually without any obvious triggers. Hypotension can also form part of autonomic neuropathies, such as those associated with diabetes and less commonly...

Diphtheriatetanus or diphtheria tetanuspertussis vaccines in combination with other vaccines

(SED-14, 1086 SEDA-23, 341 SEDA-24, 371 SEDA-25, 382) DTaP or DTwP vaccine can be combined with other antigens, such as Hemophilus influenzae type b (Hib), inactivated poliovirus (IPV), and hepatitis B vaccine. In children DTaP or DTwP vaccines are the basis for such combinations, while in adults it is mostly Td vaccine, Current safety concerns regarding combination vaccines have been defined and reviewed (17r). The author concluded that there is no evidence that adding vaccines to combination...

The cognitive effects of MDMAR

Recently, several studies have focused on the cognitive effects of MDMA, and a review of the adverse effects of MDMA in animals has raised concerns about potential toxicity in humans (14r). MDMA can selectively damage brain serotonin (5-HT) neurons in animal brains, even at doses within the range of those typically used recreationally. In many studies lasting reductions in various brain 5-HT markers have been reported in MDMA-treated animals. Axons of 5-HT neurons were damaged in MDMA-treated...

Levosalbutamol levalbuterol

Levosalbutamol is the (R)-enantiomer of the b2-agonist salbutamol (albuterol). It has been suggested to have a better therapeutic index than racemic salbutamol. As levosalbutamol has a much higher receptor affinity than the (S)-enantiomer, the therapeutic effects of racemic salbutamol are assumed to be mediated by lev-osalbutamol. However, toxicity of levosalbuta-mol is unrelated to b2-receptor binding, and so the (S)-enantiomer may significantly contribute to the toxicity of racemic...

Menthol

Menthol is a cyclic alcohol, obtained from the volatile oils of various species of Mentha. It is largely used as a flavoring or olfactory agent in a variety of products, including cigarettes, liqueurs, cough drops, mouthwashes, toothpastes, and shampoos. Menthol has been used in different medications to relieve symptoms of asthma and rhinitis. It can cause perioral dermatitis, urticaria, and stomatitis (28A). Respiratory Some reports have pointed out a relation between menthol present in...