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Drug Interaction Study of Tegretol Carbamazepine and St Johns Wort in Normal Volunteers

To their regular medicines to elevate mood or relieve stress. Preliminary research indicates that this supplement can speed the metabolism of the anti-seizure drug Tegretol, causing reduced blood levels of the drug. Patients who take Tegretol to control their seizures may have more frequent seizures if the blood level of the drug drops too low. A recent study shows that this effect is not seen when Tegretol is taken for at least 3 weeks. The present study will examine whether there is a medically important drug interaction between St. John's wort and Tegretol when Tegretol is taken for 1 day. Normal healthy volunteers between 21 and 65 years old who are not taking medicines that can affect the metabolism of drugs in the liver and have not used St. John's wort for at least 30 days may be eligible for this 25-day study. Participants will take a 400-mg dose of Tegretol after fasting overnight. Blood samples will be drawn the next day during a 12-hour clinic stay at the following...

Advances In Toxicology

During the nineteenth century, written works on toxicology contributed greatly to the systematic growth of the science. European and American scientists wrote texts which improved the chemical and medical understanding of poisons. Sophisticated methods (for the time) were developed to confirm the presence of toxins. Because arsenic was such a common means of murder, it became the focus of early analytic work. No fewer than three scientists developed methods to test for arsenic. James Marsh, Hugo Reinsch, and Max Gutzeit gave their names to methods some of which are still in use today. At this same time in history, medical science began to explore pharmaceuticals in a more rigid and systematic manner. Great scientists, especially in France and Germany, made contributions to the understanding of human physiology and drug interactions within the body.

Selective Serotonin Reuptake Inhibitors

The SSRIs have a wide range of potential drug interactions because of their effects on the hepatic microsomal enzyme systems. These interactions are often minor, but some can be dangerous. The metabolic inhibition of some commonly prescribed drugs by SSRIs is presented in Table 2.1.

Prospects For Enteroviral Therapies

Pleconaril, a compound with activity against many rhinoviruses and enteroviruses, is the first compound for which data exist to define anti-viral drug interaction with a virion at the atomic level. This compound is one of a class of compounds which resembles aril-done, a drug known to inhibit uncoating of poliovirus. X-ray diffraction studies of bound to rhino virus 14 show that the compound adheres tightly to a hydropic pocket formed by VP1, one of the structural proteins of rhinovirus 14. These hydrophobic pockets were found in the VP1 proteins of poliovirus and meningovirus and may be common to all picomaviruses. These compounds may lock into the conformation of the VP1 so that the virus cannot disassemble.

Proteomics Based Anticancer Drug Discovery

Proteomic technologies are being used in an effort to correct some of the deficiencies in traditional drug discovery. Proteins are important targets for drug discovery, particularly for cancer as well because there is a defect in the protein machinery of the cell in malignancy. Because proteome analysis can produce comprehensive molecular description of the differences between normal and diseased states, it can be used to compare the effect of candidate drugs on the disease process. The trend now is to integrate onco-proteomics with oncogenomics for drug discovery and target validation in oncology. Among the large number of proteomic technologies available for this purpose, the most important ones are three-dimensional protein structure determination, protein biochips, laser capture microdissection, and study of protein-protein and protein-drug interactions. Cancer biomarkers and signaling pathways involved in malignancy are important drug targets. The wealth of new information in...

Does gabapentin and lamotrigine have significantly fewer sideeffects while providing equal or better seizure control

Purpose - Excerpt New onset epilepsy in the elderly occurs in 45,00050,000 elderly patients each year. These patients are especially vulnerable to side effects from medications because of changes caused by the aging process and the fact that these patients often have many common diseases for which they are already receiving medications for so that the likelihood of drug interactions is increased. Two new drugs, gabapentin and lamotrigine, have recently been approved by the FDA as antiepileptic drugs. These drugs have demonstrated efficacy in the treatment of partial onset seizures, the most common seizures in the elderly. These new compounds also have favorable side effect profiles and infrequent drug-drug interactions and, therefore, would be expected to be well-tolerated in the elderly.

Models For Toxicological Testing

Different factors are believed to influence the activity of drug-metabolizing enzymes, hampering meaningful comparisons between xenobiotic metabolism of animals and humans. These include age, sex, environmental exposure, diet, pathophysiological status, drug-drug interactions, and genetics (interindividual differences in the activity level of various isoforms, polymorphisms).2 Sex differences in the expression of CYPs within the same species have been shown for rat and mouse, whereas a sex specific human CYP isozyme has not yet been reported.3 Concerning environmental exposure, there is even little comparison between rats and mice (and between strains of the same species) with respect to chemical carcinoge-nicity and in the pathways for both activation and detoxification.2,4 Experimental models are kept in a controlled environment with a defined dose regimen and dietary restrictions, limiting the chance of drug-drug interactions whereas in humans, drug-metabolizing enzymes are...

Drug eruption See eruption

Drug interaction The mutual pharmacological influence of two or more drugs taken concurrently. The influence may be antagonistic or synergistic and may be lethal in some cases. The chance of development of an undesired drug interaction increases as the number of drugs taken increases. People with HIV commonly take several medications at the same time to fight HIV and its related conditions. These drugs can interact, leading to more toxic side effects and reduced effectiveness. (Not all drugs interact in this way, as some may be combined without ill effect.) Vitamin or mineral supplements can also interact with drugs, causing elevations or decreases in drug availability. Some interactions affect the way drugs are absorbed by the gastrointestinal system. Degree of absorption is highly dependent on stomach acidity and the rate of absorption drugs that are not absorbed well do not achieve sufficient levels in the blood to exert their effects. Malabsorption can be caused by diarrhea, which...

Emergency Medicine Requires Many Skills

While one case is being stabilized, many more are waiting patiently (and often impatiently) for evaluation, treatment, discharge, or admission. The emergency physician constantly juggles many tasks at once, whether acquiring data, making decisions, or performing procedures. Patients, lab results, nurses, chest x-rays, family members, and other physicians all vie simultaneously for your immediate attention. Because you are doing so many things at once, emergency care sometimes requires knee-jerk action, after which additional thinking is necessary. In a short amount of time, you coordinate a wide range of treatment plans, from readjusting an asthma patient's medications to suturing wounds of another patient who also just received a chest tube. With recent advances in medicine, more and more patients are coming to the emergency room with complex problems, such as unusual drug interactions, or complications from procedures that did not exist before, like organ transplants. Now, emergency...

The Internist As Head Coach

Because many patients have multisystem diseases requiring specialized care, the team of physicians and other health care providers can easily become fragmented and disorganized, which in turn may seem confusing and frustrating for patients. An organized internist with leadership skills can prevent or at least minimize this frustration and confusion. By tracking medications prescribed by other physicians, monitoring potential drug interactions, following up on studies or procedures performed by subspecialists, and responding to their recommendations, the internist orchestrates multidisciplinary care and helps the patient navigate a complex system of care. In addition, the internist acts as the patient's advocate within the complex health care environment of resource utilization and restricted access to care.

Role of combination therapy in diabetes and dyslipidemia

Despite the known pharmacologic effects of fibrates and nicotinic acid in ameliorating the underlying defects of diabetic dyslipidemia (increased triglyceride-rich lipoproteins low HDL cholesterol small, dense LDL particles), the role of combining these agents with statins remains uncertain and further clinical trials are needed. Trials like the VA-HIT and DAIS are supportive of the potential of adding fibrates to statins because combined lipid disorders are common in patients who have insulin resistance and type 2 diabetes. In short-term studies, statins and fibrates were more effective in normalizing all lipid abnormalities than either agent alone without significant risk for adverse events, including myositis 51,52 . Caution should be exercised in patients who have potential drug interactions (eg, cyclo-sporin, antifungal agents, protease inhibitors, erythromycin) or renal disease. Long-term trials of combination therapy with statins and fenofi-brate are in progress (Table 5).

Epilepsy Patient and Family Guide Second Edition

Principles of drug therapy, (5) discuss anticonvulsants, (6) discuss surgical therapies, and (7) describe other epilepsy therapies. The third section is entitled Epilepsy in Children and consists of 10 chapters that discuss (1) epilepsy in infancy, (2) Epilepsy in childhood, (3) epilepsy in adolescence, (4) outgrowing epilepsy, (5) intellectual and behavioral development, (6) how to tell children and others about epilepsy, (7) how to live an active life, (8) the education of children with epilepsy, (9) mental handicaps and cerebral palsy, and (10) how children can cope with epilepsy after their parents are gone. The fourth section is entitled Epilepsy in Adults and consists of six chapters that address (1) living with epilepsy, (2) pregnancy and menopause, (3) parenting by people with epilepsy, (4) employment issues for people with epilepsy, (5) mental health in adult patients with epilepsy, and (6) epilepsy in the elderly. The fifth sections entitled Legal and Financial Issues in...

Pharmacokinetic Studies

Figure 8.1 Two-compartment model to describe drug kinetics following a single intravenous bolus injection (from Mant and Allen, 2001. Early phase studies, pharmacokinetics and adverse drug interactions. In I Di Giovanna and G Hayes, Principles of Clinical Research. Wrightson Biomedical Publishing, Petersfield, pp 117-160. 8 ) Figure 8.1 Two-compartment model to describe drug kinetics following a single intravenous bolus injection (from Mant and Allen, 2001. Early phase studies, pharmacokinetics and adverse drug interactions. In I Di Giovanna and G Hayes, Principles of Clinical Research. Wrightson Biomedical Publishing, Petersfield, pp 117-160. 8 )

When or How Should Samples Be Collected for GenotypingmRNA Expression ProfileSNP Profiling

Some examples of scientific rationale to perform pharmacogenetic and pharmacoge-nomic studies include (1) a compound metabolized by a polymorphic enzyme, (2) drug interaction studies involving any substrates with polymorphic enzymes (e.g., probe cocktail), and (3) variants in the drug target or pathways known to affect safety (e.g., long QT genes).

Reuters Health Drug Database

Mosby's GenRx database (also available on CD-Rom and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Information can be obtained at the following hyperlink The Physicians Desk Reference database (also available in CD-Rom and book format) is a full-text drug database. The database is searchable by brand name, generic name or by indication. It features multiple drug interactions reports. Information can be obtained at the following hyperlink

Contraindications and Interactions Hidden Dangers

Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause you to experience an unexpected side effect. Drug interactions may make your medications less effective, cause unexpected side effects, or increase the action of a particular drug. Some drug interactions can even be harmful to you. Be sure to read the label every time you use a nonprescription or prescription drug, and take the time to learn about drug interactions. These precautions may be critical to your health. You can reduce the risk of potentially harmful drug interactions and side effects with a little bit of knowledge and common sense. Drug labels contain important information about ingredients, uses, warnings, and directions which you should take the time to read and understand. Labels also include warnings about possible drug interactions. Further, drug labels may change as new information becomes available. This is why it's especially important to read the label...

Discussion of Case Presented Here

In addition to the heterozygote CYP2D6*4 status, the possibility of drug-drug interactions of methadone and other medications is likely in this case, indicated by the large number of comedications the decedent consumed over the time period when methadone was abused (e.g., concomitant use of methadone, alprazolam, and oxycodone). Pharma-cotherapy is increasingly complicated by the use of multidrug regimens that may result in clinically important drug interactions. In particular, some drugs are inhibitors of specific CYP enzymes and therefore could inhibit the metabolism of drugs that are substrates of these CYP enzymes, while others may serve as inducers of CYP enzymes in that enzymatic activity is induced over time, resulting in rapid metabolism of substrate drugs. Coad-ministrated drugs that share the same enzyme pathway for metabolism may compete with each other, resulting in diminished metabolism for one drug.

Thelper to Tsuppressor ratio See tcell homeostasis Tcell Ratio

Therapeutic drug monitoring Measuring of the blood levels of the medication(s) an individual is taking for a given condition or conditions. At issue are the desired blood levels for maximal treatment effectiveness and the patient's blood levels. Also at issue are toxicity, side effects, and drug interactions.

Viral load assay See viral load

Viral load blip Temporary spike in viral load to above 50 copies mL that returns to undetectable levels on the next viral load test. Viral load blips are detected in 30 percent-50 percent of patients whose viral load is otherwise stable and fully suppressed. Rises in viral load may be caused by variations in the tests themselves or anything that stimulates the patient's immune system such as a vaccination or infection. Additional causes of an increase in viral load are medication noncompli-ance and drug-drug interactions, which may lead to resistant virus. The frequency at which blips are detected depends on the frequency at which viral load testing is performed. Even though viral load blips are most frequent among patients with more drug experience, it seems that patients who have blips are at greater risk of virologic failure than patients who do not. How to respond to these blips is still unclear because most patients who have them do return to undetectable viral levels but some do...

The Synthetic Pyrimidines

Effect of the latter compound, can induce increased toxicity to 5-fluorocytosine. Adverse drug interactions can occur with other antimicrobial and anticancer drugs, cyclosporine, and other therapeutic agents. Because of its toxic potential, 5-fluorocytosine should not be administered to pregnant women or animals. This drug has been used in combination with keto-conazole for cryptococcosis in small animals (very toxic for cats) and also for respiratory apergillosis and severe candidiasis in birds.

Myositis and Myopathy

Drug metabolism After a drug has entered the body, it can be processed in several ways. some drugs, for example penicillin antibiotics, are absorbed and then eliminated unchanged by the kidneys. Others, for example codeine, are absorbed as poorly active pro-drugs that are biotransformed by the liver to a more active metabolite, in the case of codeine into morphine. The liver, in addition to activating pro-drugs, biotransforms drugs into metabolites that are less active or toxic than the parent drug. These chemical reactions are classified into Phase i and ii reactions and are carried out by enzymes. Many Phase i reactions are mediated by enzymes belonging to a group called the cyto-chrome P450 (CYP) superfamily. This is classified into families such as CYP1, 2, and 3 and further divided into subfamilies such as CYP1A, 2D, and 3A. Many drugs are metabolized by more than one CYP enzyme, but some depend on a single pathway. Drugs eliminated by a single metabolic pathway are particularly...

Asymptomatic infection

Atovaquone A recently licensed oral drug for treatment of mild-to-moderate cases of PCP as well as for salvage treatment of toxoplasmosis. Its absorption is highly dependent on ingestion with food, especially fatty food, which increases its absorption four- or fivefold. Atovaquone is known to have many drug interactions, some of which result in synergistic or additive effects against the toxoplasma parasite. It is known to be synergistic with azithromycin, clarithromycin,

HIV wasting syndrome See wasting syndrome

HIV-associated adipose redistribution syndrome (HARS) A general term referring to the variety of body fat composition changes associated with anti-retroviral therapy. The natural history and cause (or causes) is not clearly understood. There are a number of different theories about how HARS might evolve. There are a large number of pharmaceutical treatments for high cholesterol level and other lipid disorders however, there is concern about using some of these drugs for people on HAART because there is a potential for drug interactions since many share the same metabolic pathway as many antiretrovirals. Strategies to ameliorate the signs and symptoms of HARS continue to be studied. See lipodystrophy.

Treatment Approach

Masseter Muscle Injection

The current pharmaceutical agents available to treat migraine are unsatisfactory because of limited efficacy, severe adverse effects, and drug interactions. BoNT-A is a paralytic neuro-toxin that inhibits acetylcholine release at the neuromuscular junction. Although it has been approved for treating blepharospasm, strabismus, cervical dystonia, hyperfunctional glabellar lines, and hyperhidrosis, it has been safely used for various dystonias, spasticity, and tremor of the head and neck. The indication that BoNT-A may be effective for treating headache disorders was derived from anecdotal reports among patients being treating for hyperfunctional facial lines. Incidentally, these patients reported marked reductions in the frequency and severity of headache episodes and facial tension (34). These findings have been reproduced in several clinical studies for migraine headache (35-37).

Mutually monogamous sexual relationship A

The development of highly effective MAC prophylaxis has been a major advance in the treatment of HIV infection. New therapies offer promise for both prevention and treatment. At present, the drug azithromycin is preferred for prophylaxis, and the related drug clarithromycin for treatment of MAC illness. Individuals who cannot tolerate azithromycin or clarithromycin can take rifabutin. Prophylaxis is generally given when the CD4 lymphocyte count drops below 50 cells mm and stopped if CD4 count rises and remains above 50-100 cells mm. Therapy generally includes clar-ithromycin (without which treatment is much less effective), ethambutol, and one other drug (usually rifabutin or ciprofloxacin). Alternatives for prophylaxis are clarithromycin and rifabutin. MAC may become resistant to therapy if patients do not take the full doses of the anti-MAC drugs. Studies are needed to ascertain potential drug interactions and toxicities.

Blood product

Pancreatitis, and there may be a longer-term increased risk of heart attack and stroke associated with high triglygeride levels. Many persons on combination therapy have abnormally high blood lipid levels, particularly of triglycerides. High LDL and low HDL cholesterol levels also seem to be relatively common in patients on protease inhibitors and may increase the risk of heart attack and stroke. It is not known whether and how protease inhibitors cause lipid level elevations. Some researchers have suggested that the drugs act to inhibit the function of human protease enzymes and thereby affect the function of other proteins involved in lipid metabolism. Protease inhibitors are also known to affect the function of the cytochrome P450 system, a set of liver enzymes that metabolize drugs and other substances. These effects of cytochrome P450 are the reason many drugs interact with protease inhibitors. Researchers have also theorized that the effects of protease inhibitors on cytochrome...


Cytolin An experimental HIV treatment. It is a patented monoclonal antibody that prevents the CD8+ cells in the body from attacking the CD4+ cells, as occurs in HIV disease. The product is used to keep the immune system functioning while antivi-rals attack the virus. The product is being developed and produced through the funding of several HlV-positive professionals who started a company called CytoDyn. This is unusual, as most HIV-fighting products are produced by major international pharmaceutical companies. It is currently in phase I II trials in the United States. It is given as an intravenous drip once every month. No final dosing or frequency has been determined yet in the trials. Because Cytolin is a protein, its use may lessen drug interactions and need for numerous drugs in the system.

Dildo 143

Of ddl increases risk of pancreatitis as well as peripheral neuropathy. These latter two conditions are also more likely to occur if ddI is combined in treatment with d4T. A once-daily formulation of ddl has been approved by the FDA studies show similar results to twice a day dosing with the tablets. ddI should not be combined with ddC and should be taken at different times when used in combination with delavirdine, tenofovir, or indinavir. ddI has a tablet form that can be chewed or dissolved in water the once-daily formulation is a capsule. It is important to take ddI on an empty stomach at least one hour before eating or at least two hours after the last meal. Didanosine has several drug interactions that can cause levels of the drug to fluctuate in the body. Inform physicians of any medication you are taking if they prescribe this medication. It is also approved for children above six months of age with HIV infection. That formula is available in a flavored liquid that must be...

Flucytosine 185

Fluconazole An antifungal drug that is approved for fungal infections, primarily those caused by Candida albicans (thrush or candidal esophagitis) and cryptococcus neoformans (cryptococcal meningitis), a severe complication of HIV infection. Another fungal infection, coccidioidomycosis, can also be treated with fluconazole. Fluconazole can be taken by mouth or vein. Side effects are unusual. occasional problems are abdominal discomfort, nausea, rash, or signs of liver damage. Fluconazole has many drug-drug interactions with a wide variety of agents, including those frequently taken concurrently by people with HIV For exam

Exult B

Ximelagatran is a novel oral direct thrombin inhibitor, which is a prodrug rapidly absorbed in the small intestine and bioconverted to the dipeptide melagatran (429 Da), which is the active form.23 Melagatran is a selective, competitive small-molecular direct inhibitor of free and clot-bound thrombin with a complete bio-availability on subcutaneous injection. Melagatran is mainly excreted via the kidneys (around 80 ).24 After single and repeated oral dosing of ximelagatran the bioavailability of melagatran is around 20 .25 Maximum melagatran concentrations are reached in approximately two hours. A similar absorption is also seen three days after abdominal surgery.26 The main absorption site is the duodenum. Ximelagatran melagatran has no known food interaction and no clinically relevant drug interactions involving cytochrome P450 enzymes. Ximelagatran is the first oral direct thrombin inhibitor on the market.

Right to know 427

Rifabutin An oral drug approved by the U.S. food AND DRUG ADMINISTRATION for preventing mycobacterium avium complex (MAC) in people with aids and CD4 cell counts of less than 75. Rifabutin is also used in combination with other drugs for the treatment of active MAC infection. Rifabutin seems to have fewer drug interactions than rifampin, yet like isoniazid (INH) can change liver enzyme production and thus alter the metabolism of Coumadin, Dilantin, Tegretol, theophylline, and the benzodiazepines (Atavin, Valium). Other

Figure 131

The aim of an in vivo QT assay is to measure indices of ventricular repolarization such as the QT interval. This assay can be designed to meet the objectives of both ICH S7A and S7B.2542 The development of telemetry techniques in conscious animals has had a major impact on the conduct of in vivo cardiovascular safety pharmacology studies. The telemetry technique permits a continuous collection of a range of physiological parameters, including heart rate, pressures (e.g., arterial, venous, pleural, left ventricular), ECG (including the QT interval), and body temperature over longer periods of time in undisturbed animals. Thus, drug effects can be studied under physiological conditions using the clinical route of administration. Alternatively, anesthetized animals can be used under conditions where (1) the compound is poorly tolerated in the chosen species (e.g., due to emesis or tremor), (2) its bioavailability exposure is expected to be low, or (3) insufficient information is known...

Renal System

The kidney is a privileged target for toxic agents because of its physiological and pharmacoki-netics properties. It receives the largest amount of blood per gram of tissue among any other organ and therefore it is more exposed to exogenous circulating NCE than many other organs. Moreover, tubular mechanisms of ion transport acts to facilitate drug entry into renal tubular cells. From a pharmacokinetic perspective, the kidney is involved in filtration, excretion, and reabsorption of NCEs. The kidney concentrates urine so that intratubular drug concentration may be much higher than plasma concentration, and finally the kidney has a high metabolic rate. Several drugs drug classes are associated with nephrotoxicity (e.g., antibiotics, nons-teroidal antiinflammatory drugs, immunosuppressors, angiotensin-converting enzyme inhibitors, chemotherapeutic drugs, and fluorinated anesthetics).178,179 Deterioration of renal function over a period of hours to days results in the failure to excrete...

Anatomical Landmarks

Emg Spasmodic Dysphonia

The pharmaceutical agents currently available to treat dystonias are limited by partial efficacy, unwanted adverse effects, and drug interactions. Although commonly employed either alone, or in combination with BTX administration to treat segmental, multifocal, or generalized dystonias, pharmacological agents such as anticholinergics, benzodiazepines, and baclofen have demonstrated only partial benefit when used to treat focal dystonias alone. These medications, however, may be useful as an adjunct to BTX injection in SD to prolong the duration of improvement.

Protease paunch

Quency, food requirements, convenience, toxicity, and drug interaction profile when compared with other regimens. Note that the possibility of drug interactions is particularly a problem in persons who are being treated with multiple drugs, and it can influence the choice of drugs to be used in combination. For example, protease inhibitors affect the metabolism of the drug rifampin, which is sometimes given for active tuberculosis. At the same time, rifampin lowers the blood level of protease inhibitors and thus can reduce their therapeutic effectiveness. Medical complications of advanced HIV disease can also influence the use of combination anti-retroviral therapy. Wasting and anorexia can prevent individuals from following the dietary requirements necessary for effective absorption of protease inhibitors. Protease inhibitors may pose a greater risk of liver effects for individuals with HIV-related liver dysfunction. Because of the broad possibilities for detrimental drug...

Tubulin Biophysics

Can be incorporated into the various models as an experimentally determined parameter. For similar reasons, computer simulation of MT networks as cellular automata will also benefit from such a measurement. Furthermore, drug interactions with tubulin are currently under investigation and it has been theorized that electric dipole moment flips are responsible for London forces during interaction of tubulin with other molecules possessing dipole moments such as general anesthetic molecules 40 . A simplistic estimate of the tubulin dipole moment p based on a mobile charge of 18 electrons multiplied by a separation of 4 nm gives a magnitude of p 4 x 10 27 C m (or 1200 Debye) while using a more sophisticated molecular simulation, p has been quoted at around 1700 Debye 16, 87 . At physiological pH ( 7.2) MTs are negatively charged 85, 115, 127 due to the presence of a 15-residue carboxyl terminus tail and there have been suggestions that this C-terminus is important in polymerization,...